Cohort profile: BioMD-Y (biopsychosocial factors of major depression in youth) - a biobank study on the molecular genetics and environmental factors of depression in children and adolescents in Munich.

PURPOSE: BioMD-Y is a comprehensive biobank study of children and adolescents with major depression (MD) and their healthy peers in Germany, collecting a host of both biological and psychosocial information from the participants and their parents with the aim of exploring genetic and environmental risk and protective factors for MD in children and adolescents. PARTICIPANTS: Children and adolescents aged 8-18 years are recruited to either the clinical case group (MD, diagnosis of MD disorder) or the typically developing control group (absence of any psychiatric condition). FINDINGS TO DATE: To date, four publications on both genetic and environmental risk and resilience factors (including FKBP5, glucocorticoid receptor activation, polygenic risk scores, psychosocial and sociodemographic risk and resilience factors) have been published based on the BioMD-Y sample. FUTURE PLANS: Data collection is currently scheduled to continue into 2026. Research questions will be further addressed using available measures.

Evaluation of a web-based information platform on youth depression and mental health in parents of adolescents with a history of depression.

Research shows the important role of parents' mental health literacy in detecting depressive symptoms and supporting their children to seek professional help. Improving mental health literacy in parents has recently gained even greater importance due to the negative impact of the COVID-19 pandemic on children and adolescents' mental health. The aim of the present experimental pre-post-follow-up study was to examine knowledge change after the reception of contents from an innovative web-based platform ( www.ich-bin-alles.de/eltern ) containing evidence-based information on youth depression and mental health in parents of adolescents with a history of depression. A second aim was to assess evaluation of the layout and the acceptance of the platform. N = 33 parents of adolescents with a history of depression (either current or remitted depression) were presented different content domains of the website. Participants' knowledge about depression was assessed at pre- and post-intervention, and at a four week follow-up. Moreover, parents evaluated the acceptance and the layout of the website. The trial was preregistered at clinicaltrials.gov (NCT05335564). The results showed a significant increase in total knowledge from pre to post, which remained stable over the course of four weeks. Explorative analyses showed that sociodemographic variables did not influence the extent of knowledge gain. Acceptance rates were high and evaluations of the website's layout were positive. The findings show that the web-based information portal is a promising and appealing means to increase parental knowledge on youth depression. Low-threshold psychoeducational approaches like websites are particularly relevant in times of crisis and increased prevalence rates of depressive symptoms and disorders (ehealth). These results are an important basis for future studies as well as approaches that aim to impart knowledge about mental disorders like youth depression via web-based means. Furthermore, they bear implications for policy decisions concerning mental health education and campaigns.

Emotion regulation training for adolescents with major depression: Results from a randomized controlled trial.

Difficulties in emotion regulation (ER) are thought to contribute to the development and maintenance of major depression (MD) in adolescents. In healthy adults, a task-based training of ER has previously proven effective to reduce stress, but no such studies are available for MD. It is also unclear whether findings can be generalized onto adolescent populations. The final sample consisted of n = 70 adolescents with MD, who were randomized to a task-based ER training (n = 36) or a control training (n = 34). Across four sessions, the ER group was trained to downregulate negative affect to negative images via reappraisal, while the control group was instructed to attend the images. Rumination, stress-, and affect-related measures were assessed as primary outcomes, behavioral and neurophysiological responses (late positive potential, LPP), as secondary outcomes. The trial was preregistered at clinicaltrials.gov (NCT03957850). While there was no significant differential effect of the ER training on primary outcomes, we found small to moderate effects on rumination in the ER group, but not the control group. During reappraisal (compared to attend), the ER group showed an unexpected increase of the LPP during the first, but not during later training sessions. Although replication in large, multicenter trials is needed, our findings on effect sizes suggest that ER training might be promising to decrease rumination in adolescent MD. The LPP increase at the first session may represent cognitive effort, which was successfully reduced over the sessions. Future studies should research whether training effects transfer to daily life and are durable over a longer time period. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Emotion Regulation Deficits in Adolescent Girls with Major Depression, Anorexia Nervosa and Comorbid Major Depression and Anorexia Nervosa.

