Frontal alpha asymmetry during emotion regulation in adults with lifetime major depression.

Emotion regulation (ER) often is impaired in current or remitted major depression (MD), although the extent of the deficits is not fully understood. Recent studies suggest that frontal alpha asymmetry (FAA) could be a promising electrophysiological measure to investigate ER. The purpose of this study was to investigate ER differences between participants with lifetime major depression (lifetime MD) and healthy controls (HC) for the first time in an experimental task by using FAA. We compared lifetime MD (n = 34) and HC (n = 25) participants aged 18-24 years in (a) an active ER condition, in which participants were instructed to reappraise negative images and (b) a condition in which they attended to the images while an EEG was recorded. We also report FAA results from an independent sample of adolescents with current MD (n = 36) and HC adolescents (n = 38). In the main sample, both groups were able to decrease self-reported negative affect in response to negative images through ER, without significant group differences. We found no differences between groups or conditions in FAA, which was replicated within the independent adolescent sample. The lifetime MD group also reported less adaptive ER in daily life and higher difficulty of ER during the task. The lack of differences between in self-reported affect and FAA between lifetime MD and HC groups in the active ER task indicates that lifetime MD participants show no impairments when instructed to apply an adaptive ER strategy. Implications for interventional aspects are discussed.

[Overview of chronobiological and sleep medical aspects of depression in adolescents]. / Überblick zu chronobiologischen und schlafmedizinischen Aspekten bei Depressionen im Jugendalter.

Changes in sleep are reported in adolescents with depression with a frequency of up to 71%. Aspects of chronobiology and sleep based on the current scientific literature are illustrated and summarized in this narrative review. The circadian clock synchronizes organisms to the light-dark structure of the environment. The individual synchronization is called "chronotype." Chronotype changes according to age, among other factors, and adolescents experience the latest chronotypes overall. The potential discrepancy between internal and external time is called "social jetlag." Social jetlag is especially pronounced during adolescence. It is associated with numerous health risks, such as depression. Changes in sleep behavior in affective disorders and its comorbidity to depression have also been well described in the literature. In this article, underlying concepts from chronobiology and sleep medicine are initially summarized. Then, health risks of disrupted sleep-wake behavior are described, and connections to depression specifically during adolescence are drawn. The article concludes with clinical recommendations for sleep disorders and depression during adolescence as well as suggestions for further research.

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.

Psychopathological symptoms as precursors of depressive symptoms in adolescence: a prospective analysis of the GINIplus and LISA birth cohort studies.

INTRODUCTION: Depressive symptoms are highly prevalent in adolescence, highlighting the need for early identification of precursors. Research into psychopathological symptoms predicting depressive psychopathology in adolescents is therefore of great relevance. Moreover, given that the prevalence of depressive symptomatology in adolescence shows marked differences between girls and boys, insight into potential sex-specific differences in precursors is important. METHODS: This study examined the relationships between emotional problems, conduct problems, hyperactivity/inattention, peer problems, and difficulties in prosocial behaviour at age 10 (Strengths and Difficulties Questionnaire), and the presence of depressive symptoms at age 15 (Depression Screener for Teenagers). Using data from 2824 participants of the GINIplus and LISA birth cohorts, the association of each SDQ subscale at age 10 years with the presence of depressive symptoms at age 15 years was analyzed using sex-specific logistic regression, adjusting for potential confounders. RESULTS: Emotional problems [odds ratio (OR) 1.99, p = 0.002 for boys and OR 1.77, p < 0.001 for girls] and peer problems (OR 2.62, p < 0.001 for boys, OR 1.91, p = 0.001 for girls) at age 10 showed an increased risk for the presence of depressive symptoms at age 15. Additionally, boys with conduct problems at age 10 were at greater risk of showing depressive symptoms in adolescence (OR 2.50, p < 0.001). DISCUSSION: Based on the identified prospective relationships in our study, it might be of particular importance to tailor prevention approaches during childhood to peer and emotional problems to reduce the risk of depressive psychopathology in adolescence. Moreover, particularly in boys, it seems important to also target conduct problems in childhood as a precursor of depressive symptoms in the adolescent period.

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.

Sex differences in the neural underpinnings of social and monetary incentive processing during adolescence.

