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  • 1.
    Alsehli, Ahmed M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. King Abdulaziz Univ, Dept Physiol, Fac Med, Al Ehtifalat St, Jeddah 21589, Saudi Arabia..
    Olivo, Gaia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Clemensson, Laura Emily
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Williams, Michael J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    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, Sechenov Biomed Sci & Technol Pk,Trubetskay Str 8, Moscow 119991, Russia..
    The Cognitive Effects of Statins are Modified by Age2020In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1, article id 6187Article in journal (Refereed)
    Abstract [en]

    To reveal new insights into statin cognitive effects, we performed an observational study on a population-based sample of 245,731 control and 55,114 statin-taking individuals from the UK Biobank. Cognitive performance in terms of reaction time, working memory and fluid intelligence was analysed at baseline and two follow-ups (within 5-10 years). Subjects were classified depending on age (up to 65 and over 65 years) and treatment duration (1-4 years, 5-10 years and over 10 years). Data were adjusted for health- and cognition-related covariates. Subjects generally improved in test performance with repeated assessment and middle-aged persons performed better than older persons. The effect of statin use differed considerably between the two age groups, with a beneficial effect on reaction time in older persons and fluid intelligence in both age groups, and a negative effect on working memory in younger subjects. Our analysis suggests a modulatory impact of age on the cognitive side effects of statins, revealing a possible reason for profoundly inconsistent findings on statin-related cognitive effects in the literature. The study highlights the importance of characterising modifiers of statin effects to improve knowledge and shape guidelines for clinicians when prescribing statins and evaluating their side effects in patients.

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  • 2.
    Cocozza, S.
    et al.
    Univ Federico II, Dept Adv Biomed Sci, Nephrol Unit, Naples, Italy..
    Russo, C.
    Univ Federico II, Dept Adv Biomed Sci, Nephrol Unit, Naples, Italy..
    Pisani, A.
    Univ Federico II, Dept Publ Hlth, Nephrol Unit, Naples, Italy..
    Olivo, Gaia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. Univ Federico II, Dept Adv Biomed Sci, Nephrol Unit, Naples, Italy..
    Riccio, E.
    Univ Federico II, Dept Publ Hlth, Nephrol Unit, Naples, Italy..
    Cervo, A.
    Univ Federico II, Dept Adv Biomed Sci, Nephrol Unit, Naples, Italy..
    Pontillo, G.
    Univ Federico II, Dept Adv Biomed Sci, Nephrol Unit, Naples, Italy..
    Feriozzi, S.
    Belcolle Hosp, Nephrol & Dialysis Dept, Viterbo, Italy..
    Veroux, M.
    Univ Hosp Catania, Dept Med & Surg Sci & Adv Technol, Catania, Sicily, Italy..
    Battaglia, Y.
    Univ Ferrara, St Anna Hosp, Dept Specialized Med, Div Nephrol & Dialysis, Ferrara, Italy..
    Concolino, D.
    Magna Graecia Univ Catanzaro, Dept Pediat, Catanzaro, Italy..
    Pieruzzi, F.
    Univ Milano Bicocca, Nephrol Unit, Milan, Italy..
    Mignani, R.
    Infermi Hosp, Nephrol & Dialysis Dept, Rimini, Italy..
    Borrelli, P.
    IRCCS SDN, Naples, Italy..
    Imbriaco, M.
    Univ Federico II, Dept Adv Biomed Sci, Nephrol Unit, Naples, Italy..
    Brunetti, A.
    Univ Federico II, Dept Adv Biomed Sci, Nephrol Unit, Naples, Italy..
    Tedeschi, E.
    Univ Federico II, Dept Adv Biomed Sci, Nephrol Unit, Naples, Italy..
    Palma, G.
    CNR, Inst Biostruct & Bioimaging, Naples, Italy..
    Redefining the Pulvinar Sign in Fabry Disease2017In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 38, no 12, p. 2264-2269Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE:

    The pulvinar sign refers to exclusive T1WI hyperintensity of the lateral pulvinar. Long considered a common sign of Fabry disease, the pulvinar sign has been reported in many pathologic conditions. The exact incidence of the pulvinar sign has never been tested in representative cohorts of patients with Fabry disease. The aim of this study was to assess the prevalence of the pulvinar sign in Fabry disease by analyzing T1WI in a large Fabry disease cohort, determining whether relaxometry changes could be detected in this region independent of the pulvinar sign positivity.

    MATERIALS AND METHODS:

    We retrospectively analyzed brain MR imaging of 133 patients with Fabry disease recruited through specialized care clinics. A subgroup of 26 patients underwent a scan including 2 FLASH sequences for relaxometry that were compared with MRI scans of 34 healthy controls.

    RESULTS:

    The pulvinar sign was detected in 4 of 133 patients with Fabry disease (3.0%). These 4 subjects were all adult men (4 of 53, 7.5% of the entire male population) with renal failure and under enzyme replacement therapy. When we tested for discrepancies between Fabry disease and healthy controls in quantitative susceptibility mapping and relaxometry maps, no significant difference emerged for any of the tested variables.

    CONCLUSIONS:

    The pulvinar sign has a significantly lower incidence in Fabry disease than previously described. This finding, coupled with a lack of significant differences in quantitative MR imaging, allows hypothesizing that selective involvement of the pulvinar is a rare neuroradiologic sign of Fabry disease.

