Inflammatory depression is a treatment-resistant subtype of depression. A causal role of the gut microbiota as a source of low-grade inflammation remains unclear. Here, as part of an observational trial, we first analyze the gut microbiota composition in the stool, inflammatory factors and short-chain fatty acids (SCFAs) in plasma, and inflammatory and permeability markers in the intestinal mucosa of patients with inflammatory depression (ChiCTR1900025175). Gut microbiota of patients with inflammatory depression exhibits higherBacteroidesand lowerClostridium, with an increase in SCFA-producing species with abnormal butanoate metabolism. We then perform fecal microbiota transplantation (FMT) and probiotic supplementation in animal experiments to determine the causal role of the gut microbiota in inflammatory depression. After FMT, the gut microbiota of the inflammatory depression group shows increased peripheral and central inflammatory factors and intestinal mucosal permeability in recipient mice with depressive and anxiety-like behaviors.Clostridium butyricumadministration normalizes the gut microbiota, decreases inflammatory factors, and displays antidepressant-like effects in a mouse model of inflammatory depression. These findings suggest that inflammatory processes derived from the gut microbiota can be involved in neuroinflammation of inflammatory depression.

Background: The prevalence of depressive and anxiety symptoms in patients with COVID-19 is higher than usual. Previous studies have shown that there are drug-to-drug interactions between antiretroviral drugs and antidepressants. Therefore, an effective and safe treatment method was needed. Cognitive behavioral therapy (CBT) is the first-line psychological therapy in clinical treatment. Computerized CBT (cCBT) was proven to be an effective alternative to CBT and does not require face-to-face therapy between a therapist and the patient, which suited the COVID-19 pandemic response. Objective: This study aims to evaluate the efficacy of the cCBT program we developed in improving depressive and anxiety symptoms among patients with COVID-19. Methods: We customized a cCBT program focused on improving depressive and anxiety symptoms among patients with COVID-19, and then, we assessed its effectiveness. Screening was based on symptoms of depression or anxiety for patients who scored ≥7 on the Hamilton Depression Rating Scale (HAMD17) or the Hamilton Anxiety Scale (HAMA). A total of 252 patients with COVID-19 at five sites were randomized into two groups: cCBT + treatment as usual (TAU; n=126) and TAU without cCBT (n=126). The cCBT + TAU group received the cCBT intervention program for 1 week. The primary efficacy measures were the HAMD17 and HAMA scores. The secondary outcome measures were the Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), and Athens Insomnia Scale (AIS). Assessments were carried out pre- and postintervention. The patients’ symptoms of anxiety and depression in one of the centers were assessed again within 1 month after the postintervention assessment. Results: The cCBT + TAU group displayed a significantly decreased score on the HAMD17, HAMA, SDS, SAS, and AIS after the intervention compared to the TAU group (all P<.001). A mixed-effects repeated measures model revealed significant improvement in symptoms of depression (HAMD17 and SDS scores, both P<.001), anxiety (HAMA and SAS scores, both P<.001), and insomnia (AIS score, P=.002) during the postintervention and follow-up periods in the cCBT + TAU group. Additionally, the improvement of insomnia among females (P=.14) and those with middle school education (P=.48) in the cCBT + TAU group showed no significant differences when compared to the TAU group. Conclusions: The findings of this study suggest that the cCBT program we developed was an effective nonpharmacological treatment for symptoms of anxiety, depression, and insomnia among patients with COVID-19. Further research is warranted to investigate the long-term effects of cCBT for symptoms of anxiety, depression, and insomnia in patients with COVID-19. Trial Registration: Chinese Clinical Trial Registry ChiCTR2000030084; http://www.chictr.org.cn/showprojen.aspx?proj=49952

