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  • 1. Bayard, Frida
    et al.
    Abé, Christoph
    Wrobel, Nathalie
    Ingvar, Martin
    Henje Blom, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Petrovic, Predrag
    Emotional Instability Relates to Ventral Striatum Activity During Reward Anticipation in Females2020In: Frontiers in Behavioral Neuroscience, E-ISSN 1662-5153, Vol. 14, article id 76Article in journal (Refereed)
    Abstract [en]

    Both non-emotional symptoms, such as inattention, and symptoms of emotional instability (EI) are partially co-varying and normally distributed in the general population. Attention Deficit Hyperactivity Disorder (ADHD), which is associated with both inattention and emotional instability, has been related to lower reward anticipation activation in the ventral striatum. However, it is not known whether non-emotional dysregulation, such as inattention, or EI-or both-are associated with this effect. We hypothesized that altered reward processing relates specifically to EI. To test this, 29 healthy participants were recruited to this functional MRI study (n= 15 females). Reward processing was studied using a modified version of the Monetary Incentive Delay (MID) task. Brown Attention-Deficit Disorder Scales questionnaire was used to assess EI and inattention symptoms on a trait level. We observed less ventral striatal activation during reward anticipation related to the EI trait in females, also when controlling for the inattention trait, but not in the whole sample or males only. Our study suggests the existence of sex differences in the relationship between reward processing and EI/inattention traits.

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  • 2.
    Blom, Eva Henje
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Psychiatry, Division of Child and Adolescent Psychiatry, UCSF Weill Institute for Neurosciences, University of California San Francisco (UCSF), San Francisco, CA, USA.
    Tymofiyeva, Olga
    Chesney, Margaret A.
    Ho, Tiffany C.
    Moran, Patricia
    Connolly, Colm G.
    Duncan, Larissa G.
    Baldini, Lisa
    Weng, Helen Y.
    Acree, Michael
    Goldman, Veronica
    Hecht, Frederick M.
    Yang, Tony T.
    Feasibility and Preliminary Efficacy of a Novel RDoC-Based Treatment Program for Adolescent Depression: "Training for Awareness Resilience and Action" (TARA)-A Pilot Study2017In: Frontiers in Psychiatry, E-ISSN 1664-0640, Vol. 7, article id 208Article in journal (Refereed)
    Abstract [en]

    Background: The novel group treatment program Training for Awareness, Resilience, and Action (TARA) was developed to target specific mechanisms based on neuroscience findings in adolescent depression and framed within the National Institute of Mental Health Research Domain Criteria. TARA contains training of autonomic and emotional self-regulation, interoceptive awareness, relational skills, and value-based committed action.

    Methods: We performed a single-arm trial to test the feasibility and preliminary efficacy of TARA in reducing depression and anxiety levels and assessed whether the specific targeted domains of function reflected the hypothesized symptom change. Twenty-six adolescents (14–18 years old, 7 males and 19 females) participated in the 12-week group program. Assessment was performed before (T0), immediately after (T1), and 3 months after the end of TARA (T2).

    Results: Significant improvement was seen in depression symptoms (Reynolds Adolescent Depression Scale Second Edition) between T0–T1 (t-value = −3.56, p = 0.002, CI = −6.64, −1.77) and T0–T2 (t-value = −4.17, p < 0.001, CI = −11.20, −3.75) and anxiety symptoms (Multidimensional Anxiety Scale for Children) between T0–T1 (t-value = −2.26, p = 0.033, CI = −4.61, −0.21) and T0–T2 (t-value = −3.06, p = 0.006, 95% confidence interval = −9.02, −1.73). Significant improvements in psychological flexibility, sleep, and mindfulness skills were also found between T0 and T2.

    Limitations: The sample size was small without a control condition. The pilot design did not allow for testing the hypothesized brain changes and effect of TARA on relevant systemic biomarkers.

    Conclusion: TARA is feasible in a sample of clinically depressed and/or anxious adolescents and preliminary efficacy was demonstrated by reduced depression and anxiety symptoms. The specific symptom and behavioral outcomes corresponded well with the hypothesized mechanisms of change.

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  • 3.
    Blomqvist, Ida
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Chaplin, John Eric
    Henje, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Dennhag, Inga
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Item response theory validation of the Swedish pediatric PROMIS item banks of anxiety and depressive symptoms in clinical and community samplesManuscript (preprint) (Other academic)
  • 4.
    Blomqvist, Ida
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Chaplin, John Eric
    Department of Pediatrics, Institute of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden.
    Nilsson, Evalill
    Department of Medicine and Optometry, Linnaeus University, Kalmar, Sweden.
    Henje Blom, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Dennhag, Inga
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Swedish translation and cross-cultural adaptation of eight pediatric item banks from the Patient-Reported Outcomes Measurement Information System (PROMIS)®2021In: Journal of Patient-Reported Outcomes, E-ISSN 2509-8020, Vol. 5, no 1, article id 80Article in journal (Refereed)
    Abstract [en]

    Background: This study is part of the Swedish initiative for the establishment of standardized, modern patient-reported measures for national use in Swedish healthcare. The goal was to translate and culturally adapt eight pediatric Patient-Reported Outcomes Measurement Information System (PROMIS®) item banks (anger, anxiety, depressive symptoms, family relationships, fatigue, pain interference, peer relationships and physical activity) into Swedish.

    Methods: Authorization to translate all currently available pediatric PROMIS item banks (autumn, 2016) into Swedish was obtained from the PROMIS Health Organization. The translation followed the Functional Assessment of Chronic Illness Therapy translation recommendations with one major modification, which was the use of a bilingual multi-professional review workshop. The following steps were applied: translation, reconciliation, a two-day multi professional reviewer workshop, back translation, and cognitive debriefing with eleven children (8–17 years) before final review. The bilingual multi-professional review workshop provided a simultaneous, in-depth assessment from different professionals. The group consisted of questionnaire design experts, researchers experienced in using patient-reported measures in healthcare, linguists, and pediatric healthcare professionals.

    Results: All item banks had translation issues that needed to be resolved. Twenty-four items (20.7%) needed resolution at the final review stage after cognitive debriefing. The issues with translations included 1. Lack of matching definitions with items across languages (6 items); 2. Problems related to language, vocabulary, and cultural differences (6 items); and 3. Difficulties in adaptation to age-appropriate language (12 items).

    Conclusions: The translated and adapted versions of the eight Swedish pediatric PROMIS item banks are linguistically acceptable. The next stage will be cross-cultural validation studies in Sweden. Despite the fact that there are cultural differences between Sweden and the United States, our translation processes have successfully managed to address all issues. Expert review groups from already-established networks and processes regarding pediatric healthcare throughout the country will facilitate the future implementation of pediatric PROMIS item banks in Sweden.

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  • 5.
    Blomqvist, Ida
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Ekbäck, Erik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Dennhag, Inga
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Henje, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Validation of the Swedish version of the Reynolds Adolescent Depression Scale second edition (RADS-2) in a normative sample2021In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 75, no 4, p. 292-300Article in journal (Refereed)
    Abstract [en]

    Background: Due to the sharp global increase in prevalence of adolescent major depressive disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders, we need internationally validated tools for multi-dimensional assessment. Reynolds Adolescent Depression Scale second edition (RADS-2) measures dysphoric mood, anhedonia/negative affect, negative self-evaluation and somatic complaints and is widely used internationally, but not yet available in Swedish.

    Aim: The aim of this study is to test the psychometric characteristics of the Swedish version of RADS-2 in a normative sample.

    Material and method: Data was gathered from junior and high school students in Northern Sweden (N = 637). We performed: 1. Confirmatory factor analysis to examine the 4-factor structure proposed by Reynolds, 2. Measurement invariance analysis for sex (girls, boys) and age group (12-15 years, 16-20 years). 3. Reliability testing and 4. Tests for concurrent, discriminant and convergent validity using Beck's Youth Inventories of Emotional and Social Impairment Depression and Anger subscales, the Patient Reported Outcome Measurements Information System, Anxiety and Friends subscales and the World Health Organization Wellness Index.

    Results: The sample consisted of n = 637 students (n = 389 girls and n = 248 boys), mean age 15.73 (SD = 1.76); 12-20 years. The 4-factor structure was confirmed, as well as measurement invariance for sex and age group. Reliability was acceptable to excellent for all subscales and RADS-2 total scale. Concurrent, convergent and discriminant validity was good.

    Conclusion: The Swedish version of RADS-2 showed acceptable reliability and validity in a Swedish normative sample.

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  • 6.
    Blomqvist, Ida
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Henje Blom, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Hägglöf, Bruno
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Hammarström, Anne
    Increase of internalized mental health symptoms among adolescents during the last three decades2019In: European Journal of Public Health, ISSN 1101-1262, E-ISSN 1464-360X, Vol. 29, no 5, p. 925-931Article in journal (Refereed)
    Abstract [en]

    Background: Previous studies suggest an overall increase of adolescent mental health symptoms globally since the 1980s until today, especially an increase of internalizing symptoms in girls. Due to methodological limitations of these studies, further studies are warranted to obtain a more solid knowledgebase.

    Methods: This study was cross-sectional and compared two separate but geographically identical groups of adolescents in a middle-sized industrial municipality in Northern Sweden at two time-points [(i) 1981, n = 1083, (505 girls, 577 boys), response rate 99.7%; (ii) 2014, n = 682, (338 girls, 344 boys), response rate 98.3%]. All students in their last year of compulsory school were included. The same self-report questionnaire, consisting of four sub-scales (functional somatic-, anxiety-, depressive symptoms and conduct problems), was used at both occasions. Data were analyzed with descriptive statistics, two-way ANOVA and general linear model.

    Results: Symptoms of anxiety and depression and functional somatic symptoms, increased among both boys and girls from 1981 until 2014 (P < 0.001 for all subscales), and the increase of these symptoms was higher in girls. Conduct problems were significantly higher in boys in 1981 and decreased over time so that in 2014 there was no longer a significant difference between boys and girls regarding conduct problems (P = 0.286).

    Conclusion: In this population-based study spanning over 30 years, both girls and boys showed increasing internalizing problems, while conduct problems decreased. To halt this trend, we need a deeper understanding of the impact of the major societal changes that have occurred during the last three decades.

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  • 7.
    Carlberg Rindestig, Frida
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Wiberg, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Chaplin, John Eric
    Henje Blom, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Dennhag, Inga
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Psychometrics of three Swedish physical pediatric item banks from the Patient-Reported Outcomes Measurement Information System (PROMIS)®: pain interference, fatigue, and physical activity2021In: Journal of Patient-Reported Outcomes, E-ISSN 2509-8020, Vol. 5, no 1, article id 105Article in journal (Refereed)
    Abstract [en]

    Background: The Patient-Reported Outcomes Measurement Information System (PROMIS®) aims to provide self-reported item banks for several dimensions of physical, mental and social health. Here we investigate the psychometric properties of the Swedish pediatric versions of the Physical Health item banks for pain interference, fatigue and physical activity which can be used in school health care and other clinical pediatric settings. Physical health has been shown to be more important for teenagers’ well-being than ever because of the link to several somatic and mental conditions. The item banks are not yet available in Sweden.

    Methods: 12- to 19-year-old participants (n = 681) were recruited in public school settings, and at a child- and psychiatric outpatient clinic. Three one-factor models using CFA were performed to evaluate scale dimensionality. We analyzed monotonicity and local independence. The items were calibrated by fitting the graded response model. Differential Item analyses (DIF) for age, gender and language were calculated.

    Results: As part of the three one-factor models, we found support that each item bank measures a unidimensional construct. No monotonicity or local dependence were found. We found that 11 items had significant lack of fit in the item response theory (IRT) analyses. The result also showed DIF for age (seven items) and language (nine items). However, the differences on item fits and effect sizes of McFadden were negligible. After considering the analytic results, graphical illustration, item content and clinical relevance we decided to keep all items in the item banks.

    Conclusions: We translated and validated the U.S. PROMIS item banks pain interference, fatigue and physical activity into Swedish by applying CFA, IRT and DIF analyses. The results suggest adequacy of the translations in terms of their psychometrics. The questionnaires can be used in school health and other pediatric care. Future studies can be to use Computerized Adaptive Testing (CAT), which provide fewer but reliable items to the test person compared to classical testing.

