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ObjectiveMethodResultsConclusionPatients with epistemic mistrust struggle to view others as trustworthy sources of knowledge and often default to negative appraisals in social communication. The three communication systems theory posits that resolving epistemic mistrust involves three systems: the epistemic match, improving mentalizing, and the re-emergence of social learning outside therapy. This study aimed to empirically examine the theory to understand how epistemic trust develops in psychotherapy.Using a theory-building case study approach, we analyzed therapeutic processes in six depressed adolescents (Mage = 16.58, SD = 1.17) with varying treatment outcomes. Sixty-six audiotaped psychotherapy sessions were reviewed to compare good- and poor-outcome cases, identifying patterns within therapeutic interactions.Findings provide the first empirical evaluation of the three communication systems theory, offering concrete examples of how it unfolds in clinical practice and suggesting refinements in therapist and patient processes to build epistemic trust. Additional insights into the theory highlight an early “window of opportunity” to foster epistemic openness, the influence of environmental factors outside therapy, and the interactive nature of therapist-patient dynamics.This study refines the theoretical understanding of epistemic trust in psychotherapy, revealing specific therapist and patient behaviors that may facilitate its development. Implications for clinical practice and future research directions are discussed. [ABSTRACT FROM AUTHOR]

Adolescent depression in skipped-generation families is a growing concern, yet the role of grandparenting styles and gender attitudes remains understudied. Data from 1,039 adolescents (511 girls, 528 boys) in rural Chinese skipped-generation families were analyzed. Mediation analyses examined associations between grandparenting styles, gender attitudes, and depression. Higher grandparental rejection correlated with higher depression (Estimate =.35, p <.001), while higher emotional warmth correlated with lower depression (Estimate = −.32, p <.001). Emotional warmth was associated with more egalitarian gender attitudes (Estimate =.12, p <.001). Gender attitudes partially mediated the association between emotional warmth and depression among girls, but not boys. A significant gender difference was found in the association between gender attitudes and depression (p <.05). Grandparenting styles and gender are associated with depression in adolescents from skipped-generation families. Mental health interventions should focus on educating grandparents to provide emotional support and promoting egalitarian gender attitudes, especially among girls. [ABSTRACT FROM AUTHOR]

This study evaluated the role of bidirectional micro- and macro- level positive affect-related processes in the longitudinal coupling of depressive symptoms in parent-adolescent dyads. Using a measurement-burst design, including dyadic experience sampling methods (ESM) and monthly follow-ups over one year, this work investigated associations between (1) parental depressive symptoms and anhedonia and parental daily-life enhancing and dampening responses to youth positive affect; (2) parental daily-life enhancing and dampening and trajectories of youth positive affect, negative affect, and depressive symptoms across one year; and (3) youth developmental trajectories and prospective parental daily-life enhancing and dampening, and parental depressive symptoms and anhedonia at one-year follow-up. Participants included 146 early adolescents (52.1% girls, 47.9% boys; Mage[SD] = 12.71[.86]) and 139 parents (78.7% mothers; Mage[SD] = 44.11[5.08]). Parental enhancing and dampening were measured using a dyadic ESM procedure at baseline and 12-months. Youth completed monthtly questionnaires assessing depressive symptoms and trait positive and negative affect across 12 months. Parents reported on depressive symptoms and anhedonia at baseline and 12-months. Results showed that parental anhedonia negatively related to parental daily-life enhancing, and youths' perceptions of their parents' enhancing and dampening reciprocally related to youth emotional development across one year, with downstream implications for parents' own symptoms of depression. [ABSTRACT FROM AUTHOR]

ObjectiveThe purpose of this study is to examine the association between childhood material hardship and adolescent depression and how the relationship is mediated by neighborhood social cohesion and trust. Previous studies on childhood material hardship and adolescent depression have consistently pointed to the importance of social and environmental contexts in explaining health inequalities among children in socially disadvantaged families. However, little is known about the extent to which neighborhood social context contributes to increasing or decreasing the strength of the association between childhood material hardship and adolescent depression.MethodUsing data from the Future of Families and Child Wellbeing Study (FFCWS) waves 3 and 6, this study conducted Structural Equation Modeling (SEM) analysis to examine whether levels of neighborhood social cohesion and trust mediates the association between childhood material hardship and adolescent depression. The study sample consisted of 2,096 children at age 3 and 15.ResultsFindings from the SEM analysis suggest that childhood material hardship is linked with higher levels of adolescent depression and this pathway is partially mediated by neighborhood social cohesion and trust.DiscussionResults suggest that neighborhood conditions played a role in mediating the association between childhood material hardship and adolescent depression. The implications of the findings are discussed in relation to policy and practice.

Abstract Background The psychosocial factors play an important role in the development of depression in adolescents. we used metabolomics techniques to explore the links among childhood trauma, rumination, resilience, and adolescent depression. Methods We selected 57 adolescent depression patients and 53 healthy adolescents. The Childhood Trauma Questionnaire (CTQ), Hamilton Depression Scale (HAMD), Resilience Scale (CD-RISC), and Redundant Thinking Response Scale (RRS) were employed for the purpose of psychological assessment. The patients were regrouped according to their scores using the 27% high-low grouping method. Blood specimens were collected from all adolescents and metabolic data were obtained using LC–MS. Results We found no statistically significant difference between the groups in terms of age, gender, and body mass index (BMI). HAMD, CTQ, and RRS scores were significantly higher in the adolescent depression group (MDD) than in the adolescent healthy control group (HC), and CD-RISP scores were significantly lower than in the HC group (P

Abstract Objective To investigate the effects of depression on non-suicidal self-injury (NSSI) and related psychological conditions in adolescents with unipolar disorder (UD) and bipolar disorder (BD), and to provide a basis for accurate prevention and intervention of NSSI behaviors in adolescents. Methods This cross-sectional study collected data from adolescents aged 12–18 years with depressive episodes who exhibited NSSI behaviors and attended the psychiatric outpatient clinic of Huangshi City Psychiatric Specialized Hospital from 2018 to 2023. Depressive episodes were clinically diagnosed by two psychiatrists according to the ICD-10. Results In terms of NSSI behavioral patterns and severity, adolescents with UD displayed more frequent behaviour of intentionally burning themselves with cigarettes and had more instances of self-inflicted suicidal thoughts that were not carried out compared to those with BD, and the differences between the two groups were statistically significant (P