Studies have confirmed that the thalamus and the primary somatosensory cortex (SI) are associated with cognitive function. These two brain regions are closely related in structure and function. The interactions between SI and the thalamus are of crucial significance for the cognitive process. Patients with major depressive disorder (MDD) have significant cognitive impairment. Based on these observations, we used resting-state functional magnetic resonance imaging (rs-fMRI) to investigate whether there is an abnormality in the SI-thalamic functional connection in MDD. Furthermore, we explored the clinical symptoms related to this abnormality. We included 31 patients with first-episode major depressive disorder and 28 age-, gender-, and education-matched healthy controls (HC). The SI-thalamic functional connectivity was compared between the MDD and HC groups. The correlation analyses were performed between areas with abnormal connectivity and clinical characteristics. Compared with healthy subjects, the MDD patients had enhanced functional connectivity between the thalamus and SI (p < 0.05, corrected). Brain areas with significantly different levels of connectivity had a negative correlation with the Assessment of Neuropsychological Status total score (r = − 0.383, p = 0.033), delayed memory score (r = − 0.376, p = 0.037) and two-digit continuous operation test score (r = − 0.369, p = 0.041) in MDD patients. These results demonstrate that SI-thalamic functional connectivity is abnormal and associated with the core clinical symptoms in MDD. The SI-thalamic functional connectivity functions as a neurobiological feature and potential biomarker for MDD.

Investigating the neurobiological mechanism of suicidal ideation (SI) in major depressive disorder (MDD) may be beneficial to prevent the suicidal behavior. Mounting evidence showed that habenula contributed to the etiology of MDD. The habenula is a key brain region that links the forebrain to midbrain, crucial for the processing of reward and aversion. The aim of the present study was to identify whether first-episode, drug-naive MDD patients with SI displayed altered habenula neural circuitry. Forty-three and 38 drug-naïve patients with first-episode MDD with or without SI (SI+/– group) and 35 healthy control subjects (HC) underwent resting-state functional magnetic resonance imaging. The whole-brain habenula static (sFC) and dynamic functional connectivity (dFC) were calculated to identify regions showing significant difference among these three groups followed by region of interest to region of interest post hoc analysis. For sFC, compared with SI– and HC groups, SI+ group showed decreased sFC from habenula to the precuneus and the inferior frontal gyrus. Patients with MDD displayed increased sFC from habenula to the putamen but decreased sFC to the precentral gyrus. For dFC, SI+ group showed increased dFC from habenula to the superior temporal gyrus, the precuneus, but decreased dFC to the lingual gyrus, the postcentral gyrus, when comparing with SI– and HC groups. Patients with MDD, regardless of SI, displayed decreased dFC from the habenula to the angular gyrus. These findings provide evidence that SI in first-episode, drug-naïve patients with MDD may be related to an abnormality in habenula neural circuitry, which may provide the theoretical basis of novel treatments.

The lifetime prevalence of major depressive disorder (MDD) in adolescents is reported to be as high as 20%; thus, MDD constitutes a significant social and public health burden. MDD is often associated with nonsuicidal self-injury (NSSI) behavior, but the contributing factors including cognitive function have not been investigated in detail. To this end, the present study evaluated cognitive impairment and psychosocial factors in associated with MDD with NSSI behavior. Eighteen and 21 drug-naïve patients with first-episode MDD with or without NSSI (NSSI+/– group) and 24 healthy control subjects (HC) were enrolled in the study. The Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Adolescent Self-injury Questionnaire, Beck Scale for Suicide Ideation–Chinese Version (BSI-CV), Shame Scale for Middle School Students, Sensation Seeking Scale (SSS) and Childhood Trauma Questionnaire (CTQ) were used to assess depression-related behaviors, and event-related potentials (ERPs) were recorded as a measure of cognitive function. The latency of the N1, N2, P3a, P3b, and P50 components of ERPs at the Cz electrode point; P50 amplitude and P50 inhibition (S1/S2) showed significant differences between the 3 groups. CTQ scores also differed across three groups, and the NSSI– and NSSI+ groups showed significant differences in scores on the Shame Scale for Middle School Students. Thus, cognitive function was impaired in adolescents with MDD with NSSI behavior, which was mainly manifested as memory decline, attention and executive function deficits, and low anti-interference ability. We also found that childhood abuse, lack of social support, and a sense of shame contributed to NSSI behavior. These findings provide insight into the risk factors for MDD with NSSI behavior, which can help mental health workers more effectively diagnose and treat these patients.