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  • 8. Chaplin, John
    et al.
    Nilsson, Evalill
    Blomqvist, Ida
    Stackelberg, Martin
    Ericsson, Mats
    Henje, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Wicksell, Rikard
    Blomberg, Karin
    Dennhag, Inga
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Translation and cross-cultural adaptation of ten pediatric PROMIS (R) item banks into Swedish2020In: Quality of Life Research, ISSN 0962-9343, E-ISSN 1573-2649, Vol. 29, p. S175-S176Article in journal (Other academic)
  • 9. Connolly, Colm G.
    et al.
    Ho, Tiffany C.
    Henje Blom, Eva
    Department of Psychiatry, Division of Child and Adolescent Psychiatry, and Weill Institute for Neurosciences, University of California, San Francisco, 401 Parnassus Avenue, San Francisco, CA, USA; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    LeWinn, Kaja Z.
    Sacchet, Matthew D.
    Tymofiyeva, Olga
    Simmons, Alan N.
    Yang, Tony T.
    Resting-state functional connectivity of the amygdala and longitudinal changes in depression severity in adolescent depression2017In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 207, p. 86-94Article in journal (Refereed)
    Abstract [en]

    Background: The incidence of major depressive disorder (MDD) rises during adolescence, yet the neural mechanisms of MDD during this key developmental period are unclear. Altered amygdala resting-state functional connectivity (RSFC) has been associated with both adolescent and adult MDD, as well as symptom improvement in response to treatment in adults. However, no study to date has examined whether amygdala RSFC is associated with changes in depressive symptom severity in adolescents.

    Method: We examined group differences in amygdala RSFC between medication-naïve depressed adolescents (N=48) and well-matched healthy controls (N=53) cross-sectionally. We then longitudinally examined whether baseline amygdala RSFC was associated with change in depression symptoms three months later in a subset of the MDD group (N=24).

    Results: Compared to healthy controls, depressed adolescents showed reduced amygdala-based RSFC with the dorsolateral prefrontal cortex (DLPFC)and the ventromedial prefrontal cortex (VMPFC). Within the depressed group, more positive baseline RSFC between the amygdala and insulae was associated with greater reduction in depression symptoms three months later.

    Limitations: Only a subset of depressed participants was assessed at follow-up and treatment type and delivery were not standardized.

    Conclusions: Adolescent depression may be characterized by dysfunction of frontolimbic circuits (amygdala-DLPFC, amygdala-VMPFC) underpinning emotional regulation, whereas those circuits (amygdala-insula) subserving affective integration may index changes in depression symptom severity and may therefore potentially serve as a candidate biomarker for treatment response. Furthermore, these results suggest that the biomarkers of MDD presence are distinct from those associated with change in depression symptoms over time.

  • 10.
    Dennhag, Inga
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Henje, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Nilsson, Karin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Parental caregiver burden and recovery of adolescent anorexia nervosa after multi-family therapy2021In: Eating Disorders, ISSN 1064-0266, E-ISSN 1532-530X, no 5, p. 463-479Article in journal (Refereed)
    Abstract [en]

    This study investigated whether parental caregiving burden changed during adjunct multi-family therapy of adolescent anorexia nervosa and eating disorders not otherwise specified (EDNOS) and whether caregiver burden at baseline and changes in caregiver burden during treatment were associated with treatment outcome.

    Twenty-four females, 13 to 16 years old, and their parents, participated in the study. Caregiver burden was measured with the Eating Disorders Symptom Impact Scale, by mothers (n = 23) and fathers (n = 22). Treatment outcome was measured by adolescent body mass index, level of global functioning and self-rated eating disorder symptoms by the Eating Disorders Examination Questionnaire 4.0.

    All patient outcomes improved and overall caregiver burden decreased significantly during treatment. When broken down in aspects of caregiver burden the decrease in parental perceived isolation, was found to be associated with improvement of BMI and Children's Global Assessment Scale. When analyzing fathers and mothers separately, we found that maternal feelings of guilt and paternal perceived burden of dysregulated behaviors at base-line were correlated to treatment outcome. Future studies are needed to clarify the role of caregiver burden as a potential mediator of treatment results.

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  • 11.
    Ekbäck, Erik
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Blomqvist, Ida
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Dennhag, Inga
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Henje Blom, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Psychometric properties of the Swedish version of the Reynolds Adolescent Depression Scale second edition (RADS-2) in a clinical sample2023In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 77, no 4, p. 383-392Article in journal (Refereed)
    Abstract [en]

    Objective: Observed and predicted increases in the global burden of disease caused by major depressive disorder (MDD) highlight the need for psychometrically robust multi-dimensional measures to use for clinical and research purposes. Reynolds Adolescent Depression Scale second edition (RADS-2) is an internationally well-validated scale measuring different dimensions of adolescent depression. The Swedish version has previously only been evaluated in a normative sample.

    Methods: We collected data from patients in child and adolescent psychiatry and primary care and performed: (1) Confirmatory factor analysis (CFA) to evaluate the established four-factor structure, (2) Analyses of reliability and measurement invariance, (3) Analyses of convergent and discriminant validity using the Montgomery–Asberg Depression Rating Scale, the depression subscales of the Beck Youth Inventories and the Revised Child Anxiety and Depression Scale, as well as the Patient Reported Outcome Measurements Information System, peer-relationships and physical activity item banks.

    Results: Recruited participants (n = 536, 129 male and 407 female, mean age 16.45 years, SD = 2.47, range 12 − 22 years) had a variety of psychiatric diagnoses. We found support for the four-factor structure and acceptable to good reliability for the subscale and total scores. Convergent and discriminant validity were good. Measurement invariance was demonstrated for age, sex, and between the present sample and a previously published normative sample. The RADS-2-scores were significantly higher in the present sample than in the normative sample. In this clinical study, the Swedish RADS-2 demonstrated good validity and acceptable to good reliability. Our findings support the use of RADS-2 in Swedish clinical and research contexts.

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  • 12.
    Ekbäck, Erik
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Granåsen, Gabriel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Svärling, Rachel
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Blomqvist, Ida
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Henje Blom, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Clinical Effectiveness of Training for Awareness Resilience and Action Online Compared to Standard Treatment for Adolescents and Young Adults With Depression: Study Protocol and Analysis Plan for a Pragmatic, Multi-Center Randomized Controlled Superiority Trial2021In: Frontiers in Psychiatry, E-ISSN 1664-0640, Vol. 12, article id 674583Article in journal (Refereed)
    Abstract [en]

    Depression in adolescents and young adults is an increasing global health concern. Available treatments are not sufficiently effective and relapse rates remain high. The novel group-treatment program “Training for Awareness, Resilience and Action” (TARA) targets specific mechanisms based on neuroscientific findings in adolescent depression. TARA is framed within the National Institute of Mental Health's Research Domain Criteria and has documented feasibility and preliminary efficacy in the treatment of adolescent depression. Since neurodevelopment continues well into the mid-twenties, age-adapted treatments are warranted also for young adults. Patients 15–22 years old, with either major depressive disorder (MDD) or persistent depressive disorder (PDD) according to the DSM-IV/5 or a rating >40 on the clinician rating scale Children's Depression Rating Scale—Revised (CDRS-R), will be recruited from specialized Child and Adolescent Psychiatry and local Youth-Clinics and randomized to either TARA or standard treatment, including but not limited to antidepressant medication and/or psychotherapy. Outcome measures will be obtained before randomization (T0), after 3 months of treatment (T1) and at 6-months- (T2) and 24-months- (T3) follow-up. Additionally, dose-response measures will be obtained weekly in the TARA-arm and measures for mediation-analysis will be obtained halfway through treatment (T0.5). Primary outcome measure is Reynolds Adolescent Depression Scale (RADS-2) score at T1. Secondary outcome measures include RADS-2 score at T2, Multidimensional Anxiety Scale for Children at T1 and T2, and CDRS-R at T1. Additional outcome measures include self-report measures of depression-associated symptoms, systemic bio-indicators of depression from blood and hair, heartrate variability, brain magnetic resonance imaging, as well as three-axial accelerometry for sleep-objectivization. Qualitative data will be gathered to reach a more comprehensive understanding of the factors affecting adolescents and young adults with depression and the extent to which the different treatments address these factors. In summary, this article describes the design, methods and statistical analysis plan for pragmatically evaluating the clinical effectiveness of TARA. This will be the first RCT to examine the effects of TARA compared to standard treatment for adolescents and young adults with MDD or PDD. We argue that this study will extend the current knowledgebase regarding the treatment of depression.

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  • 13.
    Ekbäck, Erik
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Rådmark, Lina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Granåsen, Gabriel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Svärling, Rachel
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Sörlin, Matilda
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Schönbeck, Caspar
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Henje Blom, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Clinical effectiveness of training for awareness, resilience, and action for adolescents and young adults with depression: the pilot phase of a multicenter randomized controlled trial2023In: Frontiers in Psychiatry, E-ISSN 1664-0640, Vol. 14, article id 1130035Article in journal (Refereed)
    Abstract [en]

    Background: Depression is a top-ranking global health concern increasing in magnitude. Available treatments for adolescents and young adults are not convincingly effective and relapse rates remain high. Training for Awareness, Resilience and Action (TARA) is a group treatment program targeting specific pathophysiological mechanisms of depression in young people. TARA is feasible, acceptable, preliminarily efficacious in depressed American adolescents, and it affects postulated brain-circuitry.

    Methods: As an initial step of a multicenter randomized controlled trial (RCT) we performed a single-arm multicenter pilot-study on TARA. Thirty-five depressed individuals (15–21 years old, 28 females) received TARA for 12 weeks face-to-face or online. Data was collected before (T0), during, and after the intervention (T1). The trial was pre-registered at clinicaltrials.gov, NCT Registration: identifier [NCT04747340]. Feasibility outcomes included recruitment, attendance rates, and session ratings. Adverse events were recorded weekly and extracted from medical records at the end of the trial. Primary effectiveness outcome was self-rated depression severity on Reynolds Adolescent Depression scale 2nd ed. at T1. Secondary outcomes were Children’s Depression Rating Scale-revised (CDRS-R) and Multidimensional Anxiety Scale for Children (MASC) at T1.

    Results: TARA was feasible and safe in the present trial. No significant RADS-2-change was seen (adjusted mean difference –3.26, 95 % CI –8.35 to 1.83; p= 0.20), however a significant decrease in CDRS-R scores is reported (adjusted mean difference –9.99, 95% CI –14.76 to –5.22; p < 0.001). MASC-scores did not change significantly (adjusted mean difference 1.98, 95% CI –0.96 to 4.91; p=0.18). Additional feasibility aspects are presented and discussed.

    Discussion: Limitations include substantial loss-to-follow-up, no randomization to control, and that some participants received concomitant treatment(s). The Coronavirus pandemic complicated both implementation and interpretation of the trial. In conclusion TARA was feasible and safe in depressed adolescents and young adults. Preliminary signs of effectiveness were seen. The initiated RCT will be important and worthwhile to conduct, and several improvements to the design are suggested based on the present results.

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  • 14.
    Ekbäck, Erik
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Rådmark, Lina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Molin, Jenny
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Strömbäck, Maria
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Midgley, Nick
    Department of Clinical, Educational and Health Psychology, University College London, London, United Kingdom.
    Henje, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    The Power Threat Meaning Framework: a qualitative study of depression in adolescents and young adults2024In: Frontiers in Psychiatry, E-ISSN 1664-0640, Vol. 15, article id 1393066Article, review/survey (Refereed)
    Abstract [en]

    Introduction: Depression constitutes one of our largest global health concerns and current treatment strategies lack convincing evidence of effectiveness in youth. We suggest that this is partly due to inherent limitations of the present diagnostic paradigm that may group fundamentally different conditions together without sufficient consideration of etiology, developmental aspects, or context. Alternatives that complement the diagnostic system are available yet understudied. The Power Threat and Meaning Framework (PTMF) is one option, developed for explanatory and practical purposes. While based on scientific evidence, empirical research on the framework itself is still lacking. This qualitative study was performed to explore the experiences of adolescents and young adults with depression from the perspective of the PTMF.

    Methods: We conducted semi-structured interviews with 11 Swedish individuals aged 15– 22 years, mainly female, currently enrolled in a clinical trial for major depressive disorder. Interviews were transcribed verbatim and analyzed with framework analysis informed by the PTMF.

    Results: A complex multitude of adversities preceding the onset of depression was described, with a rich variety of effects, interpretations, and reactions. In total, 17 themes were identified in the four dimensions of the PTMF, highlighting the explanatory power of the framework in this context. Not all participants were able to formulate coherent narratives.

