Abstract Background Inflammation has become a critical pathological mechanism of Major Depressive Disorder (MDD). NLRP3 is a critical inflammatory pathway to maintain the immune balance. Recently, preclinical evidence showed that Resolvin D1 might potentially offer a new option for antidepressant treatment due to its protective effects through the inhibition of neuroinflammation. However, whether they have clinical value in the diagnosis and treatment evaluation of adolescent depression was unclear. Methods Forty-eight untreated first-episode adolescent patients with moderate to severe major depressive disorder, as well as 30 healthy adolescents (HCs, age and gender-matched), were enrolled for this study. Their ages ranged from 13 to 18 (15.75 ± 1.36) years. The patients were treated with fluoxetine for 6–8 weeks. HDRS-17 was used to evaluate the severity of depressive symptoms. Venous blood samples were collected at baseline for the two groups and at the time-point of post-antidepressant treatment for the patients. Serum concentrations of RvD1, NLRP3, IL-1β, IL-18, and IL-4 were measured by enzyme-linked immunosorbent assays (ELISA) pre- and post-fluoxetine treatment. Results Serum levels of RvD1 and anti-inflammatory cytokine IL-4 were significantly elevated in adolescents with MDD compared to healthy adolescents, but no significant difference in NLRP3, IL-1β, and IL-18 between the two groups. Meanwhile, RvD1 (positively) and IL-4 (negatively) were correlated with the severity of symptoms (HDRS-17 scores) after adjusting age, gender, and BMI. Interestingly, fluoxetine treatment significantly reduced the serum levels of RvD1, NLRP3, IL-1β, and IL-18 in MDD adolescents but increased the levels of IL-4 relative to baseline. Furthermore, we observed that serum levels of RvD1 might be an excellent distinguishing indicator for depression and healthy adolescents. Conclusions Our study is the first to compare RvD1 and NLRP3 between adolescent MDD and HCs. Our findings of reactive increase of RvD1 in adolescent MDD comprised a novel and critical contribution. Our results showed the presence of inflammation resolution unbalanced in adolescents with MDD and indicated that RvD1 might be an ideal biomarker for diagnosing and treating adolescent MDD.

Neuroimaging studies have revealed abnormal brain activities in depressed teenagers who engage in non-suicidal self-injury (NSSI). We used resting-state electroencephalography (EEG) microstate analysis, which indicates the brief overlap of brain network activation for exploring the characteristics of large-scale cortical activities in depressed adolescents engaged with NSSI to clarify the underlying temporal mechanism. A modified k-means cluster algorithm was used to segment 64-channel resting-state EEG data into microstates. Data from 27 healthy adolescents, 37 adolescents with major depressive disorder (MDD), and 53 adolescents with both MDD and NSSI were examined in this study. The resting-state microstate parameters were compared among groups using the one-way ANOVA and Spearman correlation. Then the associations between significantly different microstate parameters and the depressive severity and self-harming data in the patient groups were further analyzed. The MDD group had higher contribution (p < 0.01), occurrence (p < 0.01) of microstate A, and higher microstate E→A transition (p < 0.05) than the HC and the NSSI group. The MDD group showed a distinctly longer duration (p < 0.05) of microstate A and microstate A→C transition than the HC. The transition probability from B to C was increased in the NSSI group compared to the HC. In the MDD group, the HAMD correlated with the duration of microstate A (Spearman's rho = 0.34, p = 0.044), as the PHQ-9 correlated with its occurrence (Spearman's rho = 0.37, p = 0.028). This research revealed that whereas depressive adolescents with NSSI and MDD displayed similar patterns with healthy controls in EEG microstate, the MDD group did not. Additionally, the non-random transition from microstate E→A may protect against recent self-harm in adolescents with MDD.