The brain's reward system undergoes major changes during adolescence, and an increased reactivity to social and nonsocial incentives has been described as a typical feature during this transitional period. Little is known whether there are sex differences in the brain's responsiveness to social or monetary incentives during adolescence. The aim of this event-related potential (ERP) study was to compare the neurophysiological underpinnings of monetary and social incentive processing in adolescent boys versus girls. During ERP recording, 38 adolescents (21 females, 17 males; 13-18 years) completed an incentive delay task comprising (a) a reward versus punishment condition and (b) social versus monetary incentives. The stimulus-preceding negativity (SPN) was recorded during anticipation of reward and punishment, and the feedback P3 (fP3) along with the feedback-related negativity (FRN) after reward/punishment delivery. During anticipation of social punishment, adolescent boys compared with girls exhibited a reduced SPN. After delivery, male adolescents exhibited higher fP3 amplitudes to monetary compared with social incentives, whereas fP3 amplitudes in girls were comparable across incentive types. Moreover, whereas in boys fP3 responses were higher in rewards than in punishment trials, no such difference was evident in girls. The results indicate that adolescent boys show a reduced neural responsivity in the prospect of social punishment. Moreover, the findings imply that, once the incentive is obtained, adolescent boys attribute a relatively enhanced motivational significance to monetary incentives and show a relative hyposensitivity to punishment. The findings might contribute to our understanding of sex-specific vulnerabilities to problem behaviors related to incentive processing during adolescence.

[Rejection sensitivity in adolescents with major depression]. / Zurückweisungsempfindlichkeit bei Jugendlichen mit Depression.

Objective: Rejection sensitivity (RS) is defined as the disposition to anxiously expect rejection, to perceive it as likely, and to overreact to it. Former studies showed heightened RS in clinically depressed adults and identified it as a predictor for symptoms of depression in adolescents. However, to date there are no studies examining RS as a disposition in adolescents with clinical Depression. Method: In the present study, we compared differences in RS and behavioral intentions in depressive and healthy adolescents after a rejection situation. We included n = 28 adolescents with depression and n = 32 healthy control participants between the ages of 12­17 and applied a German version of the Children's Rejection Sensitivity Questionnaire "CRSQ". Results: It was found that, compared to controls, depressive adolescents show higher RS, are more anxious about rejection, and rate the likelihood of being rejected higher. Furthermore, adolescents with depression more often indicated to resign to rejection and blame themselves for it than their healthy counterparts. Conclusions: Our results are in concordance with the clinical picture and with cognitive theories of the disorder. In future studies, it would be important to examine whether corresponding interventions can have a positive impact on the course of the disease.

Right-lateralization of N2-amplitudes in depressive adolescents: an emotional go/no-go study.

BACKGROUND: Recent studies have proposed the process of emotion regulation as a promising target to study the neurophysiological basis of adolescent depression. Emotion regulation has repeatedly been studied with emotional go/no-go paradigms. To date, no study has examined if the left-frontal hypoactivation associated with depression generalizes to active tasks. The aim of this study was therefore to investigate the hemispheric asymmetry of the N2 component in depressed adolescents in an emotion regulation paradigm. METHODS: Twenty-four adolescents diagnosed with major depression (age 11-18) and 30 healthy controls (age 11-18) performed two emotional go/no-go tasks exhibiting negative faces as go trials and positive faces as no-go trials and vice versa. RESULTS: On the behavioral level, no significant group differences emerged. On the neural level, we found a more right-lateralized N2-amplitude in depressed subjects, while it was more left-lateralized in controls. Furthermore, both groups showed a less negative N2-amplitude to positive no-go stimuli. CONCLUSION: This study provides strong support for a general left-frontal hypoactivity in adolescent depression, which also applies to active emotional go/no-go paradigms. Furthermore, the less negative N2 to positive stimuli is consistent with a generally enhanced impulsivity of adolescents toward appetitive stimuli, which is possibly the base of the differential clinical pattern of adolescent in contrast to adult depression.

Impairment in face processing in autism spectrum disorder: a developmental perspective.

Findings on face identity and facial emotion recognition in autism spectrum disorder (ASD) are inconclusive. Moreover, little is known about the developmental trajectory of face processing skills in ASD. Taking a developmental perspective, the aim of this study was to extend previous findings on face processing skills in a sample of adolescents and adults with ASD. N = 38 adolescents and adults (13-49 years) with high-functioning ASD and n = 37 typically developing (TD) control subjects matched for age and IQ participated in the study. Moreover, n = 18 TD children between the ages of 8 and 12 were included to address the question whether face processing skills in ASD follow a delayed developmental pattern. Face processing skills were assessed using computerized tasks of face identity recognition (FR) and identification of facial emotions (IFE). ASD subjects showed impaired performance on several parameters of the FR and IFE task compared to TD control adolescents and adults. Whereas TD adolescents and adults outperformed TD children in both tasks, performance in ASD adolescents and adults was similar to the group of TD children. Within the groups of ASD and control adolescents and adults, no age-related changes in performance were found. Our findings corroborate and extend previous studies showing that ASD is characterised by broad impairments in the ability to process faces. These impairments seem to reflect a developmentally delayed pattern that remains stable throughout adolescence and adulthood.