  • 3.
    Cocozza, Sirio
    et al.
    Univ Federico II, Dept Adv Biomed Sci, Via Pansini 5, I-80131 Naples, Italy..
    Pontillo, Giuseppe
    Univ Federico II, Dept Adv Biomed Sci, Via Pansini 5, I-80131 Naples, Italy..
    Quarantelli, Mario
    CNR, Inst Biostruct & Bioimaging, Naples, Italy..
    Sacca, Francesco
    Univ Federico II, Dept Neurosci & Reprod & Odontostomatol Sci, Naples, Italy..
    Riccio, Eleonora
    Univ Federico II, Dept Publ Hlth, Nephrol Unit, Naples, Italy..
    Costabile, Teresa
    Univ Federico II, Dept Neurosci & Reprod & Odontostomatol Sci, Naples, Italy..
    Olivo, Gaia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Morra, Vincenzo Brescia
    Univ Federico II, Dept Neurosci & Reprod & Odontostomatol Sci, Naples, Italy..
    Pisani, Antonio
    Univ Federico II, Dept Publ Hlth, Nephrol Unit, Naples, Italy..
    Brunetti, Arturo
    Univ Federico II, Dept Adv Biomed Sci, Via Pansini 5, I-80131 Naples, Italy..
    Tedeschi, Enrico
    Univ Federico II, Dept Adv Biomed Sci, Via Pansini 5, I-80131 Naples, Italy..
    Default mode network modifications in Fabry disease: A resting-state fMRI study with structural correlations2018In: Human Brain Mapping, ISSN 1065-9471, E-ISSN 1097-0193, Vol. 39, no 4, p. 1755-1764Article in journal (Refereed)
    Abstract [en]

    Aim of the study was to evaluate the presence of Default Mode Network (DMN) modifications in Fabry Disease (FD), and their possible correlations with structural alterations and neuropsychological scores. Thirty-two FD patients with a genetically confirmed diagnosis of classical FD (12 males, mean age 43.3 +/- 12.2) were enrolled, along with 35 healthy controls (HC) of comparable age and sex (14 males, mean age 42.1 +/- 14.5). Resting-State fMRI data were analyzed using a seed-based approach, with six different seeds sampling the main hubs of the DMN. Structural modifications were assessed by means of Voxel-Based Morphometry (VBM) and Tract-Based Spatial Statistics analyses. Between-group differences and correlations with neuropsychological variables were probed voxelwise over the whole brain. Possible correlations between FC modifications and global measures of microstructural alteration were also tested in FD patients with a partial correlation analysis. In the FD group, clusters of increased functional connectivity involving both supratentorial and infratentorial regions emerged, partially correlated to the widespread white matter (WM) damage found in these patients. No gray matter volume differences were found at VBM between the two groups. The connectivity between right inferior frontal gyrus and precuneus was significantly correlated with the Corsi block-tapping test results (p = .0001). Widespread DMN changes are present in FD patients that correlate with WM alterations and cognitive performance. Our results confirm the current view of a cerebral involvement in FD patients not simply associated to major cerebrovascular events, but also related to significant and diffuse microstructural and functional changes.

  • 4.
    Fredriksson, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Sreedharan, Smitha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology.
    Nordenankar, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Alsiö, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Lindberg, Frida A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Hutchinson, Ashley
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Eriksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Roshanbin, Sahar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Ciuculete, Diana M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Klockars, Anica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Todkar, Aniruddha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Hägglund, Maria G
    Hellsten, Sofie V
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Hindlycke, Viktoria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Västermark, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Shevchenko, Ganna
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Olivo, Gaia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    K, Cheng
    Kullander, Klas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Moazzami, Ali
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Olszewski, Pawel K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    The polyamine transporter Slc18b1(VPAT) is important for both short and long time memory and for regulation of polyamine content in the brain.2019In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 15, no 12, article id e1008455Article in journal (Refereed)
    Abstract [en]

    SLC18B1 is a sister gene to the vesicular monoamine and acetylcholine transporters, and the only known polyamine transporter, with unknown physiological role. We reveal that Slc18b1 knock out mice has significantly reduced polyamine content in the brain providing the first evidence that Slc18b1 is functionally required for regulating polyamine levels. We found that this mouse has impaired short and long term memory in novel object recognition, radial arm maze and self-administration paradigms. We also show that Slc18b1 KO mice have altered expression of genes involved in Long Term Potentiation, plasticity, calcium signalling and synaptic functions and that expression of components of GABA and glutamate signalling are changed. We further observe a partial resistance to diazepam, manifested as significantly lowered reduction in locomotion after diazepam treatment. We suggest that removal of Slc18b1 leads to reduction of polyamine contents in neurons, resulting in reduced GABA signalling due to long-term reduction in glutamatergic signalling.