    Discussion: The PTMF provides a framework for understanding the complexities, common themes, and lived experiences of young individuals with depression. This may be essential for the development of new interventions with increased precision and effectiveness in the young.

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  • 15.
    Ekbäck, Erik
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    von Knorring, Johanna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Professional Development.
    Löfgren Burström, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Hunhammar, David
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Dennhag, Inga
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Molin, Jenny
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Henje Blom, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Training for Awareness, Resilience and Action (TARA) for medical students: a single-arm mixed methods feasibility study to evaluate TARA as an indicated intervention to prevent mental disorders and stress-related symptoms2022In: BMC Medical Education, E-ISSN 1472-6920, Vol. 22, no 1, article id 132Article in journal (Refereed)
    Abstract [en]

    Background: Medical students have a higher risk for depression, anxiety, stress-related symptoms, burnout, and suicide, and more rarely seek professional help or treatment than the general population. Appeals are being made to address the mental health and resilience of physicians-to-be. The novel program Training for Awareness, Resilience, and Action (TARA) was originally developed to treat depressed adolescents, targeting specific neuroscientific findings in this population. TARA has shown feasibility and preliminary efficacy in clinically depressed adolescents and corresponding brain-changes in mixed community adolescent samples. The present study investigated the feasibility and acceptability of TARA as a potential indicated prevention program for symptoms of depression, anxiety, stress and burnout in Swedish medical students.

    Methods: We conducted a single-arm trial with 23 self-selected students in their early semesters of medical school (mean age 25.38 years, 5 males and 18 females), with or without mental disorders. All participants received TARA. Self-reported symptoms of depression, anxiety, perceived stress and psychological inflexibility were collected before (T0) and after the intervention (T1). Qualitative data on the participants’ experiences of TARA were collected in focus-group interviews conducted halfway through the program and upon completion of the program. Individual interviews were also conducted 2 years later. Qualitative content analysis was performed.

    Results: The mean attendance rate was 61.22% and the dropout rate was 17.40%. The Child Session Rating Scale administered after every session reflected an overall acceptable content, mean total score 34.99 out of 40.00. Trends towards improvement were seen across all outcome measures, including the Hospital Anxiety and Depression Scale Anxiety (t = 1.13, p = 0.29) and Depression (t = 1.71, p = 0.11) subscales, Perceived Stress Scale (t = 0.67, p = 0.51) and Avoidance and Fusion Questionnaire for youth (t = 1.64, p = 0.10). None of the participants deteriorated markedly during the intervention. Qualitative content analysis resulted in a main theme labeled: “An uncommon meeting-ground for personal empowerment”, with 4 themes; “Acknowledging unmet needs”, “Entering a free zone”, “Feeling connected to oneself and others” and “Expanding self-efficacy”.

    Conclusion: TARA is feasible and acceptable in a mixed sample of Swedish medical students. The students’ reports of entering an uncommon meeting-ground for personal empowerment supports effectiveness studies of TARA in this context.

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  • 16.
    Grudin, Rebecca
    et al.
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
    Ahlen, Johan
    Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden; Centre for Epidemiology and Community Medicine, Region Stockholm, Stockholm, Sweden.
    Mataix-Cols, David
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
    Lenhard, Fabian
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Henje, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Månsson, Cecilia
    Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
    Sahlin, Hanna
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
    Beckman, Maria
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
    Serlachius, Eva
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden.
    Vigerland, Sarah
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
    Therapist-guided and self-guided internet-delivered behavioural activation for adolescents with depression: a randomised feasibility trial2022In: BMJ Open, E-ISSN 2044-6055, Vol. 12, no 12, article id e066357Article in journal (Refereed)
    Abstract [en]

    Objective: Access to effective treatments for adolescents with depression needs to improve. Few studies have evaluated behavioural activation (BA) for adolescent depression, and none remotely delivered BA. This study explored the feasibility and acceptability of therapist-guided and self-guided internet-delivered BA (I-BA) in preparation for a future randomised controlled trial (RCT).

    Design: A single-blinded randomised controlled feasibility trial.

    Setting: A specialist outpatient clinic in Sweden.

    Participants: Thirty-two adolescents with mild-to-moderate major depression, aged 13-17 years.

    Interventions: Ten weeks of therapist-guided I-BA or self-guided I-BA, or treatment as usual (TAU). Both versions of I-BA included parental support. TAU included referral to usual care within child and youth psychiatry or primary care.

    Outcomes: Feasibility measures included study take-up, participant retention, acceptability, safety and satisfaction. The primary outcome measure was the blinded assessor-rated Children's Depression Rating Scale, Revised. The primary endpoint was the 3-month follow-up.

    Results: 154 adolescents were screened and 32 were randomised to therapist-guided I-BA (n=11), self-guided I-BA (n=10) or TAU (n=11). Participant retention was acceptable, with two drop-outs in TAU. Most participants in TAU had been offered interventions by the primary endpoint. The mean number of completed chapters (total of 8) for adolescents was 7.5 in therapist-guided I-BA and 5.4 in self-guided I-BA. No serious adverse events were recorded. Satisfaction was acceptable in both I-BA groups. Following an intent-to-treat approach, the linear mixed-effects model revealed that both therapist-guided and self-guided I-BA (Cohen's d=2.43 and 2.23, respectively), but not TAU (Cohen's d=0.95), showed statistically significant changes on the primary outcome measure with large within-group effect sizes.

    Conclusions: Both therapist-guided and self-guided I-BA are acceptable and potentially efficacious treatments for adolescents with depression. It is feasible to conduct a large-scale RCT to establish the efficacy and cost-effectiveness of I-BA versus TAU.

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  • 17.
    Henje Blom, Eva
    et al.
    Karolinska Institutet.
    Bech, Per
    Högberg, Göran
    Larsson, Jan Olov
    Serlachius, Eva
    Screening for depressed mood in an adolescent psychiatric context by brief self-assessment scales--testing psychometric validity of WHO-5 and BDI-6 indices by latent trait analyses.2012In: Health and Quality of Life Outcomes, E-ISSN 1477-7525, Vol. 10, article id 149Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Major depressive disorder is prevalent in the adolescent psychiatric clinical setting and often comorbid with other primary psychiatric diagnoses such as ADHD or social anxiety disorder. Systematic manual-based diagnostic procedures are recommended to identify such comorbidity but they are time-consuming and often not fully implemented in clinical practice. Screening for depressive symptoms in the child psychiatric context using brief, user-friendly and easily managed self-assessment scales may be of clinical value and utility. The aim of the study is to test the psychometric validity of two such scales, which may be used in a two-step screening procedure, the WHO-Five Well-being Index (WHO-5) and the six-item version of Beck's Depression Inventory (BDI-6).

    METHOD: 66 adolescent psychiatric patients with a clinical diagnosis of major depressive disorder (MDD), 60 girls and 6 boys, aged 14-18 years, mean age 16.8 years, completed the WHO-5 scale as well as the BDI-6. Statistical validity was tested by Mokken and Rasch analyses.

    RESULTS: The correlation between WHO-5 and BDI-6 was -0.49 (p=0.0001). Mokken analyses showed a coefficient of homogeneity for the WHO-5 of 0.52 and for the BDI-6 of 0.46. Rasch analysis also accepted unidimensionality when testing males versus females (p > 0.05).

    CONCLUSIONS: The WHO-5 is psychometrically valid in an adolescent psychiatric context including both genders to assess the wellness dimension and applicable as a first step in screening for MDD. The BDI-6 may be recommended as a second step in the screening procedure, since it is statistically valid and has the ability to unidimensionally capture the severity of depressed mood.

  • 18.
    Henje Blom, Eva
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Carlberg Rindestig, Frida
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Gilbert, Paul
    Dennhag, Inga
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Psychometric validity of the Compassionate Engagement and Action Scale for Adolescents: a Swedish version2020In: Scandinavian Journal of Child and Adolescent Psychiatry and Psychology, E-ISSN 2245-8875, Vol. 8, p. 70-80Article in journal (Refereed)
    Abstract [en]

    Background:There is increasing evidence that compassion is linked to mental health and well-being while difficulties in receiving and expressing compassion to self and others is associated with mental health and social difficulties. For the most part the self-report scales that measure these processes have been developed for adults and little is known how they function in adolescents. This study investigates a Swedish adaption for adolescents of the Compassionate Engagement and Action Scales (CEAS), developed by Gilbert et al. (2017) for adults. This assesses different competencies associated with being compassionate to others, the experience receiving compassion from others, and being compassionate with one-self.

    Objective:To evaluate the psychometric properties and gender differences of CEAS for Youths - Swedish version (CEASY-SE), in a school-sample of adolescents (n = 316) aged 15-20 years.

    Method:The Compassionate Engagement and Action Scales were translated into Swedish. A back-translation method was used. It was then adapted for adolescents with age-appropriate language. Adolescents were recruited by research assistants at two public high schools.

    Results:After removing one item of each subscale, the dimensionalities of the three scales were good. Confirmatory factor analysis showed that engagement and action constituted different dimensions in each scale. Internal consistency was good to excellent in all three sub-scales (α from 0.74 to 0.92). Intra Class Correlations demonstrated good to excellent test-retest reliability over a period of three weeks (0.67 to 0.85). Convergent and divergent validity were as expected, except for Compassion for others, which did not correlate with anxiety and depression symptoms as expected. Girls showed less self-compassion compared to boys and more compassion for others.

    Conclusions:Present study suggests that CEASY-SE has good to excellent psychometric properties and further study is needed for more definite establishment of the psychometric properties. Girls and boys have different patterns of compassion.

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  • 19.
    Henje Blom, Eva
    et al.
    Karolinska Institutet, University of California San Francsisco.
    Connolly, Colm G
    Ho, Tiffany C
    LeWinn, Kaja Z
    Mobayed, Nisreen
    Han, Laura
    Paulus, Martin P
    Wu, Jing
    Simmons, Alan N
    Yang, Tony T
    Altered insular activation and increased insular functional connectivity during sad and happy face processing in adolescent major depressive disorder.2015In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 178, p. 215-23, article id S0165-0327(15)00141-XArticle in journal (Refereed)
    Abstract [en]

    BACKGROUND: Major depressive disorder (MDD) is a leading cause of disability worldwide and occurs commonly first during adolescence. The insular cortex (IC) plays an important role in integrating emotion processing with interoception and has been implicated recently in the pathophysiology of adult and adolescent MDD. However, no studies have yet specifically examined the IC in adolescent MDD during processing of faces in the sad-happy continuum. Thus, the aim of the present study is to investigate the IC during sad and happy face processing in adolescents with MDD compared to healthy controls (HCL).

    METHODS: Thirty-one adolescents (22 female) with MDD and 36 (23 female) HCL underwent a well-validated emotional processing fMRI paradigm that included sad and happy face stimuli.

    RESULTS: The MDD group showed significantly less differential activation of the anterior/middle insular cortex (AMIC) in response to sad versus happy faces compared to the HCL group. AMIC also showed greater functional connectivity with right fusiform gyrus, left middle frontal gyrus, and right amygdala/parahippocampal gyrus in the MDD compared to HCL group. Moreover, differential activation to sad and happy faces in AMIC correlated negatively with depression severity within the MDD group.

    LIMITATIONS: Small age-range and cross-sectional nature precluded assessment of development of the AMIC in adolescent depression.

    CONCLUSIONS: Given the role of the IC in integrating bodily stimuli with conscious cognitive and emotional processes, our findings of aberrant AMIC function in adolescent MDD provide a neuroscientific rationale for targeting the AMIC in the development of new treatment modalities.

