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  • 101.
    Månsson, Kristoffer N T
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. PRIMA Barn and Vuxenpsykiatri, Sweden.
    Salami, A.
    Karolinska Institute, Sweden; Umeå University, Sweden.
    Frick, A.
    Uppsala University, Sweden.
    Carlbring, P.
    Stockholm University, Sweden.
    Andersson, Gerhard
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Karolinska Institute, Sweden.
    Furmark, T.
    Uppsala University, Sweden.
    Boraxbekk, C-J
    Umeå University, Sweden.
    Neuroplasticity in response to cognitive behavior therapy for social anxiety disorder2016In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 6, no e727Article in journal (Refereed)
    Abstract [en]

    Patients with anxiety disorders exhibit excessive neural reactivity in the amygdala, which can be normalized by effective treatment like cognitive behavior therapy (CBT). Mechanisms underlying the brains adaptation to anxiolytic treatments are likely related both to structural plasticity and functional response alterations, but multimodal neuroimaging studies addressing structure-function interactions are currently missing. Here, we examined treatment-related changes in brain structure (gray matter (GM) volume) and function (blood-oxygen level dependent, BOLD response to self-referential criticism) in 26 participants with social anxiety disorder randomly assigned either to CBT or an attention bias modification control treatment. Also, 26 matched healthy controls were included. Significant time x treatment interactions were found in the amygdala with decreases both in GM volume (family-wise error (FWE) corrected P-FWE = 0.02) and BOLD responsivity (P-FWE = 0.01) after successful CBT. Before treatment, amygdala GM volume correlated positively with anticipatory speech anxiety (P-FWE = 0.04), and CBT-induced reduction of amygdala GM volume (pre-post) correlated positively with reduced anticipatory anxiety after treatment (P-FWE <= 0.05). In addition, we observed greater amygdala neural responsivity to self-referential criticism in socially anxious participants, as compared with controls (P-FWE = 0.029), before but not after CBT. Further analysis indicated that diminished amygdala GM volume mediated the relationship between decreased neural responsivity and reduced social anxiety after treatment (P = 0.007). Thus, our results suggest that improvement-related structural plasticity impacts neural responsiveness within the amygdala, which could be essential for achieving anxiety reduction with CBT.

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  • 102.
    Månsson, Kristoffer NT
    et al.
    Linköping University.
    Frick, Andreas
    Uppsala University.
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Centre for Population Studies (CPS).
    Marquand, AF
    Donders Institute, Radboud University.
    Williams, SCR
    King's College London.
    Carlbring, Per
    Stockholm University.
    Andersson, Gerhard
    Linköping University.
    Furmark, Tomas
    Uppsala University.
    Predicting long-term outcome of Internet-delivered cognitive behavior therapy for social anxiety disorder using fMRI and support vector machine learning2015In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 5, article id e530Article in journal (Refereed)
    Abstract [en]

    Cognitive behavior therapy (CBT) is an effective treatment for social anxiety disorder (SAD), but many patients do not respond sufficiently and a substantial proportion relapse after treatment has ended. Predicting an individual's long-term clinical response therefore remains an important challenge. This study aimed at assessing neural predictors of long-term treatment outcome in participants with SAD 1 year after completion of Internet-delivered CBT (iCBT). Twenty-six participants diagnosed with SAD underwent iCBT including attention bias modification for a total of 13 weeks. Support vector machines (SVMs), a supervised pattern recognition method allowing predictions at the individual level, were trained to separate long-term treatment responders from nonresponders based on blood oxygen level-dependent (BOLD) responses to self-referential criticism. The Clinical Global Impression-Improvement scale was the main instrument to determine treatment response at the 1-year follow-up. Results showed that the proportion of long-term responders was 52% (12/23). From multivariate BOLD responses in the dorsal anterior cingulate cortex (dACC) together with the amygdala, we were able to predict long-term response rate of iCBT with an accuracy of 92% (confidence interval 95% 73.2–97.6). This activation pattern was, however, not predictive of improvement in the continuous Liebowitz Social Anxiety Scale—Self-report version. Follow-up psychophysiological interaction analyses revealed that lower dACC–amygdala coupling was associated with better long-term treatment response. Thus, BOLD response patterns in the fear-expressing dACC–amygdala regions were highly predictive of long-term treatment outcome of iCBT, and the initial coupling between these regions differentiated long-term responders from nonresponders. The SVM-neuroimaging approach could be of particular clinical value as it allows for accurate prediction of treatment outcome at the level of the individual.

  • 103.
    Månsson, Kristoffer N.T.
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Lindqvist, Daniel
    Yang, Liu L.
    Svanborg, Cecilia
    Isung, Josef
    Nilsonne, Gustav
    Bergman-Nordgren, Lise
    El Alaoui, Samir
    Hedman-Lagerlöf, Erik
    Kraepelien, Martin
    Högström, Jens
    Andersson, Gerhard
    Boraxbekk, Carl-Johan
    Fischer, Håkan
    Lavebratt, Catharina
    Wolkowitz, Owen M.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Improvement in indices of cellular protection after psychological treatment for social anxiety disorder2019In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 9, no 1, article id 340Article in journal (Refereed)
    Abstract [en]

    Telomere attrition is a hallmark of cellular aging and shorter telomeres have been reported in mood and anxiety disorders. Telomere shortening is counteracted by the enzyme telomerase and cellular protection is also provided by the antioxidant enzyme glutathione peroxidase (GPx). Here, telomerase, GPx, and telomeres were investigated in 46 social anxiety disorder (SAD) patients in a within-subject design with repeated measures before and after cognitive behavioral therapy. Treatment outcome was assessed by the Liebowitz Social Anxiety Scale (self-report), administered three times before treatment to control for time and regression artifacts, and posttreatment. Venipunctures were performed twice before treatment, separated by 9 weeks, and once posttreatment. Telomerase activity and telomere length were measured in peripheral blood mononuclear cells and GPx activity in plasma. All patients contributed with complete data. Results showed that social anxiety symptom severity was significantly reduced from pretreatment to posttreatment (Cohen’s d = 1.46). There were no significant alterations in telomeres or cellular protection markers before treatment onset. Telomere length and telomerase activity did not change significantly after treatment, but an increase in telomerase over treatment was associated with reduced social anxiety. Also, lower pretreatment telomerase activity predicted subsequent symptom improvement. GPx activity increased significantly during treatment, and increases were significantly associated with symptom improvement. The relationships between symptom improvement and putative protective enzymes remained significant also after controlling for body mass index, sex, duration of SAD, smoking, concurrent psychotropic medication, and the proportion of lymphocytes to monocytes. Thus, indices of cellular protection may be involved in the therapeutic mechanisms of psychological treatment for anxiety.

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  • 104. Månsson, Kristoffer
    et al.
    Salami, Alireza
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Department of Neurobiology, Care Sciences and Society, Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Frick, Andreas
    Carlbring, Per
    Andersson, Gerhard
    Furmark, Tomas
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Neuroplasticity in response to cognitive behavior therapy for social anxiety disorder2016In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 6, article id e727Article in journal (Refereed)
    Abstract [en]

    Patients with anxiety disorders exhibit excessive neural reactivity in the amygdala, which can be normalized by effective treatment like cognitive behavior therapy (CBT). Mechanisms underlying the brain's adaptation to anxiolytic treatments are likely related both to structural plasticity and functional response alterations, but multimodal neuroimaging studies addressing structure-function interactions are currently missing. Here, we examined treatment-related changes in brain structure (gray matter (GM) volume) and function (blood-oxygen level dependent, BOLD response to self-referential criticism) in 26 participants with social anxiety disorder randomly assigned either to CBT or an attention bias modification control treatment. Also, 26 matched healthy controls were included. Significant time x treatment interactions were found in the amygdala with decreases both in GM volume (family-wise error (FWE) corrected P-FWE = 0.02) and BOLD responsivity (P-FWE = 0.01) after successful CBT. Before treatment, amygdala GM volume correlated positively with anticipatory speech anxiety (P-FWE = 0.04), and CBT-induced reduction of amygdala GM volume (pre-post) correlated positively with reduced anticipatory anxiety after treatment (P-FWE <= 0.05). In addition, we observed greater amygdala neural responsivity to self-referential criticism in socially anxious participants, as compared with controls (P-FWE = 0.029), before but not after CBT. Further analysis indicated that diminished amygdala GM volume mediated the relationship between decreased neural responsivity and reduced social anxiety after treatment (P = 0.007). Thus, our results suggest that improvement-related structural plasticity impacts neural responsiveness within the amygdala, which could be essential for achieving anxiety reduction with CBT.

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  • 105.
    O'Gorman, A.
    et al.
    Department of Psychiatry, Royal College of Surgeons in Ireland (RCSI), Beaumont Hospital, Dublin, Ireland; Institute of Food and Health, UCD School of Agriculture and Food Science, University College Dublin (UCD) Belfield, Dublin, Ireland.
    Suvitaival, T.
    Steno Diabetes Center, Gentofte, Denmark.
    Ahonen, L.
    Steno Diabetes Center, Gentofte, Denmark.
    Cannon, M.
    Department of Psychiatry, Royal College of Surgeons in Ireland (RCSI), Beaumont Hospital, Dublin, Ireland.
    Zammit, S.
    Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK; Centre for Academic Mental Health, School of Social & Community Medicine, University of Bristol, Bristol, UK.
    Lewis, G.
    Division of Psychiatry, University College London, London, UK.
    Roche, H. M.
    Nutrigenomics Research Group, UCD Conway Institute/UCD Institute of Food & Health, School of Public Health, Physiotherapy & Sports Science, University College Dublin (UCD) Belfield, Dublin, Ireland.
    Mattila, I.
    Steno Diabetes Center, Gentofte, Denmark.
    Hyötyläinen, Tuulia
    Örebro University, School of Science and Technology. Steno Diabetes Center, Gentofte, Denmark.
    Oresic, Matej
    Örebro University, School of Medical Sciences. Steno Diabetes Center, Gentofte, Denmark; Turku Centre for Biotechnology, University of Turku, Turku, Finland; Åbo Akademi University, Turku, Finland.
    Brennan, L.
    Institute of Food and Health, UCD School of Agriculture and Food Science, University College Dublin (UCD) Belfield, Dublin, Ireland.
    Cotter, D. R.
    Department of Psychiatry, Beaumont Hospital, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.
    Identification of a plasma signature of psychotic disorder in children and adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort2017In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 7, article id e1240Article in journal (Refereed)
    Abstract [en]

    The identification of an early biomarker of psychotic disorder is important as early treatment is associated with improved patient outcome. Metabolomic and lipidomic approaches in combination with multivariate statistical analysis were applied to identify plasma alterations in children (age 11) (38 cases vs 67 controls) and adolescents (age 18) (36 cases vs 117 controls) preceeding or coincident with the development of psychotic disorder (PD) at age 18 in the Avon Longitudinal Study of Parents and Children (ALSPAC). Overall, 179 lipids were identified at age 11, with 32 found to be significantly altered between the control and PD groups. Following correction for multiple comparisons, 8 of these lipids remained significant (lysophosphatidlycholines (LPCs) LPC(18: 1), LPC(18: 2), LPC(20: 3); phosphatidlycholines (PCs) PC(32: 2; PC(34: 2), PC(36: 4), PC(0-34-3) and sphingomyelin (SM) SM(d18: 1/24: 0)), all of which were elevated in the PD group. At age 18, 23 lipids were significantly different between the control and PD groups, although none remained significant following correction for multiple comparisons. In conclusion, the findings indicate that the lipidome is altered in the blood during childhood, long before the development of psychotic disorder. LPCs in particular are elevated in those who develop PD, indicating inflammatory abnormalities and altered phospholipid metabolism. These findings were not found at age 18, suggesting there may be ongoing alterations in the pathophysiological processes from prodrome to onset of PD.

  • 106.
    Olivo, Gaia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Swenne, Ingemar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Endocrinology.
    Zhukovsky, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Tuunainen, Anna-Kaisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Salonen-Ros, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Gaudio, Santino
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. Univ Campus Biomed Roma, Ctr Integrated Res, Area Diagnost Imaging, Rome, Italy.
    Brooks, Samantha J.
    Univ Cape Town, Dept Human Biol, Cape Town, South Africa.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Reduced resting-state connectivity in areas involved in processing of face-related social cues in female adolescents with atypical anorexia nervosa2018In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 8, article id 275Article in journal (Refereed)
    Abstract [en]

    Atypical anorexia nervosa (AN) has a high incidence in adolescents and can result in significant morbidity and mortality. Neuroimaging could improve our knowledge regarding the pathogenesis of eating disorders (EDs), however research on adolescents with EDs is limited. To date no neuroimaging studies have been conducted to investigate brain functional connectivity in atypical AN. We investigated resting-state functional connectivity using 3 T MRI in 22 drug-naive adolescent patients with atypical AN, and 24 healthy controls. Psychological traits related to the ED and depressive symptoms have been assessed using the Eating Disorders Examination Questionnaire (EDE-Q) and the Montgomery-Asberg Depression Rating Scale self-reported (MADRS-S) respectively. Reduced connectivity was found in patients in brain areas involved in face-processing and social cognition, such as the left putamen, the left occipital fusiform gyrus, and specific cerebellar lobules. The connectivity was, on the other hand, increased in patients compared with controls from the right inferior temporal gyrus to the superior parietal lobule and superior lateral occipital cortex. These areas are involved in multimodal stimuli integration, social rejection and anxiety. Patients scored higher on the EDE-Q and MADRS-S questionnaires, and the MADRS-S correlated with connectivity from the right inferior temporal gyrus to the superior parietal lobule in patients. Our findings point toward a role for an altered development of socio-emotional skills in the pathogenesis of atypical AN. Nonetheless, longitudinal studies will be needed to assess whether these connectivity alterations might be a neural marker of the pathology.

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  • 107.
    Olivo, Gaia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Zhukovsky, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Salonen-Ros, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Brooks, Samantha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Department of Human Biology, University of Cape Town, Cape Town, South Africa; School of Natural Sciences and Psychology, Research Centre for Brain & Behaviour, Byrom Street, Liverpool, UK.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Institute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow, Russia.
    Functional connectivity underlying hedonic response to food in female adolescents with atypical AN: The role of somatosensory and salience networks2019In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 9, article id 276Article in journal (Refereed)
    Abstract [en]

    Atypical Anorexia Nervosa (AN) usually occurs during adolescence. Patients are often in the normal-weight range at diagnosis, however they often present with signs of medical complications and severe restraint over eating, body dissatisfaction, and low self-esteem. We investigated functional circuitry underlying the hedonic response in 28 female adolescent patients diagnosed with atypical AN and 33 healthy controls. Participants were shown images of food with high (HC) or low (LC) caloric content in alternating blocks during functional MRI. The HC > LC contrast was calculated. Based on previous literature on full-threshold AN, we hypothesized that patients would exhibit increased connectivity in areas involved in sensory processing and bottom-up responses, coupled to increased connectivity from areas related to top-down inhibitory control, compared with controls. Patients showed increased connectivity in pathways related to multimodal somatosensory processing and memory retrieval. The connectivity was on the other hand decreased in patients in salience and attentional networks, and in a wide cerebello-occipital network. Our study was the first investigation of food-related neural response in atypical AN. Our findings support higher somatosensory processing in patients in response to HC food images compared with controls, however HC food was less efficient than LC food in engaging patients’ bottom-up salient responses, and was not associated with connectivity increases in inhibitory control regions. These findings suggest that the psychopathological mechanisms underlying food restriction in atypical AN differ from full-threshold AN. Elucidating the mechanisms underlying the development and maintenance of eating behaviour in atypical AN might help designing specific treatment strategies.

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  • 108.
    Ollila, Hanna M.
    et al.
    Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland ; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, United States ; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, United States ; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
    Sinnott-Armstrong, Nasa
    Department of Genetics, School of Medicine, Stanford University, CA, United States.
    Kantojärvi, Katri
    Population Health, Finnish Institute for Health and Welfare, Helsinki, Finland ; Department of Psychiatry and SleepWell Research Program, Faculty of Medicine, University of Helsinki and Helsinki University Central Hospital, Finland.
    Broberg, Martin
    Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland.
    Palviainen, Teemu
    Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland.
    Jones, Samuel
    Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland.
    Ripatti, Vili
    Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland.
    Pandit, Anita
    Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, United States.
    Rong, Robin
    Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, United States.
    Kristiansson, Kati
    Population Health, Finnish Institute for Health and Welfare, Helsinki, Finland.
    Sandman, Nils
    Department of Psychology and Speech-Language Pathology, and Turku Brain and Mind Center, University of Turku, Finland.
    Valli, Katja
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment. Department of Psychology and Speech-Language Pathology, and Turku Brain and Mind Center, University of Turku, Finland.
    Hublin, Christer
    Finnish Institute of Occupational Health, Helsinki, Finland.
    Ripatti, Samuli
    Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland ; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, United States ; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, United States.
    Widen, Elisabeth
    Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland.
    Kaprio, Jaakko
    Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland.
    Saxena, Richa
    Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, United States ; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, United States ; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States ; Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, United States.
    Paunio, Tiina
    Population Health, Finnish Institute for Health and Welfare, Helsinki, Finland ; Department of Psychiatry and SleepWell Research Program, Faculty of Medicine, University of Helsinki and Helsinki University Central Hospital, Finland.
    Nightmares share genetic risk factors with sleep and psychiatric traits2024In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 14, no 1, article id 123Article in journal (Refereed)
    Abstract [en]

    Nightmares are vivid, extended, and emotionally negative or negative dreams that awaken the dreamer. While sporadic nightmares and bad dreams are common and generally harmless, frequent nightmares often reflect underlying pathologies of emotional regulation. Indeed, insomnia, depression, anxiety, or alcohol use have been associated with nightmares in epidemiological and clinical studies. However, the connection between nightmares and their comorbidities are poorly understood. Our goal was to examine the genetic risk factors for nightmares and estimate correlation or causality between nightmares and comorbidities. We performed a genome-wide association study (GWAS) in 45,255 individuals using a questionnaire-based assessment on the frequency of nightmares during the past month and genome-wide genotyping data. While the GWAS did not reveal individual risk variants, heritability was estimated at 5%. In addition, the genetic correlation analysis showed a robust correlation (rg > 0.4) of nightmares with anxiety (rg = 0.671, p = 7.507e−06), depressive (rg = 0.562, p = 1.282e−07) and posttraumatic stress disorders (rg = 0.4083, p = 0.0152), and personality trait neuroticism (rg = 0.667, p = 4.516e−07). Furthermore, Mendelian randomization suggested causality from insomnia to nightmares (beta = 0.027, p = 0.0002). Our findings suggest that nightmares share genetic background with psychiatric traits and that insomnia may increase an individual’s liability to experience frequent nightmares. Given the significant correlations with psychiatric and psychological traits, it is essential to grow awareness of how nightmares affect health and disease and systematically collect information about nightmares, especially from clinical samples and larger cohorts. 