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  • 5.
    Gaudio, Santino
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Univ Campus Biomed Roma, Area Diagnost Imaging, Ctr Integrated Res, Rome, Italy.
    Carducci, Filippo
    Sapienza Univ, Neuroimaging Lab, Dept Physiol & Pharmacol, Rome, Italy.
    Piervincenzi, Claudia
    Sapienza Univ, Neuroimaging Lab, Dept Physiol & Pharmacol, Rome, Italy.
    Olivo, Gaia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    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.
    Altered thalamo-cortical and occipital-parietal-temporal-frontal white matter connections in patients with anorexia and bulimia nervosa: a systematic review of diffusion tensor imaging studies2019In: Journal of Psychiatry & Neuroscience, ISSN 1180-4882, E-ISSN 1488-2434, Vol. 44, no 5, p. 324-339Article, review/survey (Refereed)
    Abstract [en]

    Background: Anorexia nervosa and bulimia nervosa are complex mental disorders, and their etiology is still not fully understood. This paper reviews the literature on diffusion tensor imaging studies in patients with anorexia nervosa and bulimia nervosa to explore the usefulness of white matter microstructural analysis in understanding the pathophysiology of eating disorders.

    Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify diffusion tensor imaging studies that compared patients with an eating disorder to control groups. We searched relevant databases for studies published from database inception to August 2018, using combinations of select keywords. We categorized white matter tracts according to their 3 main classes: projection (i.e., thalamo-cortical), association (i.e., occipital-parietal-temporal-frontal) and commissural (e.g., corpus callosum).

    Results: We included 19 papers that investigated a total of 427 participants with current or previous eating disorders and 444 controls. Overall, the studies used different diffusion tensor imaging approaches and showed widespread white matter abnormalities in patients with eating disorders. Despite differences among the studies, patients with anorexia nervosa showed mainly white matter microstructural abnormalities of thalamo-cortical tracts (i.e., corona radiata, thalamic radiations) and occipital-parietal-temporal-frontal tracts (i.e., left superior longitudinal and inferior fronto-occipital fasciculi). It was less clear whether white matter alterations persist after recovery from anorexia nervosa. Available data on bulimia nervosa were partially similar to those for anorexia nervosa.

    Limitations: Study sample composition and diffusion tensor imaging analysis techniques were heterogeneous. The number of studies on bulimia nervosa was too limited to be conclusive.

    Conclusion: White matter microstructure appears to be affected in anorexia nervosa, and these alterations may play a role in the pathophysiology of this eating disorder. Although we found white matter alterations in bulimia nervosa that were similar to those in anorexia nervosa, white matter changes in bulimia nervosa remain poorly investigated, and these findings were less conclusive. Further studies with longitudinal designs and multi-approach analyses are needed to better understand the role of white matter changes in eating disorders.

  • 6.
    Gaudio, Santino
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. Eating Disorders Ctr La Cura Girasole ONLUS, Via Gregorio 7,186-B, I-00165 Rome, Italy;Univ Campus Biomed Roma, Departmental Fac Med & Surg, Area Diagnost Imaging, Via Alvaro del Portillo 200, I-00133 Rome, Italy.
    Olivo, Gaia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Zobel, Bruno Beomonte
    Univ Campus Biomed Roma, Departmental Fac Med & Surg, Area Diagnost Imaging, Via Alvaro del Portillo 200, I-00133 Rome, Italy.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Altered cerebellar-insular-parietal-cingular subnetwork in adolescents in the earliest stages of anorexia nervosa: a network-based statistic analysis2018In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 8, article id 127Article in journal (Refereed)
    Abstract [en]

    To date, few functional magnetic resonance imaging (fMRI) studies have explored resting-state functional connectivity (RSFC) in long-lasting anorexia nervosa (AN) patients via graph analysis. The aim of the present study is to investigate, via a graph approach (i.e., the network-based statistic), RSFC in a sample of adolescents at the earliest stages of AN (i.e., AN duration less than 6 months). Resting-state fMRI data was obtained from 15 treatment-naive female adolescents with AN restrictive type (AN-r) in its earliest stages and 15 age-matched healthy female controls. A network-based statistic analysis was used to isolate networks of interconnected nodes that differ between the two groups. Group comparison showed a decreased connectivity in a sub-network of connections encompassing the left and right rostral ACC, left paracentral lobule, left cerebellum (10th sub-division), left posterior insula, left medial fronto-orbital gyrus, and right superior occipital gyrus in AN patients. Results were not associated to alterations in intranodal or global connectivity. No sub-networks with an increased connectivity were identified in AN patients. Our findings suggest that RSFC may be specifically affected at the earliest stages of AN. Considering that the altered sub-network comprises areas mainly involved in somatosensory and interoceptive information and processing and in emotional processes, it could sustain abnormal integration of somatosensory and homeostatic signals, which may explain body image disturbances in AN. Further studies with larger samples and longitudinal designs are needed to confirm our findings and better understand the role and consequences of such functional alterations in AN.

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  • 7.
    Hogenkamp, Pleunie S.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Zhou, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Dahlberg, Linda Solstrand
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Stark, J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Larsen, A. L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Olivo, Gaia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Wiemerslage, Lyle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Higher resting-state activity in reward-related brain circuits in obese versus normal-weight females independent of food intake2016In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 40, no 11, p. 1687-1692Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In response to food cues, obese vs normal-weight individuals show greater activation in brain regions involved in the regulation of food intake under both fasted and sated conditions. Putative effects of obesity on task-independent low-frequency blood-oxygenation-level-dependent signals-that is, resting-state brain activity-in the context of food intake are, however, less well studied.

    OBJECTIVE: To compare eyes closed, whole-brain low-frequency BOLD signals between severely obese and normal-weight females, as assessed by functional magnetic resonance imaging (fMRI).