  • 20.
    Henje Blom, Eva
    et al.
    Karolinska Institutet, University of California San Francsisco.
    Duncan, Larissa G
    Ho, Tiffany C
    Connolly, Colm G
    LeWinn, Kaja Z
    Chesney, Margaret
    Hecht, Frederick M
    Yang, Tony T
    The development of an RDoC-based treatment program for adolescent depression: "Training for Awareness, Resilience, and Action" (TARA).2014In: Frontiers in human neuroscience, Vol. 8, article id 630Article in journal (Refereed)
    Abstract [en]

    Major depressive disorder (MDD) is one of the current leading causes of disability worldwide. Adolescence is a vulnerable period for the onset of depression, with MDD affecting 8-20% of all youth. Traditional treatment methods have not been sufficiently effective to slow the increasing prevalence of adolescent depression. We therefore propose a new model for the treatment of adolescent depression - Training for Awareness, Resilience, and Action (TARA) - that is based on current understanding of developmental and depression neurobiology. The TARA model is aligned with the Research Domain Criteria (RDoC) of the National Institute of Mental Health. In this article, we first address the relevance of RDoC to adolescent depression. Second, we identify the major RDoC domains of function involved in adolescent depression and organize them in a way that gives priority to domains thought to be driving the psychopathology. Third, we select therapeutic training strategies for TARA based on current scientific evidence of efficacy for the prioritized domains of function in a manner that maximizes time, resources, and feasibility. The TARA model takes into consideration the developmental limitation in top-down cognitive control in adolescence and promotes bottom-up strategies such as vagal afference to decrease limbic hyperactivation and its secondary effects. The program has been informed by mindfulness-based therapy and yoga, as well as modern psychotherapeutic techniques. The treatment program is semi-manualized, progressive, and applied in a module-based approach designed for a group setting that is to be conducted one session per week for 12 weeks. We hope that this work may form the basis for a novel and more effective treatment strategy for adolescent depression, as well as broaden the discussion on how to address this challenge.

  • 21.
    Henje Blom, Eva
    et al.
    Karolinska Institutet, University of California San Francsisco.
    Forsman, Mats
    Yang, Tony T
    Serlachius, Eva
    Larsson, Jan-Olov
    Latent Classes of Symptoms related to Clinically Depressed Mood in Adolescents.2014In: Scandinavian journal of child and adolescent psychiatry and psychology, Vol. 2, no 1, p. 19-28Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The diagnosis of major depressive disorder (MDD), according to the Diagnostic and Statistical Manual of Mental Disorders, is based only on adult symptomatology of depression and not adapted for age and gender. This may contribute to the low diagnostic specificity and validity of adolescent MDD. In this study, we investigated whether latent classes based on symptoms associated with depressed mood could be identified in a sample of adolescents seeking psychiatric care, regardless of traditionally defined diagnostic categories.

    METHODS: Self-reports of the Strengths and Difficulties Questionnaire and the Development and Well-Being Assessment were collected consecutively from all new patients between the ages of 13 and 17 years at two psychiatric outpatient clinics in Stockholm, Sweden. Those who reported depressed mood at intake yielded a sample of 21 boys and 156 girls. Latent class analyses were performed for all screening items and for the depression-specific items of the Development and Well-Being Assessment.

    RESULTS: The symptoms that were reported in association with depressed mood differentiated the adolescents into two classes. One class had moderate emotional severity scores on the Strengths and Difficulties Questionnaire and mainly symptoms that were congruent with the Diagnostic and Statistical Manual of Mental Disorders criteria for MDD. The other class had higher emotional severity scores and similar symptoms to those reported in the first class. However, in addition, this group demonstrated more diverse symptomatology, including vegetative symptoms, suicidal ideation, anxiety, conduct problems, body dysmorphic symptoms, and deliberate vomiting. The classes predicted functional impairment in that the members of the second class showed more functional impairment.

    LIMITATIONS: The relatively small sample size limited the generalizability of the results of this study, and the amount of items included in the analysis was restricted by the rules of latent class analysis. No conclusions about gender differences between the classes could be could be drawn as a result of the low number of boys included in the study.

    CONCLUSIONS: Two distinct classes were identified among adolescents with depressed mood. The class with highest emotional symptom severity score and the most functional impairment had a more diverse symptomatology that included symptoms that were not congruent with the traditional diagnostic criteria of MDD. However, this additional symptomatology is clinically important to consider. As a result, the clinical usefulness of the Diagnostic and Statistical Manual of Mental Disorders during the diagnostic process of adolescent depression is questioned.

  • 22.
    Henje Blom, Eva
    et al.
    Karolinska Institutet, University of California San Francsisco.
    Han, L K M
    Connolly, C G
    Ho, T C
    Lin, J
    LeWinn, K Z
    Simmons, A N
    Sacchet, M D
    Mobayed, N
    Luna, M E
    Paulus, M
    Epel, E S
    Blackburn, E H
    Wolkowitz, O M
    Yang, T T
    Peripheral telomere length and hippocampal volume in adolescents with major depressive disorder.2015In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 5, article id e676Article in journal (Refereed)
    Abstract [en]

    Several studies have reported that adults with major depressive disorder have shorter telomere length and reduced hippocampal volumes. Moreover, studies of adult populations without major depressive disorder suggest a relationship between peripheral telomere length and hippocampal volume. However, the relationship of these findings in adolescents with major depressive disorder has yet to be explored. We examined whether adolescent major depressive disorder is associated with altered peripheral telomere length and hippocampal volume, and whether these measures relate to one another. In 54 unmedicated adolescents (13-18 years) with major depressive disorder and 63 well-matched healthy controls, telomere length was assessed from saliva using quantitative polymerase chain reaction methods, and bilateral hippocampal volumes were measured with magnetic resonance imaging. After adjusting for age and sex (and total brain volume in the hippocampal analysis), adolescents with major depressive disorder exhibited significantly shorter telomere length and significantly smaller right, but not left hippocampal volume. When corrected for age, sex, diagnostic group and total brain volume, telomere length was not significantly associated with left or right hippocampal volume, suggesting that these cellular and neural processes may be mechanistically distinct during adolescence. Our findings suggest that shortening of telomere length and reduction of hippocampal volume are already present in early-onset major depressive disorder and thus unlikely to be only a result of accumulated years of exposure to major depressive disorder.

  • 23.
    Henje Blom, Eva
    et al.
    Karolinska Institutet, University of California San Francsisco.
    Ho, Tiffany C.
    Connolly, Colm G.
    LeWinn, Kaja Z.
    Sacchet, Matthew D.
    Tymofiyeva, Olga
    Weng, Helen Y.
    Yang, Tony T.
    The neuroscience and context of adolescent depression2016In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 105, no 4, p. 358-365Article, review/survey (Refereed)
    Abstract [en]

    Adolescent depression is a growing public health concern with an increased risk of negative health outcomes, including suicide. The use of antidepressants and psychotherapy has not halted its increasing prevalence, and there is a critical need for effective prevention and treatment. We reviewed the neuroscience of adolescent depression, with a focus on the neurocircuitry of sustained threat and summarised contextual factors that have an impact on brain development and the pathophysiology of depression. We also reviewed novel treatment models.

    Conclusion: Attention to the relevant neurocircuitry and contextual factors implicated in adolescent depression is necessary to advance prevention and treatment development.

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  • 24.
    Henje Blom, Eva
    et al.
    Karolinska Institutet, University of California San Francsisco.
    Larsson, Jan-Olov
    Serlachius, Eva
    Ingvar, Martin
    The differentiation between depressive and anxious adolescent females and controls by behavioural self-rating scales2010In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 122, no 3, p. 232-240Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: This study aimed to validate the ability of frequently used self-assessment scales in Swedish child and adolescent psychiatric practice to differentiate between adolescent girls with manifest anxiety disorders and depression from those with less severe symptoms.

    METHODS: The receiver-operating characteristic (ROC) curve was calculated for Beck's Depression Inventory (BDI), Beck's Anxiety Inventory (BAI), Hospital Anxiety and Depression Scale (HAD), the emotional subscale (SDQ-em), the impact score and the total difficulties score of the Strengths and Difficulties Questionnaire and Sense of Coherence (SOC) in a sample of 73 adolescent, female patients, diagnosed with one or several anxiety disorders and/or depression. ROC was also calculated for 66 age-matched controls.

    RESULTS: SOC and the SDQ-em showed the best ability to differentiate cases of anxiety disorders and/ or depression from non-cases. SOC and SDQ-em had an equivalent ability to differentiate depression from non-cases compared to the specialised scales for depression, BDI and HAD-dep. SOC and SDQ-em were significantly better in differentiating cases of anxiety from non-cases than the specialised scales BAI and HAD-anx. Selection bias and several forms to fill in can have influenced the result.

    CONCLUSIONS: SOC and SDQ-em seemed to be valid tools for identifying girls with anxiety disorders and depression. This is of clinical importance since self-reported symptoms of anxiety and depression show a major increase in adolescent girls and methods to identify those in need of treatment are needed.

  • 25.
    Henje Blom, Eva
    et al.
    Karolinska Institutet, University of California San Francsisco.
    Lekander, Mats
    Ingvar, Martin
    Åsberg, Marie
    Mobarrez, Fariborz
    Serlachius, Eva
    Pro-inflammatory cytokines are elevated in adolescent females with emotional disorders not treated with SSRIs.2012In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 136, no 3, p. 716-23Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Adults with major depressive disorder (MDD) show elevated levels of IL-6 and TNF-alpha. Studies of adolescents with MDD or anxiety disorders (AD) are few and present conflicting results.

    METHODS: We studied plasma cytokines in a clinical sample of adolescent females with MDD and/or clinical AD (n=60, mean age 16.8 years), compared to healthy controls (n=44; mean age 16.5 years).

    RESULTS: The clinical sample showed significantly higher values of IL-2 (Z=-4.09, p>0.0001), IL1-beta (Z=-2.40, p<0.05) and IL-10 (Z=-2.38, p<0.05) as compared to controls. The subgroup of the clinical sample not treated with SSRIs had a significant difference of IL-6 (Z=-2.26, p<0.05) in addition to the difference of IL-2 and IL1-beta, but showed no difference of IL-10 as compared to the controls. SSRI treatment was related to IL-6, explaining 26% of the variance in the clinical sample after controlling for BMI and symptom severity. In the clinical sample, levels of IL-6 and IFN-gamma were positively correlated with self-assessed symptoms of anxiety and/or depression (corr.coeff 0.35 resp 0.40 at p<0.05).

    LIMITATIONS: The cross-sectional design does not allow for conclusions on causality. The sample sizes were relatively small and a large drop-out in the clinical sample may have influenced the representativity.

    DISCUSSION: The study suggests that pro-inflammatory cytokines are part of the pathophysiology of emotional disorders in adolescent females and that SSRIs have anti-inflammatory properties. The findings prompt further studies on the specific mechanisms involved and may contribute to the development of more effective treatment and prevention.

  • 26.
    Henje Blom, Eva
    et al.
    Karolinska Institutet, University of California San Francsisco.
    Olsson, E M
    Serlachius, E
    Ericson, M
    Ingvar, M
    Heart rate variability (HRV) in adolescent females with anxiety disorders and major depressive disorder.2010In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 99, no 4, p. 604-11Article in journal (Refereed)
    Abstract [en]

    AIM: The aim of this study was to investigate heart rate variability (HRV) in a clinical sample of female adolescents with anxiety disorders (AD) and/or major depressive disorder (MDD) compared with healthy controls and to assess the effect of selective serotonin reuptake inhibitors (SSRI) on HRV.

    METHODS: Heart rate variability was measured in adolescent female psychiatric patients with AD and/or MDD (n = 69), mean age 16.8 years (range: 14.5-18.4), from 13 out-patient clinics and in healthy controls (n = 65), mean age 16.5 years (range: 15.9-17.7). HRV was registered in the sitting position during 4 min with no interventions.

    RESULTS: Logarithmically transformed high frequency HRV (HF), low frequency HRV (LF) and standard deviation of inter beat intervals (SDNN) were lower in the clinical sample compared with the controls (Cohen's d for HF = 0.57, LF = 0.55, SDNN = 0.60). This was not explained by body mass index, blood pressure or physical activity. Medication with SSRI explained 15.5% of the total variance of HF, 3.0% of LF and 6.5% of SDNN.

    CONCLUSIONS: Adolescent female psychiatric patients with AD and/or MDD show reduced HRV compared with healthy controls. Medication with SSRI explained a part of this difference.

  • 27.
    Henje Blom, Eva
    et al.
    Department of Clinical Neuroscience, Osher Center for Integrative Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden.
    Olsson, Erik M G
    Serlachius, Eva
    Ericson, Mats
    Ingvar, Martin
    Heart rate variability is related to self-reported physical activity in a healthy adolescent population2009In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 106, no 6, p. 877-883Article in journal (Refereed)
    Abstract [en]

    This study investigated whether there is a relationship between heart rate variability (HRV) versus lifestyle and risk factors for cardiovascular disease in a population of healthy adolescents. HRV is as an index of tonic autonomic activity and in adults HRV is related to lifestyle and risk factors for cardiovascular disease, but it is not known if this is the case in adolescents. HRV was registered for 4 min in sitting position in 99 healthy adolescents (age range 15 years 11 months-17 years 7 months) and repeated after 6 months. On both occasions there were significant correlations (P < 0.05) between physical activity and HRV, with respective r values: high frequency (HF) 0.26, 0.30; low frequency power (LF) 0.35, 0.29 and the standard deviation of inter-beat intervals (SDNN) 0.28, 0.37. There was no significant interaction between first and second measurements. In contrast, there were no correlations to sleeping patterns, eating habits and smoking. Risk factors for cardiovascular disease [body mass index (BMI = weight (kg)/length in m(2)), systolic blood pressure and p-glucose] did not show any repeatable significant correlations to HRV. Multiple regression models showed that physical activity was a predictor for HF, LF and SDNN in both measurements. In conclusion HF, LF and SDNN were reproducible after 6 months and were related to physical activity on both occasions.