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  • 109.
    O'Reilly, Lauren M.
    et al.
    Indiana University, Bloomington IN, USA.
    Kuja-Halkola, Ralf
    Karolinska Institutet, Solna, Sweden.
    Rickert, Martin E.
    Indiana University, Bloomington IN, USA.
    Class, Quetzal A
    University of Illinois, Chicago IL, USA.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Karolinska Institutet, Solna, Sweden.
    Lichtenstein, Paul
    Karolinska Institutet, Solna, Sweden.
    D'Onofrio, Brian M.
    Indiana University, Bloomington IN, USA; Karolinska Institutet, Solna, Sweden.
    The intergenerational transmission of suicidal behavior: an offspring of siblings study2020In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 10, no 1, article id 173Article in journal (Refereed)
    Abstract [en]

    We examined the extent to which genetic factors shared across generations, measured covariates, and environmental factors associated with parental suicidal behavior (suicide attempt or suicide) account for the association between parental and offspring suicidal behavior. We used a Swedish cohort of 2,762,883 offspring born 1973-2001. We conducted two sets of analyses with offspring of half- and full-siblings: (1) quantitative behavior genetic models analyzing maternal suicidal behavior and (2) fixed-effects Cox proportional hazard models analyzing maternal and paternal suicidal behavior. The analyses also adjusted for numerous measured covariates (e.g., parental severe mental illness). Quantitative behavior genetic analyses found that 29.2% (95% confidence interval [CI], 5.29, 53.12%) of the intergenerational association was due to environmental factors associated with exposure to maternal suicidal behavior, with the remainder due to genetic factors. Statistical adjustment for parental behavioral health problems partially attenuated the environmental association; however, the results were no longer statistically significant. Cox hazard models similarly found that offspring were at a 2.74-fold increased risk [95% CI, 2.67, 2.83]) of suicidal behavior if their mothers attempted/died by suicide. After adjustment for familial factors and measured covariates, associations attenuated but remained elevated for offspring of discordant half-siblings (HR, 1.57 [95% CI, 1.45, 1.71]) and full-siblings (HR, 1.62 [95% CI, 1.57, 1.67]). Cox hazard models demonstrated a similar pattern between paternal and offspring suicidal behavior. This study found that the intergenerational transmission of suicidal behavior is largely due to shared genetic factors, as well as factors associated with parental behavioral health problems and environmental factors associated with parental suicidal behavior.

  • 110. Orešič, M
    et al.
    Hyötyläinen, T
    Herukka, SK
    Sysi-Aho, M
    Mattila, I
    Seppänan-Laakso, T
    Julkunen, V
    Gopalacharyulu, PV
    Hallikainen, M
    Koikkalainen, J
    Kivipelto, Miia
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Helisalmi, S
    Lötjönen, J
    Soininen, H
    Metabolome in progression to Alzheimer's disease2011In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 1, p. e57-Article in journal (Refereed)
    Abstract [en]

    Mild cognitive impairment (MCI) is considered as a transition phase between normal aging and Alzheimer's disease (AD). MCI confers an increased risk of developing AD, although the state is heterogeneous with several possible outcomes, including even improvement back to normal cognition. We sought to determine the serum metabolomic profiles associated with progression to and diagnosis of AD in a prospective study. At the baseline assessment, the subjects enrolled in the study were classified into three diagnostic groups: healthy controls (n=46), MCI (n=143) and AD (n=47). Among the MCI subjects, 52 progressed to AD in the follow-up. Comprehensive metabolomics approach was applied to analyze baseline serum samples and to associate the metabolite profiles with the diagnosis at baseline and in the follow-up. At baseline, AD patients were characterized by diminished ether phospholipids, phosphatidylcholines, sphingomyelins and sterols. A molecular signature comprising three metabolites was identified, which was predictive of progression to AD in the follow-up. The major contributor to the predictive model was 2,4-dihydroxybutanoic acid, which was upregulated in AD progressors (P=0.0048), indicating potential involvement of hypoxia in the early AD pathogenesis. This was supported by the pathway analysis of metabolomics data, which identified upregulation of pentose phosphate pathway in patients who later progressed to AD. Together, our findings primarily implicate hypoxia, oxidative stress, as well as membrane lipid remodeling in progression to AD. Establishment of pathogenic relevance of predictive biomarkers such as ours may not only facilitate early diagnosis, but may also help identify new therapeutic avenues.

  • 111.
    Orešič, Matej
    et al.
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Hyötyläinen, Tuulia
    Örebro University, School of Science and Technology. VTT Technical Research Centre of Finland, Espoo, Finland.
    Herukka, S-K.
    Department of Neurology, Kuopio University Hospital, University of Eastern Finland, Kuopio, Finland.
    Sysi-Aho, M.
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Mattila, I.
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Seppänan-Laakso, T.
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Julkunen, V.
    Department of Neurology, Kuopio University Hospital, University of Eastern Finland, Kuopio, Finland.
    Gopalacharyulu, P. V.
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Hallikainen, M.
    Department of Neurology, Kuopio University Hospital, University of Eastern Finland, Kuopio, Finland.
    Koikkalainen, J.
    VTT Technical Research Centre of Finland, Tampere, Finland.
    Kivipelto, M.
    Aging Research Center, Karolinska Institute, Stockholm, Sweden.
    Helisalmi, S.
    Department of Neurology, Kuopio University Hospital, University of Eastern Finland, Kuopio, Finland.
    Lötjönen, J.
    VTT Technical Research Centre of Finland, Tampere, Finland.
    Soininen, H.
    Department of Neurology, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland.
    Metabolome in progression to Alzheimer's disease2011In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 1, article id e57Article in journal (Refereed)
    Abstract [en]

    Mild cognitive impairment (MCI) is considered as a transition phase between normal aging and Alzheimer's disease (AD). MCI confers an increased risk of developing AD, although the state is heterogeneous with several possible outcomes, including even improvement back to normal cognition. We sought to determine the serum metabolomic profiles associated with progression to and diagnosis of AD in a prospective study. At the baseline assessment, the subjects enrolled in the study were classified into three diagnostic groups: healthy controls (n=46), MCI (n=143) and AD (n=47). Among the MCI subjects, 52 progressed to AD in the follow-up. Comprehensive metabolomics approach was applied to analyze baseline serum samples and to associate the metabolite profiles with the diagnosis at baseline and in the follow-up. At baseline, AD patients were characterized by diminished ether phospholipids, phosphatidylcholines, sphingomyelins and sterols. A molecular signature comprising three metabolites was identified, which was predictive of progression to AD in the follow-up. The major contributor to the predictive model was 2,4-dihydroxybutanoic acid, which was upregulated in AD progressors (P=0.0048), indicating potential involvement of hypoxia in the early AD pathogenesis. This was supported by the pathway analysis of metabolomics data, which identified upregulation of pentose phosphate pathway in patients who later progressed to AD. Together, our findings primarily implicate hypoxia, oxidative stress, as well as membrane lipid remodeling in progression to AD. Establishment of pathogenic relevance of predictive biomarkers such as ours may not only facilitate early diagnosis, but may also help identify new therapeutic avenues.

  • 112.
    Paul, Elisabeth
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Östman Vasko, Lars
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Mayberg, Helen S.
    Icahn Sch Med Mt Sinai, NY USA.
    Hamilton, J. Paul
    Univ Bergen, Norway.
    Towards a multilevel model of major depression: genes, immuno-metabolic function, and cortico-striatal signaling2023In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 13, no 1, article id 171Article, review/survey (Refereed)
    Abstract [en]

    Biological assay and imaging techniques have made visible a great deal of the machinery of mental illness. Over fifty years of investigation of mood disorders using these technologies has identified several biological regularities in these disorders. Here we present a narrative connecting genetic, cytokine, neurotransmitter, and neural-systems-level findings in major depressive disorder (MDD). Specifically, we connect recent genome-wide findings in MDD to metabolic and immunological disturbance in this disorder and then detail links between immunological abnormalities and dopaminergic signaling within cortico-striatal circuitry. Following this, we discuss implications of reduced dopaminergic tone for cortico-striatal signal conduction in MDD. Finally, we specify some of the flaws in the current model and propose ways forward for advancing multilevel formulations of MDD most efficiently.

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  • 113.
    Pearce, Eiluned
    et al.
    UCL, England.
    Myles-Hooton, Pamela
    UCL, England.
    Johnson, Sonia
    UCL, England; Camden & Islington NHS Fdn Trust, England.
    Hards, Emily
    Univ Bath, England.
    Olsen, Samantha
    UCL, England.
    Clisu, Denisa
    UCL, England.
    Pais, Sarah M. A.
    UCL, England.
    Chesters, Heather A.
    UCL, England.
    Shah, Shyamal
    UCL, England.
    Jerwood, Georgia
    UCL, England.
    Politis, Marina
    UCL, England.
    Melwani, Joshua
    UCL, England.
    Andersson, Gerhard
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Shafran, Roz
    Great Ormond Street Institute of Child Health, University College London, London, UK.
    Loneliness as an active ingredient in preventing or alleviating youth anxiety and depression: a critical interpretative synthesis incorporating principles from rapid realist reviews2021In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 11, no 1, article id 628Article, review/survey (Refereed)
    Abstract [en]

    Loneliness is a relatively common problem in young people (14-24 years) and predicts the onset of depression and anxiety. Interventions to reduce loneliness thus have significant potential as active ingredients in strategies to prevent or alleviate anxiety and depression among young people. Previous reviews have focused on quantitative evidence and have not examined potential mechanisms that could be targets for intervention strategies. To build on this work, in this review we aimed to combine qualitative and quantitative evidence with stakeholder views to identify interventions that appear worth testing for their potential effectiveness in reducing loneliness, anxiety and depression in young people aged 14-24 years, and provide insights into the potential mechanisms of action. We conducted a Critical Interpretative Synthesis, a systematic review method that iteratively synthesises qualitative and quantitative evidence and is explicitly focused on building theory through a critical approach to the evidence that questions underlying assumptions. Literature searches were performed using nine databases, and eight additional databases were searched for theses and grey literature. Charity and policy websites were searched for content relevant to interventions for youth loneliness. We incorporated elements of Rapid Realistic Review approaches by consulting with young people and academic experts to feed into search strategies and the resulting conceptual framework, in which we aimed to set out which interventions appear potentially promising in terms of theoretical and empirical underpinnings and which fit with stakeholder views. We reviewed effectiveness data and quality ratings for the included randomised controlled trials only. Through synthesising 27 studies (total participants n = 105,649; range 1-102,072 in different studies) and grey literature, and iteratively consulting with stakeholders, a conceptual framework was developed. A range of Intrapersonal (e.g. therapy that changes thinking and behaviour), Interpersonal (e.g. improving social skills), and Social Strategies (e.g. enhancing social support, and providing opportunities for social contact) seem worth testing further for their potential to help young people address loneliness, thereby preventing or alleviating depression and/or anxiety. Such strategies should be co-designed with young people and personalised to fit individual needs. Plausible mechanisms of action are facilitating sustained social support, providing opportunities for young people to socialise with peers who share similar experiences, and changing thinking and behaviour, for instance through building positive attitudes to themselves and others. The most convincing evidence of effectiveness was found in support of Intrapersonal Strategies: two randomised controlled studies quality-rated as good found decreases in loneliness associated with different forms of therapy (Cognitive Behavioural Therapy or peer network counselling), although power calculations were not reported, and effect sizes were small or missing. Strategies to address loneliness and prevent or alleviate anxiety and depression need to be co-designed and personalised. Promising elements to incorporate into these strategies are social support, including from peers with similar experiences, and psychological therapy.

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  • 114.
    Perini, Irene
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Gustafsson, Per
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Igelström, Kajsa
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Jasiunaite Jokubaviciene, Brigita
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Kämpe, Robin
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Mayo, Leah
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Molander, Johanna
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Olausson, Håkan
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Zetterqvist, Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Altered relationship between subjective perception and central representation of touch hedonics in adolescents with autism-spectrum disorder2021In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 11, no 1, article id 224Article in journal (Refereed)
    Abstract [en]

    An impairment of social communication is a core symptom of autism-spectrum disorder (ASD). Affective touch is an important means of social interaction, and C-Tactile (CT) afferents are thought to play a key role in the peripheral detection and encoding of these stimuli. Exploring the neural and behavioral mechanisms for processing CT-optimal touch (similar to 3 cm/s) may therefore provide useful insights into the pathophysiology of ASD. We examined the relationship between touch hedonics (i.e. the subjective pleasantness with which affective touch stimuli are perceived) and neural processing in the posterior superior temporal sulcus (pSTS). This region is less activated to affective touch in individuals with ASD, and, in typically developing individuals (TD), is correlated positively with touch pleasantness. TD and ASD participants received brushing stimuli at CT-optimal, and CT-non-optimal speeds during fMRI. Touch pleasantness and intensity ratings were collected, and affective touch awareness, a measure of general touch hedonics was calculated. As expected, slow touch was perceived as more pleasant and less intense than fast touch in both groups, whereas affective touch awareness was moderately higher in TD compared to ASD. There was a strong, positive correlation between right pSTS activation and affective touch awareness in TD, but not in ASD. Our findings suggest that altered neural coupling between right pSTS and touch hedonics in ASD may be associated with social touch avoidance in ASD.

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  • 115.
    Pisanu, Claudia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Univ Cagliari, Dept Biomed Sci, Sect Neurosci & Clin Pharmacol, Cagliari, Italy.
    Williams, Michael J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Ciuculete, Diana-Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Olivo, Gaia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Del Zompo, Maria
    Univ Cagliari, Dept Biomed Sci, Sect Neurosci & Clin Pharmacol, Cagliari, Italy.
    Squassina, Alessio
    Univ Cagliari, Dept Biomed Sci, Sect Neurosci & Clin Pharmacol, Cagliari, Italy.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Sechenov First Moscow State Med Univ, Inst Translat Med & Biotechnol, Moscow, Russia.
    Evidence that genes involved in hedgehog signaling are associated with both bipolar disorder and high BMI2019In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 9, article id 315Article in journal (Refereed)
    Abstract [en]

    Patients with bipolar disorder (BD) show higher frequency of obesity and type 2 diabetes (T2D), but the underlying genetic determinants and molecular pathways are not well studied. Using large publicly available datasets, we (1) conducted a gene-based analysis using MAGMA to identify genes associated with BD and body mass index (BMI) or T2D and investigated their functional enrichment; and (2) performed two meta-analyses between BD and BMI, as well as BD and T2D using Metasoft. Target druggability was assessed using the Drug Gene Interaction Database (DGIdb). We identified 518 and 390 genes significantly associated with BD and BMI or BD and T2D, respectively. A total of 52 and 12 genes, respectively, were significant after multiple testing correction. Pathway analyses conducted on nominally significant targets showed that genes associated with BD and BMI were enriched for the Neuronal cell body Gene Ontology (GO) term (p = 1.0E-04; false discovery rate (FDR) = 0.025) and different pathways, including the Signaling by Hedgehog pathway (p = 4.8E -05, FDR = 0.02), while genes associated with BD and T2D showed no specific enrichment. The meta-analysis between BD and BMI identified 64 relevant single nucleotide polymorphisms (SNPs). While the majority of these were located in intergenic regions or in a locus on chromosome 16 near and in the NPIPL1 and SH2B1 genes (best SNP: rs4788101, p = 2.1E-24), five were located in the ETV5 gene (best SNP: rs1516725, p= 1E-24), which was previously associated with both BD and obesity, and one in the RPGRIP1L gene (rs1477199, p = 5.7E-09), which was also included in the Signaling by Hedgehog pathway. The meta-analysis between BD and T2D identified six significant SNPs, three of which were located in ALAS1 (best SNP: rs352165, p = 3.4E-08). Thirteen SNPs associated with BD and BMI, and one with BD and T2D, were located in genes which are part of the druggable genome. Our results support the hypothesis of shared genetic determinants between BD and BMI and point to genes involved in Hedgehog signaling as promising targets.

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  • 116.
    Polderman, T. J. C.
    et al.
    Department of Functional Genomics, Complex Trait Genetics, Center for Neurogenomics and Cognitive Research (CNCR), Vrije University, Amsterdam, The Netherlands.
    Hoekstra, R. A.
    Department of Life, Health and Chemical Sciences, Faculty of Science, The Open University, Milton Keynes, UK.
    Posthuma, D.
    Department of Functional Genomics, Complex Trait Genetics, Center for Neurogenomics and Cognitive Research (CNCR), Vrije University Amsterdam, The Netherlands.
    Larsson, Henrik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    The co-occurrence of autistic and ADHD dimensions in adults: an etiological study in 17,770 twins2014In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 4, article id e435Article in journal (Refereed)
    Abstract [en]

    Autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) often occur together. To obtain more insight in potential causes for the co-occurrence, this study examined the genetic and environmental etiology of the association between specific ASD and ADHD disorder dimensions. Self-reported data on ASD dimensions social and communication difficulties (ASDsc), and repetitive and restricted behavior and interests (ASDr), and ADHD dimensions inattention (IA), and hyperactivity/impulsivity (HI) were assessed in a community sample of 17,770 adult Swedish twins. Phenotypic, genetic and environmental associations between disorder dimensions were examined in a multivariate model, accounting for sex differences. ASDr showed the strongest associations with IA and HI in both sexes (r(p) 0.33 to 0.40). ASDsc also correlated moderately with IA (females r(p) 0.29 and males r(p) 0.35) but only modestly with HI (females r(p) 0.17 and males r(p) 0.20). Genetic correlations ranged from 0.22 to 0.64 and were strongest between ASDr and IA and HI. Sex differences were virtually absent. The ASDr dimension (reflecting restricted, repetitive and stereotyped patterns of behavior, interests and activities) showed the strongest association with dimensions of ADHD, on a phenotypic, genetic and environmental level. This study opens new avenues for molecular genetic research. As our findings demonstrated that genetic overlap between disorders is dimension-specific, future gene-finding studies on psychiatric comorbidity should focus on carefully selected genetically related dimensions of disorders.

  • 117.
    Porcheret, Kate
    et al.
    Univ Oxford, Sleep & Circadian Neurosci Inst, Nuffield Dept Clin Neurosci, Oxford OX1 3RE, England.
    van Heugten-van der Kloet, Dalena
    Univ Oxford, Sleep & Circadian Neurosci Inst, Nuffield Dept Clin Neurosci, Oxford OX1 3RE, England;Maastricht Univ, Fac Psychol & Neurosci, Dept Clin Psychol Sci, NL-6200 MD Maastricht, Netherlands.
    Goodwin, Guy M.
    Univ Oxford, Dept Psychiat, Oxford OX3 7JX, England;Oxford Hlth NHS Fdn Trust, Oxford OX3 7JX, England.
    Foster, Russell G.
    Univ Oxford, Sleep & Circadian Neurosci Inst, Nuffield Dept Clin Neurosci, Oxford OX1 3RE, England.
    Wulff, Katharina
    Univ Oxford, Sleep & Circadian Neurosci Inst, Nuffield Dept Clin Neurosci, Oxford OX1 3RE, England;Umea Univ, Dept Radiat Sci, SE-90187 Umea, Sweden;Umea Univ, Dept Mol Biol, SE-90187 Umea, Sweden.
    Holmes, Emily A.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Investigation of the impact of total sleep deprivation at home on the number of intrusive memories to an analogue trauma2019In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 9, article id 104Article in journal (Refereed)
    Abstract [en]

    Sleep enhances the consolidation of memory; however, this property of sleep may be detrimental in situations where memories of an event can lead to psychopathology, such as following a traumatic event. Intrusive memories of trauma are emotional memories that spring to mind involuntarily and are a core feature of post-traumatic stress disorder. Total sleep deprivation in a hospital setting on the first night after an analogue trauma (a trauma film) led to fewer intrusive memories compared to sleep as usual in one study. The current study aimed to test an extension of these findings: sleep deprivation under more naturalistic conditions-at home. Polysomnographic recordings show inconsistent sleep deprivation was achieved at home. Fewer intrusive memories were reported on day 1 after the trauma film in the sleep-deprived condition. On day 2 the opposite was found: more intrusive memories in the sleep-deprived condition. However, no significant differences were found with the removal of two participants with extreme values and no difference was found in the total number of intrusive memories reported in the week following the trauma film. Voluntary memory of the trauma film was found to be slightly impaired in the sleep deprivation condition. In conclusion, compared to our eariler findings using total sleep deprivation in a hospital setting, in the current study the use of inconsistent sleep deprivation at home does not replicate the pattern of results on reducing the number of intrusive memories. Considering the conditions under which sleep deprivation (naturalistic versus hospital) was achieved requires further examination.