    METHODS: Fractional amplitude of low-frequency fluctuations were measured in the morning following an overnight fast in 17 obese (age: 39±11 years, body mass index (BMI): 42.3±4.8 kg m(-)(2)) and 12 normal-weight females (age: 36±12 years, BMI: 22.7±1.8 kg m(-)(2)), both before and 30 min after consumption of a standardized meal (~260 kcal).

    RESULTS: Compared with normal-weight controls, obese females had increased low-frequency activity in clusters located in the putamen, claustrum and insula (P<0.05). This group difference was not altered by food intake. Self-reported hunger dropped and plasma glucose concentrations increased after food intake (P<0.05); however, these changes did not differ between the BMI groups.

    CONCLUSION: Reward-related brain regions are more active under resting-state conditions in obese than in normal-weight females. This difference was independent of food intake under the experimental settings applied in the current study. Future studies involving males and females, as well as utilizing repeated post-prandial resting-state fMRI scans and various types of meals are needed to further investigate how food intake alters resting-state brain activity in obese humans.International Journal of Obesity advance online publication, 28 June 2016; doi:10.1038/ijo.2016.105.

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  • 8.
    Miguet, Maud
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Functional Pharmacology and Neuroscience.
    Olivo, Gaia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Functional Pharmacology and Neuroscience.
    Ciuculete, Diana-Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Functional Pharmacology and Neuroscience.
    Elmståhl, Sölve
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Functional Pharmacology and Neuroscience. Institute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Russia.
    Perceived stress is related to lower blood pressure in a Swedish cohort2023In: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 51, no 4, p. 611-618Article in journal (Refereed)
    Abstract [en]

    Aims: General psychosocial stress and job strain have been related to blood pressure (BP) with conflicting results. This study sought to explore the contribution of several lifestyle factors in the relation between general psychosocial stress, job strain and BP.

    Methods: This cross-sectional study investigated the association of general stress and job strain with systolic BP (SBP) and diastolic BP in a sample of 9441 employed individuals from the EpiHealth cohort. General stress was measured by the Perceived Stress Scale. Job strain was assessed with the Job Content Questionnaire, assessing two dimensions of job strain: psychological job demand and decision latitude. Linear regression and sensitivity analysis were performed.

    Results: At the uncorrected model, general stress, job demand and decision latitude were all inversely associated with SBP. After further adjustment for lifestyle and health parameters, only general stress was associated with SPB (β coefficient: -0.103; 95% confidence interval -0.182 to 0.023).

    Cconclusions: General stress is associated with lower SBP independently of lifestyle in middle-aged adults. Our findings point towards a major contribution for job-unrelated stressors in determining SBP and support the pivotal role of lifestyle behaviours and health status in modulating the effect of stress on BP, calling for a careful selection of confounders.

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  • 9.
    Olivo, Gaia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Brain Structure and Function in Adolescents with Atypical Anorexia Nervosa2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Atypical anorexia nervosa (AAN) has a high incidence in adolescents, resulting in significant morbidity and mortality. The weight loss is generally less pronounced than that experienced in full-syndrome anorexia nervosa (AN), but the medical consequences can be as severe. Neuroimaging could improve our knowledge regarding the pathogenesis of eating disorders, however research on adolescents is limited, and no neuroimaging studies have been conducted in AAN. In paper I, we investigated brain structure through a voxel-based morphometry analysis in 22 drug-naïve adolescent females newly-diagnosed with AAN, and 38 age- and sex-matched healthy controls. In Paper II, we investigated white matter microstructural integrity on 25 drug-naïve adolescent patients with AAN and 25 healthy controls, using diffusion tensor imaging with a tract-based spatial statistics approach. No differences in brain structure could be detected, indicating preserved regional grey matter volumes and white matter diffusivity in patients with AAN compared to controls. These findings suggest that previous observations of brain structure alterations in full syndrome AN may constitute state-related consequences of severe underweight. Alternatively, the preservation of brain structure might indeed differentiate AAN from AN. In paper III, we investigated resting-state functional connectivity in 22 drug-naïve adolescent patients with AAN, and 24 healthy controls. We report reduced connectivity in patients in brain areas involved in face-processing and social cognition, while an increased connectivity, correlating with depressive symptoms, was found in areas involved in the multimodal integration of sensory stimuli, aesthetic judgment, and social rejection anxiety. These findings point toward a core role for an altered development of socio-emotional skills in the pathogenesis of AAN. In Paper IV, we investigated neural connectivity underlying visual processing of foods with different caloric content in a sample of 28 adolescent females diagnosed with AAN, and 33 age- and sex-matched healthy controls. Our results showed higher connectivity in patients in pathways related to the integration of sensory input and memory retrieval, in response to food with high caloric content. This, however, was coupled to lower connectivity in salience and attentional networks, and lower connectivity between areas involved in visual food cues processing and appetite regulatory regions. Thus, despite food with high caloric content is associated to greater processing of somatosensory information in patients, it is attributed less salience and engages patients’ attention less than food with low caloric content.

