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.

Background: Non-suicidal self-injury (NSSI) behaviors are common in adolescents with major depressive disorder (MDD). Brain studies specifically targeting adolescents with MDD and NSSI may provide new insights into suicide warnings in adolescents with MDD. Methods: This study examined the whole-brain neural activity in adolescents aged between 12–17 years, 50 unmedicated MDD patients with (nsMDDs) or without NSSI (nnsMDDs), and 25 healthy controls (HCs) participated in this study, and analyzed the correlation between the values of amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) in significantly different brain regions and the scores of the relevant clinical psychological scale. Results: Compared with nnsMDDs, nsMDDs had enhanced ALFF values in left middle occipital gyrus and left median cingulate and paracingulate gyri; the fALFF values of the right caudate nucleus was weakened in the nsMDDs; the ReHo values of right middle occipital gyrus and right middle temporal gyrus weakened and the ReHo values of right medial cingulate gyrus enhanced in nsMDDs. And all of differences were statistically significant. In nsMDDs, the value of ALFF in the left calcarine fissure and surrounding cortex was negatively correlated with the score of Children's depression Inventory (CDI); the value of fALFF in the right caudate nucleus was positively correlated with the score of Beck Scale for Suicidal Ideations (BSSI); the value of ReHo in the right middle temporal gyrus was positively correlated with the score of Multidimensional Anxiety Scale for Children (MASC); and the value of ReHo in the right median cingulate and paracingulate gyri was negatively correlated with the score of BSSI. Conclusions: We found that in ALFF, fALFF and ReHo, the significant differences between nsMDDs and nnsMDDs are mainly located in default mode network (DMN) and visual network (VN), and there may be brain regions related to NSSI in DMN and VN. The significant differences brain regions in ALFF, fALFF and ReHo between nsMDDs and nnsMDDs were related to the total score of the relevant clinical psychological scale, and may be related to NSSI.

Resting-state functional magnetic resonance imaging (rs-fMRI) was used to investigate the effects of electroconvulsive therapy (ECT) causing brain function changes in adolescents who suffered from depression and suicidal ideation (SI). A total of 30 patients (MDDs) and 25 healthy controls (HCs) matched by gender, age, and education level were enrolled. The amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) were used to compare differences between HCs and MDDs at baseline, and differences in ALFF and ReHo pre/post ECT in MDDs. Pearson correlation analysis was used to evaluate the relationship between altered brain function and clinical symptoms. At baseline, MDDs showed decreased ALFF in the left inferior temporal gyrus and right amygdala, decreased ReHo in left inferior temporal gyrus, and increased ReHo in the right inferior frontal gyrus, opercular part and left middle occipital gyrus. After ECT, MDDs showed increased ALFF in the right middle occipital gyrus, decreased ALFF in left temporal pole, left inferior frontal gyrus, opercular part, and right frontal middle gyrus, increased ReHo in the right middle occipital gyrus, and left inferior temporal gyrus. Pearson correlation found HAMD scores at baseline were negatively correlated with ALFF in the left inferior temporal gyrus, and HAMD and BSSI scores after ECT were negatively correlated with ALFF in the right middle occipital gyrus. The abnormal activities of amygdala, inferior temporal gyrus and middle occipital gyrus might be related to depressive and suicidal symptoms in adolescents.