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  • 118. Porcheret, Kate
    et al.
    van Heugten-van der Kloet, Dalena
    Goodwin, Guy M.
    Foster, Russell G.
    Wulff, Katharina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
    Holmes, Emily A.
    Investigation of the impact of total sleep deprivation at home on the number of intrusive memories to an analogue trauma2019In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 9, article id 104Article in journal (Refereed)
    Abstract [en]

    Sleep enhances the consolidation of memory; however, this property of sleep may be detrimental in situations where memories of an event can lead to psychopathology, such as following a traumatic event. Intrusive memories of trauma are emotional memories that spring to mind involuntarily and are a core feature of post-traumatic stress disorder. Total sleep deprivation in a hospital setting on the first night after an analogue trauma (a trauma film) led to fewer intrusive memories compared to sleep as usual in one study. The current study aimed to test an extension of these findings: sleep deprivation under more naturalistic conditions-at home. Polysomnographic recordings show inconsistent sleep deprivation was achieved at home. Fewer intrusive memories were reported on day 1 after the trauma film in the sleep-deprived condition. On day 2 the opposite was found: more intrusive memories in the sleep-deprived condition. However, no significant differences were found with the removal of two participants with extreme values and no difference was found in the total number of intrusive memories reported in the week following the trauma film. Voluntary memory of the trauma film was found to be slightly impaired in the sleep deprivation condition. In conclusion, compared to our eariler findings using total sleep deprivation in a hospital setting, in the current study the use of inconsistent sleep deprivation at home does not replicate the pattern of results on reducing the number of intrusive memories. Considering the conditions under which sleep deprivation (naturalistic versus hospital) was achieved requires further examination.

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  • 119.
    Rasmusson, Annica J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Cervenka: Psychiatry.
    Gallwitz, Maike
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Cervenka: Psychiatry.
    Soltanabadi, Bardia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Cervenka: Psychiatry.
    Ciuculete, Diana-Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Mengel-From, Jonas
    Univ Southern Denmark, Danish Twin Registry, Epidemiol Biostat & Biodemog, Dept Publ Hlth, Odense, Denmark.;Odense Univ Hosp, Dept Clin Genet, Odense, Denmark..
    Christensen, Kaare
    Univ Southern Denmark, Danish Twin Registry, Epidemiol Biostat & Biodemog, Dept Publ Hlth, Odense, Denmark.;Odense Univ Hosp, Dept Clin Genet, Odense, Denmark.;Odense Univ Hosp, Dept Clin Biochem & Pharmacol, Odense, Denmark..
    Nygaard, Marianne
    Univ Southern Denmark, Danish Twin Registry, Epidemiol Biostat & Biodemog, Dept Publ Hlth, Odense, Denmark.;Odense Univ Hosp, Dept Clin Genet, Odense, Denmark..
    Soerensen, Mette
    Univ Southern Denmark, Danish Twin Registry, Epidemiol Biostat & Biodemog, Dept Publ Hlth, Odense, Denmark.;Odense Univ Hosp, Dept Clin Genet, Odense, Denmark.;Odense Univ Hosp, Dept Clin Biochem & Pharmacol, Odense, Denmark..
    Boström, Adrian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Fredriksson, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Freyhult, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mwinyi, Jessica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Czamara, Darina
    Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany..
    Binder, Elisabeth B.
    Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany..
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. IM Sechenov First Moscow State Med Univ, Inst Translat Med & Biotechnol, Moscow, Russia..
    Cunningham, Janet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Cervenka: Psychiatry.
    Toll-like receptor 4 methylation grade is linked to depressive symptom severity2021In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 11, article id 371Article in journal (Refereed)
    Abstract [en]

    This study explores potential associations between the methylation of promoter-associated CpG sites of the toll-like receptor (TLR)-family, plasma levels of pro-inflammatory proteins and depressive symptoms in young female psychiatric patients. Ratings of depressive symptoms and blood samples were obtained from 92 young women seeking psychiatric care. Methylation of 32 promoter-associated CpG sites in TLR1 to TLR10 was analysed using the Illumina Infinium Methylation EPIC BeadChip. Expression levels of 91 inflammatory proteins were determined by proximity extension assay. Statistical correlations between depressive state, TLR1-10 methylation and inflammatory proteins were investigated. Four additional cohorts were studied to evaluate the generalizability of the findings. In the discovery cohort, methylation grade of cg05429895 (TLR4) in blood was inversely correlated with depressive symptoms score in young adults. After correction for multiple testing, plasma levels of macrophage inflammatory protein 1 beta (MIP-1 beta/CCL4) were associated with both TLR4 methylation and depressive symptom severity. A similar inverse association between TLR4 methylation in blood and affective symptoms score was also found in a cohort of 148 both males and females (<40 years of age) from the Danish Twin Registry. These findings were not, however, replicated in three other external cohorts; which differed from the first two cohorts by a higher age and mixed ethnicities, thus limiting the generalizability of our findings. However, TLR4 methylation inversely correlated with TLR4 mRNA expression in the Danish Twin Study indicating a functional significance of methylation at this particular CpG. Higher depression scores in young Scandinavian adults was associated with decreased methylation of TLR4 in blood.

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  • 120.
    Risal, Sanjiv
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Manti, Maria
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Lu, Haojiang
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Fornes, Romina
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Benrick, Anna
    Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; School of Health Sciences, University of Skövde, Skövde, Sweden.
    Deng, Qiaolin
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Cesta, Carolyn E.
    Department of Medicine, Solna, Centre for Pharmacoepidemiology, Karolinska Institutet, Stockholm, Sweden.
    Rosenqvist, Mina A.
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Stener-Victorin, Elisabet
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Prenatal androgen exposure causes a sexually dimorphic transgenerational increase in offspring susceptibility to anxiety disorders2021In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 11, no 1, article id 45Article in journal (Refereed)
    Abstract [en]

    If and how obesity and elevated androgens in women with polycystic ovary syndrome (PCOS) affect their offspring’s psychiatric health is unclear. Using data from Swedish population health registers, we showed that daughters of mothers with PCOS have a 78% increased risk of being diagnosed with anxiety disorders. We next generated a PCOS-like mouse (F0) model induced by androgen exposure during late gestation, with or without diet-induced maternal obesity, and showed that the first generation (F1) female offspring develop anxiety-like behavior, which is transgenerationally transmitted through the female germline into the third generation of female offspring (F3) in the androgenized lineage. In contrast, following the male germline, F3 male offspring (mF3) displayed anxiety-like behavior in the androgenized and the obese lineages. Using a targeted approach to search for molecular targets within the amygdala, we identified five differentially expressed genes involved in anxiety-like behavior in F3 females in the androgenized lineage and eight genes in the obese lineage. In mF3 male offspring, three genes were dysregulated in the obese lineage but none in the androgenized lineage. Finally, we performed in vitro fertilization (IVF) using a PCOS mouse model of continuous androgen exposure. We showed that the IVF generated F1 and F2 offspring in the female germline did not develop anxiety-like behavior, while the F2 male offspring (mF2) in the male germline did. Our findings provide evidence that elevated maternal androgens in PCOS and maternal obesity may underlie the risk of a transgenerational transmission of anxiety disorders in children of women with PCOS.

  • 121.
    Risal, Sanjiv
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Manti, Maria
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Lu, Haojiang
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Fornes, Romina
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden / School of Medical Sciences, Örebro University, Sweden.
    Benrick, Anna
    University of Skövde, School of Health Sciences. University of Skövde, Digital Health Research (DHEAR). Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Deng, Quiaolin
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Cesta, Carolyn E.
    Department of Medicine, Solna, Centre for Pharmacoepidemiology, Karolinska Institutet, Stockholm, Sweden.
    Rosenqvist, Mina A.
    School of Medical Sciences, Örebro University, Sweden.
    Stener-Victorin, Elisabet
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Prenatal androgen exposure causes a sexually dimorphic transgenerational increase in offspring susceptibility to anxiety disorders2021In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 11, no 1, article id 45Article in journal (Refereed)
    Abstract [en]

    If and how obesity and elevated androgens in women with polycystic ovary syndrome (PCOS) affect their offspring’s psychiatric health is unclear. Using data from Swedish population health registers, we showed that daughters of mothers with PCOS have a 78% increased risk of being diagnosed with anxiety disorders. We next generated a PCOS-like mouse (F0) model induced by androgen exposure during late gestation, with or without diet-induced maternal obesity, and showed that the first generation (F1) female offspring develop anxiety-like behavior, which is transgenerationally transmitted through the female germline into the third generation of female offspring (F3) in the androgenized lineage. In contrast, following the male germline, F3 male offspring (mF3) displayed anxiety-like behavior in the androgenized and the obese lineages. Using a targeted approach to search for molecular targets within the amygdala, we identified five differentially expressed genes involved in anxiety-like behavior in F3 females in the androgenized lineage and eight genes in the obese lineage. In mF3 male offspring, three genes were dysregulated in the obese lineage but none in the androgenized lineage. Finally, we performed in vitro fertilization (IVF) using a PCOS mouse model of continuous androgen exposure. We showed that the IVF generated F1 and F2 offspring in the female germline did not develop anxiety-like behavior, while the F2 male offspring (mF2) in the male germline did. Our findings provide evidence that elevated maternal androgens in PCOS and maternal obesity may underlie the risk of a transgenerational transmission of anxiety disorders in children of women with PCOS.

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  • 122.
    Ruan, Xixian
    et al.
    Cent South Univ, Xiangya Hosp 3, Dept Gastroenterol, Changsha, Peoples R China..
    Chen, Jie
    Zhejiang Univ, Sch Med, Sch Publ Hlth, Dept Big Data Hlth Sci, Hangzhou, Zhejiang, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Zhejiang, Peoples R China..
    Sun, Yuhao
    Zhejiang Univ, Sch Med, Sch Publ Hlth, Dept Big Data Hlth Sci, Hangzhou, Zhejiang, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Zhejiang, Peoples R China..
    Zhang, Yao
    Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Dept Gastroenterol, Shanghai, Peoples R China..
    Zhao, Jianhui
    Zhejiang Univ, Sch Med, Sch Publ Hlth, Dept Big Data Hlth Sci, Hangzhou, Zhejiang, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Zhejiang, Peoples R China..
    Wang, Xiaoyan
    Cent South Univ, Xiangya Hosp 3, Dept Gastroenterol, Changsha, Peoples R China..
    Li, Xue
    Zhejiang Univ, Sch Med, Sch Publ Hlth, Dept Big Data Hlth Sci, Hangzhou, Zhejiang, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Zhejiang, Peoples R China..
    Yuan, Shuai
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, Stockholm, Sweden..
    Larsson, Susanna C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Medical epidemiology. Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, Stockholm, Sweden..
    Depression and 24 gastrointestinal diseases: a Mendelian randomization study2023In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 13, article id 146Article in journal (Refereed)
    Abstract [en]

    The causality of the association between depression and gastrointestinal diseases is undetermined. We conducted Mendelian randomization (MR) analyses to systematically explore the associations of depression with 24 gastrointestinal diseases. Independent genetic variants associated with depression at the genome-wide significance level were selected as instrumental variables. Genetic associations with 24 gastrointestinal diseases were obtained from the UK Biobank study, the FinnGen study, and large consortia. Multivariable MR analysis was conducted to explore the mediation effects of body mass index, cigarette smoking, and type 2 diabetes. After multiple-testing corrections, genetic liability to depression was associated with an increased risk of irritable bowel syndrome, non-alcohol fatty liver disease, alcoholic liver disease, gastroesophageal reflux, chronic pancreatitis, duodenal ulcer, chronic gastritis, gastric ulcer, diverticular disease, cholelithiasis, acute pancreatitis, and ulcerative colitis. For the causal effect of genetic liability to depression on non-alcoholic fatty liver disease, a substantial proportion was mediated by body mass index. Genetic predisposition to smoking initiation mediated half of effect of depression on acute pancreatitis. This MR study suggests that depression may play a causal role in many gastrointestinal diseases.

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    FULLTEXT01
  • 123.
    Rukh, Gull
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Dang, Junhua
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Olivo, Gaia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Ciuculete, Diana-Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Rask-Andersen, Mathias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Sechenov First Moscow State Med Univ, Inst Translat Med & Biotechnol, Moscow, Russia.
    Personality, lifestyle and job satisfaction: causal association between neuroticism and job satisfaction using Mendelian randomisation in the UK biobank cohort2020In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 10, no 1, article id 11Article in journal (Refereed)
    Abstract [en]

    Job-related stress has been associated with poor health outcomes but little is known about the causal nature of these findings. We employed Mendelian randomisation (MR) approach to investigate the causal effect of neuroticism, education, and physical activity on job satisfaction. Trait-specific genetic risk score (GRS) based on recent genome wide association studies were used as instrumental variables (IV) using the UK Biobank cohort (N = 315,536). Both single variable and multivariable MR analyses were used to determine the effect of each trait on job satisfaction. We observed a clear evidence of a causal association between neuroticism and job satisfaction. In single variable MR, one standard deviation (1 SD) higher genetically determined neuroticism score (4.07 units) was associated with -0.31 units lower job satisfaction (95% confidence interval (CI): -0.38 to -0.24; P = 9.5 x 10(-20)). The causal associations remained significant after performing sensitivity analyses by excluding invalid genetic variants from GRS(Neuroticism) (beta(95%CI): -0.28(-0.35 to -0.21); P = 3.4 x 10(-15)). Education (0.02; -0.08 to 0.12; 0.67) and physical activity (0.08; -0.34 to 0.50; 0.70) did not show any evidence for causal association with job satisfaction. When genetic instruments for neuroticism, education and physical activity were included together, the association of neuroticism score with job satisfaction was reduced by only -0.01 units, suggesting an independent inverse causal association between neuroticism score (P = 2.7 x 10(-17)) and job satisfaction. Our findings show an independent causal association between neuroticism score and job satisfaction. Physically active lifestyle may help to increase job satisfaction despite presence of high neuroticism scores. Our study highlights the importance of considering the confounding effect of negative personality traits for studies on job satisfaction.

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    FULLTEXT01
  • 124.
    Sariaslan, A.
    et al.
    Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Fazel, S.
    Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
    D'Onofrio, B. M.
    Department of Psychological and Brain Sciences, Indiana University, Bloomington, USA.
    Långström, N.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Bergen, S. E.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Kuja-Halkola, R.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lichtenstein, P.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Schizophrenia and subsequent neighborhood deprivation: revisiting the social drift hypothesis using population, twin and molecular genetic data2016In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 6, article id e796Article in journal (Refereed)
    Abstract [en]

    Neighborhood influences in the etiology of schizophrenia have been emphasized in a number of systematic reviews, but causality remains uncertain. To test the social drift hypothesis, we used three complementary genetically informed Swedish cohorts. First, we used nationwide Swedish data on approximately 760 000 full- and half-sibling pairs born between 1951 and 1974 and quantitative genetic models to study genetic and environmental influences on the overlap between schizophrenia in young adulthood and subsequent residence in socioeconomically deprived neighborhoods. Schizophrenia diagnoses were ascertained using the National Patient Registry. Second, we tested the overlap between childhood psychotic experiences and neighborhood deprivation in early adulthood in the longitudinal Twin Study of Child and Adolescent Development (TCHAD; n=2960). Third, we investigated to what extent polygenic risk scores for schizophrenia predicted residence in deprived neighborhoods during late adulthood using the TwinGene sample (n=6796). Sibling data suggested that living in deprived neighborhoods was substantially heritable; 65% (95% confidence interval (95% CI): 60-71%) of the variance was attributed to genetic influences. Although the correlation between schizophrenia and neighborhood deprivation was moderate in magnitude (r=0.22; 95% CI: 0.20-0.24), it was entirely explained by genetic influences. We replicated these findings in the TCHAD sample. Moreover, the association between polygenic risk for schizophrenia and neighborhood deprivation was statistically significant (R(2)=0.15%, P=0.002). Our findings are primarily consistent with a genetic selection interpretation where genetic liability for schizophrenia also predicts subsequent residence in socioeconomically deprived neighborhoods. Previous studies may have overemphasized the relative importance of environmental influences in the social drift of schizophrenia patients. Clinical and policy interventions will therefore benefit from the future identification of potentially causal pathways between different dimensions of cognitive functions and socioeconomic trajectories derived from studies adopting family-based research designs.

  • 125. Sariaslan, Amir
    et al.
    Fanshawe, Thomas
    Pitkänen, Joonas
    Cipriani, Andrea
    Martikainen, Pekka
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences, Centre for Health Equity Studies (CHESS). University of Helsinki, Finland; Max Planck Institute for Demographic Research, Germany.
    Fazel, Seena
    Predicting suicide risk in 137,112 people with severe mental illness in Finland: external validation of the Oxford Mental Illness and Suicide tool (OxMIS)2023In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 13, no 1, article id 126Article in journal (Refereed)
    Abstract [en]

    Oxford Mental Illness and Suicide tool (OxMIS) is a standardised, scalable, and transparent instrument for suicide risk assessment in people with severe mental illness (SMI) based on 17 sociodemographic, criminal history, familial, and clinical risk factors. However, alongside most prediction models in psychiatry, external validations are currently lacking. We utilised a Finnish population sample of all persons diagnosed by mental health services with SMI (schizophrenia-spectrum and bipolar disorders) between 1996 and 2017 (n = 137,112). To evaluate the performance of OxMIS, we initially calculated the predicted 12-month suicide risk for each individual by weighting risk factors by effect sizes reported in the original OxMIS prediction model and converted to a probability. This probability was then used to assess the discrimination and calibration of the OxMIS model in this external sample. Within a year of assessment, 1.1% of people with SMI (n = 1475) had died by suicide. The overall discrimination of the tool was good, with an area under the curve of 0.70 (95% confidence interval: 0.69–0.71). The model initially overestimated suicide risks in those with elevated predicted risks of >5% over 12 months (Harrell’s Emax = 0.114), which applied to 1.3% (n = 1780) of the cohort. However, when we used a 5% maximum predicted suicide risk threshold as is recommended clinically, the calibration was excellent (ICI = 0.002; Emax = 0.005). Validating clinical prediction tools using routinely collected data can address research gaps in prediction psychiatry and is a necessary step to translating such models into clinical practice.