Abstract Background Abnormal cognitive response to pain is consistently associated with deleterious outcomes among adolescents with depression. Highly relevant to both pain and cognition, dorsolateral prefrontal cortex (DLPFC) is important to understanding pain cognition. Our study aimed to characterize the circuit of DLPFC and the efficacy of transcranial magnetic stimulation (TMS) over DLPFC on pain cognition in adolescents with depression. Methods Using neuroimaging data, we first compared functional connectivity (FC) of DLPFC between 60 adolescents with depression and 65 controls. The patients were then divided into add-on TMS group (N = 30) and Sertraline group (N = 30). Clinical outcome was determined using Pain Vigilance and Awareness Questionnaire (PVAQ) and Pain Catastrophizing Scale (PCS). Finally, we conducted regression analysis to assess the effect that FC of DLPFC contributes to in predicting clinical outcome. Results FC analysis showed that compared to controls, patients displayed hyperconnection of left DLPFC - left triangular part of inferior frontal gyrus (IFG), which was significantly correlated with higher PCS total-, magnification- and helplessness-scores. Patients also showed hyperconnection of right DLPFC - right supramarginal gyrus (SMG), which was correlated with lower PCS total- and rumination- scores. After intervention, the add-on TMS group displayed significantly decreased score on PVAQ, PCS total and rumination. FC of left DLPFC - bilateral triangular part of IFG, - right SMG, as well as right DLPFC - left putamen, could predict the improvement of pain vigilance and magnification. Conclusion Our results point to a key role of DLPFC acting as a connection linking cognitive control and pain processing in adolescents with depression. Trial registration The study is registered in https://www.chictr.org.cn/ with a registration number ChiCTR2000039503 (date: 10.30.2020).

Abstract Background Previous research has indicated that personality traits, loneliness, and problematic internet use (PIU) significantly contribute to the prevalence of adolescent depression. However, the specific interrelationships among these variables in explaining the occurrence of depression remain unclear. Drawing upon susceptibility theory and cognitive-behavioral theory, this study explored whether personality traits influences adolescent depression through loneliness and PIU. Methods A total of 2476 adolescents (aged 12–18) from all over the country completed a psycho-social test, including the 10-Item Big Five Personality Inventory (BFI-10), three-Item Loneliness Scale (T-ILS), Problematic Internet Use Questionnaire-Short Form (PIUQ-SF-6) and the Patient Health Questionnaire-9 (PHQ-9). The mediation model was built and bootstrap method was used to test the mediating effect. Results Results showed that neuroticism, conscientiousness, openness, and agreeableness have a direct role on depression. Loneliness and PIU partially mediated the relationship between neuroticism, conscientiousness, agreeableness and depression, and completely mediated the relationship between extroversion and depression. Conclusions The results suggest that loneliness and PIU play important mediating roles in the relationship between personality traits and depression. This remind us that alleviating sense of loneliness and reducing overuse of the internet are a strategy for improve depression among adolescents.

Background: The psychosocial factors play an important role in the development of depression in adolescents. we used metabolomics techniques to explore the links among childhood trauma, rumination, resilience, and adolescent depression. Methods: We selected 57 adolescent depression patients and 53 healthy adolescents. The Childhood Trauma Questionnaire (CTQ), Hamilton Depression Scale (HAMD), Resilience Scale (CD-RISC), and Redundant Thinking Response Scale (RRS) were employed for the purpose of psychological assessment. The patients were regrouped according to their scores using the 27% high-low grouping method. Blood specimens were collected from all adolescents and metabolic data were obtained using LC–MS. Results: We found no statistically significant difference between the groups in terms of age, gender, and body mass index (BMI). HAMD, CTQ, and RRS scores were significantly higher in the adolescent depression group (MDD) than in the adolescent healthy control group (HC), and CD-RISP scores were significantly lower than in the HC group (P < 0.001). There were significant differences between the low childhood trauma group (LCT) and high childhood trauma group (HCT), the low rumination group (LRR) and high rumination group (HRR), and the low resilience group (LPR) and high resilience group (HPR) (P < 0.001). RRS, CTQ and HAMD scores were positively correlated, RRS and CTQ scores were positively correlated, CD-RIS was negatively correlated with HAMD, RRS and CTQ scores (P < 0.01). More importantly, we found that DHEAS and LPA (22:6) were identified as significant differential metabolites in both the depressed and normal groups, as well as in the high and low childhood trauma groups. N-Acetyl-L-aspartic acid and DHEAS were identified as significant differential metabolites in both the depressed and normal groups, as well as in the high and low childhood rumination groups. Pseudouridine and LPA(22:6) were identified as significant differential metabolites in both the depressed and normal groups, as well as in the high and low childhood resilience groups. Conclusion: Psychological factors (childhood trauma, rumination, resilience) are biologically linked to the development of depression in adolescents. The impact of rumination on adolescent depression may be associated with DHEA. The impact of childhood trauma and resilience on adolescent depression may be associated with LPA (22:6). [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of depression on non-suicidal self-injury (NSSI) and related psychological conditions in adolescents with unipolar disorder (UD) and bipolar disorder (BD), and to provide a basis for accurate prevention and intervention of NSSI behaviors in adolescents. Methods: This cross-sectional study collected data from adolescents aged 12–18 years with depressive episodes who exhibited NSSI behaviors and attended the psychiatric outpatient clinic of Huangshi City Psychiatric Specialized Hospital from 2018 to 2023. Depressive episodes were clinically diagnosed by two psychiatrists according to the ICD-10. Results: In terms of NSSI behavioral patterns and severity, adolescents with UD displayed more frequent behaviour of intentionally burning themselves with cigarettes and had more instances of self-inflicted suicidal thoughts that were not carried out compared to those with BD, and the differences between the two groups were statistically significant (P < 0.05). For psychological status, Nurses′ Global Assessment of Suicide Risk (NGASR) scores were significantly higher in adolescents with BD than in those with UD (P < 0.05). There was a significant negative correlation between anxiety scores and the frequency of NSSI in adolescents with BD (P < 0.05); that is, the more anxious the adolescents with BD, the lower the frequency of NSSI. The NGASR scores of adolescents with UD and BD were significantly and positively correlated with the frequency of NSSI occurrences (P < 0.05); higher NGASR scores of adolescents with UD and BD corresponded with higher frequencies of NSSI. Conclusion: The differences in NSSI behaviors between adolescents with UD and those with BD were statistically significant in terms of self-injury method and severity. Adolescents with UD experienced more severe consequences related to NSSI behaviors. Regarding psychological conditions, adolescents with BD are at a higher risk of suicide. An inverse relationship was observed between anxiety severity and the frequency of NSSI in adolescents with BD; severe anxiety was associated with lower NSSI frequency. Additionally, higher suicide risk was associated with a higher frequency of NSSI in adolescent patients with either UD or BD. Therefore, different prevention and intervention measures are needed to address NSSI behaviors in adolescents with UD and BD. [ABSTRACT FROM AUTHOR]

