Personality traits predict treatment outcome of an antidepressant in untreated adolescents with depression: An 8-week, open-label, flexible-dose study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 %. CONCLUSION: Personality dysfunction in adolescents is associated with MDD. The antidepressant treatment response is influenced by the degree of extroversion in adolescents with MDD.

[Effect of Sertraline on Serum Cytokine Levels in Adolescents With First-Episode Major Depressive Disorder].

Objective: To investigate the changes in serum inflammatory cytokines and the predictive factors for the efficacy of sertraline following medication therapy in adolescents with first-episode major depressive disorder (MDD). Methods: A total of 61 adolescent patients with first-episode drug-naïve MDD were enrolled for the MDD group and 55 healthy adolescents were enrolled for the healthy control (HC) group. Sertraline tablets were administered to the MDD group for 8 weeks after enrollment, while no medication was given to the HC group. In the MDD group, blood samples were collected to measure the cytokine levels and clinical data, including scores for the 17-item Hamilton Depression Scale (HAMD-17) and the Connor-Davidson Resilience Scale (CD-RISC), were assessed at baseline and at the end of the 8-week medication, whereas in the HC group, blood samples and clinical data were collected only at baseline. The correlation between the levels of serum inflammatory cytokines and depression severity in the MDD group was analyzed and stepwise linear regression of HAMD-17 in the MDD group was performed to find serologic indicators that could be used to predict the efficacy of sertraline. Results: At baseline, the levels of interleukin (IL)-1ß and IL-6 in the MDD group were significantly higher than those in the HC group (all P<0.0001), while the tumor necrosis factor (TNF)-α level in the MDD group was significantly lower than that in the HC group ( P=0.006). After 8 weeks of medication treatment, the MDD group showed decreased levels of IL-1ß and IL-6 and increased level of TNF-α compared to the pre-treatment levels. In addition, the HAMD-17 score, CD-RISC total score, and scores for perceived competence, trust and tolerance, and control, three factors of CD-RISC, all improved after treatment. There was no significant difference in serum cytokine levels at baseline between the subgroup showing response to the treatment and the non-responding subgroup. There was a weak correlation between IL-6 levels before and after treatment and CD-RISC scores and the scores for the trust and tolerance factor of CD-RISC before and after treatment. The baseline IL-1ß and TNF-α levels did not show significant effect on posttreatment HAMD-17 scores. Conclusions: Serum cytokine levels of adolescents with first-episode MDD differ significantly from those of healthy adolescents. Although IL-6 was found to be correlated with depression severity, there was not enough support for it to be used as a predictor of the antidepression efficacy of sertraline.

Serum extracellular vesicle microRNA dysregulation and childhood trauma in adolescents with major depressive disorder.

Major depressive disorder (MDD) seriously endangers adolescent mental and physical health. Extracellular vesicles (EVs) are mediators of cellular communication and are involved in many physiological brain processes. Although EV miRNAshave been implicated in adults with major psychiatric disorders, investigation into their effects in adolescent MDDremains scarce. In discovery set, we conducted a genome-wide miRNA sequencing of serum EVs from 9 untreated adolescents with MDD and 8 matched healthy controls (HCs), identifying 32 differentially expressed miRNAs (18 upregulated and 14 downregulated). In the validation set, 8 differentially expressed and highly enriched miRNAs were verified in independent samples using RT-PCR, with 4 (miR-450a-2-3p, miR-3691-5p, miR-556-3p, and miR-2115-3p) of the 8 miRNAs found to be significantly elevated in 34 untreated adolescents with MDD compared with 38 HCs and consistent with the sequencing results. After the Bonferroni correction, we found that three miRNAs (miR-450a-2-3p, miR-556-3p, and miR-2115-3p) were still significantly different. Among them, miR-450a-2-3p showed the most markeddifferential expression and was able to diagnose disease with 67.6% sensitivity and 84.2% specificity. Furthermore, miR-450a-2-3p partially mediated the associations between total childhood trauma, emotional abuse, and physical neglect and adolescent MDD. We also found that the combination of miR-450a-2-3p and emotional abuse could effectively diagnose MDD in adolescents with 82.4% sensitivity and 81.6% specificity. Our data demonstrate the association of serum EV miRNA dysregulation with MDD pathophysiology and, furthermore, show that miRNAs may mediate the relationship between early stress and MDD susceptibility. We also provide a valid integrated model for the diagnosis of adolescent MDD.