  • 126.
    Schwarz, Emanuel
    et al.
    Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, Mannheim, Germany..
    Doan, Nhat Trung
    Norwegian Centre for Mental Disorders Research (NORMENT), KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Pergola, Giulio
    Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Sense Organs, Bari, Italy..
    Westlye, Lars T.
    Univ Oslo, Inst Clin Med, Norwegian Ctr Mental Disorders Res NORMENT, KG Jebsen Ctr Psychosis Res,Div Mental Hlth & Add, Oslo, Norway.;Univ Oslo, Dept Psychol, Oslo, Norway..
    Kaufmann, Tobias
    Univ Oslo, Inst Clin Med, Norwegian Ctr Mental Disorders Res NORMENT, KG Jebsen Ctr Psychosis Res,Div Mental Hlth & Add, Oslo, Norway..
    Wolfers, Thomas
    Radboud Univ Nijmegen, Dept Human Genet, Med Ctr, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Ctr Cognit Neuroimaging, Nijmegen, Netherlands..
    Brecheisen, Ralph
    Maastricht Univ, Med Ctr, Maastricht, Netherlands..
    Quarto, Tiziana
    Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Sense Organs, Bari, Italy.;Univ Helsinki, Dept Psychol & Logoped, Cognit Brain Res Unit, Fac Med, Helsinki, Finland..
    Ing, Alex J.
    Kings Coll London, Ctr Populat Neurosci & Stratified Med PONS, London, England.;Kings Coll London, MRC SGDP Ctr, Inst Psychiat Psychol & Neurosci, London, England..
    Di Carlo, Pasquale
    Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Sense Organs, Bari, Italy..
    Gurholt, Tiril P.
    Univ Oslo, Inst Clin Med, Norwegian Ctr Mental Disorders Res NORMENT, KG Jebsen Ctr Psychosis Res,Div Mental Hlth & Add, Oslo, Norway..
    Harms, Robbert L.
    Brain Innovat BV, Maastricht, Netherlands..
    Noirhomme, Quentin
    Brain Innovat BV, Maastricht, Netherlands..
    Moberget, Torgeir
    Univ Oslo, Inst Clin Med, Norwegian Ctr Mental Disorders Res NORMENT, KG Jebsen Ctr Psychosis Res,Div Mental Hlth & Add, Oslo, Norway..
    Agartz, Ingrid
    Univ Oslo, Inst Clin Med, Norwegian Ctr Mental Disorders Res NORMENT, KG Jebsen Ctr Psychosis Res,Div Mental Hlth & Add, Oslo, Norway.;Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm, Sweden.;Diakonhjemmet Hosp, Dept Psychiat Res, Oslo, Norway..
    Andreassen, Ole A.
    Univ Oslo, Inst Clin Med, Norwegian Ctr Mental Disorders Res NORMENT, KG Jebsen Ctr Psychosis Res,Div Mental Hlth & Add, Oslo, Norway..
    Bellani, Marcella
    Azienda Osped Univ Integrata Verona, Sect Psychiat, Verona, VR, Italy.;Univ Verona, Dept Neurosci Biomed & Movements Sci, Verona, VR, Italy..
    Bertolino, Alessandro
    Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Sense Organs, Bari, Italy.;Azienda Osped Univ Consorziale Policlin Bari, Policlin Bari, Inst Psichiatry, Bari, BA, Italy..
    Blasi, Giuseppe
    Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Sense Organs, Bari, Italy.;Azienda Osped Univ Consorziale Policlin, Bari, Italy..
    Brambilla, Paolo
    Univ Milan, Fdn IRCCS Ca Granda Osped Maggiore Policlin, Dept Neurosci & Mental Hlth, Milan, Italy..
    Buitelaar, Jan K.
    Radboudumc, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.;Karakter Child & Adolescent Psychiat Univ Ctr, Nijmegen, Netherlands..
    Cervenka, Simon
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm, Sweden..
    Flyckt, Lena
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm, Sweden..
    Frangou, Sophia
    Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA..
    Franke, Barbara
    Radboudumc, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Dept Human Genet, Med Ctr, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Dept Psychiat, Med Ctr, Nijmegen, Netherlands..
    Hall, Jeremy
    Cardiff Univ, Neurosci & Mental Hlth Res Inst, Maindy Rd, Cardiff CF24 4HQ, S Glam, Wales..
    Heslenfeld, Dirk J.
    Vrije Univ Amsterdam, Dept Cognit Psychol, Amsterdam, Netherlands..
    Kirsch, Peter
    Heidelberg Univ, Cent Inst Mental Hlth, Med Fac Mannheim, Dept Clin Psychol, Heidelberg, Germany.;Bernstein Ctr Computat Neurosci Heidelberg Mannhe, Mannheim, Germany..
    McIntosh, Andrew M.
    Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh EH10 5HF, Midlothian, Scotland.;Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Noethen, Markus M.
    Univ Bonn, Sch Med, Inst Human Genet, Bonn, Germany.;Univ Hosp Bonn, Bonn, Germany.;Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany..
    Papassotiropoulos, Andreas
    Univ Basel, Dept Psychol, Div Mol Neurosci, CH-4055 Basel, Switzerland.;Univ Basel, Transfac Res Platform Mol & Cognit Neurosci, Basel, Switzerland.;Univ Basel, Psychiat Univ Clin, CH-4055 Basel, Switzerland.;Univ Basel, Dept Biozentrum, Life Sci Training Facil, CH-4056 Basel, Switzerland..
    de Quervain, Dominique J-F
    Univ Basel, Transfac Res Platform Mol & Cognit Neurosci, Basel, Switzerland.;Univ Basel, Psychiat Univ Clin, CH-4055 Basel, Switzerland.;Univ Basel, Dept Psychol, Div Cognit Neurosci, CH-4055 Basel, Switzerland..
    Rietschel, Marcella
    Heidelberg Univ, Cent Inst Mental Hlth, Med Fac Mannheim, Dept Genet Epidemiol Psychiat, Heidelberg, Germany..
    Schumann, Gunter
    Kings Coll London, Ctr Populat Neurosci & Stratified Med PONS, London, England.;Kings Coll London, MRC SGDP Ctr, Inst Psychiat Psychol & Neurosci, London, England..
    Tost, Heike
    Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, Mannheim, Germany..
    Witt, Stephanie H.
    Heidelberg Univ, Cent Inst Mental Hlth, Med Fac Mannheim, Dept Genet Epidemiol Psychiat, Heidelberg, Germany..
    Zink, Mathias
    Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, Mannheim, Germany.;Dist Hosp Mittelfranken, Dept Psychiat Psychotherapy & Psychosomat, Ansbach, Germany..
    Meyer-Lindenberg, Andreas
    Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, Mannheim, Germany..
    Bettella, Francesco
    Univ Oslo, Inst Clin Med, Norwegian Ctr Mental Disorders Res NORMENT, KG Jebsen Ctr Psychosis Res,Div Mental Hlth & Add, Oslo, Norway..
    Brandt, Christine L.
    Univ Oslo, Inst Clin Med, Norwegian Ctr Mental Disorders Res NORMENT, KG Jebsen Ctr Psychosis Res,Div Mental Hlth & Add, Oslo, Norway..
    Clarke, Toni-Kim
    Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh EH10 5HF, Midlothian, Scotland..
    Coynel, David
    Univ Basel, Transfac Res Platform Mol & Cognit Neurosci, Basel, Switzerland.;Univ Basel, Dept Psychol, Div Cognit Neurosci, CH-4055 Basel, Switzerland..
    Degenhardt, Franziska
    Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany..
    Djurovic, Srdjan
    Univ Oslo, Inst Clin Med, Norwegian Ctr Mental Disorders Res NORMENT, KG Jebsen Ctr Psychosis Res,Div Mental Hlth & Add, Oslo, Norway.;Oslo Univ Hosp, Dept Med Genet, Oslo, Norway..
    Eisenacher, Sarah
    Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, Mannheim, Germany..
    Fastenrath, Matthias
    Univ Basel, Transfac Res Platform Mol & Cognit Neurosci, Basel, Switzerland.;Univ Basel, Dept Psychol, Div Cognit Neurosci, CH-4055 Basel, Switzerland..
    Fatouros-Bergman, Helena
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm, Sweden..
    Forstner, Andreas J.
    Univ Bonn, Sch Med, Inst Human Genet, Bonn, Germany.;Univ Hosp Bonn, Bonn, Germany.;Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany.;Univ Basel, Dept Biomed, Human Genom Res Grp, Basel, Switzerland.;Univ Basel, Dept Psychiat UPK, Basel, Switzerland.;Univ Hosp Basel, Inst Med Genet & Pathol, Basel, Switzerland..
    Frank, Josef
    Heidelberg Univ, Cent Inst Mental Hlth, Med Fac Mannheim, Dept Genet Epidemiol Psychiat, Heidelberg, Germany..
    Gambi, Francesco
    G DAnnunzio Univ Chieti Pescara, Dept Neurosci Imaging & Clin Sci, Pescara, Italy..
    Gelao, Barbara
    Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Sense Organs, Bari, Italy..
    Geschwind, Leo
    Univ Basel, Dept Psychol, Div Mol Neurosci, CH-4055 Basel, Switzerland.;Univ Basel, Transfac Res Platform Mol & Cognit Neurosci, Basel, Switzerland..
    Di Giannantonio, Massimo
    G DAnnunzio Univ Chieti Pescara, Dept Neurosci Imaging & Clin Sci, Pescara, Italy.;Natl Hlth Trust, Dept Mental Hlth, Chieti, Italy..
    Di Giorgio, Annabella
    Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Sense Organs, Bari, Italy.;Fdn Casa Sollievo Sofferenza IRCCS San Giovanni R, San Giovanni Rotondo, Italy..
    Hartman, Catharina A.
    Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot regulat, Dept Psychiat, Groningen, Netherlands..
    Heilmann-Heimbach, Stefanie
    Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany..
    Herms, Stefan
    Univ Bonn, Sch Med, Inst Human Genet, Bonn, Germany.;Univ Hosp Bonn, Bonn, Germany.;Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany.;Univ Basel, Dept Biomed, Basel, Switzerland.;Univ Basel, Inst Med Genet & Pathol, Human Genom Res Grp, Basel, Switzerland.;Univ Basel, Div Med Genet, Dept Biomed, Basel, Switzerland.;Univ Hosp Basel, Basel, Switzerland..
    Hoekstra, Pieter J.
    Univ Groningen, Univ Med Ctr Groningen, Dept Child & Adolescent Psychiat, Groningen, Netherlands..
    Hoffmann, Per
    Univ Bonn, Sch Med, Inst Human Genet, Bonn, Germany.;Univ Hosp Bonn, Bonn, Germany.;Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany.;Univ Basel, Dept Biomed, Basel, Switzerland.;Univ Basel, Inst Med Genet & Pathol, Human Genom Res Grp, Basel, Switzerland.;Univ Basel, Div Med Genet, Dept Biomed, Basel, Switzerland.;Univ Hosp Basel, Basel, Switzerland..
    Hoogman, Martine
    Radboud Univ Nijmegen, Dept Human Genet, Med Ctr, Nijmegen, Netherlands.;Radboudumc, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands..
    Jonsson, Erik G.
    Univ Oslo, Dept Psychol, Oslo, Norway.;Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm, Sweden..
    Loos, Eva
    Univ Basel, Transfac Res Platform Mol & Cognit Neurosci, Basel, Switzerland.;Univ Basel, Dept Psychol, Div Cognit Neurosci, CH-4055 Basel, Switzerland..
    Maggioni, Eleonora
    Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Sense Organs, Bari, Italy.;Univ Milan, Fdn IRCCS Ca Granda Osped Maggiore Policlin, Dept Neurosci & Mental Hlth, Milan, Italy..
    Oosterlaan, Jaap
    Emma Childrens Hosp, Acad Med Ctr, Amsterdam, Netherlands..
    Papalino, Marco
    Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Sense Organs, Bari, Italy..
    Rampino, Antonio
    Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Sense Organs, Bari, Italy..
    Romaniuk, Liana
    Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh EH10 5HF, Midlothian, Scotland..
    Selvaggi, Pierluigi
    Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Sense Organs, Bari, Italy.;Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Neuroimaging, London, England..
    Sepede, Gianna
    Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Sense Organs, Bari, Italy.;G DAnnunzio Univ Chieti Pescara, Dept Neurosci Imaging & Clin Sci, Pescara, Italy..
    Sonderby, Ida E.
    Univ Oslo, Inst Clin Med, Norwegian Ctr Mental Disorders Res NORMENT, KG Jebsen Ctr Psychosis Res,Div Mental Hlth & Add, Oslo, Norway..
    Spalek, Klara
    Univ Basel, Transfac Res Platform Mol & Cognit Neurosci, Basel, Switzerland.;Univ Basel, Dept Psychol, Div Cognit Neurosci, CH-4055 Basel, Switzerland..
    Sussmann, Jessika E.
    Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh EH10 5HF, Midlothian, Scotland..
    Thompson, Paul M.
    Univ Southern Calif, Stevens Inst Neuroimaging & Informat, Imaging Genet Ctr, Los Angeles, CA USA..
    Vasquez, Alejandro Arias
    Radboud Univ Nijmegen, Dept Human Genet, Med Ctr, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Dept Psychiat, Med Ctr, Nijmegen, Netherlands..
    Vogler, Christian
    Univ Basel, Dept Psychol, Div Mol Neurosci, CH-4055 Basel, Switzerland.;Univ Basel, Transfac Res Platform Mol & Cognit Neurosci, Basel, Switzerland..
    Whalley, Heather
    Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh EH10 5HF, Midlothian, Scotland..
    Farde, L.
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm, Sweden..
    Flyckt, L.
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm, Sweden..
    Engberg, G.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Erhardt, S.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Fatouros-Bergman, H.
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm, Sweden..
    Cervenka, S.
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm, Sweden..
    Schwieler, L.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Agartz, I
    Univ Oslo, Inst Clin Med, Norwegian Ctr Mental Disorders Res NORMENT, KG Jebsen Ctr Psychosis Res,Div Mental Hlth & Add, Oslo, Norway.;Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm, Sweden.;Diakonhjemmet Hosp, Dept Psychiat Res, Oslo, Norway..
    Collste, K.
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm, Sweden..
    Victorsson, P.
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm, Sweden..
    Malmqvist, A.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Hedberg, M.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Orhan, F.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Reproducible grey matter patterns index a multivariate, global alteration of brain structure in schizophrenia and bipolar disorder2019In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 9, article id 12Article in journal (Refereed)
    Abstract [en]

    Schizophrenia is a severe mental disorder characterized by numerous subtle changes in brain structure and function. Machine learning allows exploring the utility of combining structural and functional brain magnetic resonance imaging (MRI) measures for diagnostic application, but this approach has been hampered by sample size limitations and lack of differential diagnostic data. Here, we performed a multi-site machine learning analysis to explore brain structural patterns of T1 MRI data in 2668 individuals with schizophrenia, bipolar disorder or attention-deficit/hyperactivity disorder, and healthy controls. We found reproducible changes of structural parameters in schizophrenia that yielded a classification accuracy of up to 76% and provided discrimination from ADHD, through it lacked specificity against bipolar disorder. The observed changes largely indexed distributed grey matter alterations that could be represented through a combination of several global brain-structural parameters. This multi-site machine learning study identified a brain-structural signature that could reproducibly differentiate schizophrenia patients from controls, but lacked specificity against bipolar disorder. While this currently limits the clinical utility of the identified signature, the present study highlights that the underlying alterations index substantial global grey matter changes in psychotic disorders, reflecting the biological similarity of these conditions, and provide a roadmap for future exploration of brain structural alterations in psychiatric patients.

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  • 127.
    Serpeloni, F.
    et al.
    University of Konstanz, Germany.
    Radtke, K.
    University of Konstanz, Germany; University of Konstanz, Germany.
    de Assis, S. G.
    Fundacao Oswaldo Cruz, Brazil.
    Henning, F.
    University of Federal Rio de Janeiro, Brazil.
    Nätt, Daniel
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Elbert, T.
    University of Konstanz, Germany.
    Grandmaternal stress during pregnancy and DNA methylation of the third generation: an epigenome-wide association study2017In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 7, article id e1202Article in journal (Refereed)
    Abstract [en]

    Stress during pregnancy may impact subsequent generations, which is demonstrated by an increased susceptibility to childhood and adulthood health problems in the children and grandchildren. Although the importance of the prenatal environment is well reported with regards to future physical and emotional outcomes, little is known about the molecular mechanisms that mediate the long-term consequences of early stress across generations. Recent studies have identified DNA methylation as a possible mediator of the impact of prenatal stress in the offspring. Whether psychosocial stress during pregnancy also affects DNA methylation of the grandchildren is still not known. In the present study we examined the multigenerational hypothesis, that is, grandmaternal exposure to psychosocial stress during pregnancy affecting DNA methylation of the grandchildren. We determined the genome-wide DNA methylation profile in 121 children (65 females and 56 males) and tested for associations with exposure to grandmaternal interpersonal violence during pregnancy. We observed methylation variations of five CpG sites significantly (FDR amp;lt; 0.05) associated with the grandmothers report of exposure to violence while pregnant with the mothers of the children. The results revealed differential methylation of genes previously shown to be involved in circulatory system processes (FDRo0.05). This study provides support for DNA methylation as a biological mechanism involved in the transmission of stress across generations and motivates further investigations to examine prenatal-dependent DNA methylation as a potential biomarker for health problems.

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  • 128.
    Shang, Pei
    et al.
    Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Coll Med & Sci, Rochester, MN 55905 USA.;First Hosp Jilin Univ, Dept Neurol, Changchun, Peoples R China..
    Ho, Ada Man-Choi
    Mayo Clin, Dept Psychiat & Psychol, Coll Med & Sci, Rochester, MN 55905 USA..
    Tufvesson-Alm, Maximilian
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Lindberg, Daniel R.
    Mayo Clin, Sch Med & Sci, Mayo Clin MD PhD Program, Rochester, MN USA.;Mayo Clin, Neurosci Program, Coll Med & Sci, Rochester, MN 55905 USA..
    Grant, Caroline W.
    Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Coll Med & Sci, Rochester, MN 55905 USA..
    Orhan, Funda
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Eren, Feride
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Bhat, Maria
    AstraZeneca, Sci Life Lab, Res & Dev Innovat Med Personalised Healthcare & B, SE-17177 Solna, Sweden..
    Engberg, Goran
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Schwieler, Lilly
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Fatouros-Bergman, Helena
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden.;Reg Stockholm, Stockholm Hlth Care Serv, Stockholm, Sweden..
    Imbeault, Sophie
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Iverson, Ryan M.
    Mayo Clin, Div Biomed Stat & Informat, Coll Med, Rochester, MN USA..
    Dasari, Surendra
    Mayo Clin, Div Biomed Stat & Informat, Coll Med, Rochester, MN USA..
    Piehl, Fredrik
    Karolinska Univ Hosp, Ctr Mol Med, Karolinska Inst, Dept Clin Neurosci,Unit Neuroimmunol, Stockholm, Sweden..
    Cervenka, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Psychiatry. Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden.;Reg Stockholm, Stockholm Hlth Care Serv, Stockholm, Sweden..
    Sellgren, Carl M.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden.;Reg Stockholm, Stockholm Hlth Care Serv, Stockholm, Sweden..
    Erhardt, Sophie
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Choi, Doo-Sup
    Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Coll Med & Sci, Rochester, MN 55905 USA.;Mayo Clin, Dept Psychiat & Psychol, Coll Med & Sci, Rochester, MN 55905 USA.;Mayo Clin, Neurosci Program, Coll Med & Sci, Rochester, MN 55905 USA..
    Identification of cerebrospinal fluid and serum metabolomic biomarkers in first episode psychosis patients2022In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 12, no 1, article id 229Article in journal (Refereed)
    Abstract [en]

    Psychotic disorders are currently diagnosed by examining the patient's mental state and medical history. Identifying reliable diagnostic, monitoring, predictive, or prognostic biomarkers would be useful in clinical settings and help to understand the pathophysiology of schizophrenia. Here, we performed an untargeted metabolomics analysis using ultra-high pressure liquid chromatography coupled with time-of-flight mass spectroscopy on cerebrospinal fluid (CSF) and serum samples of 25 patients at their first-episode psychosis (FEP) manifestation (baseline) and after 18 months (follow-up). CSF and serum samples of 21 healthy control (HC) subjects were also analyzed. By comparing FEP and HC groups at baseline, we found eight CSF and 32 serum psychosis-associated metabolites with non-redundant identifications. Most remarkable was the finding of increased CSF serotonin (5-HT) levels. Most metabolites identified at baseline did not differ between groups at 18-month follow-up with significant improvement of positive symptoms and cognitive functions. Comparing FEP patients at baseline and 18-month follow-up, we identified 20 CSF metabolites and 90 serum metabolites that changed at follow-up. We further utilized Ingenuity Pathway Analysis (IPA) and identified candidate signaling pathways involved in psychosis pathogenesis and progression. In an extended cohort, we validated that CSF 5-HT levels were higher in FEP patients than in HC at baseline by reversed-phase high-pressure liquid chromatography. To conclude, these findings provide insights into the pathophysiology of psychosis and identify potential psychosis-associated biomarkers.

