The relationship between serum resolvin D1, NLRP3, cytokine levels, and adolescents with first-episode medication-naïve major depressive disorder.

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-1ß, 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-1ß, 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-1ß, 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.

Predicting Responses to Electroconvulsive Therapy in Adolescents with Treatment-Refractory Depression Based on Resting-State fMRI.

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.

A propensity score matching study: The prevalence of mental health problems among pregnant women at first antenatal care increased in Chongqing during the first wave of the COVID-19 pandemic.

Background: The 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. Methods: Two 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. Results: Prevalence 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). Conclusion: The 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.

Prospective study on Maresin-1 and cytokine levels in medication-naïve adolescents with first-episode major depressive disorder.

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-1ß, 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-1ß. 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-1ß levels decreased significantly. Moreover, Maresin-1 level negatively correlated with depression severity, suggesting that reduced levels of Maresin-1 promoted the progression of MDD.

Psychiatric symptoms in a female with subacute combined degeneration of the spinal cord (SCD): a case report.

BACKGROUND: Subacute combined degeneration of the spinal cord (SCD) is mainly caused by deficiency of Vitamin B12 and characterized by deep hypoesthesia, sensory ataxia and spasmodic paralysis of lower limbs. SCD often accompanies with megaloblastic anemia. Psychiatric symptoms could be the initial manifestations of SCD by lack of Vitamin B12, but are rarely considered secondary to physical discomfort and psychological factors in SCD. Additionally, treatment experience for psychiatric symptoms in SCD remains little reported. CASE REPORT: We presented a case of a 37-year-old female who complained of being persecuted and controlled for one week and thus was admitted to the psychiatry department. Before that, she had went through persistent paresthesia and numbness of her lower extremities for two-month. Low Vitamin B12 level and hemoglobin concentration, neurologic symptoms and bone marrow smear results supported the clinical diagnosis of SCD and megaloblastic anemia. With supplementation of Vitamin B12 and blood transfusion and short-term prescription of antipsychotics and antidepressants, physical symptoms were improved and psychological symptoms disappeared within 2 weeks. CONCLUSIONS: Psychiatric symptoms of SCD could be generated from lack of Vitamin B12, anemia and neurologic symptoms, where short-term use of antipsychotics and antidepressants may be effective.

Changes in gray matter volume following electroconvulsive therapy in adolescent depression with suicidal ideation: A longitudinal structural magnetic resonance imaging study.

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.

The Influence of Self-Esteem and Psychological Flexibility on Medical College Students' Mental Health: A Cross-Sectional Study.

Background: Mental 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. Methods: A 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. Results: 57.8% 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. Conclusions: Psychological 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.

Microglia Loss and Astrocyte Activation Cause Dynamic Changes in Hippocampal [18F]DPA-714 Uptake in Mouse Models of Depression.

Major depression is a serious and chronic mental illness. However, its etiology is poorly understood. Although glial cells have been increasingly implicated in the pathogenesis of depression, the specific role of microglia and astrocytes in stress-induced depression remains unclear. Translocator protein (TSPO) has long been considered a marker of neuroinflammation and microglial activation. However, this protein is also present on astrocytes. Thus, it is necessary to explore the relationships between TSPO, microglia, and astrocytes in the context of depression. In this study, C57BL/6J male mice were subjected to chronic unpredictable stress (CUS) for 5 weeks. Subsequently, sucrose preference and tail suspension tests (TSTs) were performed to assess anhedonia and despair in these mice. [18F]DPA-714 positron emission tomography (PET) was adopted to dynamically assess the changes in glial cells before and 2, 4, or 5 weeks after CUS exposure. The numbers of TSPO+ cells, ionized calcium-binding adaptor molecule (Iba)-1+ microglial cells, TSPO+/Iba-1+ cells, glial fibrillary acidic protein (GFAP)+ astrocytes, TSPO+/GFAP+ cells, and TUNEL-stained microglia were quantified using immunofluorescence staining. Real-time PCR was used to evaluate interleukin (IL)-1ß, IL-4, and IL-18 expression in the hippocampus. We observed that hippocampal [18F]DPA-714 uptake significantly increased after 2 weeks of CUS. However, the signal significantly decreased after 5 weeks of CUS. CUS significantly reduced the number of Iba-1+, TSPO+, and TSPO+/Iba-1+ cells in the hippocampus, especially in the CA1 and dentate gyrus (DG) subregions. However, this intervention increased the number of GFAP+ astrocytes in the CA2/CA3 subregions of the hippocampus. In addition, microglial apoptosis in the early stage of CUS appeared to be involved in microglia loss. Further, the expression of pro-inflammatory cytokines (IL-1ß and IL-18) was significantly decreased after CUS. In contrast, the expression of the anti-inflammatory cytokine IL-4 was significantly increased after 2 weeks of CUS. These results suggested that the CUS-induced dynamic changes in hippocampal [18F]DPA-714 uptake and several cytokines may be due to combined microglial and astrocyte action. These findings provide a theoretical reference for the future clinical applications of TSPO PET.