This study explores the rising trend of loneliness and depression among adolescents in the context of Chinese culture, investigating the relationship between different patterns of disclosure and secrecy and adolescent anxiety and loneliness. A person‐centered approach was used to explore disclosure and secrecy in relationships of 253 adolescents (M = 15.52, range = 14–18, 54.4% female) from Nanjing's public schools and the impact of these patterns on their levels of depression and loneliness. The results indicate that adolescent disclosure and secrecy toward parents and good friends are correlated with adolescent depression and loneliness. Five groups can be identified based on disclosure and secrecy, with each group demonstrating significant differences in the degree of disclosure and secrecy and distinct characteristics. Significant differences exist in the levels of adolescent depression and loneliness among the different groups. This study emphasizes the value of a person‐centered approach. Findings suggest that having multiple avenues for dialogue is more beneficial than merely increasing the volume of disclosure within any single channel. This emphasizes the importance of a diversified support network in enhancing adolescent well‐being. The research also recognizes that small samples can uncover more complex or diversified groups that exhibit unique behavioral patterns within specific cultures. [ABSTRACT FROM AUTHOR]

Background: Abnormal cognitive response to pain is consistently associated with deleterious outcomes among adolescents with depression. Highly relevant to both pain and cognition, dorsolateral prefrontal cortex (DLPFC) is important to understanding pain cognition. Our study aimed to characterize the circuit of DLPFC and the efficacy of transcranial magnetic stimulation (TMS) over DLPFC on pain cognition in adolescents with depression. Methods: Using neuroimaging data, we first compared functional connectivity (FC) of DLPFC between 60 adolescents with depression and 65 controls. The patients were then divided into add-on TMS group (N = 30) and Sertraline group (N = 30). Clinical outcome was determined using Pain Vigilance and Awareness Questionnaire (PVAQ) and Pain Catastrophizing Scale (PCS). Finally, we conducted regression analysis to assess the effect that FC of DLPFC contributes to in predicting clinical outcome. Results: FC analysis showed that compared to controls, patients displayed hyperconnection of left DLPFC - left triangular part of inferior frontal gyrus (IFG), which was significantly correlated with higher PCS total-, magnification- and helplessness-scores. Patients also showed hyperconnection of right DLPFC - right supramarginal gyrus (SMG), which was correlated with lower PCS total- and rumination- scores. After intervention, the add-on TMS group displayed significantly decreased score on PVAQ, PCS total and rumination. FC of left DLPFC - bilateral triangular part of IFG, - right SMG, as well as right DLPFC - left putamen, could predict the improvement of pain vigilance and magnification. Conclusion: Our results point to a key role of DLPFC acting as a connection linking cognitive control and pain processing in adolescents with depression. Trial registration: The study is registered in https://www.chictr.org.cn/ with a registration number ChiCTR2000039503 (date: 10.30.2020). [ABSTRACT FROM AUTHOR]

Introduction: Given worsening youth mental health over the past years, mobile medical units are a potential avenue to increase access to mental healthcare services.Methods: This 1-year retrospective study examined a self-administered psychosocial assessment, and referrals made to mental health services for adolescent patients served by a mobile medical unit. We extracted psychosocial assessment responses, Patient Health Questionnaire (PHQ-9) scores, and mental health referral information for patients seen by the mobile medical unit in 2022 and examined rates and predictors of depression and referral to mental health services.Results: Of the 326 patients who completed the psychosocial assessment, one in five had moderate to severe depression symptoms based on PHQ-9 scores. Factors associated with referral to mental healthcare included female gender identity, LGBTQ+ identity, and several factors from the psychosocial assessment. Additionally, 13.8% wanted a mental health referral, and 16.6% were referred to mental healthcare. Patients who desired to see a mental health provider had higher odds of being referred (p < 0.0001). All patients with moderate to severe depression who were not already connected to mental healthcare and wanted a referral were referred.Conclusion: This study documents the impact of a mobile medical unit programme in identifying adolescent patients with mental health needs and referring them to mental healthcare. [ABSTRACT FROM AUTHOR]

Purpose: Delaying high school start times prolongs weekday sleep. However, it is not clear if longer sleep reduces depression symptoms and if the impact of such policy change is the same across groups of adolescents. Methods: We examined how gains in weekday sleep impact depression symptoms in 2,134 high school students (mean age 15.16 ± 0.35 years) from the Minneapolis metropolitan area. Leveraging a natural experiment design, we used the policy change to delay school start times as an instrument to estimate the effect of a sustained gain in weekday sleep on repeatedly measured Kandel-Davies depression symptoms. We also evaluated whether allocating the policy change to subgroups with expected benefit could improve the impact of the policy. Results: Over 2 years, a sustained half-hour gain in weekday sleep expected as a result of the policy change to delay start times decreased depression symptoms by 0.78 points, 95%CI (-1.32,-0.28), or 15.6% of a standard deviation. The benefit was driven by a decrease in fatigue and sleep-related symptoms. While symptoms of low mood, hopelessness, and worry were not affected by the policy on average, older students with greater daily screen use and higher BMI experienced greater improvements in mood symptoms than would be expected on average, signaling heterogeneity. Nevertheless, universal implementation outperformed prescriptive strategies. Conclusion: High school start time delays are likely to universally decrease fatigue and overall depression symptoms in adolescents. Students who benefit most with respect to mood are older, spend more time on screens and have higher BMI. [ABSTRACT FROM AUTHOR]

Purpose: This study longitudinally investigated the predictors and mediators of adolescent smartphone addiction by examining the impact of parental smartphone addiction at T1 on adolescent smartphone addiction at T3, as well as the separate and sequential role of adolescent self-esteem and depression at T2 as mediating factors. Design/methodology/approach: This study used a hierarchical regression and the PROCESS macro (Model 6) to investigate research model by collecting 3,904 parent-adolescent pairs. Panel data were collected from three waves of the Korean Children and Youth Panel Survey (KCYPS). Findings: First, the result showed that parental smartphone addiction at T1 significantly and positively predicted adolescent smartphone addiction at T3. Second, the serial mediation analysis revealed that the impact of parental smartphone addiction at T1 on adolescent smartphone addiction at T3 was mediated by adolescent self-esteem and depression at T2 independently and serially. Originality/value: The findings enhance our comprehension of the impact of parental smartphone addiction, adolescent self-esteem and depression, on adolescent smartphone addiction. [ABSTRACT FROM AUTHOR]