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  • 129.
    Stiernman, Louise
    et al.
    Umeå Univ, Dept Clin Sci, Umeå, Sweden..
    Dubol, Manon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comasco: Neuropsychopharmacology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Neuropsychopharmacology.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Reproductive Health. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comasco: Neuropsychopharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Neuropsychopharmacology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Reproductive Health.
    Boraxbekk, Carl-Johan
    Umeå Univ, Dept Radiat Sci, Diagnost Radiol, Umeå, Sweden.;Univ Copenhagen, Inst Clin Med, Fac Med & Hlth Sci, Copenhagen, Denmark.;Copenhagen Univ Hosp Amager & Hvidovre, Danish Res Ctr Magnet Resonance DRCMR, Ctr Funct & Diagnost Imaging & Res, Copenhagen, Denmark.;Umeå Univ, Umeå Ctr Funct Brain Imaging UFBI, Umeå, Sweden.;Copenhagen Univ Hosp Bispebjerg, Inst Sports Med Copenhagen ISMC, Copenhagen, Denmark.;Copenhagen Univ Hosp Bispebjerg, Dept Neurol, Copenhagen, Denmark..
    Johansson, Maja
    Umeå Univ, Dept Clin Sci, Umeå, Sweden..
    Bixo, Marie
    Umeå Univ, Dept Clin Sci, Umeå, Sweden..
    Emotion-induced brain activation across the menstrual cycle in individuals with premenstrual dysphoric disorder and associations to serum levels of progesterone-derived neurosteroids2023In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 13, no 1, article id 124Article in journal (Refereed)
    Abstract [en]

    Premenstrual dysphoric disorder (PMDD) is a debilitating disorder characterized by severe mood symptoms in the luteal phase of the menstrual cycle. PMDD symptoms are hypothesized to be linked to an altered sensitivity to normal luteal phase levels of allopregnanolone (ALLO), a GABA(A)-modulating progesterone metabolite. Moreover, the endogenous 3 beta-epimer of ALLO, isoallopregnanolone (ISO), has been shown to alleviate PMDD symptoms through its selective and dose-dependent antagonism of the ALLO effect. There is preliminary evidence showing altered recruitment of brain regions during emotion processing in PMDD, but whether this is associated to serum levels of ALLO, ISO or their relative concentration is unknown. In the present study, subjects with PMDD and asymptomatic controls underwent functional magnetic resonance imaging (fMRI) in the mid-follicular and the late-luteal phase of the menstrual cycle. Brain responses to emotional stimuli were investigated and related to serum levels of ovarian steroids, the neurosteroids ALLO, ISO, and their ratio ISO/ALLO. Participants with PMDD exhibited greater activity in brain regions which are part of emotion-processing networks during the late-luteal phase of the menstrual cycle. Furthermore, activity in key regions of emotion processing networks - the parahippocampal gyrus and amygdala - was differentially associated to the ratio of ISO/ALLO levels in PMDD subjects and controls. Specifically, a positive relationship between ISO/ALLO levels and brain activity was found in PMDD subjects, while the opposite was observed in controls. In conclusion, individuals with PMDD show altered emotion-induced brain responses in the late-luteal phase of the menstrual cycle which may be related to an abnormal response to physiological levels of GABA(A)-active neurosteroids.

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  • 130.
    Stiernman, Louise
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Dubol, Manon
    Department of Women's and Children's Health, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Comasco, Erika
    Department of Women's and Children's Health, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Sundström-Poromaa, Inger
    Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Institute for Clinical Medicine, Faculty of Medical and Health Sciences, University of Copenhagen, Copenhagen, Denmark; Danish Research Centre for Magnetic Resonance (DRCMR), Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, Denmark; Institute of Sports Medicine Copenhagen (ISMC) and Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark.
    Johansson, Inga-Maj
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Bixo, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Emotion-induced brain activation across the menstrual cycle in individuals with premenstrual dysphoric disorder and associations to serum levels of progesterone-derived neurosteroids2023In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 13, no 1, article id 124Article in journal (Refereed)
    Abstract [en]

    Premenstrual dysphoric disorder (PMDD) is a debilitating disorder characterized by severe mood symptoms in the luteal phase of the menstrual cycle. PMDD symptoms are hypothesized to be linked to an altered sensitivity to normal luteal phase levels of allopregnanolone (ALLO), a GABAA-modulating progesterone metabolite. Moreover, the endogenous 3β-epimer of ALLO, isoallopregnanolone (ISO), has been shown to alleviate PMDD symptoms through its selective and dose-dependent antagonism of the ALLO effect. There is preliminary evidence showing altered recruitment of brain regions during emotion processing in PMDD, but whether this is associated to serum levels of ALLO, ISO or their relative concentration is unknown. In the present study, subjects with PMDD and asymptomatic controls underwent functional magnetic resonance imaging (fMRI) in the mid-follicular and the late-luteal phase of the menstrual cycle. Brain responses to emotional stimuli were investigated and related to serum levels of ovarian steroids, the neurosteroids ALLO, ISO, and their ratio ISO/ALLO. Participants with PMDD exhibited greater activity in brain regions which are part of emotion-processing networks during the late-luteal phase of the menstrual cycle. Furthermore, activity in key regions of emotion processing networks - the parahippocampal gyrus and amygdala - was differentially associated to the ratio of ISO/ALLO levels in PMDD subjects and controls. Specifically, a positive relationship between ISO/ALLO levels and brain activity was found in PMDD subjects, while the opposite was observed in controls. In conclusion, individuals with PMDD show altered emotion-induced brain responses in the late-luteal phase of the menstrual cycle which may be related to an abnormal response to physiological levels of GABAA-active neurosteroids.

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  • 131.
    Strom, Nora I.
    et al.
    Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany; Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Sweden; Department of Biomedicine, Aarhus University, Aarhus, Denmark.
    Smit, Dirk J. A.
    Department of Psychiatry, Amsterdam University Medical Centers, Amsterdam, The Netherlands; Amsterdam Neuroscience, Amsterdam, The Netherlands.
    Silzer, Talisa
    Department of Psychiatry, Hospital for Sick Children, Toronto, ON, Canada.
    Iyegbe, Conrad
    Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, England; Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, New York, USA.
    Burton, Christie L.
    Department of Psychiatry, Hospital for Sick Children, Toronto, ON, Canada.
    Pool, René
    Department of Biological Psychology, Vrije Universiteit, Amsterdam, Netherlands.
    Lemire, Mathieu
    Department of Psychiatry, Hospital for Sick Children, Toronto, ON, Canada.
    Crowley, James J.
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Sweden; Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, USA.
    Hottenga, Jouke-Jan
    Netherlands Twin Register, Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
    Ivanov, Volen Z.
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Magnusson, Patrik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Rück, Christian
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Sweden.
    Schachar, Russell J.
    Department of Psychiatry, Hospital for Sick Children, Toronto, ON, Canada.
    Wu, Hei Man
    Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, New York, USA.
    Meier, Sandra M.
    Department of Psychiatry, Dalhousie University, Halifax, NS, Canada; Community Health & Epidemiology, Dalhousie University, NS, Dalhousie, Canada.
    Crosbie, Jennifer
    Department of Psychiatry, Hospital for Sick Children, Toronto, ON, Canada.
    Arnold, Paul D.
    The Mathison Centre for Mental Health Research & Education, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Departments of Psychiatry and Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
    Mattheisen, Manuel
    Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany; Department of Psychiatry, Dalhousie University, Halifax, NS, Canada; Community Health & Epidemiology, Dalhousie University, NS, Dalhousie, Canada.
    Boomsma, Dorret I.
    Netherlands Twin Register, Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands; Amsterdam Public Health Research Institute, Amsterdam, The Netherlands; Amsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands .
    Mataix-Cols, David
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Sweden.
    Cath, Danielle
    Rijksuniversiteit Groningen and Department of Psychiatry, University Medical Center Groningen, Groningen, Netherlands; Department of specialized training, Drenthe Mental Health Care Institute, Assen, The Netherlands.
    Meta-analysis of genome-wide association studies of hoarding symptoms in 27,537 individuals2022In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 12, no 1, article id 479Article in journal (Refereed)
    Abstract [en]

    Hoarding Disorder (HD) is a mental disorder characterized by persistent difficulties discarding or parting with possessions, often resulting in cluttered living spaces, distress, and impairment. Its etiology is largely unknown, but twin studies suggest that it is moderately heritable. In this study, we pooled phenotypic and genomic data from seven international cohorts (N = 27,537 individuals) and conducted a genome wide association study (GWAS) meta-analysis of parent- or self-reported hoarding symptoms (HS). We followed up the results with gene-based and gene-set analyses, as well as leave-one-out HS polygenic risk score (PRS) analyses. To examine a possible genetic association between hoarding symptoms and other phenotypes we conducted cross-trait PRS analyses. Though we did not report any genome-wide significant SNPs, we report heritability estimates for the twin-cohorts between 26-48%, and a SNP-heritability of 11% for an unrelated sub-cohort. Cross-trait PRS analyses showed that the genetic risk for schizophrenia and autism spectrum disorder were significantly associated with hoarding symptoms. We also found suggestive evidence for an association with educational attainment. There were no significant associations with other phenotypes previously linked to HD, such as obsessive-compulsive disorder, depression, anxiety, or attention-deficit hyperactivity disorder. To conclude, we found that HS are heritable, confirming and extending previous twin studies but we had limited power to detect any genome-wide significant loci. Much larger samples will be needed to further extend these findings and reach a "gene discovery zone". To move the field forward, future research should not only include genetic analyses of quantitative hoarding traits in larger samples, but also in samples of individuals meeting strict diagnostic criteria for HD, and more ethnically diverse samples.

  • 132.
    Suvitaival, T.
    et al.
    Steno Diabetes Center, Gentofte, Denmark.
    Mantere, O.
    Mental Health Unit, National Institute for Health and Welfare, Helsinki, Finland; Department of Psychiatry, McGill University, Montréal QC, Canada; Bipolar Disorders Clinic, Douglas Mental Health University Institute, Montréal QC, Canada.
    Kieseppä, T.
    Mental Health Unit, National Institute for Health and Welfare, Helsinki, Finland; Department of Psychiatry, Helsinki University, Helsinki, Finland; Department of Psychiatry, Helsinki University Hospital, Helsinki, Finland.
    Mattila, I.
    Steno Diabetes Center, Gentofte, Denmark.
    Pöhö, P.
    Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
    Hyötyläinen, Tuulia
    Örebro University, School of Science and Technology. Steno Diabetes Center, Gentofte, Denmark.
    Suvisaari, J.
    Mental Health Unit, National Institute for Health and Welfare, Helsinki, Finland.
    Orešič, M.
    Steno Diabetes Center, Gentofte, Denmark; Turku Centre for Biotechnology, University of Turku, Turku, Finland; Turku Centre for Biotechnology, Åbo Akademi University, Turku, Finland.
    Serum metabolite profile associates with the development of metabolic co-morbidities in first-episode psychosis2016In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 6, no 11, article id e951Article in journal (Refereed)
    Abstract [en]

    Psychotic patients are at high risk for developing obesity, metabolic syndrome and type 2 diabetes. These metabolic co-morbidities are hypothesized to be related to both treatment side effects as well as to metabolic changes occurring during the psychosis. Earlier metabolomics studies have shown that blood metabolite levels are predictive of insulin resistance and type 2 diabetes in the general population as well as sensitive to the effects of antipsychotics. In this study, we aimed to identify the metabolite profiles predicting future weight gain and other metabolic abnormalities in psychotic patients. We applied comprehensive metabolomics to investigate serum metabolite profiles in a prospective study setting in 36 first-episode psychosis patients during the first year of the antipsychotic treatment and 19 controls. While corroborating several earlier findings when comparing cases and controls and the effects of the antipsychotic medication, we also found that prospective weight gain in psychotic patients was associated with increased levels of triacylglycerols with low carbon number and double-bond count at baseline, that is, lipids known to be associated with increased liver fat. Our study suggests that metabolite profiles may be used to identify the psychotic patients most vulnerable to develop metabolic co-morbidities, and may point to a pharmacological approach to counteract the antipsychotic-induced weight gain.

  • 133.
    Svensson, Jonas E.
    et al.
    Karolinska Institutet, Sweden;Region Stockholm, Sweden;Karolinska University Hospital, Sweden.
    Svanborg, Cecilia
    Karolinska Institutet, Sweden;Region Stockholm, Sweden;Karolinska University Hospital, Sweden.
    Plaven-Sigray, Pontus
    Karolinska Institutet, Sweden;Region Stockholm, Sweden;Karolinska University Hospital, Sweden;Copenhagen Univ Hosp, Denmark.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet, Sweden;Region Stockholm, Sweden;Karolinska University Hospital, Sweden.
    Halldin, Christer
    Karolinska Institutet, Sweden;Region Stockholm, Sweden;Karolinska University Hospital, Sweden.
    Schain, Martin
    Copenhagen Univ Hosp, Denmark.
    Lundberg, Johan
    Karolinska Institutet, Sweden;Region Stockholm, Sweden;Karolinska University Hospital, Sweden.
    Serotonin transporter availability increases in patients recovering from a depressive episode2021In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 11, no 1, article id 264Article in journal (Refereed)
    Abstract [en]

    Molecular imaging studies have shown low cerebral concentration of serotonin transporter in patients suffering from depression, compared to healthy control subjects. Whether or not this difference also is present before disease onset and after remission (i.e. a trait), or only at the time of the depressive episode (i.e. a state) remains to be explored. We examined 17 patients with major depressive disorder with positron emission tomography using [C-11]MADAM, a radioligand that binds to the serotonin transporter, before and after treatment with internet-based cognitive behavioral therapy. In all, 17 matched healthy control subjects were examined once. Cerebellum was used as reference to calculate the binding potential. Differences before and after treatment, as well as between patients and controls, were assessed in a composite cerebral region and in the median raphe nuclei. All image analyses and confirmatory statistical tests were preregistered. Depression severity decreased following treatment (p<0.001). [C-11]MADAM binding in patients increased in the composite region after treatment (p=0.01), while no change was observed in the median raphe (p=0.51). No significant difference between patients at baseline and healthy controls were observed in the composite region (p=0.97) or the median raphe (p=0.95). Our main finding was that patients suffering from a depressive episode show an overall increase in cerebral serotonin transporter availability as symptoms are alleviated. Our results suggest that previously reported cross-sectional molecular imaging findings of the serotonin transporter in depression most likely reflect the depressive state, rather than a permanent trait. The finding adds new information on the pathophysiology of major depressive disorder.

  • 134. Szatkiewicz, Jin
    et al.
    Crowley, James J.
    Nordin Adolfsson, Annelie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Åberg, Karolina A.
    Alaerts, Maaike
    Genovese, Giulio
    McCarroll, Steven
    Del-Favero, Jurgen
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Sullivan, Patrick F.
    The genomics of major psychiatric disorders in a large pedigree from Northern Sweden2019In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 9, article id 60Article in journal (Refereed)
    Abstract [en]

    We searched for genetic causes of major psychiatric disorders (bipolar disorder, schizoaffective disorder, and schizophrenia) in a large, densely affected pedigree from Northern Sweden that originated with three pairs of founders born around 1650. We applied a systematic genomic approach to the pedigree via karyotyping (N = 9), genome-wide SNP arrays (N = 418), whole-exome sequencing (N = 26), and whole-genome sequencing (N = 10). Comprehensive analysis did not identify plausible variants of strong effect. Rather, pedigree cases had significantly higher genetic risk scores compared to pedigree and community controls.