  • 28.
    Henje Blom, Eva
    et al.
    Karolinska Institutet.
    Serlachius, Eva
    Chesney, Margaret A
    Olsson, Erik M G
    Adolescent girls with emotional disorders have a lower end-tidal CO2 and increased respiratory rate compared with healthy controls.2014In: Psychophysiology, ISSN 1540-5958, Vol. 51, no 5, p. 412-8Article in journal (Refereed)
    Abstract [en]

    Hyperventilation has been linked to emotional distress in adults. This study investigates end-tidal carbon dioxide (ETCO2 ), respiratory rate (RR), and heart rate variability (HRV) in adolescent girls with emotional disorders and healthy controls. ETCO2 , RR, HRV, and ratings of emotional symptom severity were collected in adolescent female psychiatric patients with emotional disorders (n = 63) and healthy controls (n = 62). ETCO2 and RR differed significantly between patients and controls. ETCO2, HR, and HRV were significant independent predictors of group status, that is, clinical or healthy, while RR was not. ETCO2 and RR were significantly related to emotional symptom severity and to HRV in the total group. ETCO2 and RR were not affected by use of selective serotonin reuptake inhibitors. It is concluded that emotional dysregulation is related to hyperventilation in adolescent girls. Respiratory-based treatments may be relevant to investigate in future research.

  • 29.
    Henje Blom, Eva
    et al.
    Karolinska Institutet, University of California San Francsisco.
    Serlachius, Eva
    Larsson, Jan-Olov
    Theorell, Töres
    Ingvar, Martin
    Low Sense of Coherence (SOC) is a mirror of general anxiety and persistent depressive symptoms in adolescent girls - a cross-sectional study of a clinical and a non-clinical cohort.2010In: Health and Quality of Life Outcomes, E-ISSN 1477-7525, Vol. 8, article id 58Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Sense of Coherence (SOC) scale is assumed to measure a distinct salutogenic construct separated from measures of anxiety and depression. Our aim was to challenge this concept.

    METHODS: The SOC-scale, Beck's Depression Inventory (BDI), Beck's Anxiety Inventory (BAI) , the emotional subscale of the Strengths and Difficulties Questionnaire (SDQ-em) and self-assessed health-related and physiological parameters were collected from a sample of non-clinical adolescent females (n = 66, mean age 16.5 years with a range of 15.9-17.7 years) and from female psychiatric patients (n = 73), mean age 16.8 years with a range of 14.5-18.4 years), with diagnoses of major depressive disorders (MDD) and anxiety disorders.

    RESULTS: The SOC scores showed high inverse correlations to BDI, BAI and SDQ-em. In the non-clinical sample the correlation coefficient was -0.86 to -0.73 and in the clinical samples -0.74 to -0.53 (p < 0.001). Multiple regression models showed that BDI was the strongest predictor of SOC in the non-clinical (beta coefficient -0.47) and clinical sample (beta coefficient -0.52). The total degree of explanation of self assessed anxiety and depression on the SOC variance estimated by multiple R2 = 0.74, adjusted R2 = 0.73 in the non-clinical sample and multiple R2 = 0.66, adjusted R2 = 0.65 in the clinical sample.Multivariate analyses failed to isolate SOC as a separate construct and the SOC-scale, BDI, BAI and SDQ-em showed similar patterns of correlations to self-reported and physiological health parameters in both samples. The SOC-scale was the most stable measure over six months.

    CONCLUSIONS: The SOC-scale did not appear to be a measure of a distinct salutogenic construct, but an inverse measure of persistent depressive symptoms and generalized social anxiety similar to the diagnostic criteria for major depressive disorder (MDD), dysthymic disorder, generalized anxiety disorder (GAD) or generalized social anxiety disorder (SAD) according to DSM-IV. These symptoms were better captured with SOC than by the specialized scales for anxiety and depression. Self-assessment scales that adequately identify MDD, dysthymic disorder, GAD and SAD need to be implemented. Comorbidity of these disorders is common in adolescent females and corresponds to a more severe symptomatology and impaired global function.

  • 30.
    Henje Blom, Eva
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Wiberg, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Dennhag, Inga
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Translation and validation of the Swedish version of the self-compassion scale for youth2024In: Australian psychologist, ISSN 0005-0067, E-ISSN 1742-9544, Vol. 59, no 1, p. 24-35Article in journal (Refereed)
    Abstract [en]

    Objective: Compassion-focused interventions for young people have started to emerge to treat depressive symptoms, and reliable and valid measures of the construct “self-compassion” is needed for this age-group in Swedish. This study aims to validate the Swedish translation of the Self-Compassion Scale for Youth (SCS-Y).

    Method: Self-report questionnaires were collected from students (N = 316) aged 15–20 recruited from schools in Sweden, in a cross-sectional design. Confirmatory factor analyses, internal consistency, test-retest reliability, measurement invariance and convergent and divergent validity were calculated.

    Results: A model with one general bi-factor and six specific factors had the best fit and confirmed the factor structure of SCS-Y. Internal consistencies were good, except for the subscale mindfulness for boys which was questionable. Three-week test-retest reliability was good. We found measurement invariance for age and no equivalence for sex. Evidence was found for convergent and divergent validity using correlations. Sex differences were found: girls scored higher on self-judgement, feelings of isolation and showed more over-identification, than boys.

    Conclusions: The Swedish version of SCS-Y (SCS-Y-SE) is a reliable and valid self-report questionnaire, with some limitations, to assess self-compassion in clinical practice and research.

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  • 31. Ho, Tiffany C
    et al.
    Connolly, Colm G
    Henje Blom, Eva
    Karolinska Institutet, University of California San Francsisco.
    LeWinn, Kaja Z
    Strigo, Irina A
    Paulus, Martin P
    Frank, Guido
    Max, Jeffrey E
    Wu, Jing
    Chan, Melanie
    Tapert, Susan F
    Simmons, Alan N
    Yang, Tony T
    Emotion-Dependent Functional Connectivity of the Default Mode Network in Adolescent Depression.2015In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 78, no 9, p. 635-46, article id S0006-3223(14)00697-0Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Functional magnetic resonance imaging research suggests that major depressive disorder (MDD) in both adults and adolescents is marked by aberrant connectivity of the default mode network (DMN) during resting state. However, emotional dysregulation is also a key feature of MDD. No studies to date have examined emotion-related DMN pathology in adolescent depression. Comprehensively understanding the dynamics of DMN connectivity across brain states in individuals with depression with short disease histories could provide insight into the etiology of MDD.

    METHODS: We collected functional magnetic resonance imaging data during an emotion identification task and during resting state from 26 medication-free adolescents (13-17 years old) with MDD and 37 well-matched healthy control subjects. We examined between-group differences in blood oxygenation level-dependent task responses and emotion-dependent and resting-state functional connectivity of the two primary nodes of the DMN: medial prefrontal cortex and posterior cingulate cortex (PCC). Additionally, we examined between-group differences in DMN functional connectivity and its relationship to depression severity and onset.

    RESULTS: Relative to healthy control subjects, unmedicated adolescents with MDD demonstrated reduced medial prefrontal cortex and PCC emotion-related deactivation and greater medial prefrontal cortex and PCC emotion-dependent functional connectivity with precuneus, cingulate gyrus, and striatum/subcallosal cingulate gyrus. The PCC-subcallosal cingulate connectivity remained inflexibly elevated in the subjects with MDD versus healthy control subjects during resting state. Stronger PCC emotion-dependent functional connectivity was associated with greater depression severity and an earlier age of depression onset.

    CONCLUSIONS: Adolescent depression is associated with inflexibly elevated DMN connections. Given more recent evidence of DMN maturation throughout adolescence, our findings suggest that early-onset depression adversely affects normal development of functional brain networks.

  • 32. Ho, Tiffany C
    et al.
    Yang, Guang
    Wu, Jing
    Cassey, Pete
    Brown, Scott D
    Hoang, Napoleon
    Chan, Melanie
    Connolly, Colm G
    Henje Blom, Eva
    Karolinska Institutet, University of California San Francsisco.
    Duncan, Larissa G
    Chesney, Margaret A
    Paulus, Martin P
    Max, Jeffrey E
    Patel, Ronak
    Simmons, Alan N
    Yang, Tony T
    Functional connectivity of negative emotional processing in adolescent depression.2014In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 155, p. 65-74, article id S0165-0327(13)00767-2Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The subgenual anterior cingulate cortex (sgACC) and its connected circuitry have been heavily implicated in emotional functioning in adolescent-onset major depressive disorder (MDD). While several recent studies have examined sgACC functional connectivity (FC) in depressed youth at rest, no studies to date have investigated sgACC FC in adolescent depression during negative emotional processing.

    METHODS: Nineteen medication-naïve adolescents with MDD and 19 matched healthy controls (HCL) performed an implicit fear facial affect recognition task during functional magnetic resonance imaging (fMRI). We defined seeds in bilateral sgACC and assessed FC using the psychophysiological interaction method. We also applied cognitive behavioral modeling to estimate group differences in perceptual sensitivity in this task. Finally, we correlated connectivity strength with clinical data and perceptual sensitivity.

    RESULTS: Depressed adolescents showed increased sgACC-amygdala FC and decreased sgACC-fusiform gyrus, sgACC-precuneus, sgACC-insula, and sgACC-middle frontal gyrus FC compared to HCL (p<0.05, corrected). Among the MDD, sgACC-precuneus FC negatively correlated with depression severity (p<0.05, corrected). Lastly, MDD adolescents exhibited poorer perceptual sensitivity in the task than HCL, and individual differences in perceptual sensitivity significantly correlated with sgACC FC and depression scores (p<0.05, corrected).

    LIMITATIONS: Subjects were clinically homogenous, possibly limiting generalizability of the findings.

    CONCLUSIONS: Adolescent depression is associated with biased processing of negative stimuli that may be driven by sgACC dysregulation and may possibly lead to an imbalance among intrinsic functional brain networks. This work also establishes the use of combining neuroimaging and cognitive behavioral modeling methods to investigate cognitive and neural differences between psychiatric and healthy populations.

  • 33. Ho, Tiffany C.
    et al.
    Zhang, Shunan
    Sacchet, Matthew D.
    Weng, Helen
    Connolly, Colm G.
    Henje Blom, Eva
    Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA; Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Han, Laura K. M.
    Mobayed, Nisreen O.
    Yang, Tony T.
    Fusiform gyrus dysfunction is associated with perceptual processing efficiency to emotional faces in adolescent depression: a model-based approach2016In: Frontiers in Psychology, E-ISSN 1664-1078, Vol. 7, article id 40Article in journal (Refereed)
    Abstract [en]

    While the extant literature has focused on major depressive disorder (MDD) as being characterized by abnormalities in processing affective stimuli (e.g., facial expressions), little is known regarding which specific aspects of cognition influence the evaluation of affective stimuli, and what are the underlying neural correlates. To investigate these issues, we assessed 26 adolescents diagnosed with MDD and 37 well-matched healthy controls (HCL) who completed an emotion identification task of dynamically morphing faces during functional magnetic resonance imaging (fMRI). We analyzed the behavioral data using a sequential sampling model of response time (RT) commonly used to elucidate aspects of cognition in binary perceptual decision making tasks: the Linear Ballistic Accumulator (LBA) model. Using a hierarchical Bayesian estimation method, we obtained group-level and individual-level estimates of LBA parameters on the facial emotion identification task. While the MDD and HCL groups did not differ in mean RT, accuracy, or group-level estimates of perceptual processing efficiency (i.e., drift rate parameter of the LBA), the MDD group showed significantly reduced responses in left fusiform gyrus compared to the HCL group during the facial emotion identification task. Furthermore, within the MDD group, fMRI signal in the left fusiform gyrus during affective face processing was significantly associated with greater individual-level estimates of perceptual processing efficiency. Our results therefore suggest that affective processing biases in adolescents with MDD are characterized by greater perceptual processing efficiency of affective visual information in sensory brain regions responsible for the early processing of visual information. The theoretical, methodological, and clinical implications of our results are discussed.