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.

Clinical high risk state of major depressive episodes: Assessment of prodromal phase, its occurrence, duration and symptom patterns by the instrument the DEpression Early Prediction-INventory (DEEP-IN).

BACKGROUND: To decrease the incidence of major depressive episodes, indicated prevention that targets clinical high-risk individuals with first detectable signs that forecast mental disorder is a highly relevant topic of preventive psychiatry. Still little is known about the prodrome of MDE. The aim of the current study was to identify the occurrence of a clinical high-risk state of depression, its duration and symptom constellation. METHODS: Seventy-three patients with a diagnosed affective disorder in partial remission were assessed with our newly developed semi-structured extensive clinical instrument, the DEpression Early Prediction-INventory (DEEP-IN). Within DEEP-IN the course of prodromal symptoms was explored by using a life-chart method. RESULTS: The significant majority of patients (93.2 %) reported a prodromal phase. The mean duration was 7.9 months (SD = 12.5). Within the group with an identified prodromal phase, psychopathological (95.6 %) as well as somatic symptoms (88.2 %) were reported. Somatic symptoms showed a moderate-to-strong effect of sex with higher prevalence in females than in males (97.6 % vs 73.1 %; V = 0.370). LIMITATIONS: This feasibility study had only a small sample size. CONCLUSIONS: The majority of patients with affective disorders reported a clinical prodromal phase with both psychopathological and somatic symptoms that developed months before the onset of the depressive episode. The development of structured instruments for the assessment of depressive risk states is a promising approach for indicated prevention of depression in the future.

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.

Can we diagnose mental disorders in children? A large-scale assessment of machine learning on structural neuroimaging of 6916 children in the adolescent brain cognitive development study.

Background: Prediction of mental disorders based on neuroimaging is an emerging area of research with promising first results in adults. However, research on the unique demographic of children is underrepresented and it is doubtful whether findings obtained on adults can be transferred to children. Methods: Using data from 6916 children aged 9-10 in the multicenter Adolescent Brain Cognitive Development study, we extracted 136 regional volume and thickness measures from structural magnetic resonance images to rigorously evaluate the capabilities of machine learning to predict 10 different psychiatric disorders: major depressive disorder, bipolar disorder (BD), psychotic symptoms, attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder, conduct disorder, post-traumatic stress disorder, obsessive-compulsive disorder, generalized anxiety disorder, and social anxiety disorder. For each disorder, we performed cross-validation and assessed whether models discovered a true pattern in the data via permutation testing. Results: Two of 10 disorders can be detected with statistical significance when using advanced models that (i) allow for non-linear relationships between neuroanatomy and disorder, (ii) model interdependencies between disorders, and (iii) avoid confounding due to sociodemographic factors: ADHD (AUROC = 0.567, p = 0.002) and BD (AUROC = 0.551, p = 0.002). In contrast, traditional models perform consistently worse and predict only ADHD with statistical significance (AUROC = 0.529, p = 0.002). Conclusion: While the modest absolute classification performance does not warrant application in the clinic, our results provide empirical evidence that embracing and explicitly accounting for the complexities of mental disorders via advanced machine learning models can discover patterns that would remain hidden with traditional models.

Evaluation of an information booklet for adolescents on depression: evidence from a randomized controlled study.

BACKGROUND: Adolescents with depression often show barriers to seek treatment offers due to various reasons, including limited knowledge about the manifestation of the disorder, its treatment options, or fear of stigmatization. Psychoeducational approaches might reduce these barriers by increasing depression literacy. The aim of the present randomized controlled study was to evaluate whether an innovative and age-appropriate evidence-based information booklet about youth depression increases depression-specific knowledge in adolescents with depression and is also appealing to the target group. METHODS: 50 adolescents with a history of depression (current/remitted) aged 12-18 years participated in the study including a pre-, post- and follow-up assessment. Participants were randomly assigned to one of two groups. The experimental group received a target group-specific information booklet about youth depression including seven subdomains. The active control group received an information booklet about asthma in youth that was highly comparable to the depression booklet in terms of format and length. Before and after reading, and at a four-week follow-up, we assessed knowledge about youth depression based on a questionnaire. Furthermore, participants evaluated the acceptability of the information booklets. RESULTS: Unlike the active control group, the experimental group showed a significant increase in depression-specific knowledge from pre to post and from pre to follow-up across all subdomains. This increase was evident in four subdomains ("symptoms", "treatment", "antidepressants", and "causes"). The overall reception of the information booklet about depression was positive and participants stated that they would recommend the information booklet about depression to their peers. CONCLUSION: This is the first randomized controlled study to demonstrate that an information booklet about youth depression effectively imparts depression-specific knowledge to participants with a history of depression and shows high acceptance. Information booklets that are appealing and increase depression-specific knowledge might be a promising low-threshold and cost-effective approach to reduce barriers to treatment and raise awareness.