BACKGROUND: The school climate concept has been promising, but has long‐standing critiques that have not been adequately addressed to date. The School as a Protective Factor approach represents one attempt to offer a new approach that builds on and extends beyond the concept of school climate while addressing previously identified limitations. CONTRIBUTIONS TO THEORY: The School as a Protective Factor approach offers a new framework for conceptualizing, measuring, and establishing protective school social and learning environments that co‐promote academic achievement and student health in schools, especially student mental health and substance use/abuse prevention. This new framework includes clear definitions, explicit goals, firmly established constructs, validated measures, and an intentionally parsimonious approach that prioritizes the implementation of well‐established, high‐impact constructs. CONCLUSIONS AND IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: The School as a Protective Factor approach presents a simple, easy‐to‐use means of ensuring a school social environment that meets the developmental, academic, and health needs of all children and adolescents while maximizing protection across a range of desired outcomes. Perhaps most importantly, it does so in a manner that is manageable and easily integrated into every aspect of schooling, resonates with the practical experience of school personnel, and includes brief, effective, and free measurement tools. [ABSTRACT FROM AUTHOR]

BACKGROUND: The conceptual framework for School as a Protective Factor approach was presented in a companion article in this issue of the journal. The current article describes the validation of the School as a Protective Factor‐Brief (SPF‐Brief), a 13‐item survey measuring the 3 core constructs and 13 defining characteristics of this framework. METHODS: The SPF‐Brief was validated through 2 studies. The developmental study used a longitudinal design including 1349 participants who completed surveys over 5 semesters, while the validation study used a cross‐sectional design with 2775 participants. Both studies included middle and high school students. Factor analysis, growth model analysis, criterion‐related validation, and outcome analysis were employed. RESULTS: Analyses provided strong evidence supporting the reliability and validity of the instrument and conceptual framework. Higher SPF‐Brief scores were associated with higher math grades, English grades, and quality of life, as well as lower rates of anxiety, depression, conduct disorder, alcohol, e‐cigarette, tobacco, and cannabis use. Effect size estimates ranged from moderate to strong. CONCLUSIONS: These findings suggest the utility of the SPF‐Brief instrument and the School as a Protective Factor framework. Together, they may offer advantages to the traditional school climate approach. [ABSTRACT FROM AUTHOR]

Background: Previous research has indicated that personality traits, loneliness, and problematic internet use (PIU) significantly contribute to the prevalence of adolescent depression. However, the specific interrelationships among these variables in explaining the occurrence of depression remain unclear. Drawing upon susceptibility theory and cognitive-behavioral theory, this study explored whether personality traits influences adolescent depression through loneliness and PIU. Methods: A total of 2476 adolescents (aged 12–18) from all over the country completed a psycho-social test, including the 10-Item Big Five Personality Inventory (BFI-10), three-Item Loneliness Scale (T-ILS), Problematic Internet Use Questionnaire-Short Form (PIUQ-SF-6) and the Patient Health Questionnaire-9 (PHQ-9). The mediation model was built and bootstrap method was used to test the mediating effect. Results: Results showed that neuroticism, conscientiousness, openness, and agreeableness have a direct role on depression. Loneliness and PIU partially mediated the relationship between neuroticism, conscientiousness, agreeableness and depression, and completely mediated the relationship between extroversion and depression. Conclusions: The results suggest that loneliness and PIU play important mediating roles in the relationship between personality traits and depression. This remind us that alleviating sense of loneliness and reducing overuse of the internet are a strategy for improve depression among adolescents. [ABSTRACT FROM AUTHOR]

Abstract Background Hippocampal disruptions represent potential neuropathological biomarkers in depressed adolescents with cognitive dysfunctions. Given heterogeneous outcomes of whole-hippocampus analyses, we investigated subregional abnormalities in depressed adolescents and their associations with symptom severity and cognitive dysfunctions. Methods MethodsSeventy-nine first-episode depressive patients (ag = 15.54 ± 1.83) and 71 healthy controls (age = 16.18 ± 2.85) were included. All participants underwent T1 and T2 imaging, completed depressive severity assessments, and performed cognitive assessments on memory, emotional recognition, cognitive control, and attention. Freesurfer was used to segment each hippocampus into 12 subfields. Multivariable analyses of variance were performed to identify overall and disease severity-related abnormalities in patients. LASSO regression was also conducted to explore the associations between hippocampal subfields and patients’ cognitive abilities. Results Depressed adolescents showed decreases in dentate gyrus, CA1, CA2/3, CA4, fimbria, tail, and molecular layer. Analyses of overall symptom severity, duration, self-harm behavior, and suicidality suggested that severity-related decreases mainly manifested in CA regions and involved surrounding subfields with disease severity increases. LASSO regression indicated that hippocampal subfield abnormalities had the strongest associations with memory impairments, with CA regions and dentate gyrus showing the highest weights. Conclusions Hippocampal abnormalities are widespread in depressed adolescents and such abnormalities may spread from CA regions to surrounding areas as the disease progresses. Abnormalities in CA regions and dentate gyrus among these subfields primarily link with memory impairments in patients. These results demonstrate that hippocampal subsections may serve as useful biomarkers of depression progression in adolescents, offering new directions for early clinical intervention.

Wenliang Liu, Gongying Li, Mengya Zhu, Lin Yang Department of Psychological, Huai’an No. 3 People’s Hospital, Huaian, People’s Republic of ChinaCorrespondence: Gongying Li, Department of Psychological, Huai’an No. 3 People’s Hospital, No. 272, Huaihai West Road, Huaian, 223001, People’s Republic of China, Tel +86-517-83285124, Email ligongying2005@126.comObjective: To investigate the association between single nucleotide polymorphisms (SNPs) of tryptophan hydroxylase 2 (TPH2) (rs11178997, rs11178998, and rs120074175) and negative life events in adolescent depression with Non-suicidal self-injury (NSSI).Methods: Genomic DNA was extracted from 197 adolescents with depression (participants group, including NSSI group and non-NSSI group), as well as from 100 healthy controls (control group), in northern China. PCR technology was utilized to amplify DNA fragments and detect genotypes in both groups. The Adolescent Life Event Scale (ASLEC) was employed to conduct a questionnaire survey among the participants and control groups. Differences in allele and genotype frequency distribution between the two groups were analyzed using the X^2 test, while generalized multifactor dimensionality reduction (GMDR) was used to analyze gene-environment interactions.Results: Significant differences were observed in ASLEC scores between the control group and both the NSSI group and non-NSSI group (P< 0.05). Additionally, significant differences were found in the interpersonal relationship factor and punishment factor between the NSSI group and non-NSSI group (P < 0.05). Moreover, a significant difference was identified in SNP genotype of rs11178997 between the depression group (NSSI group + non-NSSI group) and control group (P< 0.05). GMDR analysis revealed an interaction among rs11178997, rs11178998, and ASLEC.Conclusion: Adolescents with depression, particularly females, may exhibit a tendency to employ NSSI as an emotional coping mechanism when confronted with greater family and interpersonal challenges. The AT genotype of TPH2 gene locus rs11178997 is more prevalent among adolescents with depression. Furthermore, the occurrence of NSSI may be associated with an interaction involving polymorphic sites rs11178997 and rs11178998 along with life events.Keywords: adolescent depression, non-suicidal self-injury, tryptophan hydroxylase 2, gene polymorphism, life events in adolescence