BackgroundThe 2019 coronavirus disease (COVID-19) pandemic increased the risks of mental health challenges, especially anxiety and depression. However, the impact of COVID-19 on mental health during pregnancy has not been fully established. Therefore, we investigated the impact of the COVID-19 pandemic on maternal mental health.MethodsTwo cohorts of pregnant women at their first antenatal care in the First Affiliated Hospital of Chongqing Medical University were enrolled in this study. One cohort was enrolled before the COVID-19 outbreak, from 1 June to 31 December 2019 (n = 5,728, pre-COVID-19 group), while the other was enrolled during the COVID-19 pandemic, from 24 January to 23 March 2020 (n = 739, COVID-19 pandemic group). Symptoms of depression, anxiety, and somatization disorders were assessed by the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-15 (PHQ-15), with a cutoff point of 10 for moderate-to-severe depression, anxiety, and somatoform symptoms. The propensity score matching method (1:1) was used to balance differences in demographic characteristics between groups. A chi-square analysis was performed to compare differences in demographic characteristics between the groups.ResultsPrevalence of moderate-to-severe depression, anxiety, and somatoform symptoms among pregnant women at their first antenatal care visit during the COVID-19 pandemic (9.5, 2.2, and 20.8%, respectively) was significantly lower than those before the pandemic (16.3, 4.4, and 25.7%, respectively) (p < 0.05). Compared with the same period before the pandemic, during the pandemic, the number of women newly registered for antenatal care decreased by nearly 50%. There were significant differences in the distributions of demographic characteristics between the groups (p < 0.05). After matching the demographic characteristics, differences in the prevalence of maternal mental health disorders between the groups reversed dramatically. Prevalence of moderate-to-severe depression, anxiety, and somatoform symptoms during the COVID-19 pandemic in this population (2.3, 9.6, and 20.8%, respectively) was significantly higher than those before the pandemic (0.3, 3.9, and 10%, respectively) (p < 0.05).ConclusionThe COVID-19 pandemic increased mental health risks among pregnant women. As a large proportion of pregnant women with mental health challenges delay their prenatal care or change healthcare facilities after the outbreak of public health emergencies, there is a need to establish a balanced healthcare system in medical institutions at all levels.

Background Inflammation and immune activation may play a role in the pathological mechanism of Major Depressive Disorder (MDD). Evidence from cross-sectional and longitudinal studies of adolescents and adults has shown that MDD is associated with increased plasma pro-inflammatory cytokines (e.g., IL-1β, IL-6). It has been reported that Specialized Pro-resolving Mediators (SPMs) mediate inflammation resolution, and Maresin-1 can activate the process of inflammation and promote inflammation resolution by promoting macrophage phagocytosis. However, no clinical studies have been conducted to evaluate the relationship between the levels of Maresin-1 and cytokine and the severity of MDD symptomatology in adolescents. Methods 40 untreated adolescent patients with primary and moderate to severe MDD and 30 healthy participants as the healthy control (HC) group aged between 13 and 18 years old were enrolled. They received clinical and Hamilton Depression Rating Scale (HDRS-17) evaluation and then, blood samples were collected. Patients in the MDD group were re-evaluated for HDRS-17, and blood samples were taken after a six to eight-week fluoxetine treatment. Results The adolescent patients with MDD had lower serum levels of Maresin-1 and higher serum levels of interleukin 6 (IL-6) compared with the HC group. Fluoxetine treatment alleviated depressive symptoms in MDD adolescent patients, which was reflected by higher serum levels of Maresin-1 and IL-4 and lower HDRS-17 scores, serum levels of IL-6, and IL-1β. Moreover, the serum level of Maresin-1 was negatively correlated with the depression severity scores on the HDRS-17. Conclusion Adolescent patients with primary MDD had lower levels of Maresin-1 and higher levels of IL-6 compared with the HC group, implying that the peripheral level of pro-inflammatory cytokines may be elevated in MDD, resulting in the insufficiency of inflammation resolution. The Maresin-1 and IL-4 levels increased after anti-depressant treatment, whereas IL-6 and IL-1β levels decreased significantly. Moreover, Maresin-1 level negatively correlated with depression severity, suggesting that reduced levels of Maresin-1 promoted the progression of MDD.

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.