  • 34. LeWinn, Kaja Z.
    et al.
    Strigo, Irina A.
    Connolly, Colm G.
    Ho, Tiffany C.
    Tymofiyeva, Olga
    Sacchet, Matthew D.
    Weng, Helen Y.
    Henje Blom, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Simmons, Alan N.
    Yang, Tony T.
    An exploratory examination of reappraisal success in depressed adolescents: Preliminary evidence of functional differences in cognitive control brain regions2018In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 240, p. 155-164Article in journal (Refereed)
    Abstract [en]

    Background: Most neuroimaging studies of adolescent depression employ tasks not designed to engage brain regions necessary for the cognitive control of emotion, which is central to many behavioral therapies for depression. Depressed adults demonstrate less effective activation of these regions and greater amygdala activation during cognitive reappraisal; we examined whether depressed adolescents show similar patterns of brain activation.

    Methods: We collected functional magnetic resonance imaging (fMRI) data during cognitive reappraisal in 41 adolescents with major depressive disorder (MDD) and 34 matched controls (ages 13-17). We examined group differences in (1) activations associated with reappraisal and reappraisal success (i.e., negative affect reduction during reappraisal) using whole brain and amygdala region-of-interest analyses, and (2) functional connectivity of regions from the group-by-reappraisal success interaction.

    Results: We found no significant group differences in whole brain or amygdala analyses during reappraisal. In the group-by-reappraisal success interaction, activations in the left dorsomedial prefrontal cortex (dmPFC) and left dorsolateral PFC (dlPFC) were associated with reappraisal success in healthy controls but not depressed adolescents. Depressed adolescents demonstrated reduced connectivity between the left dmPFC and the anterior insula/inferior frontal gyri bilaterally (AI/IFG) and between left dlPFC and left AI/IFG.

    Limitations: Our results should be considered exploratory given our less conservative statistical threshold in the group-by-reappraisal interaction.

    Conclusions: We find preliminary evidence that depressed adolescents engage cognitive control regions less efficiently than healthy controls, suggesting delayed maturation of regulatory prefrontal cortex regions; more research is needed to determine whether cognitive therapies improve functioning of these regions in depressed youth.

  • 35.
    Radmark, Lina
    et al.
    Karolinska Inst, Dept Clin Neurosci, Tomtebodavagen 18A, S-17177 Stockholm, Sweden.;Karolinska Inst, Dept Neurobiol Care Sci & Soc, Ctr Social Sustainabil, CSS, Alfred Nobels Alle 23, S-14183 Huddinge, Sweden..
    Osika, Walter
    Karolinska Inst, Dept Clin Neurosci, Tomtebodavagen 18A, S-17177 Stockholm, Sweden.;Karolinska Inst, Dept Neurobiol Care Sci & Soc, Ctr Social Sustainabil, CSS, Alfred Nobels Alle 23, S-14183 Huddinge, Sweden.;Stockholm Hlth Care Serv, Northern Stockholm Psychiat, Vardvagen 1, S-11281 Stockholm, Sweden..
    Wallen, Martin Benka
    Stockholm Cty Council, Stockholm Hlth Care Serv, Stockholm, Sweden..
    Nissen, Eva
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Lönnberg, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social medicine/CHAP. Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Branstrom, Richard
    Karolinska Inst, Dept Clin Neurosci, Tomtebodavagen 18A, S-17177 Stockholm, Sweden..
    Henje, Eva
    Umeå Univ, Dept Clin Sci Child & Adolescent Psychiat, S-90185 Umeå, Sweden..
    Gardner, Renee
    Karolinska Inst, Dept Global Publ Hlth, Solnavagen 1 E, S-10431 Stockholm, Sweden..
    Fransson, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Reproductive Health Research. Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Solnavagen 9, S-17165 Stockholm, Sweden..
    Karlsson, Hakan
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Niemi, Maria
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Ctr Social Sustainabil, CSS, Alfred Nobels Alle 23, S-14183 Huddinge, Sweden.;Karolinska Inst, Dept Global Publ Hlth, Solnavagen 1 E, S-10431 Stockholm, Sweden..
    Autonomic function and inflammation in pregnant women participating in a randomized controlled study of Mindfulness Based Childbirth and Parenting2023In: BMC Pregnancy and Childbirth, ISSN 1471-2393, E-ISSN 1471-2393, Vol. 23, no 1, article id 237Article in journal (Refereed)
    Abstract [en]

    Background Pregnancy and childbirth are significant events in many women's lives, and the prevalence of depressive symptoms increases during this vulnerable period. Apart from well documented cognitive, affective, and somatic symptoms, stress and depression are associated with physiological changes, such as reduced heart-rate variability (HRV) and activation of the inflammatory response system. Mindfulness Based Interventions may potentially have an effect on both HRV, inflammatory biomarkers, and self-assessed mental health. Therefore, the aim of this study was to assess the effects of a Mindfulness Childbirth and Parenting (MBCP) intervention on HRV, serum inflammatory marker levels, through an RCT study design with an active control group. Methods This study is a sub-study of a larger RCT, where significant intervention effects were found on perinatal depression (PND) and perceived stress. Participants were recruited through eight maternity health clinics in Stockholm, Sweden. In this sub-study, we included altogether 80 women with increased risk for PND, and blood samples and HRV measures were available from 60 of the participants (26 in the intervention and 34 in the control group). Results Participants who received MBCP reported a significantly larger reduction in perceived stress and a significantly larger increase in mindfulness, compared to participants who received the active control treatment. However, in this sub-study, the intervention had no significant effect on PND, inflammatory serum markers or measures of HRV. Conclusions No significant differences were found regarding changes in HRV measures and biomarkers of inflammation, larger studies may be needed in the future.

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  • 36.
    Rådmark, Lina
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Neurobiology, Care Sciences and Society, CSS, Center for Social Sustainability, Karolinska Institutet, Huddinge, Sweden.
    Osika, Walter
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Neurobiology, Care Sciences and Society, CSS, Center for Social Sustainability, Karolinska Institutet, Huddinge, Sweden; Northern Stockholm Psychiatry, Stockholm Health Care Services, Stockholm, Sweden.
    Wallén, Martin Benka
    Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
    Nissen, Eva
    Karolinska Institutet, Department Women's and Children's Health, Stockholm, Sweden.
    Lönnberg, Gunilla
    Karolinska Institutet, Department Women's and Children's Health, Stockholm, Sweden; Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
    Bränström, Richard
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Henje, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Gardner, Renee
    Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden.
    Fransson, Emma
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Department of Women´s and Children´s Health, Uppsala University, Akademiska sjukhuset, Uppsala, Sweden.
    Karlsson, Håkan
    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Niemi, Maria
    Department of Neurobiology, Care Sciences and Society, CSS, Center for Social Sustainability, Karolinska Institutet, Huddinge, Sweden; Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden.
    Autonomic function and inflammation in pregnant women participating in a randomized controlled study of mindfulness based childbirth and parenting2023In: BMC Pregnancy and Childbirth, ISSN 1471-2393, E-ISSN 1471-2393, Vol. 23, no 1, article id 237Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Pregnancy and childbirth are significant events in many women's lives, and the prevalence of depressive symptoms increases during this vulnerable period. Apart from well documented cognitive, affective, and somatic symptoms, stress and depression are associated with physiological changes, such as reduced heart-rate variability (HRV) and activation of the inflammatory response system. Mindfulness Based Interventions may potentially have an effect on both HRV, inflammatory biomarkers, and self-assessed mental health. Therefore, the aim of this study was to assess the effects of a Mindfulness Childbirth and Parenting (MBCP) intervention on HRV, serum inflammatory marker levels, through an RCT study design with an active control group.

    METHODS: This study is a sub-study of a larger RCT, where significant intervention effects were found on perinatal depression (PND) and perceived stress. Participants were recruited through eight maternity health clinics in Stockholm, Sweden. In this sub-study, we included altogether 80 women with increased risk for PND, and blood samples and HRV measures were available from 60 of the participants (26 in the intervention and 34 in the control group).

    RESULTS: Participants who received MBCP reported a significantly larger reduction in perceived stress and a significantly larger increase in mindfulness, compared to participants who received the active control treatment. However, in this sub-study, the intervention had no significant effect on PND, inflammatory serum markers or measures of HRV.

    CONCLUSIONS: No significant differences were found regarding changes in HRV measures and biomarkers of inflammation, larger studies may be needed in the future.

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  • 37. Sacchet, Matthew D.
    et al.
    Ho, Tiffany C.
    Connolly, Colm G.
    Tymofiyeva, Olga
    Lewinn, Kaja Z.
    Han, Laura K.M.
    Henje Blom, Eva
    Department of Clinical Neuroscience, Karolinska Institutet, Solna, Sweden; Department of Psychiatry, Division of Child and Adolescent Psychiatry, University of California San Francisco, San Francisco, CA, USA.
    Tapert, Susan F.
    Max, Jeffrey E.
    Frank, Guido K.W.
    Paulus, Martin P.
    Simmons, Alan N.
    Gotlib, Ian H.
    Yang, Tony T.
    Large-scale hypoconnectivity between resting-state functional networks in unmedicated adolescent major depressive disorder2016In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 41, no 12, p. 2951-2960Article in journal (Refereed)
    Abstract [en]

    Major depressive disorder (MDD) often emerges during adolescence, a critical period of brain development. Recent resting-state fMRI studies of adults suggest that MDD is associated with abnormalities within and between resting-state networks (RSNs). Here we tested whether adolescent MDD is characterized by abnormalities in interactions among RSNs. Participants were 55 unmedicated adolescents diagnosed with MDD and 56 matched healthy controls. Functional connectivity was mapped using resting-state fMRI. We used the network-based statistic (NBS) to compare large-scale connectivity between groups and also compared the groups on graph metrics. We further assessed whether group differences identified using nodes defined from functionally defined RSNs were also evident when using anatomically defined nodes. In addition, we examined relations between network abnormalities and depression severity and duration. Finally, we compared intranetwork connectivity between groups and assessed the replication of previously reported MDD-related abnormalities in connectivity. The NBS indicated that, compared with controls, depressed adolescents exhibited reduced connectivity (p<0.024, corrected) between a specific set of RSNs, including components of the attention, central executive, salience, and default mode networks. The NBS did not identify group differences in network connectivity when using anatomically defined nodes. Longer duration of depression was significantly correlated with reduced connectivity in this set of network interactions (p=0.020, corrected), specifically with reduced connectivity between components of the dorsal attention network. The dorsal attention network was also characterized by reduced intranetwork connectivity in the MDD group. Finally, we replicated previously reported abnormal connectivity in individuals with MDD. In summary, adolescents with MDD show hypoconnectivity between large-scale brain networks compared with healthy controls. Given that connectivity among these networks typically increases during adolescent neurodevelopment, these results suggest that adolescent depression is associated with abnormalities in neural systems that are still developing during this critical period.

  • 38. Schmalzl, Laura
    et al.
    Powers, Chivon
    Henje Blom, Eva
    Karolinska Institutet, University of California San Francsisco.
    Neurophysiological and neurocognitive mechanisms underlying the effects of yoga-based practices: towards a comprehensive theoretical framework.2015In: Frontiers in human neuroscience, Vol. 9, article id 235Article in journal (Refereed)
    Abstract [en]

    During recent decades numerous yoga-based practices (YBP) have emerged in the West, with their aims ranging from fitness gains to therapeutic benefits and spiritual development. Yoga is also beginning to spark growing interest within the scientific community, and yoga-based interventions have been associated with measureable changes in physiological parameters, perceived emotional states, and cognitive functioning. YBP typically involve a combination of postures or movement sequences, conscious regulation of the breath, and various techniques to improve attentional focus. However, so far little if any research has attempted to deconstruct the role of these different component parts in order to better understand their respective contribution to the effects of YBP. A clear operational definition of yoga-based therapeutic interventions for scientific purposes, as well as a comprehensive theoretical framework from which testable hypotheses can be formulated, is therefore needed. Here we propose such a framework, and outline the bottom-up neurophysiological and top-down neurocognitive mechanisms hypothesized to be at play in YBP.