Based on ecological systems theory and the genetic and environmental research paradigm, the current study explored the effect of school interpersonal relationship quality (peer and teacher-student) on adolescent depression and the role of perceived stress and the OXTR gene. Based on the statistical power of previous G*E interaction studies, A follow-up survey was conducted with 603 Chinese adolescents (average age = 14.76 ± 0.72 years at the time of the initial measurement; range: 13 to 15) using a questionnaire method (Short Form of the Center for Epidemiological Studies Depression Scale, The Chinese version of Perceived Stress Scale, short form of Friendship Quality Questionnaire and Teacher-student Relationship) and DNA typing technique. The study found that (1) school interpersonal relationship quality influenced adolescent depression; (2) perceived stress fully mediated the relationship between school interpersonal relationship quality and adolescent depression; (3) the OXTR gene rs2254298 and rs53576 polymorphisms moderated both the direct pathway and the second half of the indirect pathway. Specifically, individuals carrying the rs2254298 polymorphism A/G genotype and the rs53576 polymorphism A genotype exhibited a significantly enhanced effect of interpersonal relationship quality and perceived stress on adolescent depression, supporting the differential susceptibility model. [ABSTRACT FROM AUTHOR]

Background: Adolescents face an increased risk of depression due to hormonal fluctuations and the impact on physiological and immunological biomarkers, which are associated with a heightened risk of symptoms of depression during puberty. Aims: Investigate the roles of interleukin-6 (IL-6) and vitamin D (Vt.D) as influential factors in increasing the risk of depression among adolescents. Methods: Cross-sectional study of 130 adolescents aged 12 to 18, between November 2023 and February 2024. This study examined serum IL-6 and Vt.D levels. Additionally, the calculation relies on the Beck Depression Inventory to measure the severity of depression. Results: Adolescents have a significant increase in depression symptoms, with 59.2% showing signs of depression. Depressed adolescents show a significant increase (p<0.001) in IL-6 and decreased Vt. D levels compared to non-depressed individuals. Depression scores were significantly correlated positively with IL-6 levels and negatively with Vt. D levels and Linear regression analysis exhibit a significant positive predictor of IL-6 (B: 4.430; 95% CI: 3.023 to 5.836). Vt. D is a significantly negative predictor (B: -0.145; 95% CI: -0.220 to -0.071) associated with depression scores. Logistics regression showed the risk of depression is higher in females (59.7%; OR: 2.33; p=0.002) compared to males (40.3%; OR: 0.939; p=0.803), overweight and obese adolescents (OR: 3.750, p=0.019; and OR: 2.333, p=0.022), than normal weight and underweight peers. They highly predicted depression in adolescents with deficiency Vt. D (OR: 24.4, p<0.001), and depressed severity increased with no take Vt. D supplement (OR: 1.769, p=004), more than those who had taken Vt. D Supplement (OR: 0.571, p=0.207). Discussion: Vitamin D affects serotonin synthesis by a unique biological mechanism. Serotonin is always involved in the pathophysiology of depression. Vitamin D may have a neuroprotective effect on the inflammatory process in the body. Support immunomodulation leads to an increase in inflammatory cytokines and vitamins, which suppresses the synthesis of inflammatory cytokines such as IL-6 by monocytes. Conclusions: The likelihood of severe adolescent depression was found to be associated with elevated IL-6 levels and a deficiency in Vitamin D, serving as available predictors. [ABSTRACT FROM AUTHOR]

Obesity is a well-recognized risk factor for adolescent depressive symptoms, but mediating mechanisms of this association have scarcely been studied. This study is unique in examining an indirect pathway of this link via body esteem (BE) prospectively from childhood (8–12 years) to adolescence (13–18 years). In addition, potential gender moderation was examined. This study utilized data from a case–control study comparing 100 children with and without obesity matched on important confounders (age, gender, and socioeconomic status). Our findings provide support for the mediating role of BE in the link between childhood weight status and adolescent depressive symptoms at a 5-year follow-up. This mediation effect did not differ between boys and girls. The findings suggest the relevance of specifically targeting children's BE in preventive intervention programs among children with obesity to prevent future mental health problems. [ABSTRACT FROM AUTHOR]

Treating depression in adolescents is a significant challenge, and major depressive disorder (MDD) with suicidal ideation and treatment-resistant depression (TRD) are common and potentially devastating to optimal psychological and physical development in this age group. Suicide is among the leading causes of youth mortality, and TRD occurs in up to 40% of adolescents with MDD. TRD involves severe, persistent symptoms that are hard to treat, significantly reducing functioning and quality of life. We conducted a literature search focusing on key terms related to ketamine and esketamine for MDD with suicidal ideation and TRD in adolescents, aiming to review the potential utility of these molecules in adolescents for these conditions. Ketamine has shown efficacy in reducing depressive symptoms in adolescents with TRD. Esketamine has shown efficacy in reducing depressive symptoms and treating suicidal ideation in adolescents. Both ketamine and esketamine have demonstrated favorable safety and tolerability profiles. Using these drugs for serious conditions like adolescent MDD with suicidal thoughts and TRD can effectively treat symptoms, reduce self-harm and suicide risks, and provide a window for longer-term therapeutic interventions. The prompt and effective treatment of TRD could improve adolescents' quality of life. However, more research is needed to optimize treatment protocols and evaluate long-term effects. [ABSTRACT FROM AUTHOR]

PURPOSE: Children of mothers with prenatal depression have elevated risk for depression later in life. Pregnant women are hesitant to use antidepressants due to fear of adverse fetal effects. To inform prevention, this study examined associations between maternal prenatal depression and antidepressant use, and adolescent depressive symptoms and suicidality. PATIENTS AND METHODS: Prospective data from 74,695 mother-adolescent dyads from the Kaiser Permanente Northern California integrated healthcare delivery system were used. Three prenatal exposure groups were examined: maternal depression and antidepressants (Med); depression and no antidepressants (No-Med); neither depression nor antidepressants (NDNM). Adolescent depressive symptoms (Patient Health Questionnaire-2 score ≥3) and suicidality were assessed for 12- to 18-year-olds. Associations were analyzed using mixed effects logistic regression, adjusted for confounders. RESULTS: Maternal prenatal depression was associated with higher odds of adolescent depressive symptoms (Med odds ratio [OR]: 1.50, 95% confidence interval [CI]: 1.23-1.84; No-Med OR: 1.59, CI: 1.34-1.88) and suicidality (Med OR: 2.36, CI: 1.67-3.34; No-Med OR: 1.54, CI: 1.10-2.14) compared to no prenatal depression (NDNM). Adolescents exposed to prenatal depression and antidepressants were not at greater odds of depressive symptoms (Med OR: 0.95, CI: 0.74-1.21) compared to those not exposed to antidepressants (No-Med). However, they showed non-significant but greater odds of suicidality (Med OR: 1.54, CI: 0.99-2.39). CONCLUSION: Our findings suggest that maternal prenatal depression is associated with adolescent depressive symptoms and suicidality, and that exposure to antidepressants in utero does not increase risk of depressive symptoms, specifically. While not statistically significant, the increased odds of suicidality among adolescents exposed to antidepressants suggest a possible association; however, further investigation is needed. After replication, the findings of this study may inform shared clinical decision-making when considering options regarding antidepressant use for the treatment of maternal prenatal depression.