In adolescence, both major depression (MD) and anorexia nervosa (AN) are associated with deficits in emotion regulation (ER). However, studies have yet to compare ER profiles within the disorders and the effect of comorbid MD+AN is unclear. This study examined the habitual use of ER in 229 girls, aged 12-18 years, with MD (n = 84), AN (n = 37), comorbid MD+AN (n = 25), and healthy girls (n = 83). Girls with MD, AN and MD+AN reported more maladaptive and less adaptive ER strategies than healthy girls. MD and MD+AN groups showed more frequent use of maladaptive ER compared to only AN, with no differences between only MD and MD+AN. This suggests that MD+AN is not necessarily associated with higher ER deficits, rather, an additional diagnosis of MD exacerbates impairments in AN. Identifying specific ER profiles can provide important targets in prevention and treatment for AN, MD and AN+MD.

Evaluation of a Web-based Information Platform for Youths on Mental Health During the COVID-19 Pandemic.

During the corona pandemic, youths were confronted with substantial challenges and in urgent need of information on how to prevent mental health problems. This experimental pre-post-follow-up study examined the efficacy and reception of an innovative website ( www.corona-und-du.info ) containing evidence-based information for youths on how to overcome psychological distress during the pandemic. 34 youths aged 11-18 years were presented domains of the website in the laboratory. Standardized questionnaires were applied to assess changes in knowledge, the reception of the website, and changes in behavioral intention to seek psychological help. For all content domains, we found a significant knowledge gain with large effect sizes from pre to post, and from pre to follow-up. The reception of the website was very positive, and participants indicated increased intention to seek psychological support when needed. The results constitute an important basis for future attempts to promote mental health information in youths in times of crisis.

Visual attention during cognitive reappraisal in adolescent major depression: Evidence from two eye-tracking studies.

Adolescent major depression (MD) is associated with impaired emotion regulation. However, results on cognitive reappraisal (CR) are mixed. Investigation of gaze behavior during CR allows a more thorough understanding of intact and deviant CR processes in MD. These studies examined for the first time the role of visual attention during CR in MD. We applied an established CR paradigm in two separate studies, with each study focusing on a different CR strategy. In Study 1, we investigated "distancing" in 39 adolescents with MD and 44 healthy controls (HCs). In Study 2, we applied "reinterpretation" in an independent sample of 37 HCs and 19 adolescents with MD. In both studies, adolescents either down-regulated negative affect to negative pictures via CR or attended them, while eye-movements were continuously recorded. Results of both studies showed that adolescents with MD and HCs did not differ in self-reported ER success. The groups showed comparable gaze behaviour patterns for emotional interest areas and entire pictures. Findings suggest that adolescents with MD are capable of applying CR when instructed and show intact visual attention processes. Future studies should examine whether repeatedly instructing adolescents with MD to apply CR might lead to improved emotion regulation in daily life.

Sex differences in the genetic regulation of the blood transcriptome response to glucocorticoid receptor activation.

Substantial sex differences have been reported in the physiological response to stress at multiple levels, including the release of the stress hormone, cortisol. Here, we explore the genomic variants in 93 females and 196 males regulating the initial transcriptional response to cortisol via glucocorticoid receptor (GR) activation. Gene expression levels in peripheral blood were obtained before and after GR-stimulation with the selective GR agonist dexamethasone to identify differential expression following GR-activation. Sex stratified analyses revealed that while the transcripts responsive to GR-stimulation were mostly overlapping between males and females, the quantitative trait loci (eQTLs) regulation differential transcription to GR-stimulation was distinct. Sex-stratified eQTL SNPs (eSNPs) were located in different functional genomic elements and sex-stratified transcripts were enriched within postmortem brain transcriptional profiles associated with Major Depressive Disorder (MDD) specifically in males and females in the cingulate cortex. Female eSNPs were enriched among SNPs linked to MDD in genome-wide association studies. Finally, transcriptional sensitive genetic profile scores derived from sex-stratified eSNPS regulating differential transcription to GR-stimulation were predictive of depression status and depressive symptoms in a sex-concordant manner in a child and adolescent cohort (n = 584). These results suggest the potential of eQTLs regulating differential transcription to GR-stimulation as biomarkers of sex-specific biological risk for stress-related psychiatric disorders.

Study protocol for a randomised-controlled study on emotion regulation training for adolescents with major depression: the KONNI study.