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  • 135.
    Sønderby, Ida E.
    et al.
    NORMENT, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.
    van der Meer, Dennis
    NORMENT, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands.
    Moreau, Clara
    Sainte Justine Hospital Research Center, QC, Montreal, Canada; Centre de recherche de l'Institut universitaire de gériatrie de Montréal, QC, Montreal, Canada.
    Kaufmann, Tobias
    NORMENT, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany.
    Walters, G Bragi
    deCODE Genetics (Amgen), Reykjavík, Iceland; Faculty of Medicine, University of Iceland, Reykjavík, Iceland.
    Ellegaard, Maria
    Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, Glostrup, Denmark.
    Abdellaoui, Abdel
    Department of Psychiatry, University of Amsterdam, Amsterdam, Netherlands; Department of Biological Psychology and Netherlands Twin Register, VU University Amsterdam, Amsterdam, Netherlands.
    Ames, David
    University of Melbourne Academic Unit for Psychiatry of Old Age, Kew, Australia; National Ageing Research Institute, Parkville, Australia.
    Amunts, Katrin
    Institute of Neuroscience and Medicine, INM-1, Research Centre Jülich, Jülich, Germany; C. and O. Vogt Institute for Brain Research, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University Duesseldorf, Düsseldorf, Germany.
    Andersson, Micael
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Armstrong, Nicola J.
    Murdoch University, Mathematics and Statistics, Perth, Australia.
    Bernard, Manon
    Research Institute, Hospital for Sick Children, ON, Toronto, Canada.
    Blackburn, Nicholas B.
    South Texas Diabetes and Obesity Institute, Department of Human Genetics, School of Medicine, University of Texas Rio Grande Valley, Brownsville, United States.
    Blangero, John
    South Texas Diabetes and Obesity Institute, Department of Human Genetics, School of Medicine, University of Texas Rio Grande Valley, Brownsville, United States.
    Boomsma, Dorret I.
    Department of Biological Psychology and Netherlands Twin Register, VU University Amsterdam, Amsterdam, Netherlands; Amsterdam Neuroscience, Amsterdam, Netherlands; Amsterdam Public Health Research Institute, VU Medical Center, Amsterdam, Netherlands.
    Brodaty, Henry
    Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia; Dementia Centre for Research Collaboration, School of Psychiatry, University of New South Wales, Sydney, Australia.
    Brouwer, Rachel M.
    Department of Psychiatry, University Medical Center Brain Center, Utrecht University, Utrecht, Netherlands.
    Bülow, Robin
    Institute of Diagnostic Radiology and Neuroradiology, Greifswald, University Medicine Greifswald, Germany.
    Bøen, Rune
    NORMENT, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
    Cahn, Wiepke
    Department of Psychiatry, University Medical Center Brain Center, Utrecht University, Utrecht, Netherlands; Altrecht Science, Utrecht, Netherlands.
    Calhoun, Vince D.
    Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, Emory University, Atlanta, United States; Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, United States.
    Caspers, Svenja
    Institute of Neuroscience and Medicine, INM-1, Research Centre Jülich, Jülich, Germany; Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
    Ching, Christopher R K
    Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, United States.
    Cichon, Sven
    Institute of Neuroscience and Medicine, INM-1, Research Centre Jülich, Jülich, Germany; Department of Biomedicine, University of Basel, Basel, Switzerland; Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
    Ciufolini, Simone
    Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
    Crespo-Facorro, Benedicto
    University Hospital Marqués de Valdecilla, IDIVAL, Centro de Investigación Biomédica en Red Salud Mental (CIBERSAM), Santander, Spain; University Hospital Virgen del Rocío, IBiS, Centre de Investigació Biomédica en Red Salud Mental (CIBERSAM), Sevilla, Spain.
    Curran, Joanne E.
    South Texas Diabetes and Obesity Institute, Department of Human Genetics, School of Medicine, University of Texas Rio Grande Valley, Brownsville, United States.
    Dale, Anders M.
    Center for Multimodal Imaging and Genetics, University of California, San Diego, United States.
    Dalvie, Shareefa
    Department of Psychiatry and Neuroscience Institute, University of Cape Town, Western Cape, Cape Town, South Africa.
    Dazzan, Paola
    Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
    de Geus, Eco J C
    Department of Biological Psychology and Netherlands Twin Register, VU University Amsterdam, Amsterdam, Netherlands; Amsterdam Neuroscience, Amsterdam, Netherlands; Amsterdam Public Health Research Institute, VU Medical Center, Amsterdam, Netherlands.
    de Zubicaray, Greig I.
    Faculty of Health, Queensland University of Technology, Brisbane, Australia.
    de Zwarte, Sonja M C
    Department of Psychiatry, University Medical Center Brain Center, Utrecht University, Utrecht, Netherlands.
    Desrivieres, Sylvane
    Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
    Doherty, Joanne L.
    MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom; Cardiff University Brain Research Imaging Centre School of Psychology, Cardiff University, Cardiff, United Kingdom.
    Donohoe, Gary
    Centre for Neuroimaging and Cognitive Genomics, School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland.
    Draganski, Bogdan
    Laboratory for Research in Neuroimaging LREN, Centre for Research in Neurosciences, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Neurology Department, Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
    Ehrlich, Stefan
    Division of Psychological and Social Medicine, Faculty of Medicine, TU Dresden, Dresden, Germany.
    Eising, Else
    Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, Netherlands.
    Espeseth, Thomas
    Department of Psychology, University of Oslo, Oslo, Norway; Bjørknes College, Oslo, Norway.
    Fejgin, Kim
    Signal Transduction, H. Lundbeck A/S ,Ottiliavej 9, Denmark.
    Fisher, Simon E.
    Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, Netherlands; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands.
    Fladby, Tormod
    Department of Neurology, Akershus University Hospital, Norway; Institute of Clinical Medicine, University of Oslo, Campus Ahus, Oslo, Norway.
    Frei, Oleksandr
    NORMENT, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Frouin, Vincent
    Neurospin, Université Paris-SaclayGif-sur-Yvette, CEA, France.
    Fukunaga, Masaki
    Division of Cerebral Integration, National Institute for Physiological Sciences, Okazaki, Japan; Department of Life Science, Sokendai, Japan.
    Gareau, Thomas
    Neurospin, Université Paris-SaclayGif-sur-Yvette, CEA, France.
    Ge, Tian
    Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, MA, Boston, United States; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, MA, Boston, United States; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, MA, Cambridge, United States.
    Glahn, David C.
    Boston Children's Hospital, MA, Boston, United States; Institute of Living, CT, Hartford, United States; Harvard Medical School, MA, Boston, United States.
    Grabe, Hans J.
    Department of Psychiatry and Psychotherapy, Greifswald, University Medicine Greifswald, Germany; German Center of Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Greifswald, Germany.
    Groenewold, Nynke A.
    Department of Psychiatry and Neuroscience Institute, University of Cape Town, Western Cape, Cape Town, South Africa.
    Gústafsson, Ómar
    deCODE Genetics (Amgen), Reykjavík, Iceland.
    Haavik, Jan
    Department of Biomedicine, University of Bergen, Bergen, Norway; Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
    Haberg, Asta K.
    Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway; St Olav's Hospital, Department of Radiology and Nuclear Medicine, Trondheim, Norway.
    Hall, Jeremy
    MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom; School of Medicine, Cardiff University, Cardiff, United Kingdom.
    Hashimoto, Ryota
    Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan; Osaka University, Osaka, Japan.
    Hehir-Kwa, Jayne Y.
    Princess Màxima Center for Pediatric Oncology, Utrecht, Netherlands.
    Hibar, Derrek P.
    Genentech, Inc., South San Francisco, 94080, CA, USA.
    Hillegers, Manon H J
    Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-Sophia, Rotterdam, Netherlands.
    Hoffmann, Per
    Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland; Institute of Human Genetics, University of Bonn Medical School, Bonn, Germany.
    Holleran, Laurena
    Centre for Neuroimaging and Cognitive Genomics, School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland.
    Holmes, Avram J.
    Psychology Department, Yale University, CT, New Haven, United States; Department of Psychiatry, Yale University, CT, New Haven, United States; Department of Psychiatry, Massachusetts General Hospital, MA, Boston, United States.
    Homuth, Georg
    Interfaculty Institute for Genetics and Functional Genomics, Greifswald, University Medicine Greifswald, Germany.
    Hottenga, Jouke-Jan
    Department of Biological Psychology and Netherlands Twin Register, VU University Amsterdam, Amsterdam, Netherlands; Amsterdam Neuroscience, Amsterdam, Netherlands; Amsterdam Public Health Research Institute, VU Medical Center, Amsterdam, Netherlands.
    Hulshoff Pol, Hilleke E.
    Department of Psychiatry, University Medical Center Brain Center, Utrecht University, Utrecht, Netherlands.
    Ikeda, Masashi
    Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan.
    Jahanshad, Neda
    Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, United States.
    Jockwitz, Christiane
    Institute of Neuroscience and Medicine, INM-1, Research Centre Jülich, Jülich, Germany; Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
    Johansson, Stefan
    Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway.
    Jönsson, Erik G.
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm Health Care Services, Stockholm Region, Stockholm, Sweden; Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Jørgensen, Niklas R.
    Department of Clinical Biochemistry, Copenhagen University Hospital Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Kikuchi, Masataka
    Department of Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan.
    Knowles, Emma E M
    Boston Children's Hospital, MA, Boston, United States; Harvard Medical School, MA, Boston, United States.
    Kumar, Kuldeep
    Sainte Justine Hospital Research Center, QC, Montreal, Canada.
    Le Hellard, Stephanie
    Norwegian Centre for Mental Disorders Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Dr Einar Martens Research Group for Biological Psychiatry, Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway.
    Leu, Costin
    Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, MA, Cambridge, United States; Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, OH, Cleveland, United States; Chalfont Centre for Epilepsy, Chalfont-St-Peter, United Kingdom.
    Linden, David E J
    School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands; MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom.
    Liu, Jingyu
    Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, Emory University, Atlanta, United States.
    Lundervold, Arvid
    Department of Biomedicine, University of Bergen, Bergen, Norway; Mohn Medical Imaging and Visualization Centre, Department of Radiology, Haukeland University Hospital, Bergen, Norway.
    Lundervold, Astri Johansen
    Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.
    Maillard, Anne M.
    Service des Troubles du Spectre de l'Autisme et apparentés, Lausanne University Hospital, Lausanne, Switzerland.
    Martin, Nicholas G.
    Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
    Martin-Brevet, Sandra
    Laboratory for Research in Neuroimaging LREN, Centre for Research in Neurosciences, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
    Mather, Karen A.
    Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia; Neuroscience Research Australia, Randwick, Australia.
    Mathias, Samuel R.
    Boston Children's Hospital, MA, Boston, United States; Harvard Medical School, MA, Boston, United States.
    McMahon, Katie L.
    Herston Imaging Research Facility and School of Clinical Sciences, Queensland University of Technology, Brisbane, Australia.
    McRae, Allan F.
    Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia; Queensland Brain Institute, University of Queensland, Brisbane, Australia.
    Medland, Sarah E.
    Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
    Meyer-Lindenberg, Andreas
    Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
    Moberget, Torgeir
    NORMENT, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway.
    Modenato, Claudia
    Laboratory for Research in Neuroimaging LREN, Centre for Research in Neurosciences, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; University of Lausanne, Lausanne, Switzerland.
    Sánchez, Jennifer Monereo
    Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, Netherlands; School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands.
    Morris, Derek W.
    Centre for Neuroimaging and Cognitive Genomics, School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland.
    Mühleisen, Thomas W.
    Institute of Neuroscience and Medicine, INM-1, Research Centre Jülich, Jülich, Germany; C. and O. Vogt Institute for Brain Research, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University Duesseldorf, Düsseldorf, Germany; Department of Biomedicine, University of Basel, Basel, Switzerland.
    Murray, Robin M.
    Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
    Nielsen, Jacob
    Signal Transduction, H. Lundbeck A/S ,Ottiliavej 9, Denmark.
    Nordvik, Jan E.
    CatoSenteret Rehabilitation Center, Son, Norway.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Loohuis, Loes M Olde
    Center for Neurobehavioral Genetics, University of California, Los Angeles, United States.
    Ophoff, Roel A.
    Center for Neurobehavioral Genetics, University of California, Los Angeles, United States; Department of Psychiatry, Erasmus University Medical Center, Rotterdam, Netherlands.
    Owen, Michael J.
    MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom.
    Paus, Tomas
    Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, ON, Toronto, Canada; Physiology and Nutritional Sciences, University of Toronto, ON, Toronto, Canada.
    Pausova, Zdenka
    Research Institute, Hospital for Sick Children, ON, Toronto, Canada; Physiology and Nutritional Sciences, University of Toronto, ON, Toronto, Canada.
    Peralta, Juan M.
    South Texas Diabetes and Obesity Institute, Department of Human Genetics, School of Medicine, University of Texas Rio Grande Valley, Brownsville, United States.
    Pike, G Bruce
    Departments of Radiology and Clinical Neurosciences, University of Calgary, AB, Calgary, Canada.
    Prieto, Carlos
    Bioinformatics Service, Nucleus, University of Salamanca, Salamanca, Spain.
    Quinlan, Erin B.
    Centre for Population Neuroscience and Precision Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
    Reinbold, Céline S
    Department of Biomedicine, University of Basel, Basel, Switzerland; Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland; Department of Psychology, University of Oslo, Oslo, Norway.
    Marques, Tiago Reis
    Department of Psychosis, Institute of Psychiatry, Psychology & Neuroscience, Kings College, London, United Kingdom; Psychiatric Imaging Group, MRC London Institute of Medical Sciences (LMS), Hammersmith Hospital, Imperial College, London, United Kingdom.
    Rucker, James J H
    Institute of Psychiatry, Psychology and Neuroscience, London, United Kingdom.
    Sachdev, Perminder S.
    Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia; Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, Australia.
    Sando, Sigrid B.
    Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway; University Hospital of Trondheim, Department of Neurology and Clinical Neurophysiology, Trondheim, Norway.
    Schofield, Peter R.
    Neuroscience Research Australia, Sydney, Australia; School of Medical Sciences, University of New South Wales, Sydney, Australia.
    Schork, Andrew J.
    Institute of Biological Psychiatry, Roskilde, Denmark; Translational Genetics Institute (TGEN), AZ, Phoenix, United States.
    Schumann, Gunter
    Centre for Population Neuroscience and Precision Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
    Shin, Jean
    Research Institute, Hospital for Sick Children, ON, Toronto, Canada; Physiology and Nutritional Sciences, University of Toronto, ON, Toronto, Canada.
    Shumskaya, Elena
    Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands; Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands.
    Silva, Ana I.
    School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands; MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom; Cardiff University Brain Research Imaging Centre School of Psychology, Cardiff University, Cardiff, United Kingdom.
    Sisodiya, Sanjay M.
    Chalfont Centre for Epilepsy, Chalfont-St-Peter, United Kingdom.
    Steen, Vidar M.
    Norwegian Centre for Mental Disorders Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Dr Einar Martens Research Group for Biological Psychiatry, Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway.
    Stein, Dan J.
    Department of Psychiatry and Neuroscience Institute, University of Cape Town, South African Medical Research Council Unit on Risk and Resilience in Mental Disorders, Cape Town, South Africa.
    Strike, Lachlan T.
    Queensland Brain Institute, University of Queensland, Brisbane, Australia.
    Suzuki, Ikuo K.
    VIB Center for Brain & Disease Research, Stem Cell and Developmental Neurobiology Lab, Leuven, Belgium; University of Brussels (ULB), Institute of Interdisciplinary Research (IRIBHM) ULB Neuroscience Institute, Brussels, Belgium; University of Tokyo, Department of Biological Sciences, Graduate School of Science, Tokyo, Japan.
    Tamnes, Christian K.
    NORMENT, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; PROMENTA Research Center, Department of Psychology, University of Oslo, Oslo, Norway; Department of Psychiatry, Diakonhjemmet Hospital, Oslo, Norway.
    Teumer, Alexander
    Institute for Community Medicine, Greifswald, University Medicine Greifswald, Germany.
    Thalamuthu, Anbupalam
    Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
    Tordesillas-Gutiérrez, Diana
    University Hospital Marqués de Valdecilla, IDIVAL, Centro de Investigación Biomédica en Red Salud Mental (CIBERSAM), Santander, Spain; Department of Radiology, Marqués de Valdecilla University Hospital, Valdecilla Biomedical Research Institute IDIVAL, Santander, Spain.
    Uhlmann, Anne
    Department of Psychiatry and Neuroscience Institute, University of Cape Town, Western Cape, Cape Town, South Africa.
    Ulfarsson, Magnus O.
    deCODE Genetics (Amgen), Reykjavík, Iceland; Faculty of Electrical and Computer Engineering, University of Iceland, Reykjavík, Iceland.
    van 't Ent, Dennis
    Department of Biological Psychology and Netherlands Twin Register, VU University Amsterdam, Amsterdam, Netherlands; Amsterdam Neuroscience, Amsterdam, Netherlands.
    van den Bree, Marianne B M
    MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom; School of Medicine, Cardiff University, Cardiff, United Kingdom.
    Vanderhaeghen, Pierre
    VIB-KU Leuven Center for Brain & Disease Research, Leuven, Belgium; KU Leuven, Department of Neurosciences & Leuven Brain Institute, Leuven, Belgium; Université Libre de Bruxelles (U.L.B.), Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), ULB Neuroscience Institute (UNI), Brussels, Belgium.
    Vassos, Evangelos
    Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; National Institute for Health Research, Mental Health Biomedical Research Centre, South London and Maudsley National Health Service Foundation Trust and King's College London, London, United Kingdom.
    Wen, Wei
    Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
    Wittfeld, Katharina
    Department of Psychiatry and Psychotherapy, Greifswald, University Medicine Greifswald, Germany; German Center of Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Greifswald, Germany.
    Wright, Margaret J.
    Queensland Brain Institute, University of Queensland, Brisbane, Australia; Centre for Advanced Imaging, University of Queensland, Brisbane, Australia.
    Agartz, Ingrid
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm Health Care Services, Stockholm Region, Stockholm, Sweden; Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychiatry, Diakonhjemmet Hospital, Oslo, Norway.
    Djurovic, Srdjan
    Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; Norwegian Centre for Mental Disorders Research, Department of Clinical Science, University of Bergen, Bergen, Norway.
    Westlye, Lars T.
    NORMENT, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway; KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.
    Stefansson, Hreinn
    deCODE Genetics (Amgen), Reykjavík, Iceland.
    Stefansson, Kari
    deCODE Genetics (Amgen), Reykjavík, Iceland; Faculty of Medicine, University of Iceland, Reykjavík, Iceland.
    Jacquemont, Sébastien
    Sainte Justine Hospital Research Center, QC, Montreal, Canada; Department of Pediatrics, University of Montreal, QC, Montreal, Canada.
    Thompson, Paul M.
    Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, United States.
    Andreassen, Ole A.
    NORMENT, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans2021In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 11, no 1, article id 182Article in journal (Refereed)
    Abstract [en]

    Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.

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  • 136.
    Tate, Ashley E.
    et al.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Solna, Sweden..
    Akingbuwa, Wonuola A.
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.;Amsterdam Univ Med Ctr, Amsterdam Publ Hlth Res Inst, Amsterdam, Netherlands..
    Karlsson, Robert
    Karolinska Inst, Dept Med Epidemiol & Biostat, Solna, Sweden..
    Hottenga, Jouke-Jan
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands..
    Pool, Rene
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.;Amsterdam Univ Med Ctr, Amsterdam Publ Hlth Res Inst, Amsterdam, Netherlands..
    Boman, Magnus
    KTH, School of Electrical Engineering and Computer Science (EECS), Computer Science, Software and Computer systems, SCS. Karolinska Inst, Dept Learning Informat Management & Eth, Solna, Sweden..
    Larsson, Henrik
    Karolinska Inst, Dept Med Epidemiol & Biostat, Solna, Sweden.;Örebro Univ, Sch Med Sci, Örebro, Sweden..
    Lundström, Sebastian
    Univ Gothenburg, Ctr Eth Law & Mental Hlth CELAM, Gothenburg, Sweden.;Univ Gothenburg, Gillberg Neuropsychiat Ctr, Gothenburg, Sweden..
    Lichtenstein, Paul
    Karolinska Inst, Dept Med Epidemiol & Biostat, Solna, Sweden..
    Middeldorp, Christel M.
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.;Univ Queensland, Child Hlth Res Ctr, Brisbane, Qld, Australia.;Childrens Hlth Queensland Hosp & Hlth Serv, Child & Youth Mental Hlth Serv, Brisbane, Qld, Australia..
    Bartels, Meike
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands..
    Kuja-Halkola, Ralf
    Karolinska Inst, Dept Med Epidemiol & Biostat, Solna, Sweden..
    A genetically informed prediction model for suicidal and aggressive behaviour in teens2022In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 12, no 1, article id 488Article in journal (Refereed)
    Abstract [en]

    Suicidal and aggressive behaviours cause significant personal and societal burden. As risk factors associated with these behaviours frequently overlap, combined approaches in predicting the behaviours may be useful in identifying those at risk for either. The current study aimed to create a model that predicted if individuals will exhibit suicidal behaviour, aggressive behaviour, both, or neither in late adolescence. A sample of 5,974 twins from the Child and Adolescent Twin Study in Sweden (CATSS) was broken down into a training (80%), tune (10%) and test (10%) set. The Netherlands Twin Register (NTR; N = 2702) was used for external validation. Our longitudinal data featured genetic, environmental, and psychosocial predictors derived from parental and self-report data. A stacked ensemble model was created which contained a gradient boosted machine, random forest, elastic net, and neural network. Model performance was transferable between CATSS and NTR (macro area under the receiver operating characteristic curve (AUC) [95% CI] AUCCATSS(test set) = 0.709 (0.671-0.747); AUCNTR = 0.685 (0.656-0.715), suggesting model generalisability across Northern Europe. The notable exception is suicidal behaviours in the NTR, which was no better than chance. The 25 highest scoring variable importance scores for the gradient boosted machines and random forest models included self-reported psychiatric symptoms in mid-adolescence, sex, and polygenic scores for psychiatric traits. The model's performance is comparable to current prediction models that use clinical interviews and is not yet suitable for clinical use. Moreover, genetic variables may have a role to play in predictive models of adolescent psychopathology.