Adolescent depression presents a significant global mental health concern, exerting profound impacts on various facets of young people's lives. Cognitive Behavioral Therapy (CBT) has emerged as a leading intervention for tackling adolescent depression, grounded in principles derived from cognitive theory. This review delves into the effectiveness, mechanisms, and outcomes of CBT in addressing adolescent depression, synthesizing findings from a range of empirical studies including randomized controlled trials, meta-analyses, and systematic reviews. The review underscores the consistent efficacy of CBT in diminishing depressive symptoms among adolescents, elucidating mechanisms such as cognitive restructuring and behavioral activation that underpin its therapeutic effects. Additionally, CBT yields favorable outcomes beyond mere symptom reduction, encompassing enhancements in social connections and academic performance. Nonetheless, challenges such as limited accessibility and hurdles in engaging adolescents persist in CBT implementation. To surmount these obstacles, forthcoming research ought to concentrate on devising innovative delivery approaches, such as internet-based interventions and school-centered programs. In essence, CBT stands as a pivotal component in the treatment of adolescent depression, furnishing a holistic framework to address the intricate interplay of cognitive, emotional, and behavioral elements, thereby fostering the mental well-being of adolescents on a global scale.

Abstract Background Depressive episodes in adolescents are often accompanied by various physical symptoms, but few studies have explored the association between depression and fever, This case study is the first to report the relationship between unexplained recurrent high fever and depression. Case presentation H is a 15 year old adolescent female currently in junior year. 2 + months ago, H gradually felt depressed after a class change. Around the time, the patient suddenly developed chills with no obvious trigger and fever. H was treated with anti-infective and anti-viral treatments all of which did not show significant improvement. No significant abnormality was seen in any of the related examinations. Considering that the patient’s anxiety, depression and somatic symptoms were obvious during the course of the disease, she was given venlafaxine hydrochloride extended-release capsule 75 mg/d; tandospirone citrate capsule 10 mg Bid; alprazolam tablets 0.4 mg qn to improve mood and sleep; supplemented with transcranial repetitive magnetic stimulation therapy 2 times/d; visible light therapy 1 time/d and psychological counseling once. Over the 6 days of treatment, the patient’s body temperature gradually returned to the normal range and her mood improved significantly. Conclusion Depression should be considered a potential cause of unexplained recurrent fevers in adolescents, even when the temperature is significantly outside the normal range.

Purpose: The aim of this literature review is to examine evidence of time trends and birth cohort effects in depressive disorders and symptoms among US adolescents in peer-reviewed articles from January 2004 to April 2022. Methods: We conducted an integrative systematic literature review. Three reviewers participated at different stages of article review. Of the 2234 articles identified in three databases (Pubmed, ProQuest Central, Ebscohost), 10 met inclusion criteria (i.e., adolescent aged United States populations, included information about birth cohort and survey year, focused on depressive symptoms/disorders). Results: All 10 articles observed increases in depressive symptoms and disorders in adolescents across recent survey years with increases observed between 1991 and 2020. Of the 3 articles that assessed birth cohort trends, birth cohort trends were less prominent than time period trends. Proposed explanations for increases included social media, economic-related reasons, changes in mental health screening and diagnosis, declining mental health stigma, increased treatment, and, in more recent years, the COVID-19 pandemic. Conclusions: Multiple cross-sectional surveys and cohort studies documented rising prevalence of depressive symptoms and disorder among adolescents from 1991 to 2020. Mechanisms driving this increase are still unknown. Research to identify these mechanisms is needed to inform depression screening and intervention efforts for adolescents. [ABSTRACT FROM AUTHOR]

Objective: Among adolescents with depression, the occurrence of non-suicidal self-injury (NSSI) behavior is prevalent, constituting a high-risk factor for suicide. However, there has been limited research on the neuroimaging mechanisms underlying adolescent depression and NSSI behavior, and the potential association between the two remains unclear. Therefore, this study aims to investigate the alterations in functional connectivity (FC) of the regions in the prefrontal cortex with the whole brain, and elucidates the relationship between these alterations and NSSI behavior in adolescents with depression. Methods: A total of 68 participants were included in this study, including 35 adolescents with depression and 33 healthy controls. All participants underwent assessments using the 17-item Hamilton Depression Rating Scale (17-HAMD) and the Ottawa Self-Harm Inventory. In addition, functional magnetic resonance imaging (fMRI) data of the participants' brains were collected. Subsequently, the FCs of the regions in the prefrontal cortex with the whole brain was calculated. The FCs showing significant differences were then subjected to correlation analyses with 17-HAMD scores and NSSI behavior scores. Result: Compared to the healthy control group, the adolescent depression group exhibited decreased FCs in several regions, including the right frontal eye field, left dorsolateral prefrontal cortex, right orbitofrontal cortex, left insula and right anterior cingulate coetex. The 17-HAMD score was positively correlated with the frequency of NSSI behavior within 1 year (rs = 0.461, p = 0.005). The FC between the right anterior cingulate cortex and the right precuneus showed a negative correlation with the 17-HAMD scores (rs = -0.401, p = 0.023). Additionally, the FC between the right orbitofrontal cortex and the right insula, demonstrated a negative correlation with the frequency of NSSI behavior within 1 year (rs = -0.438, p = 0.012, respectively). Conclusion: Adolescents with depression showed decreased FCs of the prefrontal cortex with multiple brain regions, and some of these FCs were associated with the NSSI frequency within 1 year. This study provided neuroimaging evidence for the neurophysiological mechanisms underlying adolescent depression and its comorbidity with NSSI behavior. [ABSTRACT FROM AUTHOR]