INTRODUCTION: Major depression (MD) often has its onset during adolescence and is associated with significant morbidity and mortality. One important factor for the development and maintenance of adolescent MD are disturbances in emotion regulation and the underlying neural processes. Cognitive reappraisal (CR) is a particular adaptive emotion regulation strategy. Previously, it has been shown in healthy adults that a task-based training in CR is efficient to reduce negative affect, and that these effects translate into everyday life.This randomised controlled trial examines for the first time whether a task-based training in CR proves effective in MD adolescents. Specifically, we will investigate whether the CR training improves the ability to downregulate negative affect in MD individuals as assessed by behavioural and neurobiological indices, and whether training effects generalise outside the laboratory. METHODS AND ANALYSIS: Adolescents with MD will be randomly allocated to a group that either receives a task-based training in CR or a control training. Both involve four training sessions over a time period of 2 weeks. In the CR training, participants will be instructed to downregulate negative affective responses to negative pictures via CR, while the control training involves picture viewing. During the training sessions, the Late Positive Potential, gaze fixations on negative picture aspects and affective responses to pictures will be collected. Before and after the training programmes, and at a 2-week follow-up, overall negative and positive affect, rumination and perceived stress will be assessed as primary outcomes. Analyses of variance will be conducted to test the effectiveness of the CR training with regard to both primary outcomes and task-based behavioural and neurobiological parameters. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of the Medical Faculty of the LMU Munich, Germany. The results will be published in peer-reviewed journals and disseminated through conferences, social media and public events. TRIAL REGISTRATION DETAILS: ClinicalTrials.gov NCT03957850, registered 21st May 2019; URL: https://clinicaltrials.gov/ct2/show/NCT03957850.

Psychosocial stressors and protective factors for major depression in youth: evidence from a case-control study.

BACKGROUND: Severe adverse life events, such as traumatic experiences, are well-known stressors implicated in (youth) major depression (MD). However, to date, far less is known about the role of more common psychosocial stressors in the context of MD, which are part of everyday life during youth. In addition, it is not well-understood whether and how distinct stressors interact with protective factors in youths diagnosed with MD. Thus, the present study aimed at examining several specific psychosocial stressors implicated in a first-episode juvenile MD and addressed the question whether protective factors might moderate the relationship between stressors and a diagnosis of MD. METHODS: One-hundred male and female youths with MD and 101 typically developing (TD) controls (10-18 years) were included. A large number of qualitatively different psychosocial stressors occurring in various areas of life were assessed via self-report. Moreover, we also investigated sociodemographic and pre- and postnatal stressors, as well as the presence of familial affective disorders via parental-report. Social support and a positive family climate were conceptualized as protective factors and were assessed via self-report. RESULTS: Results showed that the proportion of youths experiencing specific psychosocial stressors was higher in the MD than in the TD group. In particular, the proportion of youths indicating changes at home or at school, experiences of violence, delinquent behavior, as well as the proportion of youths who were exposed to sociodemographic stressors was higher in the MD than in the TD group. Moreover, the percentage of youths with a family history of an affective disorder, or whose mothers experienced psychological burdens during/after pregnancy was elevated in the MD group. Youths with MD experienced less social support and a less positive family climate than their TD peers. These factors, however, did not buffer the influence of specific stressors on MD. CONCLUSION: We could show that next to more severe adverse life events, more common psychosocial stressors are linked to youth MD. Importantly, by identifying distinct stressors in youth MD, our results can increase treatment and prevention efforts aiming to improve the outcomes in youths affected by MD or in at-risk individuals.

Interactions between FKBP5 variation and environmental stressors in adolescent Major Depression.

OBJECTIVE: Major Depression (MD) results from a complex interplay between environmental stressors and biological factors. Previous studies in adults have shown that adverse life events interact with genetic variation in FKBP5, a gene implicated in the stress-response system, to predict depressive symptoms and MD. This is the first study to investigate interactions between FKBP5 variants and a range of environmental stressors in adolescents with a clinical diagnosis of MD. METHOD: 148 male and female adolescents with MD and 143 typically developing (TD) controls (13-18 years) were included in the present study. For self-reported environmental stressors, subjective severity was assessed to allow a classification of these factors as mild, moderate and severe. Sociodemographic stressors were assessed via parental-report. RESULTS: With a heightened number of sociodemographic, moderate and total number of stressors, participants carrying at least one copy of the FKBP5 CATT haplotype or at least one minor allele of various FKBP5 SNPs had the highest risk for being in the MD group. No genetic main effects were found. Sociodemographic stressors as well as self-reported mild, moderate, and severe stressors were more common in depressed than in TD adolescents. CONCLUSION: This is the first study to show interactions between genetic variation in FKBP5 and environmental stressors in a sample of clinically depressed adolescents. The current study provides important starting-points for preventive efforts and highlights the need for a fine-grained analysis of different forms and severities of environmental stressors and their interplay with genetic variation for understanding the complex etiology of (youth) MD.