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  • 10.
    Olivo, Gaia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Uppsala Univ, Dept Neurosci Funct Pharmacol, S-75124 Uppsala, Sweden.
    Gaudio, Santino
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Univ Campus Biomed Roma, CIR, Area Diagnost Imaging, I-00128 Rome, 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 119146, Russia.
    Brain and Cognitive Development in Adolescents with Anorexia Nervosa: A Systematic Review of fMRI Studies2019In: Nutrients, E-ISSN 2072-6643, Vol. 11, no 8, article id 1907Article, review/survey (Refereed)
    Abstract [en]

    Anorexia nervosa (AN) is an eating disorder often occurring in adolescence. AN has one of the highest mortality rates amongst psychiatric illnesses and is associated with medical complications and high risk for psychiatric comorbidities, persisting after treatment. Remission rates range from 23% to 33%. Moreover, weight recovery does not necessarily reflect cognitive recovery. This issue is of particular interest in adolescence, characterized by progressive changes in brain structure and functional circuitries, and fast cognitive development. We reviewed existing literature on fMRI studies in adolescents diagnosed with AN, following PRISMA guidelines. Eligible studies had to: (1) be written in English; (2) include only adolescent participants; and (3) use block-design fMRI. We propose a pathogenic model based on normal and AN-related neural and cognitive maturation during adolescence. We propose that underweight and delayed puberty-caused by genetic, environmental, and neurobehavioral factors-can affect brain and cognitive development and lead to impaired cognitive flexibility, which in turn sustains the perpetuation of aberrant behaviors in a vicious cycle. Moreover, greater punishment sensitivity causes a shift toward punishment-based learning, leading to greater anxiety and ultimately to excessive reappraisal over emotions. Treatments combining physiological and neurobehavioral rationales must be adopted to improve outcomes and prevent relapses.

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  • 11.
    Olivo, Gaia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Gour, Shaili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Low neuroticism and cognitive performance are differently associated to overweight and obesity: A cross-sectional and longitudinal UK Biobank study.2019In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 101, p. 167-174Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A growing body of research has linked personality traits to cognitive performance. This relationship might play a role in the predisposition toward obesity. Neuroticism and executive function seem to be particularly involved, and reduced executive function has been proposed to underlie the association of neuroticism with sedentary behaviors and fatty food consumption. Despite the link between neuroticism, cognitive functions and obesity has been largely reported, conflicting evidence exists. Moreover, information regarding other cognitive domains, and studies on overweight individuals, are still scarce.

    METHODS: We examined cross-sectional associations of neuroticism and cognitive function with overweight and obesity in a sample of 170 310 individuals from the UK Biobank cohort, adjusted for sociodemographic and life-style factors. Measures on fluid intelligence (FI) (reasoning ability), trail making test (TMT) (executive function), numeric memory test and pairs matching (PM) task (short-term memory) were extracted from the database. Correlations between neuroticism and cognitive performance were explored. Moreover, we investigated whether neuroticism and executive function could predict BMI variability over time.

    RESULTS: Reduced FI and short-term memory were associated with overweight and obesity, while reduced executive function was associated with obesity but not with overweight. Low neuroticism was associated with being overweight rather than lean or obese independently of gender and life-style. Furthermore, baseline neuroticism scores could predict BMI variations over 5-10 years follow-up, and high neuroticism correlated with lower cognitive performance.

    CONCLUSIONS: Lower cognitive performance is associated with both overweight and obesity, except for executive function, which was only related to obesity. Neuroticism correlated with performance on most of the cognitive domains tested, supporting the link between personality and cognition. Our findings also support the role of neuroticism in leading to greater weight variability over time, rather than to overweight/obesity itself.

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  • 12.
    Olivo, Gaia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Latini, Francesco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Wiemerslage, Lyle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Disruption of Accumbens and Thalamic White Matter Connectivity Revealed by Diffusion Tensor Tractography in Young Men with Genetic Risk for Obesity2018In: Frontiers in Human Neuroscience, E-ISSN 1662-5161, Vol. 12, article id 75Article in journal (Refereed)
    Abstract [en]

    Background: Neurovascular coupling is associated with white matter (WM) structural integrity, and it is regulated by specific subtypes of dopaminergic receptors. An altered activity of such receptors, highly expressed in reward-related regions, has been reported in carriers of obesity-risk alleles of the fat mass and obesity associated (FTO) gene. Among the reward-related regions, the thalamus and the nucleus accumbens are particularly vulnerable to blood pressure dysregulation due to their peculiar anatomo-vascular characteristics, and have been consistently reported to be altered in early-stage obesity. We have thus hypothesized that a disruption in thalamus and nucleus accumbens WM microstructure, possibly on neurovascular basis, could potentially be a predisposing factor underlying the enhanced risk for obesity in the risk-allele carriers.

    Methods: We have tested WM integrity in 21 male participants genotyped on the FTO risk single nucleotide polymorphisms (SNP) rs9939609, through a deterministic tractography analysis. Only homozygous participants (9 AA, 12 TT) were included. 11 tracts were selected and categorized as following according to our hypothesis: “risk tracts”, “obesity-associated tracts”, and a control tract (forcpes major). We investigated whether an association existed between genotype, body mass index (BMI) and WM microstructural integrity in the “risk-tracts” (anterior thalamic radiation and accumbofrontal fasciculus) compared to other tracts. Moreover, we explored whether WM diffusivity could be related to specific personality traits in terms of punishment and reward sensitivity, as measure by the BIS/BAS questionnaire.