Background: Nonsuicidal self-injury (NSSI) is a common mental health threat in adolescents, peaking in adolescence with a lifetime prevalence of ~17%–60%, making it a high-risk risk factor for suicide. In this study, we compared changes in microstate parameters in depressed adolescents with NSSI, depressed adolescents, and healthy adolescents during exposure to negative emotional stimuli, and further explored the improvement of clinical symptoms and the effect of microstate parameters of repetitive transcranial magnetic stimulation (rTMS) in depressed adolescents with NSSI, and more evidence was provided for potential mechanisms and treatment optimization for the occurrence of NSSI behaviors in adolescents.Methods: Sixty-six patients with major depressive disorder (MDD) exhibiting NSSI behavior (MDD + NSSI group), 52 patients with MDD (MDD group), and 20 healthy subjects (HC group) were recruited to perform neutral and negative emotional stimulation task. The age range of all subjects was 12–17 years. All participants completed the Hamilton Depression Scale, the Patient Health Questionnaire-9, the Ottawa Self-Injury Scale and a self-administered questionnaire to collect demographic information. We provided two different treatments to 66 MDD adolescents with NSSI; 31 patients received medication and completed post-treatment scale assessments and EEG acquisitions, and 21 patients received medication combined with rTMS and completed post-treatment scale assessments and EEG acquisitions. Multichannel EEG was recorded continuously from 64 scalp electrodes using the Curry 8 system. EEG signal preprocessing and analysis was performed offline, using the EEGLAB toolbox in MATLAB. Use the Microstate Analysis Toolbox in EEGLAB for segmentation and computation of microstates, and calculate a topographic map of the microstate segmentation of the EEG signal for a single subject in each dataset, and four parameters were obtained for each microstate classification: global explained variance (GEV), mean duration (Duration), average number of occurrences per second (Occurrence), and average percentage of total analysis time occupied (Coverage), which were then statistically analyzed.Results: Our results indicate that MDD adolescents with NSSI exhibit abnormalities in MS 3, MS 4, and MS 6 parameters when exposed to negative emotional stimuli compared to MDD adolescents and healthy adolescents. The results also showed that medication combined with rTMS treatment improved depressive symptoms and NSSI performance more significantly in MDD adolescents with NSSI compared to medication treatment, and affected MS 1, MS 2, and MS 4 parameters in MDD adolescents with NSSI, providing microstate evidence for the moderating effect of rTMS.Conclusion: MDD adolescents with NSSI showed abnormal changes in several microstate parameters when receiving negative emotional stimuli, and compared to those not receiving rTMS treatment, MDD adolescents with NSSI treated with rTMS showed more significant improvements in depressive symptoms and NSSI performance, as well as improvements in EEG microstate abnormalities.

Objects: The efficacy of electroconvulsive therapy (ECT) in the treatment of adolescents with treatment-refractory depression is still unsatisfactory, and the individual differences are large. It is not clear which factors are related to the treatment effect. Resting-state fMRI may be a good tool to predict the clinical efficacy of this treatment, and it is helpful to identify the most suitable population for this treatment. Methods: Forty treatment-refractory depression adolescents were treated by ECT and evaluated using HAMD and BSSI scores before and after treatment, and were then divided into a treatment response group and a non-treatment group according to the reduction rate of the HAMD scale. We extracted the ALFF, fALFF, ReHo, and functional connectivity of patients as predicted features after a two-sample t-test and LASSO to establish and evaluate a prediction model of ECT in adolescents with treatment-refractory depression. Results: Twenty-seven patients achieved a clinical response; symptoms of depression and suicidal ideation were significantly improved after treatment with ECT, which was reflected in a significant decrease in the scores of HAMD and BSSI (p < 0.001). The efficacy was predicted by ALFF, fALFF, ReHo, and whole-brain-based functional connectivity. We found that models built on a subset of features of ALFF in the left insula, fALFF in the left superior parietal gyrus, right superior parietal gyrus, and right angular, and functional connectivity between the left superior frontal gyrus, dorsolateral–right paracentral lobule, right middle frontal gyrus, orbital part–left cuneus, right olfactory cortex–left hippocampus, left insula–left thalamus, and left anterior cingulate gyrus–right hippocampus to have the best predictive performance (AUC > 0.8). Conclusions: The local brain function in the insula, superior parietal gyrus, and angular gyrus as well as characteristic changes in the functional connectivity of cortical–limbic circuits may serve as potential markers for efficacy judgment of ECT and help to provide optimized individual treatment strategies for adolescents with depression and suicidal ideation in the early stages of treatment.