Polygenic Risk: Predicting Depression Outcomes in Clinical and Epidemiological Cohorts of Youths.

OBJECTIVE: Identifying risk factors for major depression and depressive symptoms in youths could have important implications for prevention efforts. This study examined the association of polygenic risk scores (PRSs) for a broad depression phenotype derived from a large-scale genome-wide association study (GWAS) in adults, and its interaction with childhood abuse, with clinically relevant depression outcomes in clinical and epidemiological youth cohorts. METHODS: The clinical cohort comprised 279 youths with major depression (mean age=14.76 years [SD=2.00], 68% female) and 187 healthy control subjects (mean age=14.67 years [SD=2.45], 63% female). The first epidemiological cohort included 1,450 youths (mean age=13.99 years [SD=0.92], 63% female). Of those, 694 who were not clinically depressed at baseline underwent follow-ups at 6, 12, and 24 months. The replication epidemiological cohort comprised children assessed at ages 8 (N=184; 49.2% female) and 11 (N=317; 46.7% female) years. All cohorts were genome-wide genotyped and completed measures for major depression, depressive symptoms, and/or childhood abuse. Summary statistics from the largest GWAS to date on depression were used to calculate the depression PRS. RESULTS: In the clinical cohort, the depression PRS predicted case-control status (odds ratio=1.560, 95% CI=1.230-1.980), depression severity (ß=0.177, SE=0.069), and age at onset (ß=-0.375, SE=0.160). In the first epidemiological cohort, the depression PRS predicted baseline depressive symptoms (ß=0.557, SE=0.200) and prospectively predicted onset of moderate to severe depressive symptoms (hazard ratio=1.202, 95% CI=1.045-1.383). The associations with depressive symptoms were replicated in the second epidemiological cohort. Evidence was found for an additive, but not an interactive, effect of the depression PRS and childhood abuse on depression outcomes. CONCLUSIONS: Depression PRSs derived from adults generalize to depression outcomes in youths and may serve as an early indicator of clinically significant levels of depression.

Resting frontal EEG asymmetry in adolescents with major depression: Impact of disease state and comorbid anxiety disorder.

OBJECTIVE: Greater relative right- than left-frontal cortical activity has been frequently found in adults with major depression (MD). As the few studies in adolescents with MD have been inconclusive, the aim of this study was to assess frontal alpha asymmetry (FAA) in an adolescent sample with MD whilst taking into account possible confounding variables such as disease state and comorbid anxiety disorder. METHODS: An 8-minute resting frontal EEG was assessed in 34 healthy controls (HCs), 16 adolescents with MD in remission without comorbid anxiety disorder (rMDa-), 22 adolescents with acute depression without comorbid anxiety disorder (MDa-), and 23 adolescents with acute depression and comorbid anxiety disorder (MDa+). Alpha power was analyzed over corresponding frontal Regions of Interests. RESULTS: Compared to HCs, MDa+ adolescents demonstrated more left- than right-sided EEG alpha power, indicating greater right-than left-frontal cortical activity. No other group differences emerged. CONCLUSIONS: The results suggest that greater relative right-frontal cortical activity in adolescent MD is not a result of disease state but can be attributed to comorbid anxiety disorder. SIGNIFICANCE: Results suggest that FAA is not linked to adolescent depression per se and highlight the importance of considering comorbid disorders when examining asymmetry patterns in adolescent MD.

State or trait? Auditory event-related potentials in adolescents with current and remitted major depression.

OBJECTIVE: Event-related potential (ERP) studies have revealed abnormal neurophysiological patterns underlying selective attention in patients with Major Depression (MD). Only few included both patients in acute and remitted state to address the question whether these abnormalities are state- or trait- dependent and none focused on adolescent MD. Thus, the aim of our study was to address this question in an adolescent sample. METHODS: 22 adolescents with acute MD, 20 adolescents with remitted MD (rMD) and 32 healthy controls (HC) performed a standard two-tone auditory oddball task while ERPs (N100, P200, N200, P300) were collected. RESULTS: Adolescents with rMD showed a reduced N200 amplitude to target tones across frontal, central and parietal recording sites. Adolescents with MD exhibited a reduced N200 amplitude to targets in the frontal region compared to HC. No differences emerged between rMD and the MD group. CONCLUSIONS: The reduced N200 amplitude in adolescents with rMD and MD presumably reflects difficulties in stimulus classification and response selection. Our results indicate that this neurophysiological characteristic is a trait marker of adolescent depression.