    Results: An effect of the genotype and an interaction effect of genotype and BMI were detected on the fractional anisotropy (FA) of the “risk tracts”. Correlations between WM diffusivity parameters and measures of punishment and reward sensitivity were also detected in many WM tracts of both networks.

    Conclusions: A disruption of the structural connectivity from the nucleus accumbens and the thalamus might occur early in carriers of the FTO AA risk-allele, and possibly act as a predisposing factor to the development of obesity.

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  • 13.
    Olivo, Gaia
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). University of Gothenburg, Sweden.
    Lövdén, Martin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). University of Gothenburg, Sweden.
    Manzouri, Amirhossein
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Biological psychology. Karolinska Institutet, Sweden.
    Terlau, Laura
    Jenner, Bo
    Jafari, Arian
    Petersson, Sven
    Li, Tie-Qiang
    Fischer, Håkan
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Biological psychology.
    Månsson, Kristoffer N. T.
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Biological psychology. Karolinska Institutet, Sweden; Dartmouth College, USA.
    Estimated gray matter volume rapidly changes after a short motor task2022In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 32, no 19, p. 4356-4369, article id bhab488Article in journal (Refereed)
    Abstract [en]

    Skill learning induces changes in estimates of gray matter volume (GMV) in the human brain, commonly detectable with magnetic resonance imaging (MRI). Rapid changes in GMV estimates while executing tasks may however confound between- and within-subject differences. Fluctuations in arterial blood flow are proposed to underlie this apparent task-related tissue plasticity. To test this hypothesis, we acquired multiple repetitions of structural T1-weighted and functional blood-oxygen level-dependent (BOLD) MRI measurements from 51 subjects performing a finger-tapping task (FTT; á 2 min) repeatedly for 30–60 min. Estimated GMV was decreased in motor regions during FTT compared with rest. Motor-related BOLD signal changes did not overlap nor correlate with GMV changes. Nearly simultaneous BOLD signals cannot fully explain task-induced changes in T1-weighted images. These sensitive and behavior-related GMV changes pose serious questions to reproducibility across studies, and morphological investigations during skill learning can also open new avenues on how to study rapid brain plasticity.

  • 14. Olivo, Gaia
    et al.
    Nilsson, Jonna
    Garzon, Benjamin
    Lebedev, Alexander
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Tarassova, Olga
    Ekblom, Maria
    Lövdén, Martin
    Immediate effects of a single session of physical exercise on cognition and cerebral blood flow: A randomized controlled study of older adults2021In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 225, article id 117500Article in journal (Refereed)
    Abstract [en]

    Background: Regular physical activity is beneficial for cognitive performance in older age. A single bout of aerobic physical exercise can transiently improve cognitive performance. Researchers have advanced improvements in cerebral circulation as a mediator of long-term effects of aerobic physical exercise on cognition, but the immediate effects of exercise on cognition and cerebral perfusion are not well characterized and the effects in older adults are largely unknown.

    Methods: Forty-nine older adults were randomized to a 30-min aerobic exercise at moderate intensity or relaxation. Groups were matched on age and cardiovascular fitness (VO2 max). Average Grey Matter Blood Flow (GMBF), measured by a pulsed arterial-spin labeling (pASL) magnetic resonance imaging (MRI) acquisition, and working memory performance, measured by figurative n-back tasks with increasing loads were assessed before and 7 min after exercising/resting.

    Results: Accuracy on the n-back task increased from before to after exercising/resting regardless of the type of activity. GMBF decreased after exercise, relative to the control (resting) group. In the exercise group, higher n-back performance after exercise was associated with lower GMBF in the right hippocampus, left medial frontal cortex and right orbitofrontal cortex, and higher cardiovascular fitness was associated with lower GMBF.

    Conclusion: The decrease of GMBF reported in younger adults shortly after exercise also occurs in older adults and relates to cardiovascular fitness, potentially supporting the link between cardiovascular fitness and cerebrovascular reactivity in older age.

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  • 15.
    Olivo, Gaia
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Nilsson, Jonna
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). The Swedish School of Sport and Health Sciences, Sweden.
    Garzón, Benjamín
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). University of Gothenburg, Sweden.
    Lebedev, Alexander
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Karolinska Institutet, Sweden.
    Wåhlin, Anders
    Tarassova, Olga
    Ekblom, Maria
    Lövdén, Martin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). University of Gothenburg, Sweden.
    Immediate effects of a single session of physical exercise on cognition and cerebral blood flow: A randomized controlled study of older adults2021In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 225, article id 117500Article in journal (Refereed)
    Abstract [en]

    Background: Regular physical activity is beneficial for cognitive performance in older age. A single bout of aerobic physical exercise can transiently improve cognitive performance. Researchers have advanced improvements in cerebral circulation as a mediator of long-term effects of aerobic physical exercise on cognition, but the immediate effects of exercise on cognition and cerebral perfusion are not well characterized and the effects in older adults are largely unknown.

    Methods: Forty-nine older adults were randomized to a 30-min aerobic exercise at moderate intensity or relaxation. Groups were matched on age and cardiovascular fitness (VO2 max). Average Grey Matter Blood Flow (GMBF), measured by a pulsed arterial-spin labeling (pASL) magnetic resonance imaging (MRI) acquisition, and working memory performance, measured by figurative n-back tasks with increasing loads were assessed before and 7 min after exercising/resting.