Emotion regulation in adolescents with major depression - Evidence from a combined EEG and eye-tracking study.

BACKGROUND: Adolescent major depression (MD) is characterized by deficits in emotion regulation (ER). Little is known about the neurophysiological correlates that are associated with these deficits. Moreover, the additional examination of visual attention during ER would allow a more in-depth understanding of ER deficits but has not yet been applied simultaneously. METHODS: N = 33 adolescents with MD and n = 35 healthy controls (HCs) aged 12-18 years performed an ER task during which they either a) down-regulated their negative affective response to negative images via cognitive reappraisal or b) attended the images without changing their affective response. During the task, the Late Positive Potential (LPP), gaze fixations on emotional image aspects, and self-reported affective responses were collected simultaneously. RESULTS: Compared to HCs, adolescents with MD demonstrated reduced ER success based on self-report but did not differ in LPP amplitudes. Participants in both groups showed increased amplitudes in the middle LPP window when they reappraised negative pictures compared to when they attended them. Only in the HC group, increased LPP amplitudes during reappraisal were paralleled by more positive affective responses. LIMITATION: The applied stimuli were part of picture databases and might therefore have limited self-relevance. CONCLUSIONS: Increased LPP amplitude during ER in both groups might be specific to adolescence and might suggest that ER at this age is challenging and requires a high amount of cognitive resources. These findings provide an important starting point for future interventional studies in youth MD.

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).

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.

[Self-report and parental report of empathy in adolescents with autism]. / Selbst- und Fremdbeurteilung der Empathie bei Jugendlichen mit Autismus.

OBJECTIVE: A deficit in empathy has repeatedly been described as a central feature of autistic disorders. However, little is known about how adolescents with autism evaluate their own empathic abilities, and how their parents judge these skills. The present study assesses affective components of empathy via both self-report and parental report. METHOD: 18 boys with autism and 18 typically developing boys participated in the study. A German translation of the Bryant Index of Empathy was used for the self-assessment of empathy. Parents rated the empathic abilities of their sons using a German version of the Griffith Empathy Measure. Both questionnaires are comparable with regards to content and mainly tap into affective components of empathy. RESULTS: Self-reports of empathy in adolescents with autism did not differ from controls. In contrast, parents of adolescents with autism judged their sons to be less empathic compared to parents of typically developing adolescents. CONCLUSIONS: The discrepancy between unimpaired self-reported empathy and parental report of impaired empathy in adolescents with autism might result from their difficulties in effectively conveying empathic feelings to other people. Alternatively, the results may be explained by impaired introspection on inner experiences in individuals with autism.

Neural processes of reward and punishment processing in childhood and adolescence: An event-related potential study on age differences.

Reward and punishment processing are subject to substantial developmental changes during youth. However, little is known about the neurophysiological correlates that are associated with these developmental changes, particularly with regard to both anticipatory and outcome processing stages. Thus, the aim of this study was to address this research gap in a sample of typically developing children and adolescents. Fifty-four children and adolescents (8-18 years) performed a Monetary Incentive Delay Task comprising a monetary reward and punishment condition. Using event-related brain potential recordings, the cue-P3 and the stimulus-preceding negativity (SPN) were analyzed during the anticipation phase, while the Reward Positivity and the feedback-P3 were analyzed during the outcome phase. When anticipating monetary loss or no gain, SPN amplitude in the right hemisphere decreased with age. Moreover, exploratory analyses revealed a decrease in feedback-P3 amplitudes in response to monetary loss with increasing age. No other group differences were observed. Age-related changes in the SPN and fP3 component suggest that sensitivity to negative outcomes decreases from childhood to late adolescence, supporting the notion that adolescence is associated with reduced harm-avoidance. Longitudinal research including young adults is needed to substantiate our findings and its clinical implications regarding disturbed developmental trajectories in psychiatric populations.

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.