The incidence of adolescent depression has markedly risen in recent years, with a high recurrence rate into adulthood. Diagnosis in adolescents is challenging due to subjective factors, highlighting the crucial need for objective diagnostic markers. Our study enrolled 204 participants, including healthy controls (n = 88) and first-episode adolescent depression patients (n = 116). Serum samples underwent gas chromatography–mass spectrometry (GC–MS) analysis to assess non-esterified fatty acids (NEFA) expression. Machine learning and ROC analysis were employed to identify potential biomarkers, followed by bioinformatics analysis to explore underlying mechanisms. Nearly all differentially expressed NEFA exhibited significant downregulation. Notably, nonanoic acid, cis-10-pentadecenoic acid, cis-10-carboenoic acid, and cis-11-eicosenoic acid demonstrated excellent performance in distinguishing adolescent depression patients. Metabolite-gene interaction analysis revealed these NEFAs interacted with multiple genes. KEGG pathway analysis on these genes suggested that differentially expressed NEFA may impact PPAR and cAMP signaling pathways. Inclusion of diverse populations for evaluation is warranted. Biomarkers identified in this study require samples that are more in line with the experimental design for external validation, and further basic research is necessary to validate the potential depressive mechanisms of NEFA. The overall reduction in NEFA expression in first-episode adolescent depression patients suggests a potential mediation of depression symptoms through cAMP and PPAR signaling pathways. NEFA levels show promise as a diagnostic tool for identifying first-episode adolescent depression patients. • The first detailed evaluation of the expression changes of NEFA in first-episode adolescent depression patients • Overall inhibition of NEFA expression levels in adolescent first-episode depression patients • NEFA can serve as a good diagnostic marker in adolescent first-episode depression patients. • NEFA may induce depression by affecting cAMP and PPAR signaling pathways. [ABSTRACT FROM AUTHOR]

Determinants related to suicide attempts for adolescents have been the subject of several studies. Here, we aimed to reveal the factors that constitute the idea of suicide by examining the depression-anxiety status and self-concept of adolescents, as well as their socio-demographic characteristics. A total of 100 adolescents between the ages of 12 and 18 who were admitted to İzmir Tepecik Teaching and Research Hospital between January 2013 and December 2015 due to a suicide attempt were included in the study. In addition to the questionnaire containing socio-demographic information and familial characteristics, the Beck depression scale, the state and trait anxiety inventory, and the Piers-Harris self-concept scale were filled out by the adolescents. Compared with the control group, adolescent suicide attempters report a greater rate of smoking and alcohol use, having a broken family, a suicide attempt history, and a family history of psychiatric disorders. In addition, higher levels of depression and anxiety and lower levels of self-concept were detected among the suicidal adolescents. The study results show that suicidal adolescents who have high levels of depression and anxiety, as well as low self-concept, may lead the adolescent to suicide attempts by reducing their capacity to cope with problems [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, the mental health state of adolescents had caused widespread concern, especially the various problems caused by the relationship between adolescents and their parents in the long isolation at home. Based on the mindfulness reperceiving model and Rogers's Self-theory, this study aimed to explore the roles of adolescents' self-concept clarity and mindfulness level in the relationship between parental psychological control and adolescent depression. A total of 1,100 junior high school students from China completed the questionnaires regarding parental psychological control, depression, self-concept clarity, and mindfulness. Moderated mediation analyses suggest that parental psychological control affects adolescent depression via self-concept clarity. The association between parental psychological control and depression is moderated by self-concept clarity. The effect was stronger among adolescents with high mindfulness levels than those with low. This study suggests that it is necessary to consider both parental factors and adolescents' factors in the future. The interventions on self-concept or mindfulness may ameliorate adolescent mental problems more effectively. [ABSTRACT FROM AUTHOR]

Background: Depressive episodes in adolescents are often accompanied by various physical symptoms, but few studies have explored the association between depression and fever, This case study is the first to report the relationship between unexplained recurrent high fever and depression. Case presentation: H is a 15 year old adolescent female currently in junior year. 2 + months ago, H gradually felt depressed after a class change. Around the time, the patient suddenly developed chills with no obvious trigger and fever. H was treated with anti-infective and anti-viral treatments all of which did not show significant improvement. No significant abnormality was seen in any of the related examinations. Considering that the patient's anxiety, depression and somatic symptoms were obvious during the course of the disease, she was given venlafaxine hydrochloride extended-release capsule 75 mg/d; tandospirone citrate capsule 10 mg Bid; alprazolam tablets 0.4 mg qn to improve mood and sleep; supplemented with transcranial repetitive magnetic stimulation therapy 2 times/d; visible light therapy 1 time/d and psychological counseling once. Over the 6 days of treatment, the patient's body temperature gradually returned to the normal range and her mood improved significantly. Conclusion: Depression should be considered a potential cause of unexplained recurrent fevers in adolescents, even when the temperature is significantly outside the normal range. [ABSTRACT FROM AUTHOR]

Antidepressant response in adults with major depressive disorder (MDD) is probably influenced by personality dimensions. However, personality dimensions in depression and their association with antidepressant treatment in adolescents are relatively unknown. We sought to investigate whether personality traits (PTs) can influence antidepressant treatment response in adolescents with depression. Eighty-two adolescents with MDD who had completed the 8 weeks of treatment with selective serotonin reuptake inhibitors (SSRI) were enrolled. The Revised NEO Five-Factor Inventory (NEO-FFI-R) was used to measure their personality at baseline, and the 17-item Hamilton Depression Rating Scale (HAMD-17) and Children's Depression Rating Scale-Revised (CDRS-R) were used to evaluate depressive symptoms at baseline and 8 weeks. Moreover, logistic regression was performed to investigate the relationship between personality dimensions and antidepressant response. Receiver operating characteristic analyses were employed to determine the accuracy of a PT-based model in predicting the antidepressant response rate. Adolescents with MDD had significantly different PTs at baseline. Multivariable logistic regression analysis showed that extroversion scores were associated with response to antidepressant treatment, the lower the extroversion score, the better the response to antidepressant treatment, after correcting for variables with significant differences and trends or all potential confounding variables. It was also found that the combination of disease duration, extraversion-gregariousness, and agreeableness-trust effectively predicted antidepressant response in adolescents with MDD, with a sensitivity of 79.4 % and specificity of 68.7 %. Personality dysfunction in adolescents is associated with MDD. The antidepressant treatment response is influenced by the degree of extroversion in adolescents with MDD. • Personality dysfunction in adolescents is associated with major depression disorder. • The degree of extroversion were associated with response to antidepressant treatment in adolescents. • Personality traits can effectively predict antidepressant response in adolescents with depression. [ABSTRACT FROM AUTHOR]