The prevalence of and factors associated with antenatal depression among all pregnant women first attending antenatal care: a cross-sectional study in a comprehensive teaching hospital.

BACKGROUND: Antenatal depression has become a common and serious problem, significantly affecting maternal and fetal health. However, evaluation and intervention methods for pregnant women in obstetric clinics are inadequate. This study aimed to determine the prevalence of and risk factors for depression among all pregnant women at their first attending antenatal care in the obstetrics clinic, a comprehensive teaching hospital, southwest of China. METHODS: From June to December 2019, 5780 pregnant women completed online psychological assessments, and data from 5728 of the women were analyzed. The women were categorized into two groups according to the presence or absence of depression. Depression was assessed by the Patient Health Questionnaire-9 (PHQ-9), with a cutoff point of 10 for depression. Anxiety and somatic symptoms were measured by the Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-15 (PHQ-15), respectively. Univariate analysis and binary logistic regression analysis were used to determine the association among antenatal depression, anxiety, somatic symptoms and participants' characteristics. RESULTS: The prevalence of antenatal depression among all the pregnant women at their first attending antenatal care was 16.3%, higher in the first trimester (18.1%). Anxiety symptoms (Mild anxiety AOR = 2.937; 95% CI: 2.448-3.524) and somatic symptoms (Mild somatic symptoms AOR = 3.938; 95% CI: 2.888-3.368) were major risk factors for antenatal depression among women and the risk increased more with the anxiety level or somatic symptoms level. Gestational weeks (second trimester AOR = 0.611; 95% CI: 0.483-0.773; third trimester AOR = 0.337; 95% CI: 0.228-0.498) and urban residence (AOR = 0.786; 95% CI: 0.652-0.947) were protective factors for antenatal depression among women. CONCLUSIONS: About one in six pregnant women would experience depression, and special attention should be paid to some risk factors (i.e., early pregnancy, anxiety symptoms, somatic symptoms, rural residence). Online psychological assessments might be a time-saving and convenient screening method for pregnant women in obstetric clinics.

Two-week rTMS-induced neuroimaging changes measured with fMRI in depression.

OBJECTIVE: To study the neuroimaging mechanisms of repetitive transcranial magnetic stimulation (rTMS) in treating major depressive disorder (MDD). METHODS: Twenty-seven treatment-naive patients with major depressive disorder (MDD) and 27 controls were enrolled. All of them were scanned with resting-state functional magnetic resonance imaging (fMRI) at baseline, and 15 patients were rescanned after two-week rTMS. The amplitude of low frequency fluctuation (ALFF) and functional connection degree (FCD), based on voxels and 3 brain networks (default mode network [DMN], central executive network [CEN], salience network[SN]),were used as imaging indicators to analyze. The correlations of brain imaging changes after rTMS with clinical efficacy were calculated. RESULTS: At baseline, patients groups showed increased ALFF in the right orbital frontal cortex (OFC) and decreased ALFF in the left striatal cortex and medial prefrontal cortex (PFC), while increased FCD in the right dorsal anterior cingulate cortex and OFC and decreased FCD in the right inferior parietal lobe and in the CEN. After rTMS, patients showed increased ALFF in the left dorsolateral prefrontal cortex (DLPFC)and superior frontal gyrus, FCD in the right dorsal anterior cingulate cortex, superior temporal gyrus and CEN, as well as decreased FCD in the bilateral lingual gyrus than pre-rTMS . These rTMS induced neuroimaging changes did not significantly correlated with clinical effecacy. CONCLUSIONS: This study indicated that rTMS resulted in changes of ALFF and FCD in some brain regions and CEN. But we could not conclude this is the neuroimaging mechanism of rTMS according to the correlation analysis.