  • 137.
    Tate, Ashley E.
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
    Akingbuwa, Wonuola A.
    Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Amsterdam Public Health Research Institute, Amsterdam University Medical Centres, Amsterdam, the Netherlands.
    Karlsson, Robert
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
    Hottenga, Jouke-Jan
    Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
    Pool, René
    Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Amsterdam Public Health Research Institute, Amsterdam University Medical Centres, Amsterdam, the Netherlands.
    Boman, Magnus
    Division of Software and Computer Systems, School of Electrical Engineering and Computer Science KTH, Stockholm, Sweden; Department of Learning, Informatics, Management and Ethics, Karolinska Institute, Solna, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
    Lundström, Sebastian
    Centre for Ethics, Law and Mental Health (CELAM), University of Gothenburg, Gothenburg, Sweden; Gillberg Neuropsychiatry Centre, University of Gothenburg, Gothenburg, Sweden .
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
    Middeldorp, Christel M.
    Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Child Health Research Centre, the University of Queensland, Brisbane, QLD, Australia; Child and Youth Mental Health Service, Children’s Health Queensland Hospital and Health Services, Brisbane, QLD, Australia .
    Bartels, Meike
    Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
    Kuja-Halkola, Ralf
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
    A genetically informed prediction model for suicidal and aggressive behaviour in teens2022In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 12, no 1, article id 488Article in journal (Refereed)
    Abstract [en]

    Suicidal and aggressive behaviours cause significant personal and societal burden. As risk factors associated with these behaviours frequently overlap, combined approaches in predicting the behaviours may be useful in identifying those at risk for either. The current study aimed to create a model that predicted if individuals will exhibit suicidal behaviour, aggressive behaviour, both, or neither in late adolescence. A sample of 5,974 twins from the Child and Adolescent Twin Study in Sweden (CATSS) was broken down into a training (80%), tune (10%) and test (10%) set. The Netherlands Twin Register (NTR; N = 2702) was used for external validation. Our longitudinal data featured genetic, environmental, and psychosocial predictors derived from parental and self-report data. A stacked ensemble model was created which contained a gradient boosted machine, random forest, elastic net, and neural network. Model performance was transferable between CATSS and NTR (macro area under the receiver operating characteristic curve (AUC) [95% CI] AUCCATSS(test set) = 0.709 (0.671-0.747); AUCNTR = 0.685 (0.656-0.715), suggesting model generalisability across Northern Europe. The notable exception is suicidal behaviours in the NTR, which was no better than chance. The 25 highest scoring variable importance scores for the gradient boosted machines and random forest models included self-reported psychiatric symptoms in mid-adolescence, sex, and polygenic scores for psychiatric traits. The model's performance is comparable to current prediction models that use clinical interviews and is not yet suitable for clinical use. Moreover, genetic variables may have a role to play in predictive models of adolescent psychopathology.

  • 138. Theorell, Jakob
    et al.
    Ramberger, Melanie
    Harrison, Ruby
    Mgbachi, Victor
    Jacobson, Leslie
    Waters, Patrick
    Erhardt, Sophie
    Sellgren, Carl M
    Cervenka, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Cervenka: Psychiatry. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Solna, Sweden.
    Piehl, Fredrik
    Irani, Sarosh R
    Screening for pathogenic neuronal autoantibodies in serum and CSF of patients with first-episode psychosis2021In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 11, no 1, article id 566Article in journal (Refereed)
    Abstract [en]

    Patients with autoimmune encephalitides, especially those with antibodies to the N-methyl-D-aspartate receptor (NMDAR), often present with prominent psychosis and respond well to immunotherapies. Although most patients progress to develop various neurological symptoms, it has been hypothesised that a subgroup of patients with first-episode psychosis (FEP) suffer from a forme fruste of autoimmune encephalitis. Without accurate identification, this immunotherapy-responsive subgroup may be denied disease-modifying treatments. Thirty studies addressing aspects of this hypothesis were identified in a systematic review. Amongst other shortcomings, 15/30 reported no control group and only 6/30 determined cerebrospinal fluid (CSF) autoantibodies. To ourselves address these-and other-limitations, we investigated a prospectively ascertained clinically well-characterised cohort of 71 FEP patients without traditional neurological features, and 48 healthy controls. Serum and CSF were tested for autoantibodies against seven neuronal surface autoantigens using live cell-based assays. These identified 3/71 (4%) patient sera with weak binding to either contactin-associated protein-like 2, the NMDAR or glycine receptor versus no binding from 48 control samples (p = 0.28, Fisher's test). The three seropositive individuals showed no CSF autoantibodies and no differences from the autoantibody-negative patients in their clinical phenotypes, or across multiple parameters of peripheral and central inflammation. All individuals were negative for CSF NMDAR antibodies. In conclusion, formes frustes of autoimmune encephalitis are not prevalent among FEP patients admitted to psychiatric care. Our findings do not support screening for neuronal surface autoantibodies in unselected psychotic patients.

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  • 139.
    Triolo, Federico
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Murri, Martino Belvederi
    Calderón-Larrañaga, Amaia
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Vetrano, Davide Liborio
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). IRCCS Fondazione Policlinico Universitario “A. Gemelli", Italy; Università Cattolica del Sacro Cuore; Italy.
    Sjöberg, Linnea
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Sweden.
    Dekhtyar, Serhiy
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Bridging late-life depression and chronic somatic diseases: a network analysis2021In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 11, article id 557Article in journal (Refereed)
    Abstract [en]

    The clinical presentation of late-life depression is highly heterogeneous and likely influenced by the co-presence of somatic diseases. Using a network approach, this study aims to explore how depressive symptoms are interconnected with each other, as well as with different measures of somatic disease burden in older adults. We examined cross-sectional data on 2860 individuals aged 60+ from the Swedish National Study on Aging and Care in Kungsholmen, Stockholm. The severity of sixteen depressive symptoms was clinically assessed with the Comprehensive Psychopathological Rating Scale. We combined data from individual clinical assessment and health-registers to construct eight system-specific disease clusters (cardiovascular, neurological, gastrointestinal, metabolic, musculoskeletal, respiratory, sensory, and unclassified), along with a measure of overall somatic burden. The interconnection among depressive symptoms, and with disease clusters was explored through networks based on Spearman partial correlations. Bridge centrality index and network loadings were employed to identify depressive symptoms directly connecting disease clusters and depression. Sadness, pessimism, anxiety, and suicidal thoughts were the most interconnected symptoms of the depression network, while somatic symptoms of depression were less interconnected. In the network integrating depressive symptoms with disease clusters, suicidal thoughts, reduced appetite, and cognitive difficulties constituted the most consistent bridge connections. The same bridge symptoms emerged when considering an overall measure of somatic disease burden. Suicidal thoughts, reduced appetite, and cognitive difficulties may play a key role in the interconnection between late-life depression and somatic diseases. If confirmed in longitudinal studies, these bridging symptoms could constitute potential targets in the prevention of late-life depression.

  • 140.
    Tripathi, Anushree
    et al.
    Institute of Psychiatry and Neurosciences of Paris (IPNP), INSERM U1266, Pathophysiology of Psychiatric Disorders, Université de Paris.
    Spedding, Michael
    Schenker, Esther
    Didriksen, Michael
    Cressant, Arnaud
    Jay, Therese M.
    Cognition- and circuit-based dysfunction in a mouse model of 22q11.2 microdeletion syndrome: effects of stress2020In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 10, no 1, article id 41Article in journal (Refereed)
    Abstract [en]

    Genetic microdeletion at the 22q11 locus is associated with very high risk for schizophrenia. The 22q11.2 microdeletion (Df(h22q11)/+) mouse model shows cognitive deficits observed in this disorder, some of which can be linked to dysfunction of the prefrontal cortex (PFC). We used behavioral (n = 10 per genotype), electrophysiological (n = 7 per genotype per group), and neuroanatomical (n = 5 per genotype) techniques to investigate schizophrenia-related pathology of Df(h22q11)/+ mice, which showed a significant decrease in the total number of parvalbumin positive interneurons in the medial PFC. The Df(h22q11)/+ mice when tested on PFC-dependent behavioral tasks, including gambling tasks, perform significantly worse than control animals while exhibiting normal behavior on hippocampus-dependent tasks. They also show a significant decrease in hippocampus-medial Prefrontal cortex (H-PFC) synaptic plasticity (long-term potentiation, LTP). Acute platform stress almost abolished H-PFC LTP in both wild-type and Df(h22q11)/+ mice. H-PFC LTP was restored to prestress levels by clozapine (3 mg/kg i.p.) in stressed Df(h22q11)/+ mice, but the restoration of stress-induced LTP, while significant, was similar between wild-type and Df(h22q11)/+ mice. A medial PFC dysfunction may underlie the negative and cognitive symptoms in human 22q11 deletion carriers, and these results are relevant to the current debate on the utility of clozapine in such subjects.

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  • 141.
    Van Booven, Derek
    et al.
    Univ Miami, FL 33136 USA.
    Li, Mengying
    Univ Miami, FL 33136 USA.
    Rao, J. Sunil
    Univ Miami, FL 33136 USA.
    Blokhin, Ilya O.
    Univ Miami, FL 33136 USA; Jackson Mem Hosp, FL 33136 USA.
    Mayfield, R. Dayne
    Univ Texas Austin, TX 78712 USA.
    Barbier, Estelle
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Wahlestedt, Claes
    Univ Miami, FL 33136 USA.
    Alcohol use disorder causes global changes in splicing in the human brain2021In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 11, no 1, article id 2Article in journal (Refereed)
    Abstract [en]

    Alcohol use disorder (AUD) is a widespread disease leading to the deterioration of cognitive and other functions. Mechanisms by which alcohol affects the brain are not fully elucidated. Splicing constitutes a nuclear process of RNA maturation, which results in the formation of the transcriptome. We tested the hypothesis as to whether AUD impairs splicing in the superior frontal cortex (SFC), nucleus accumbens (NA), basolateral amygdala (BLA), and central nucleus of the amygdala (CNA). To evaluate splicing, bam files from STAR alignments were indexed with samtools for use by rMATS software. Computational analysis of affected pathways was performed using Gene Ontology Consortium, Gene Set Enrichment Analysis, and LncRNA Ontology databases. Surprisingly, AUD was associated with limited changes in the transcriptome: expression of 23 genes was altered in SFC, 14 in NA, 102 in BLA, and 57 in CNA. However, strikingly, mis-splicing in AUD was profound: 1421 mis-splicing events were detected in SFC, 394 in NA, 1317 in BLA, and 469 in CNA. To determine the mechanism of mis-splicing, we analyzed the elements of the spliceosome: small nuclear RNAs (snRNAs) and splicing factors. While snRNAs were not affected by alcohol, expression of splicing factor heat shock protein family A (Hsp70) member 6 (HSPA6) was drastically increased in SFC, BLA, and CNA. Also, AUD was accompanied by aberrant expression of long noncoding RNAs (lncRNAs) related to splicing. In summary, alcohol is associated with genome-wide changes in splicing in multiple human brain regions, likely due to dysregulation of splicing factor(s) and/or altered expression of splicing-related lncRNAs.

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  • 142.
    van Egmond, Lieve T
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Bukhari, Shervin
    Benedet, Andrea Lessa
    Ashton, Nicholas J
    Meth, Elisa M S
    Boukas, Alexander
    Engström, Joachim
    Ilemosoglou, Maria
    Blennow, Kaj
    Zetterberg, Henrik
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Acute sleep loss increases CNS health biomarkers and compromises the ability to stay awake in a sex-and weight-specific manner.2022In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 12, no 1, article id 379Article in journal (Refereed)
    Abstract [en]

    Night shift work impairs vigilance performance, reduces the ability to stay awake, and compromises brain health. To investigate if the magnitude of these adverse night shift work effects differs between sexes and weight groups, 47 men and women with either normal weight or obesity participated in one night of sleep and one night of total sleep loss. During the night of sleep loss, participants' subjective sleepiness, vigilance performance, and ability to stay awake during 2-min quiet wake with eyes closed were repeatedly assessed. In addition, blood was collected in the morning after sleep loss and sleep to measure central nervous system (CNS) health biomarkers. Our analysis showed that women were sleepier during the night of sleep loss (P < 0.05) and spent more time in microsleep during quiet wake testing (P < 0.05). Finally, higher blood levels of neurofilament light chain, a biomarker of axonal damage, were found among women in the morning after sleep loss (P < 0.002). Compared with normal-weight subjects, those with obesity were more prone to fall asleep during quiet wake (P < 0.05) and exhibited higher blood levels of the CNS health biomarker pTau181 following sleep loss (P = 0.001). Finally, no differences in vigilance performance were noted between the sex and weight groups. Our findings suggest that the ability to stay awake during and the CNS health biomarker response to night shift work may differ between sexes and weight groups. Follow-up studies must confirm our findings under more long-term night shift work conditions.

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  • 143.
    Vannucci, Caterina
    et al.
    Univ Bologna, Sch Psychol & Educ Sci, Bologna, Italy.;Univ Birmingham, Sch Psychol, Birmingham, W Midlands, England.;IMT Sch Adv Studies, MoMiLab Res Unit, Lucca, Italy..
    Bonsall, Michael B.
    Univ Oxford, Dept Biol, Oxford, England..
    Di Simplicio, Martina
    Imperial Coll London, Dept Brain Sci, Div Psychiat, London, England..
    Cairns, Aimee
    Univ Birmingham, Sch Psychol, Birmingham, W Midlands, England.;Univ Warwick, Warwick Med Sch, Coventry, W Midlands, England..
    Holmes, Emily A.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Heyes, Stephanie Burnett
    Univ Birmingham, Sch Psychol, Birmingham, W Midlands, England..
    Positive moods are all alike?: differential affect amplification effects of 'elated' versus 'calm' mental imagery in young adults reporting hypomanic-like experiences2022In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 12, no 1, article id 453Article in journal (Refereed)
    Abstract [en]

    Positive mood amplification is a hallmark of the bipolar disorder spectrum (BPDS). We need better understanding of cognitive mechanisms contributing to such elevated mood. Generation of vivid, emotionally compelling mental imagery is proposed to act as an 'emotional amplifier' in BPDS. We used a positive mental imagery generation paradigm to manipulate affect in a subclinical BPDS-relevant sample reporting high (n = 31) vs. low (n = 30) hypomanic-like experiences on the Mood Disorder Questionnaire (MDQ). Participants were randomized to an 'elated' or 'calm' mental imagery condition, rating their momentary affect four times across the experimental session. We hypothesized greater affect increase in the high (vs. low) MDQ group assigned to the elated (vs. calm) imagery generation condition. We further hypothesized that affect increase in the high MDQ group would be particularly apparent in the types of affect typically associated with (hypo)mania, i.e., suggestive of high activity levels. Mixed model and time-series analysis showed that for the high MDQ group, affect increased steeply and in a sustained manner over time in the 'elated' imagery condition, and more shallowly in 'calm'. The low-MDQ group did not show this amplification effect. Analysis of affect clusters showed high-MDQ mood amplification in the 'elated' imagery condition was most pronounced for active affective states. This experimental model of BPDS-relevant mood amplification shows evidence that positive mental imagery drives changes in affect in the high MDQ group in a targeted manner. Findings inform cognitive mechanisms of mood amplification, and spotlight prevention strategies targeting elated imagery, while potentially retaining calm imagery to preserve adaptive positive emotionality.

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  • 144.
    Wallert, J.
    et al.
    Karolinska Institute, Sweden.
    Boberg, J.
    Karolinska Institute, Sweden.
    Kaldo, V.
    Karolinska Institute, Sweden; Linnaeus University, Sweden.
    Mataix-Cols, D.
    Karolinska Institute, Sweden.
    Flygare, O.
    Karolinska Institute, Sweden.
    Crowley, J. J.
    Karolinska Institute, Sweden.
    Halvorsen, M.
    Karolinska Institute, Sweden; University of North Carolina at Chapel Hill, USA.
    Ben Abdesslem, Fehmi
    RISE Research Institutes of Sweden, Digital Systems, Data Science.
    Boman, Magnus
    RISE Research Institutes of Sweden. Karolinska Institute, Sweden.
    Andersson, E.
    Karolinska Institute, Sweden.
    Hentati Isacsson, N.
    Karolinska Institute, Sweden.
    Ivanova, E.
    Karolinska Institute, Sweden.
    Rück, C.
    Karolinska Institute, Sweden.
    Predicting remission after internet-delivered psychotherapy in patients with depression using machine learning and multi-modal data2022In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 12, no 1, article id 357Article in journal (Refereed)
    Abstract [en]

    This study applied supervised machine learning with multi-modal data to predict remission of major depressive disorder (MDD) after psychotherapy. Genotyped adult patients (n = 894, 65.5% women, age 18–75 years) diagnosed with mild-to-moderate MDD and treated with guided Internet-based Cognitive Behaviour Therapy (ICBT) at the Internet Psychiatry Clinic in Stockholm were included (2008–2016). Predictor types were demographic, clinical, process (e.g., time to complete online questionnaires), and genetic (polygenic risk scores). Outcome was remission status post ICBT (cut-off ≤10 on MADRS-S). Data were split into train (60%) and validation (40%) given ICBT start date. Predictor selection employed human expertise followed by recursive feature elimination. Model derivation was internally validated through cross-validation. The final random forest model was externally validated against a (i) null, (ii) logit, (iii) XGBoost, and (iv) blended meta-ensemble model on the hold-out validation set. Feature selection retained 45 predictors representing all four predictor types. With unseen validation data, the final random forest model proved reasonably accurate at classifying post ICBT remission (Accuracy 0.656 [0.604, 0.705], P vs null model = 0.004; AUC 0.687 [0.631, 0.743]), slightly better vs logit (bootstrap D = 1.730, P = 0.084) but not vs XGBoost (D = 0.463, P = 0.643). Transparency analysis showed model usage of all predictor types at both the group and individual patient level. A new, multi-modal classifier for predicting MDD remission status after ICBT treatment in routine psychiatric care was derived and empirically validated. The multi-modal approach to predicting remission may inform tailored treatment, and deserves further investigation to attain clinical usefulness. © 2022, The Author(s).