    Results: Accuracy on the n-back task increased from before to after exercising/resting regardless of the type of activity. GMBF decreased after exercise, relative to the control (resting) group. In the exercise group, higher n-back performance after exercise was associated with lower GMBF in the right hippocampus, left medial frontal cortex and right orbitofrontal cortex, and higher cardiovascular fitness was associated with lower GMBF.

    Conclusion: The decrease of GMBF reported in younger adults shortly after exercise also occurs in older adults and relates to cardiovascular fitness, potentially supporting the link between cardiovascular fitness and cerebrovascular reactivity in older age.

  • 16.
    Olivo, Gaia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Solstrand Dahlberg, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Wiemerslage, Lyle
    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.
    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 CIR, Area Diagnost Imaging, Rome, Italy.
    Brooks, Samantha J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Atypical anorexia nervosa is not related to brain structural changes in newly diagnosed adolescent patients.2018In: International Journal of Eating Disorders, ISSN 0276-3478, E-ISSN 1098-108X, Vol. 51, no 1, p. 39-45Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Patients with atypical anorexia nervosa (AN) have many features overlapping with AN in terms of genetic risk, age of onset, psychopathology and prognosis of outcome, although the weight loss may not be a core factor. While brain structural alterations have been reported in AN, there are currently no data regarding atypical AN patients.

    METHOD: We investigated brain structure through a voxel-based morphometry analysis in 22 adolescent females newly-diagnosed with atypical AN, and 38 age- and sex-matched healthy controls (HC). ED-related psychopathology, impulsiveness and obsessive-compulsive traits were assessed with the Eating Disorder Examination Questionnaire (EDE-Q), Barratt Impulsiveness Scale (BIS-11) and Obsessive-compulsive Inventory Revised (OCI-R), respectively. Body mass index (BMI) was also calculated.

    RESULTS: Patients and HC differed significantly on BMI (p < .002), EDE-Q total score (p < .000) and OCI-R total score (p < .000). No differences could be detected in grey matter (GM) regional volume between groups.

    DISCUSSION: The ED-related cognitions in atypical AN patients would suggest that atypical AN and AN could be part of the same spectrum of restrictive-ED. However, contrary to previous reports in AN, our atypical AN patients did not show any GM volume reduction. The different degree of weight loss might play a role in determining such discrepancy. Alternatively, the preservation of GM volume might indeed differentiate atypical AN from AN.

  • 17.
    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.
    Saaid, Avista
    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.
    Brooks, Samantha J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. Univ Cape Town, Dept Human Biol, Cape Town, South Africa;Res Ctr Brain & Behav, Sch Nat Sci & Psychol, Liverpool, Merseyside, England.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Preserved white matter microstructure in adolescent patients with atypical anorexia nervosa2019In: International Journal of Eating Disorders, ISSN 0276-3478, E-ISSN 1098-108X, Vol. 52, no 2, p. 166-174Article in journal (Refereed)
    Abstract [en]

    Objective: Patients with atypical anorexia nervosa (AN) are often in the normal-weight range at presentation; however, signs of starvation and medical instability are not rare. White matter (WM) microstructural correlates of atypical AN have not yet been investigated, leaving an important gap in our knowledge regarding the neural pathogenesis of this disorder.

    Method: We investigated WM microstructural integrity in 25 drug-naive adolescent patients with atypical AN and 25 healthy controls, using diffusion tensor imaging (DTI) with a tract-based spatial statistics (TBSS) approach. Psychological variables related to the eating disorder and depressive symptoms were also evaluated by administering the eating disorder examination questionnaire (EDE-Q) and the Montgomery-angstrom sberg depression rating scale (MADRS-S) respectively, to all participants.

    Results: Patients and controls were in the normal-weight range and did not differ from the body mass index standard deviations for their age. No between groups difference in WM microstructure could be detected.

    Discussion: Our findings support the hypothesis that brain structural alterations may not be associated to early-stage atypical AN. These findings also suggest that previous observations of alterations in WM microstructure in full syndrome AN may constitute state-related consequences of severe weight loss. Whether the preservation of WM structure is a pathogenetically discriminant feature of atypical AN or only an effect of a less severe nutritional disturbance, will have to be verified by future studies on larger samples, possibly directly comparing AN and atypical AN.

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  • 18.
    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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  • 19.
    Olivo, Gaia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Wiemerslage, Lyle
    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.
    Zhukowsky, Christina
    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, Area Diagnost Imaging, CIR, Rome, Italy.
    Brooks, Samantha J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. Univ Cape Town, Deptartment Psychiat & Mental Hlth, Cape Town, South Africa.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Limbic-thalamo-cortical projections and reward-related circuitry integrity affects eating behavior: A longitudinal DTI study in adolescents with restrictive eating disorders2017In: PLOS ONE, E-ISSN 1932-6203, Vol. 12, no 3, article id e0172129Article in journal (Refereed)
    Abstract [en]