Objective: We evaluated the presence and impact of unblinding during the influential Treatment for Adolescents with Depression Study (ClinicalTrials.gov Identifier: NCT00006286). Method: Our analysis was part of a Restoring Invisible and Abandoned Trials reanalysis. Treatment for Adolescents with Depression Study trialled fluoxetine, placebo, cognitive behaviour therapy or their combination, in treating adolescents with major depressive disorder. We analysed the accuracy of guesses of fluoxetine or placebo allocation, and their effects on change in Children's Depression Rating Scale-Revised at 12 weeks. Results: Of 221 participants allocated to fluoxetine or placebo, 151 adolescents (68%) had their guess about pill-treatment-arm allocation recorded at week 6, and guesses were recorded for 154 independent evaluators, 159 parents and 164 pharmacotherapists. All of these groups guessed treatment allocation more accurately than would be expected by chance (60–66% accuracy; all p -values ⩽ 0.004). Guesses did not become more accurate between 6 and 12 weeks and were not predicted by adverse events, though event documentation was poor. Treatment guess had a substantial and statistically significant effect on outcome (Children's Depression Rating Scale-Revised change mean difference 9.12 [4.69; 13.55], β = 0.334, p < 0.001), but actual treatment arm did not (1.53 [−2.83; 5.89], β = 0.056, p = 0.489). Removing guess from the analysis increased the apparent effect of treatment arm, making it almost statistically significant at the conventional alpha-level of 0.05 (p = 0.06). Conclusions: For Treatment for Adolescents with Depression Study, treatment guesses strongly predicted outcomes and may have led to the exaggeration of drug effectiveness in the absence of actual effects. The integrity of double-blinding in trials should be routinely assessed and reported. [ABSTRACT FROM AUTHOR]

Abstract Background Current research has been focusing on non-suicidal self-injury (NSSI) behaviors among adolescents with depression. Although family intimacy and adaptability are considered protective factors for NSSI, evidence supporting this relationship is lacking. Objective This study aims to examine the mechanisms operating in the relationship between family intimacy and adaptability and NSSI behaviors among adolescents. Methods A self-administered general demographic information questionnaire, the Behavioral Functional Assessment Scale for Non-Suicidal Self-Injury, the Family Intimacy and Adaptability Scale, the Connor-Davidson Resilience Scale, and the Self-Assessment of Depression Scale were distributed among adolescents with depression in three tertiary hospitals in Jiangsu Province. Results The relationship between family intimacy and adaptability and NSSI was assessed among 596 adolescents with depression. The results revealed the following: (1) Family intimacy and adaptability were negatively correlated with NSSI behavior. (2) Psychological resilience and depression levels acted as chain mediators in the relationship between family intimacy and adaptability and NSSI behavior. Conclusions Enhancing psychological resilience, controlling depressive symptoms, and reducing depression severity among adolescents by improving their family intimacy and adaptability are conducive to preventing and mitigating their NSSI behaviors.

Abstract Background Childhood trauma is a pivotal risk factor for adolescent depression. While the association between childhood trauma and depression is well-established, the mediating role of self-concept has not been acknowledged. Specifically, limited attention has been paid to how childhood maltreatment impacts adolescent depression through physical and social self-concept, both in clinical and community samples. This study aims to investigate how distinct and cumulative childhood trauma affects adolescent depression, as well as the potential mediating role of self-concept in their relationships. Methods We recruited 227 depressed adolescents (dataset 1, 45 males, age = 15.34 ± 1.96) and 574 community adolescents (dataset 2, 107 males, age = 16.79 ± 0.65). Each participant was assessed on five subtypes of childhood trauma severity, cumulative trauma index, physical and social self-concept, and depression. Mediation models were tested separately in the clinical and community samples. Results Clinically depressed adolescents experienced a higher level of trauma severity, a greater number of trauma subtypes, and had lower levels of physical and social self-concept compared to community adolescents. Analyses on childhood trauma severity and cumulative trauma index jointly indicated that physical and social self-concept played mediation roles in the relationships between childhood trauma experiences and depression. Moreover, the mediating effects of self-concept were stronger in depressed adolescents when compared to community samples. Conclusions Our findings suggest that physical and social self-concept play mediating roles in the pathway linking childhood trauma and adolescent depression, particularly in clinically depressed individuals.

Ling Yang,1,2 Maolin Cao,3 Jing Tian,1 Peijin Cui,1 Ling Ai,3 Xue Li,4 Hua Li,5 Menghan Gao,1 Liang Fang,1,2,6 Libo Zhao,1,2 Fang Gong,2,6 Chanjuan Zhou1,3,4,6 1Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Cerebrovascular Disease Research, Chongqing, People’s Republic of China; 3Department of General Practice, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Central Laboratory, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 5Department of Ophthalmology, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 6Chongqing Clinical Research Center for Geriatric Disease, Chongqing, People’s Republic of ChinaCorrespondence: Fang Gong; Chanjuan Zhou, Yongchuan Hospital of Chongqing Medical University, No. 439 Xuanhua Road, Yongchuan, Chongqing, 402160, People’s Republic of China, Email 1512367841@qq.com; chanjuanzhou@hospital.cqmu.edu.cnPurpose: The quality of life of worldwide adolescents has been seriously affected by depression. Notably, the inflammatory response is closely associated with the pathophysiology of depression. The present study applied a novel targeted proteomics technology, Olink proximity extension assay (PEA), to profile circulating immune-related proteins in adolescents with depression.Methods: In the present study, the expression levels of 92 inflammation-related proteins were compared between adolescents with depression (ADs) (n=15) and healthy controls (HCs) (n=15), using the OLINK PEA inflammation panel. We further validated 5 top proteins that were identified through KEGG and GO analyses between 40 HCs and 50 ADs, including CCL4, CXCL5, CXCL6, CXCL11, and IL-18 using enzyme linked immunosorbent assay (ELISA).Results: We identified 13 differentially expressed proteins between the two cohorts, including 5 up-regulated and 8 down-regulated proteins. Among them, the TRAIL protein levels were significantly negatively correlated with the HAMA-14 score (r=− 0.538, p= 0.038), and the levels of transforming growth factor α (TGF-α) were significantly associated with a change in appetite (r = -0.658, p = 0.008). After validation by ELISA, CCL4, CXCL5, CXCL11, and IL-18 showed significant changes between ADs and HCs (p < 0.05), while CXCL6 showed an up-regulated tendency in ADs (p=0.0673). The pooled diagnostic efficacy (area under the curve [AUC]) of these five inflammation markers in clinical diagnosis for adolescent depression was 0.819 (95% CI: 0.735– 0.904).Conclusion: We report a number of inflammation-related plasma biomarkers, which uncover a potential involvement of chemokines, cytokines, and cytokine receptors in adolescent depression. Their roles in the pathophysiology of depression need to be further elucidated.Keywords: olink proximity extension assay, biomarkers, adolescent depression, inflammation