  • 145.
    Wallert, John
    et al.
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Huddinge, Sweden.;Stockholm HealthCare Serv, Huddinge, Sweden..
    Boberg, Julia
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Huddinge, Sweden.;Stockholm HealthCare Serv, Huddinge, Sweden..
    Kaldo, Viktor
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Huddinge, Sweden.;Stockholm HealthCare Serv, Huddinge, Sweden.;Linnaeus Univ, Fac Hlth & Life Sci, Dept Psychol, Växjö, Sweden..
    Mataix-Cols, David
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Huddinge, Sweden.;Stockholm HealthCare Serv, Huddinge, Sweden.;Stockholm Hlth Care Serv, CAP Res Ctr, Stockholm, Sweden..
    Flygare, Oskar
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Huddinge, Sweden.;Stockholm HealthCare Serv, Huddinge, Sweden..
    Crowley, James J.
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Huddinge, Sweden.;Stockholm HealthCare Serv, Huddinge, Sweden.;Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA..
    Halvorsen, Matthew
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Huddinge, Sweden.;Stockholm HealthCare Serv, Huddinge, Sweden.;Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA..
    Ben Abdesslem, Fehmi
    KTH. Res Inst Sweden, Kista, Sweden.
    Boman, Magnus
    KTH, School of Electrical Engineering and Computer Science (EECS), Computer Science, Software and Computer systems, SCS. Res Inst Sweden, Kista, Sweden; Karolinska Inst, Dept Learning Informat Management & Eth, Solna, Sweden..
    Andersson, Evelyn
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Huddinge, Sweden.;Stockholm HealthCare Serv, Huddinge, Sweden..
    Isacsson, Nils Hentati
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Huddinge, Sweden.;Stockholm HealthCare Serv, Huddinge, Sweden..
    Ivanova, Ekaterina
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Huddinge, Sweden.;Stockholm HealthCare Serv, Huddinge, Sweden..
    Ruck, Christian
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Huddinge, Sweden.;Stockholm HealthCare Serv, Huddinge, Sweden..
    Predicting remission after internet-delivered psychotherapy in patients with depression using machine learning and multi-modal data2022In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 12, no 1, article id 357Article in journal (Refereed)
    Abstract [en]

    This study applied supervised machine learning with multi-modal data to predict remission of major depressive disorder {MDD) after psychotherapy. Genotyped adult patients (n = 894, 65.5% women, age 18-75 years) diagnosed with mild-to-moderate MDD and treated with guided Internet-based Cognitive Behaviour Therapy (ICBT) at the Internet Psychiatry Clinic in Stockholm were included (2008-2016). Predictor types were demographic, clinical, process (e.g., time to complete online questionnaires), and genetic (polygenic risk scores). Outcome was remission status post ICBT (cut-off <= 10 on MADRS-S). Data were split into train (60%) and validation (40%) given ICBT start date. Predictor selection employed human expertise followed by recursive feature elimination. Model derivation was internally validated through cross-validation. The final random forest model was externally validated against a (i) null, (ii) logit, (iii) XGBoost, and {iv) blended meta-ensemble model on the hold-out validation set. Feature selection retained 45 predictors representing all four predictor types. With unseen validation data, the final random forest model proved reasonably accurate at classifying post ICBT remission (Accuracy 0.656 [0.604, 0.705], P vs null model = 0.004; AUC 0.687 [0.631, 0.743]), slightly better vs logit (bootstrap D = 1.730, P = 0.084) but not vs XGBoost (D = 0.463, P = 0.643). Transparency analysis showed model usage of all predictor types at both the group and individual patient level. A new, multi-modal classifier for predicting MDD remission status after ICBT treatment in routine psychiatric care was derived and empirically validated. The multi-modal approach to predicting remission may inform tailored treatment, and deserves further investigation to attain clinical usefulness.

  • 146.
    Wallert, John
    et al.
    Karolinska Institutet, Sweden;Stockholm Healthcare Services, Sweden.
    Boberg, Julia
    Karolinska Institutet, Sweden;Stockholm Healthcare Services, Sweden.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet, Sweden;Stockholm Healthcare Services, Sweden.
    Mataix-Cols, David
    Karolinska Institutet, Sweden;Stockholm Healthcare Services, Sweden.
    Flygare, Oskar
    Karolinska Institutet, Sweden;Stockholm Healthcare Services, Sweden.
    Crowley, James J.
    Karolinska Institutet, Sweden;Stockholm Healthcare Services, Sweden;Univ N Carolina, USA.
    Halvorsen, Matthew
    Karolinska Institutet, Sweden;Stockholm Healthcare Services, Sweden;Univ N Carolina, USA.
    Ben Abdesslem, Fehmi
    RISE, Sweden;KTH Royal instute of technology, Sweden.
    Boman, Magnus
    RISE, Sweden;KTH Royal instute of technology, Sweden;Karolinska Institutet, Sweden.
    Andersson, Evelyn
    Karolinska Institutet, Sweden;Stockholm Healthcare Services, Sweden.
    Isacsson, Nils Hentati
    Karolinska Institutet, Sweden;Stockholm Healthcare Services, Sweden.
    Ivanova, Ekaterina
    Karolinska Institutet, Sweden;Stockholm Healthcare Services, Sweden.
    Ruck, Christian
    Karolinska Institutet, Sweden;Stockholm Healthcare Services, Sweden.
    Predicting remission after internet-delivered psychotherapy in patients with depression using machine learning and multi-modal data2022In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 12, no 1, article id 357Article in journal (Refereed)
    Abstract [en]

    This study applied supervised machine learning with multi-modal data to predict remission of major depressive disorder {MDD) after psychotherapy. Genotyped adult patients (n = 894, 65.5% women, age 18-75 years) diagnosed with mild-to-moderate MDD and treated with guided Internet-based Cognitive Behaviour Therapy (ICBT) at the Internet Psychiatry Clinic in Stockholm were included (2008-2016). Predictor types were demographic, clinical, process (e.g., time to complete online questionnaires), and genetic (polygenic risk scores). Outcome was remission status post ICBT (cut-off <= 10 on MADRS-S). Data were split into train (60%) and validation (40%) given ICBT start date. Predictor selection employed human expertise followed by recursive feature elimination. Model derivation was internally validated through cross-validation. The final random forest model was externally validated against a (i) null, (ii) logit, (iii) XGBoost, and {iv) blended meta-ensemble model on the hold-out validation set. Feature selection retained 45 predictors representing all four predictor types. With unseen validation data, the final random forest model proved reasonably accurate at classifying post ICBT remission (Accuracy 0.656 [0.604, 0.705], P vs null model = 0.004; AUC 0.687 [0.631, 0.743]), slightly better vs logit (bootstrap D = 1.730, P = 0.084) but not vs XGBoost (D = 0.463, P = 0.643). Transparency analysis showed model usage of all predictor types at both the group and individual patient level. A new, multi-modal classifier for predicting MDD remission status after ICBT treatment in routine psychiatric care was derived and empirically validated. The multi-modal approach to predicting remission may inform tailored treatment, and deserves further investigation to attain clinical usefulness.

  • 147. Witt, S. H.
    et al.
    Streit, F.
    Jungkunz, M.
    Frank, J.
    Awasthi, S.
    Reinbold, C. S.
    Treutlein, J.
    Degenhardt, F.
    Forstner, A. J.
    Heilmann-Heimbach, S.
    Dietl, L.
    Schwarze, C. E.
    Schendel, D.
    Strohmaier, J.
    Abdellaoui, A.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Air, T. M.
    Akil, H.
    Alda, M.
    Alliey-Rodriguez, N.
    Andreassen, O. A.
    Babadjanova, G.
    Bass, N. J.
    Bauer, M.
    Baune, B. T.
    Bellivier, F.
    Bergen, S.
    Bethell, A.
    Biernacka, J. M.
    Blackwood, D. H. R.
    Boks, M. P.
    Boomsma, D. I.
    Borglum, A. D.
    Borrmann-Hassenbach, M.
    Brennan, P.
    Budde, M.
    Buttenschon, H. N.
    Byrne, E. M.
    Cervantes, P.
    Clarke, T-K
    Craddock, N.
    Cruceanu, C.
    Curtis, D.
    Czerski, P. M.
    Dannlowski, U.
    Davis, T.
    de Geus, E. J. C.
    Di Florio, A.
    Djurovic, S.
    Domenici, E.
    Edenberg, H. J.
    Etain, B.
    Fischer, S. B.
    Forty, L.
    Fraser, C.
    Frye, M. A.
    Fullerton, J. M.
    Gade, K.
    Gershon, E. S.
    Giegling, I.
    Gordon, S. D.
    Gordon-Smith, K.
    Grabe, H. J.
    Green, E. K.
    Greenwood, T. A.
    Grigoroiu-Serbanescu, M.
    Guzman-Parra, J.
    Hall, L. S.
    Hamshere, M.
    Hauser, J.
    Hautzinger, M.
    Heilbronner, U.
    Herms, S.
    Hitturlingappa, S.
    Hoffmann, P.
    Holmans, P.
    Hottenga, J-J
    Jamain, S.
    Jones, I.
    Jones, L. A.
    Jureus, A.
    Kahn, R. S.
    Kammerer-Ciernioch, J.
    Kirov, G.
    Kittel-Schneider, S.
    Kloiber, S.
    Knott, S. V.
    Kogevinas, M.
    Landen, M.
    Leber, M.
    Leboyer, M.
    Li, Q. S.
    Lissowska, J.
    Lucae, S.
    Martin, N. G.
    Mayoral-Cleries, F.
    McElroy, S. L.
    McIntosh, A. M.
    McKay, J. D.
    McQuillin, A.
    Medland, S. E.
    Middeldorp, C. M.
    Milaneschi, Y.
    Mitchell, P. B.
    Montgomery, G. W.
    Morken, G.
    Mors, O.
    Muehleisen, T. W.
    Mueller-Myhsok, B.
    Myers, R. M.
    Nievergelt, C. M.
    Nurnberger, J. I.
    O'Donovan, M. C.
    Loohuis, L. M. O.
    Ophoff, R.
    Oruc, L.
    Owen, M. J.
    Paciga, S. A.
    Penninx, B. W. J. H.
    Perry, A.
    Pfennig, A.
    Potash, J. B.
    Preisig, M.
    Reif, A.
    Rivas, F.
    Rouleau, G. A.
    Schofield, P. R.
    Schulze, T. G.
    Schwarz, M.
    Scott, L.
    Sinnamon, G. C. B.
    Stahl, E. A.
    Strauss, J.
    Turecki, G.
    Van der Auwera, S.
    Vedder, H.
    Vincent, J. B.
    Willemsen, G.
    Witt, C. C.
    Wray, N. R.
    Xi, H. S.
    Tadic, A.
    Dahmen, N.
    Schott, B. H.
    Cichon, S.
    Noethen, M. M.
    Ripke, S.
    Mobascher, A.
    Rujescu, D.
    Lieb, K.
    Roepke, S.
    Schmahl, C.
    Bohus, M.
    Rietschel, M.
    Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia2017In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 7, article id e1155Article in journal (Refereed)
    Abstract [en]

    Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case–control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P=4.42 × 10−7) and PKP4 (P=8.67 × 10−7); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, PFDR=0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (rg=0.28 [P=2.99 × 10−3]), SCZ (rg=0.34 [P=4.37 × 10−5]) and MDD (rg=0.57 [P=1.04 × 10−3]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies.

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  • 148.
    Wright, Astill L.
    et al.
    Division of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, UK.
    Horstmann, Louise
    Division of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, UK.
    Holmes, Emily A.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Bisson, Jonathan I
    Division of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, UK.
    Consolidation/reconsolidation therapies for the prevention and treatment of PTSD and re-experiencing: a systematic review and meta-analysis2021In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 11, no 1, article id 453Article in journal (Refereed)
    Abstract [en]

    Translational research highlights the potential of novel 'memory consolidation/reconsolidation therapies' to treat re-experiencing symptoms and post-traumatic stress disorder (PTSD). This systematic review and meta-analysis assessed the efficacy of so-called memory consolidation/reconsolidation therapies in randomised controlled trials (RCTs) for prevention and treatment of PTSD and symptoms of re-experiencing in children and adults (PROSPERO: CRD42020171167). RCTs were identified and rated for risk of bias. Available data was pooled to calculate risk ratios (RR) for PTSD prevalence and standardised mean differences (SMD) for PTSD/re-experiencing severity. Twenty-five RCTs met inclusion criteria (16 prevention and nine treatment trials). The methodology of most studies had a significant risk of bias. We found a large effect of reconsolidation interventions in the treatment of PTSD (11 studies, n = 372, SMD: -1.42 (-2.25 to -0.58), and a smaller positive effect of consolidation interventions in the prevention of PTSD (12 studies, n = 2821, RR: 0.67 (0.50 to 0.90). Only three protocols (hydrocortisone for PTSD prevention, Reconsolidation of Traumatic Memories (RTM) for treatment of PTSD symptoms and cognitive task memory interference procedure with memory reactivation (MR) for intrusive memories) were superior to control. There is some emerging evidence of consolidation and reconsolidation therapies in the prevention and treatment of PTSD and intrusive memories specifically. Translational research should strictly adhere to protocols/procedures describing precise reconsolidation conditions (e.g. MR) to both increase the likelihood of positive findings and more confidently interpret negative findings of putative reconsolidation agents.

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  • 149.
    Xue, Pei
    et al.
    Uppsala Univ, Sweden.
    Merikanto, Ilona
    Univ Helsinki, Finland.
    Chung, Frances
    Univ Toronto, Canada.
    Morin, Charles M.
    Univ Laval, Canada.
    Espie, Colin
    Univ Oxford, England.
    Bjorvatn, Bjorn
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Cedernaes, Jonathan
    Uppsala Univ, Sweden; Uppsala Univ, Sweden; Northwestern Univ, IL USA.
    Landtblom, Anne-Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Uppsala Univ, Sweden.
    Penzel, Thomas
    Charite, Germany.
    De Gennaro, Luigi
    Sapienza Univ Rome, Italy; IRCCS Fdn Santa Lucia, Italy.
    Holzinger, Brigitte
    Med Univ Vienna, Austria.
    Matsui, Kentaro
    Natl Ctr Hosp, Japan.
    Hrubos-Strom, Harald
    Akershus Univ Hosp, Norway; Univ Oslo, Norway.
    Korman, Maria
    Ariel Univ, Israel.
    Leger, Damien
    Hop Hotel Dieu Paris, France; Univ Paris, France.
    Mota-Rolim, Sergio
    Onofre Lopes Univ Hosp, Brazil; Univ Fed Rio Grande do Norte, Brazil.
    Bolstad, Courtney J.
    Mississippi State Univ, MS USA.
    Nadorff, Michael
    Mississippi State Univ, MS USA.
    Plazzi, Giuseppe
    IRCCS Ist Sci Neurol Bologna, Italy; Univ Modena & Reggio Emilia, Italy.
    Reis, Catia
    Univ Catolica Portuguesa, Portugal; Univ Lisbon, Portugal; Univ Lisbon, Portugal.
    Chan, Rachel Ngan Yin
    Chinese Univ Hong Kong, Peoples R China.
    Wing, Yun Kwok
    Chinese Univ Hong Kong, Peoples R China.
    Yordanova, Juliana
    Bulgarian Acad Sci, Bulgaria.
    Bjelajac, Adrijana Koscec
    Inst Med Res & Occupat Hlth, Croatia.
    Inoue, Yuichi
    Tokyo Med Univ, Japan; Japan Somnol Ctr, Japan.
    Partinen, Markku
    Univ Helsinki, Finland; Terveystalo Healthcare Serv, Finland.
    Dauvilliers, Yves
    Univ Montpellier, France.
    Benedict, Christian
    Uppsala Univ, Sweden.
    Persistent short nighttime sleep duration is associated with a greater post-COVID risk in fully mRNA-vaccinated individuals2023In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 13, no 1, article id 32Article in journal (Refereed)
    Abstract [en]

    Short nighttime sleep duration impairs the immune response to virus vaccination, and long nighttime sleep duration is associated with poor health status. Thus, we hypothesized that short (&lt;6 h) and long (&gt;9 h) nighttime sleepers have a higher post-COVID risk than normal nighttime sleepers, despite two doses of mRNA vaccine (which has previously been linked to lower odds of long-lasting COVID-19 symptoms). Post-COVID was defined as experiencing at least one core COVID-19 symptom for at least three months (e.g., shortness of breath). Multivariate logistic regression adjusting for age, sex, BMI, and other factors showed in 9717 respondents (age span 18-99) that two mRNA vaccinations lowered the risk of suffering from post-COVID by about 21% (p &lt; 0.001). When restricting the analysis to double-vaccinated respondents (n = 5918), short and long sleepers exhibited a greater post-COVID risk than normal sleepers (adjusted OR [95%-CI], 1.56 [1.29, 1.88] and 1.87 [1.32, 2.66], respectively). Among respondents with persistent sleep duration patterns during the pandemic compared to before the pandemic, short but not long sleep duration was significantly associated with the post-COVID risk (adjusted OR [95%-CI], 1.59 [1.24, 2.03] and 1.18 [0.70, 1.97], respectively). No significant association between sleep duration and post-COVID symptoms was observed in those reporting positive SARS-CoV-2 test results (n = 538). Our findings suggest that two mRNA vaccinations against SARS-CoV-2 are associated with a lower post-COVID risk. However, this protection may be less pronounced among those sleeping less than 6 h per night. Our findings warrant replication in cohorts with individuals with confirmed SARS-CoV-2 infection.

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  • 150.
    Xue, Pei
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Merikanto, Ilona
    Chung, Frances
    Morin, Charles M
    Espie, Colin
    Bjorvatn, Bjørn
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Landtblom, Anne-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Penzel, Thomas
    De Gennaro, Luigi
    Holzinger, Brigitte
    Matsui, Kentaro
    Hrubos-Strøm, Harald
    Korman, Maria
    Leger, Damien
    Mota-Rolim, Sérgio
    Bolstad, Courtney J
    Nadorff, Michael
    Plazzi, Giuseppe
    Reis, Catia
    Chan, Rachel Ngan Yin
    Wing, Yun Kwok
    Yordanova, Juliana
    Bjelajac, Adrijana Koscec
    Inoue, Yuichi
    Partinen, Markku
    Dauvilliers, Yves
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Persistent short nighttime sleep duration is associated with a greater post-COVID risk in fully mRNA-vaccinated individuals.2023In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 13, no 1, p. 32-, article id 32Article in journal (Refereed)
    Abstract [en]

    Short nighttime sleep duration impairs the immune response to virus vaccination, and long nighttime sleep duration is associated with poor health status. Thus, we hypothesized that short (<6 h) and long (>9 h) nighttime sleepers have a higher post-COVID risk than normal nighttime sleepers, despite two doses of mRNA vaccine (which has previously been linked to lower odds of long-lasting COVID-19 symptoms). Post-COVID was defined as experiencing at least one core COVID-19 symptom for at least three months (e.g., shortness of breath). Multivariate logistic regression adjusting for age, sex, BMI, and other factors showed in 9717 respondents (age span 18-99) that two mRNA vaccinations lowered the risk of suffering from post-COVID by about 21% (p < 0.001). When restricting the analysis to double-vaccinated respondents (n = 5918), short and long sleepers exhibited a greater post-COVID risk than normal sleepers (adjusted OR [95%-CI], 1.56 [1.29, 1.88] and 1.87 [1.32, 2.66], respectively). Among respondents with persistent sleep duration patterns during the pandemic compared to before the pandemic, short but not long sleep duration was significantly associated with the post-COVID risk (adjusted OR [95%-CI], 1.59 [1.24, 2.03] and 1.18 [0.70, 1.97], respectively). No significant association between sleep duration and post-COVID symptoms was observed in those reporting positive SARS-CoV-2 test results (n = 538). Our findings suggest that two mRNA vaccinations against SARS-CoV-2 are associated with a lower post-COVID risk. However, this protection may be less pronounced among those sleeping less than 6 h per night. Our findings warrant replication in cohorts with individuals with confirmed SARS-CoV-2 infection.

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