  • 39. Tymofiyeva, Olga
    et al.
    Connolly, Colm G.
    Ho, Tiffany C.
    Sacchet, Matthew D.
    Henje Blom, Eva
    Department of Psychiatry, University of California San Francisco, United States; Department of Clinical Neuroscience, Karolinska Institute, Sweden.
    LeWinn, Kaja Z.
    Xu, Duan
    Yang, Tony T.
    DTI-based connectome analysis of adolescents with major depressive disorder reveals hypoconnectivity of the right caudate2017In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 207, p. 18-25Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Adolescence is a vulnerable period for the onset of major depressive disorder (MDD). While some studies have shown white matter alterations in adolescent MDD, there is still a gap in understanding how the brain is affected at a network level.

    METHODS: We compared diffusion tensor imaging (DTI)-based brain networks in a cohort of 57 adolescents with MDD and 41 well-matched healthy controls who completed self-reports of depression symptoms and stressful life events. Using atlas-based brain regions as network nodes and tractography streamline count or mean fractional anisotropy (FA) as edge weights, we examined weighted local and global network properties and performed Network-Based Statistic (NBS) analysis.

    RESULTS: While there were no significant group differences in the global network properties, the FA-weighted node strength of the right caudate was significantly lower in depressed adolescents and correlated positively with age across both groups. The NBS analysis revealed a cluster of lower FA-based connectivity in depressed subjects centered on the right caudate, including connections to frontal gyri, insula, and anterior cingulate. Within this cluster, the most robust difference between groups was the connection between the right caudate and middle frontal gyrus. This connection showed a significant diagnosis by stress interaction and a negative correlation with total stress in depressed adolescents.

    LIMITATIONS: Use of DTI-based tractography, one atlas-based parcellation, and FA values to characterize brain networks represent this study's limitations.

    CONCLUSIONS: Our results allowed us to suggest caudate-centric models of dysfunctional processes underlying adolescent depression, which might guide future studies and help better understand and treat this disorder.

  • 40. Tymofiyeva, Olga
    et al.
    Henje Blom, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry. Department of Psychiatry and Weill Institute for Neurosciences, University of California San Francisco, United States.
    Ho, Tiffany C.
    Connolly, Colm G.
    Lindqvist, Daniel
    Wolkowitz, Owen M.
    Lin, Jue
    LeWinn, Kaja Z.
    Sacchet, Matthew D.
    Han, Laura K. M.
    Yuan, Justin P.
    Bhandari, Sarina P.
    Xu, Duan
    Yang, Tony T.
    High levels of mitochondrial DNA are associated with adolescent brain structural hypoconnectivity and increased anxiety but not depression2018In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 232, p. 283-290Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Adolescent anxiety and depression are highly prevalent psychiatric disorders that are associated with altered molecular and neurocircuit profiles. Recently, increased mitochondrial DNA copy number (mtDNA-cn) has been found to be associated with several psychopathologies in adults, especially anxiety and depression. The associations between mtDNA-cn and anxiety and depression have not, however, been investigated in adolescents. Moreover, to date there have been no studies examining associations between mtDNA-cn and brain network alterations in mood disorders in any age group.

    METHODS: The first aim of this study was to compare salivary mtDNA-cn between 49 depressed and/or anxious adolescents and 35 well-matched healthy controls. The second aim of this study was to identify neural correlates of mtDNA-cn derived from diffusion tensor imaging (DTI) and tractography, in the full sample of adolescents.

    RESULTS: There were no diagnosis-specific alterations in mtDNA-cn. However, there was a positive correlation between mtDNA-cn and levels of anxiety, but not depression, in the full sample of adolescents. A subnetwork of connections largely corresponding to the left fronto-occipital fasciculus had significantly lower fractional anisotropy (FA) values in adolescents with higher than median mtDNA-cn.

    LIMITATIONS: Undifferentiated analysis of free and intracellular mtDNA and use of DTI-based tractography represent this study's limitations.

    CONCLUSIONS: The results of this study help elucidate the relationships between clinical symptoms, molecular changes, and neurocircuitry alterations in adolescents with and without anxiety and depression, and they suggest that increased mtDNA-cn is associated both with increased anxiety symptoms and with decreased fronto-occipital structural connectivity in this population.

  • 41. Tymofiyeva, Olga
    et al.
    Henje Blom, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry. Department of Psychiatry and Behavioral Sciences, The Langley Porter Psychiatric Institute, Division of Child and Adolescent Psychiatry, Weill Institute for Neurosciences, University of California, San Francisco, USA .
    Yuan, Justin P.
    Huang, Chiung-Yu
    Connolly, Colm G.
    Ho, Tiffany C.
    Bhandari, Sarina
    Parks, Kendall C.
    Sipes, Benjamin S.
    Yang, Tony T.
    Xu, Duan
    Reduced anxiety and changes in amygdala network properties in adolescents with training for awareness, resilience, and action (TARA)2021In: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 29, article id 102521Article in journal (Refereed)
    Abstract [en]

    Mindfulness-based approaches show promise to improve emotional health in youth and may help treat and prevent adolescent depression and anxiety. However, there is a fundamental gap in understanding the neural reorganization that takes place as a result of such interventions. The Training for Awareness, Resilience, and Action (TARA) program, initially developed for depressed adolescents, uses a framework drawn from neuroscience, mindfulness, yoga, and modern psychotherapeutic techniques to promote emotional health. The goal of this study was to assess the effects of the TARA training on emotional health and structural white matter brain networks in healthy youth. We analyzed data from 23 adolescents who underwent the 12-week TARA training in a controlled within-subject study design and whose brain networks were assessed using diffusion MRI connectomics. Compared to the control time period, adolescents showed a significant decrease in anxiety symptoms with TARA (Cohen's d = -0.961, p = 0.006); moreover, the node strength of the Right Amygdala decreased significantly after TARA (Cohen's d = -1.026, p = 0.004). Post-hoc analyses indicated that anxiety at baseline before TARA was positively correlated with Right Amygdala node strength (r = 0.672, p = 0.001). While change in Right Amygdala node strength with TARA was not correlated with change in anxiety (r = 0.146, p = 0.51), it was associated with change in depression subscale of Anhedonia / Negative Affect (r = 0.575, p = 0.004, exploratory analysis), possibly due to overlapping constructs captured in our anxiety and depression scales. Our results suggest that increased structural connectivity of Right Amygdala may underlie increased anxiety in adolescents and be lowered through anxiety-reducing training such as TARA. The results of this study contribute to our understanding of the neural mechanisms of TARA and may facilitate neuroscience-based prevention and treatment of adolescent anxiety and depression.

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  • 42.
    Tymofiyeva, Olga
    et al.
    Department of Radiology and Biomedical Imaging, University of California, CA, San Francisco, United States.
    Hu, Melody Y.
    Division of Child and Adolescent Psychiatry, Department of Psychiatry and Behavioral Sciences, Langley Porter Psychiatric Institute, University of California, CA, San Francisco, United States.
    Sipes, Benjamin S.
    Department of Radiology and Biomedical Imaging, University of California, CA, San Francisco, United States.
    Jakary, Angela
    Department of Radiology and Biomedical Imaging, University of California, CA, San Francisco, United States.
    Glidden, David V.
    Department of Epidemiology and Biostatistics, University of California, CA, San Francisco, United States.
    Jariwala, Namasvi
    Department of Radiology and Biomedical Imaging, University of California, CA, San Francisco, United States.
    Bhandari, Sarina
    Department of Radiology and Biomedical Imaging, University of California, CA, San Francisco, United States.
    Parks, Kendall C.
    Department of Radiology and Biomedical Imaging, University of California, CA, San Francisco, United States.
    Nguyen, Ca
    Department of Radiology and Biomedical Imaging, University of California, CA, San Francisco, United States.
    Henje Blom, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Yang, Tony T.
    Division of Child and Adolescent Psychiatry, Department of Psychiatry and Behavioral Sciences, Langley Porter Psychiatric Institute, University of California, CA, San Francisco, United States; Weill Institute for Neurosciences, University of California, CA, San Francisco, United States.
    A feasibility study of a remotely-delivered mindfulness-based training for adolescents during the COVID-19 pandemic2022In: Frontiers in Psychiatry, E-ISSN 1664-0640, Vol. 13, article id 838694Article in journal (Refereed)
    Abstract [en]

    Social distancing, home confinement, economic challenges, and COVID-19-related illness and deaths during the COVID-19 pandemic can significantly affect mental health in youth. One promising approach to reduce anxiety and depression in adolescents is the neuroscience-based mindfulness intervention Training for Awareness, Resilience, and Action (TARA). The objective of this individually randomized waitlist-controlled trial (RCT) was (1) to test the feasibility of TARA, delivered partially over Zoom, and (2) to assess changes in the emotional wellbeing in healthy adolescents between the ages of 14–18 years old during the COVID-19 pandemic. Methods: Twenty-one healthy adolescents were randomized to the TARA intervention or to the waitlist control group in February 2020, just before the start of the pandemic. The TARA group intervention was delivered in person for the first five sessions and remotely over Zoom for the remaining seven sessions due to the pandemic. The participants’ acceptability of TARA was assessed weekly using the Child Session Rating Scale (CSRS). The primary outcome was the emotional wellbeing measured using emotional symptoms subscale of the Strengths and Difficulties Questionnaire (SDQ) pre/post-TARA. We also explored weekly changes in TARA participants’ wellbeing using the Child Outcome Rating Scale (CORS). Results: The overall session rating in TARA participants improved after the switch to Zoom (Cohen’s d = 1.2, p = 0.008). The results of the two-way ANOVA showed no statistically significant difference in the change of the SDQ emotional symptoms during the 12 weeks between the TARA group and waitlist-control group (timepoint × group interaction: F = 0.77, p = 0.38). The exploratory analysis using the CORS in the TARA participants showed a significant improvement in their functioning over the weeks of training. Conclusion: Our results support the feasibility of TARA delivered over Zoom. While our primary outcome did not provide support for the improvement of the emotional wellbeing with TARA compared to a passive control group, our exploratory analysis in the intervention group indicated an improved functioning over the weeks of TARA training. The important general positive impact of this study lies in the possibility of offering a neuroscience-based mindfulness intervention remotely to youth living in remote areas and for all youth during pandemic times.

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  • 43. Tymofiyeva, Olga
    et al.
    Yuan, Justin P.
    Huang, Chiung-Yu
    Connolly, Colm G.
    Henje Blom, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry. Department of Psychiatry and the Langley Porter Psychiatric Institute, Division of Child and Adolescent Psychiatry, Weill Institute for Neurosciences, University of California, San Francisco, USA.
    Xu, Duan
    Yang, Tony T.
    Application of machine learning to structural connectome to predict symptom reduction in depressed adolescents with cognitive behavioral therapy (CBT)2019In: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 23, article id 101914Article in journal (Refereed)
    Abstract [en]

    Purpose: Adolescent major depressive disorder (MDD) is a highly prevalent, incapacitating and costly illness. Many depressed teens do not improve with cognitive behavioral therapy (CBT), a first-line treatment for adolescent MDD, and face devastating consequences of increased risk of suicide and many negative health outcomes. "Who will improve with CBT?" is a crucial question that remains unanswered, and treatment planning for adolescent depression remains biologically unguided. The purpose of this study was to utilize machine learning applied to patients' brain imaging data in order to help predict depressive symptom reduction with CBT.

    Methods: We applied supervised machine learning to diffusion MRI-based structural connectome data in order to predict symptom reduction in 30 depressed adolescents after three months of CBT. A set of 21 attributes was chosen, including the baseline depression score, age, gender, two global network properties, and node strengths of brain regions previously implicated in depression. The practical and robust J48 pruned tree classifier was utilized with a 10-fold cross-validation.

    Results: The classification resulted in an 83% accuracy of predicting depressive symptom reduction. The resulting tree of size seven with only three attributes highlights the role of the right thalamus in predicting depressive symptom reduction with CBT. Additional analysis showed a significant negative correlation between the change in the depressive symptoms and the node strength of the right thalamus.

    Conclusions: Our results demonstrate that a machine learning algorithm that exclusively uses structural connectome data and the baseline depression score can predict with a high accuracy depressive symptom reduction in adolescent MDD with CBT. This knowledge can help improve treatment planning for adolescent depression.