BackgroundNonsuicidal self-injury (NSSI) may be a type of addiction, that is characterized by cue reactivity. We aimed to explore the behavioral performance and neural reactivity during exposure to self-injury cues in adolescents with NSSI and major depressive disorder (MDD).MethodsEighteen MDD patients, 18 MDD patients with NSSI, and 19 healthy controls (HC) were recruited to perform a two-choice oddball paradigm. All subjects were 12–18 years old. Neutral cues and self-injury related cues separately served as deviant stimuli. Difference waves in N2 and P3 (N2d and P3d) were derived from deviant waves minus standard waves. Accuracy cost and reaction time (RT) cost were used as behavioral indexes, while the N2d and P3d were used as electrophysiological indexes; the N2d reflects early conflict detection, and the P3d reflects the process of response inhibition.ResultsNo significant main effects of group or cue or an effect of their interaction were observed on accuracy cost and P3d latency. For RT cost, N2d amplitude, and N2d latency, there was a significant main effect of cue. For P3d amplitude, there was a significant main effect of cue and a significant group × cue interaction. In the NSSI group, the P3d amplitude with self-injury cues was significantly larger than that with neutral cues. However, there was no such effect in the MDD and HC groups.ConclusionsAdolescents with NSSI showed altered neural reactivity during exposure to self-injury cue. Further studies with larger sample sizes are needed to confirm our results.

BackgroundMental health problems has become a major public health issue among medical students. Self-esteem and psychological flexibility were important associated factors for mental health, but their relations have not been discussed in medical students. The present study aimed to assess the status of mental health problems among medical students and identified whether psychological flexibility had a mediating role in the effects of self-esteem on the top three most common psychological symptoms. MethodsA total of 810 undergraduate students from 18 classes comprised in the sample. Nine dimensions of psychological symptoms was assessed by the Symptom Checklist-90-revised (SCL-90-R). Self-esteem was measured by the Self-esteem Scale (SES) and psychological flexibility was evaluated by the Acceptance and Action Questionnaire 2nd Edition (AAQ-II) and Cognitive Fusion Questionnaire (CFQ-F). Univariate analysis and logistic regression analysis were used to determine the relationship among the top three common psychological symptoms, self-esteem, psychological flexibility, and participants' characteristics. The mediating effect of psychological flexibility between self-esteem and psychological symptoms was detected by bootstrap method. Results57.8% of the medical undergraduate students reported positive at least one of the nine psychological symptom dimensions assessed by the SCL-90-R and 13.8% of students had moderate or more severe symptoms. The symptoms of obsessive-compulsiveness, interpersonal sensitivity, and depression were the three most common psychological symptoms among the medical students. Meanwhile, self-esteem and psychological flexibility were negatively associated to the symptoms of obsessive-compulsiveness, interpersonal sensitivity, and depression. And, almost 50% effects of self-esteem on these three symptoms in medical students exert indirect effects through psychological flexibility. ConclusionsPsychological distress was quite common in the Chinese medical students. The three most common psychological symptoms were successively obsessive-compulsiveness, interpersonal sensitivity, and depression. Low self-esteem and psychological inflexibility might be the risk factors for these top three symptoms, and psychological flexibility might play a mediating role in the effects of self-esteem on these psychological symptoms.

Objective We aimed to investigate changes in whole-brain gray matter volumes (GMVs) before and after electroconvulsive therapy (ECT) in adolescents with major depressive disorder (MDD) and suicidal ideation (SI). Methods Thirty adolescents with MDD and SI were observed, and structural magnetic resonance imaging (sMRI) was performed at baseline and after ECT for each patient. But Twenty-five healthy controls (HCs) were scanned only at baseline. The voxel-based morphometry (VBM) techniques were used to examine GMVs. Results Compared with HCs, MDDs at baseline showed decreased GMVs in the left middle temporal gyrus, right superior temporal gyrus, right middle temporal gyrus, left precuneus, right precuneus, and left superior frontal gyrus. After ECT, MDDs showed increased GMVs in the right superior frontal gyrus and right superior temporal gyrus. Pearson’s correlation found that Beck Scale for Suicide Ideation (BSSI) scores at baseline were negatively correlated with GMVs in the left superior frontal gyrus and HAMD and BSSI scores after ECT were negatively correlated with GMVs in the right superior temporal gyrus. Conclusion Frontal–temporal–precuneus structure changes may be a potential cause of depressive and suicidal symptoms in adolescents. ECT may improve depressive and suicidal symptoms in adolescents by regulating brain structures to compensate original defects.