    Few studies have used diffusion tensor imaging (DTI) to investigate the micro-structural alterations of WM in patients with restrictive eating disorders (rED), and longitudinal data are lacking. Twelve patients with rED were scanned at diagnosis and after one year of family-based treatment, and compared to twenty-four healthy controls (HCs) through DTI analysis. A tract-based spatial statistics procedure was used to investigate diffusivity parameters: fractional anisotropy (FA) and mean, radial and axial diffusivities (MD, RD and AD, respectively). Reduced FA and increased RD were found in patients at baseline in the corpus callosum, corona radiata and posterior thalamic radiation compared with controls. However, no differences were found between follow-up patients and controls, suggesting a partial normalization of the diffusivity parameters. In patients, trends for a negative correlation were found between the baseline FA of the right anterior corona radiata and the Eating Disorder Examination Questionnaire total score, while a positive trend was found between the baseline FA in the splenium of corpus callosum and the weight loss occurred between maximal documented weight and time of admission. A positive trend for correlation was also found between baseline FA in the right anterior corona radiata and the decrease in the Obsessive-Compulsive Inventory Revised total score over time. Our results suggest that the integrity of the limbic-thalamo-cortical projections and the reward-related circuitry are important for cognitive control processes and reward responsiveness in regulating eating behavior.

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  • 20.
    Olivo, Gaia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Zhou, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Zhukovsky, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Hogenkamp, Pleunie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Nikontovic, Lamia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Stark, Julia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Wiemerslage, Lyle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Resting-state brain connectivity changes in obese women after Roux-en-Y gastric bypass surgery: A longitudinal study2017In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, no 1, article id 6616Article in journal (Refereed)
    Abstract [en]

    Bariatric surgery is an effective method to rapidly induce weight loss in severely obese people, however its impact on brain functional connectivity after longer periods of follow-up is yet to be assessed. We investigated changes in connectivity in 16 severely obese women one month before, one month after and one year after Roux-en-Y gastric bypass surgery (RYGB). 12 lean controls were also enrolled. Resting-state fMRI was acquired for all participants following an overnight fast and after a 260 kcal load. Connectivity between regions involved in food-related saliency attribution and reward-driven eating behavior was stronger in presurgery patients compared to controls, but progressively weakened after follow-up. At one year, changes in networks related to cognitive control over eating and bodily perception also occurred. Connectivity between regions involved in emotional control and social cognition had a temporary reduction early after treatment but had increased again after one year of follow-up. Furthermore, we could predict the BMI loss by presurgery connectivity in areas linked to emotional control and social interaction. RYGBP seems to reshape brain functional connectivity, early affecting cognitive control over eating, and these changes could be an important part of the therapeutic effect of bariatric surgery.

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  • 21.
    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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  • 22.
    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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  • 23.
    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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  • 24.
    Wiemerslage, Lyle
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Islam, R.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    van der Kamp, C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Cao, Hao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Olivo, Gaia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Ence-Eriksson, F
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Castillo, S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Larsen, A L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Bandstein, Marcus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Dahlberg, L S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Perland, E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Gustavsson, V
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Nilsson, J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Vogel, H
    Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
    Schürmann, A
    German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Rask-Andersen, Mathias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    A DNA methylation site within the KLF13 gene is associated with orexigenic processes based on neural responses and ghrelin levels2017In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 41, no 6, p. 990-994Article in journal (Refereed)
    Abstract [en]

    We investigated five methylation markers recently linked to body-mass index, for their role in the neuropathology of obesity. In neuroimaging experiments, our analysis involving 23 participants showed that methylation levels for the cg07814318 site, which lies within the KLF13 gene, correlated with brain activity in the claustrum, putamen, cingulate gyrus, and frontal gyri, some of which have been previously associated to food signaling, obesity, or reward. Methylation levels at cg07814318 also positively correlated with ghrelin levels. Moreover, expression of KLF13 was augmented in the brains of obese and starved mice. Our results suggest the cg07814318 site could be involved in orexigenic processes, and also implicate KLF13 in obesity. Our findings are the first to associate methylation levels in blood with brain activity in obesity-related regions, and further support previous findings between ghrelin, brain activity, and genetic differences.

  • 25.
    Wiemerslage, Lyle
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Zhou, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Olivo, Gaia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Stark, Julia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Hogenkamp, Pleunie S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    A resting-state fMRI study of obese females between pre- and postprandial states before and after bariatric surgery.2017In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 45, no 3, p. 333-341Article in journal (Refereed)
    Abstract [en]

    Past studies utilizing resting-state functional MRI (rsfMRI), have shown that obese humans exhibit altered activity in brain areas related to reward compared to normal-weight controls. However, to what extent bariatric surgery-induced weight loss alters resting-state brain activity in obese humans is less well-studied. Thus, we measured the fractional amplitude of low-frequency fluctuations (fALFF) from eyes-closed, rsfMRI in obese females (n = 11, mean age = 42 years, mean BMI = 41 kg/m(2) ) in both a pre- and post-prandial state at two time points: four weeks before, and four weeks after bariatric surgery. Several brain areas showed altered resting-state activity following bariatric surgery, including the putamen, insula, cingulate, thalamus, and frontal regions. Activity augmented by surgery was also dependent on prandial state. For example, in the fasted state, activity in the middle frontal, and pre- and postcentral gyri was found to be decreased after surgery. In the sated state, activity within the insula was increased before, but not after surgery. Collectively, our results suggest that resting-state neural functions are rapidly affected following bariatric surgery and the associated weight loss and change in diet. 

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