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  • 44. Tymofiyeva, Olga
    et al.
    Yuan, Justin P.
    Kidambi, Roma
    Huang, Chiung-Yu
    Henje Blom, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry. Department of Psychiatry and Behavioral Sciences, The Langley Porter Psychiatric Institute, Division of Child and Adolescent Psychiatry, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States.
    Rubinstein, Mark L.
    Jariwala, Namasvi
    Max, Jeffrey E.
    Yang, Tony T.
    Xu, Duan
    Neural Correlates of Smartphone Dependence in Adolescents2020In: Frontiers in Human Neuroscience, E-ISSN 1662-5161, Vol. 14, article id 564629Article in journal (Refereed)
    Abstract [en]

    Increases in depressive and suicide-related symptoms among United States adolescents have been recently linked to increased use of smartphones. Understanding of the brain mechanisms that underlie the potential smartphone dependence may help develop interventions to address this important problem. In this exploratory study, we investigated the neural mechanisms underlying potential smartphone dependence in a sample of 19 adolescent volunteers who completed self-assessments of their smartphone dependence, depressive symptoms, and sleep problems. All 19 adolescents underwent diffusion MRI that allowed for assessment of white matter structural connectivity within the framework of connectomics. Based on previous literature on the neurobiology of addiction, we hypothesized a disruption of network centrality of three nodes in the mesolimbic network: Nucleus Accumbens, anterior cingulate cortex, and amygdala. Our results showed positive correlations between the node centrality of the right amygdala and self-reported smartphone dependence, between smartphone dependence and sleep problems, and between sleep problems and depressive symptoms. A higher phone dependence was observed in females compared to males. Supported by these results, we propose a model of how smartphone dependence can be linked to aberrations in brain networks, sex, sleep disturbances, and depression in adolescents.

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  • 45.
    Vestin, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Blomqvist, Ida
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Henje Blom, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Dennhag, Inga
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Psychometric validation of the Montgomery–åsberg Depression Rating Scale–Youth (MADRS-Y) in a clinical sample2024In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725Article in journal (Refereed)
    Abstract [en]

    Background: Depression in adolescence is a serious major global health problem with increasing rates of prevalence. Measures of depression that are valid for young people are clearly needed in clinical contexts.

    Methods: The study included 577 patients from child and adolescent psychiatry (n = 471) and primary care (n = 106) aged 12–22 years in Sweden (Mage=16.7 years; 76% female). The reliability and validity for Montgomery–Åsberg Depression Rating Scale–Youth (MADRS-Y) were investigated. To confirm the latent structure, we used a single-factor confirmatory factor analysis (CFA). A Kruskal–Wallis test was performed to test total score differences between diagnostic groups. Using Spearman’s rho correlations, we examine whether single items in the MADRS-Y correlate with suicidal ideation measured by The Suicidal Ideation Questionnaire-JR (SIQ-JR).

    Results: The internal consistency using McDonald’s coefficient omega was excellent. The CFA of the 12-item MADRS-Y supported a one factor structure. Evidence of convergent and discriminant validity was shown. There was a significant difference in MADRS-Y scores across diagnostic groups, with higher results for depressive disorders. A strong correlation with suicidal ideation was found for two items.

    Conclusions: The results support MADRS-Y as a brief, reliable, and valid self-report questionnaire of depressive symptoms for young patients in a clinical setting.

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  • 46.
    Vestin, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Åsberg, Marie
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Wiberg, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Henje, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Dennhag, Inga
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Psychometric validity of the Montgomery and Åsberg depression rating scale for youths (MADRS-Y)2023In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 77, no 5, p. 421-431Article in journal (Refereed)
    Abstract [en]

    Background: Because of all the serious consequences of major depressive disorder (MDD), it is important to screen for MDD in adolescents. The aim of this study was to test the psychometric properties of the newly developed self-report depression scale MADRS-Y for adolescents in a normative Swedish sample.

    Methods: The study included 620 adolescents in the age range of 12–20 years old. The normative sample was randomly split into two equal parts, to perform principal component analysis (PCA) on sample one and confirmatory factor analysis (CFA) on sample two. We investigated the psychometrics.

    Results: The result from the PCA suggested that all 12 potential items should be used, and the items loaded on the same construct of depression. The CFA supported the one-factor structure with good fit indices. Measurement invariance was confirmed, allowing interpretation regardless of gender or age differences. Reliability was good, α.89, for both samples separately. Test-retest reliability was good to excellent (intraclass correlation coefficients =.87 and.91). Evidence of convergent and discriminant validity was shown.

    Conclusions: The results in the current study suggest that the MADRS-Y is a brief, reliable, and valid self-report questionnaire of depressive symptoms for adolescents in the general population.

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  • 47. Yuan, Justin P.
    et al.
    Connolly, Colm G.
    Henje Blom, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry. Department of Psychiatry and Behavioral Sciences, The Langley Porter Psychiatric Institute, Division of Child and Adolescent Psychiatry, Weill Institute for Neurosciences, University of California, San Francisco, United States.
    Sugrue, Leo P.
    Yang, Tony T.
    Xu, Duan
    Tymofiyeva, Olga
    Gray Matter Changes in Adolescents Participating in a Meditation Training2020In: Frontiers in Human Neuroscience, E-ISSN 1662-5161, Vol. 14, article id 319Article in journal (Refereed)
    Abstract [en]

    Meditation has shown to benefit a wide range of conditions and symptoms, but the neural mechanisms underlying the practice remain unclear. Magnetic resonance imaging (MRI) studies have investigated the structural brain changes due to the practice by examining volume, density, or cortical thickness changes. However, these studies have focused on adults; meditation's structural effects on the adolescent brain remain understudied. In this study, we investigated how meditation training affects the structure of the adolescent brain by scanning a group of 38 adolescents (16.48 +/- 1.29 years) before and after participating in a 12-week meditation training. Subjects underwent Training for Awareness, Resilience, and Action (TARA), a program that mainly incorporates elements from mindfulness meditation and yoga-based practices. A subset of the adolescents also received an additional control scan 12 weeks before TARA. We conducted voxel-based morphometry (VBM) to assess gray matter volume changes pre- to post-training and during the control period. Subjects showed significant gray matter (GM) volume decreases in the left posterior insula and to a lesser extent in the left thalamus and left putamen after meditation training. There were no significant changes during the control period. Our results support previous findings that meditation affects regions associated with physical and emotional awareness. However, our results are different from previous morphometric studies in which meditation was associated with structural increases. We posit that this discrepancy may be due to the differences between the adolescent brain and the adult brain.

  • 48. Yuan, Justin P.
    et al.
    Henje Blom, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry. Department of Psychiatry and the Langley Porter Psychiatric Institute Weill Institute for Neurosciences University of California, San Francisco.
    Flynn, Trevor
    Chen, Yiran
    Ho, Tiffany C.
    Connolly, Colm G.
    Dumont Walter, Rebecca A.
    Yang, Tony T.
    Xu, Duan
    Tymofiyeva, Olga
    Test-retest reliability of graph theoretic metrics in adolescent brains2019In: Brain Connectivity, ISSN 2158-0014, E-ISSN 2158-0022, Vol. 9, no 2, p. 144-154Article in journal (Refereed)
    Abstract [en]

    Graph theory analysis of structural brain networks derived from diffusion tensor imaging (DTI) has become a popular analytical method in neuroscience, enabling advanced investigations of neurological and psychiatric disorders. The purpose of this study was to investigate: 1) the effects of edge weighting schemes, and 2) the effects of varying interscan periods on graph metrics' test-retest reliability within the adolescent brain. We compared a binary (B) network definition with three weighting schemes: fractional anisotropy (FA), streamline count (SC), and streamline count with density and length correction (SDL). Two commonly used global and two local graph metrics were examined. The analysis was conducted with two groups of adolescent volunteers who received DTI scans either 12 weeks apart (16.62±1.10yrs) or within the same scanning session (30 minutes apart) (16.65±1.14yrs). The intraclass correlation coefficient (ICC) was used to assess test-retest reliability and the coefficient of variation (CV) was used to assess precision. On average, each edge scheme produced reliable results at both time intervals. Weighted measures outperformed binary measures, with SDL-weights producing the most reliable metrics. All edge schemes except FA displayed high CV values, leaving FA as the only edge scheme that consistently showed high precision while also producing reliable results. Overall findings suggest that FA-weights are more suited for DTI connectome studies in adolescents.

  • 49.
    Åslund, Li
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Sweden; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Sweden.
    Jernelöv, Susanna
    Department of Clinical Neuroscience, Karolinska Institutet, Sweden; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Sweden.
    Serlachius, Eva
    Department of Clinical Neuroscience, Karolinska Institutet, Sweden; Child and Adolescent Psychiatry, Department of Clinical Sciences, Faculty of Medicine, Lund University, Sweden; Child and Adolescent Psychiatry, Region Skåne, Sweden.
    Vigerland, Sarah
    Department of Clinical Neuroscience, Karolinska Institutet, Sweden; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Sweden.
    Wicksell, Rikard K
    Department of Clinical Neuroscience, Karolinska Institutet, Sweden; Pain Clinic, Capio St Göran Hospital, Sweden.
    Henje Blom, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Lekander, Mats
    Department of Clinical Neuroscience, Karolinska Institutet, Sweden; Stress Research Institute, Stockholm University, Sweden.
    Internet-delivered cognitive behavioral therapy for adolescents with insomnia: Feasibility and preliminary efficacy2023In: Clinical Child Psychology and Psychiatry, ISSN 1359-1045, E-ISSN 1461-7021Article in journal (Refereed)
    Abstract [en]

    Background: Insomnia is common in adolescents. This study evaluated feasibility and preliminary efficacy of a six-week internet-delivered cognitive-behavioral therapy for insomnia (ICBT-I) in adolescents.

    Methods: In this uncontrolled pilot study, participants (n = 27, 78% female) completed assessments pre- and post intervention. Data on recruitment, adherence to treatment, treatment activity, satisfaction and credibility was collected to assess feasibility. Self-reported insomnia symptoms, sleep parameters as well as depression, anxiety and daytime function were also assessed.

    Results: Participants showed good adherence to treatment and found the intervention overall credible and satisfactory. From pre- to post-assessment, statistically significant improvements were found for insomnia symptoms (p <.001; d = 1.02), sleep onset latency (p <.001; d =.39), wake after sleep onset (p =.001; d =.34), sleep efficiency (p <.001; d =.5) and depression (p =.01, d =.37). Changes in scores of total sleep time, generalized anxiety, daytime sleepiness and functional disability were not significant.

    Conclusions: The present study indicates that ICBT-I is well accepted by adolescents, that insomnia symptoms and sleep parameters can improve following the intervention, and that co-morbid symptoms of depression can be reduced. Due to the limited sample size and the uncontrolled design, the suggested results need to be replicated in well-powered controlled clinical trials.

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  • 50.
    Åslund, Lie
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Sweden; Centre for Psychiatry Research, Stockholm Health Care Services, Region Stockholm, CAP Research Centre, Sweden.
    Andreasson, Anna
    Stress Research Institute, Stockholm University, Sweden.
    Lekander, Mats
    Department of Clinical Neuroscience, Karolinska Institutet, Sweden; Stress Research Institute, Stockholm University, Sweden.
    Henje, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Dennhag, Inga
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Disturbed sleep and patterns of psychiatric symptoms and function in a school-based sample of adolescents2023In: Clinical Child Psychology and Psychiatry, ISSN 1359-1045, E-ISSN 1461-7021, Vol. 28, no 4, p. 1524-1535Article in journal (Refereed)
    Abstract [en]

    Background: Sleep problems are common in adolescence and often related to psychopathology and impaired functioning. However, most studies have used summative scores, and little is known about how adolescents with disrupted sleep perceive their specific symptoms and dysfunctions. This study explored differences in levels of psychiatric symptoms and functional ability between Swedish adolescents with and without self-reported disturbed sleep in a school-based sample.

    Methods: Swedish adolescents (n = 618, mean age 15.7+/-1.9yrs) answered the PROMIS pediatric measures for fatigue, anxiety, depression, pain interference, anger, physical activity and peer and family relationships. Logistic regression analyses were performed to assess differences between respondents with and without disturbed sleep.

    Results: Disturbed sleep was associated with higher levels of symptoms of fatigue, anxiety, depression, anger and pain interference, as well as lower functional abilities in terms of physical activity and peer- and family relationships. Adolescents reporting disturbed sleep generally displayed a pattern of impaired executive functioning, internal emotional distress and school- and sleep related worry and dysfunction, as compared to physical disability, aggressive behavior, stress and generalized worry.

    Conclusions: The present study adds to the understanding of how disturbed sleep and specific psychiatric symptoms and functional ability are interrelated, which may also have clinical implications.

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