Systems biological assessment of altered cytokine responses to bacteria and fungi reveals impaired immune functionality in schizophrenia.

Evidence suggests that complex interactions between the immune system and brain have important etiological and therapeutic implications in schizophrenia. However, the detailed cellular and molecular basis of immune dysfunction in schizophrenia remains poorly characterized. To better understand the immune changes and molecular pathways, we systemically compared the cytokine responses of peripheral blood mononuclear cells (PBMCs) derived from patients with schizophrenia and controls against bacterial, fungal, and purified microbial ligands, and identified aberrant cytokine response patterns to various pathogens, as well as reduced cytokine production after stimulation with muramyl dipeptide (MDP) in schizophrenia. Subsequently, we performed single-cell RNA sequencing on unstimulated and stimulated PBMCs from patients and controls and revealed widespread suppression of antiviral and inflammatory programs as well as impaired chemokine/cytokine-receptor interaction networks in various immune cell subpopulations of schizophrenic patients after MDP stimulation. Moreover, serum MDP levels were elevated in these patients and correlated with the course of the disease, suggesting increased bacterial translocation along with disease progression. In vitro assays revealed that MDP pretreatment altered the functional response of normal PBMCs to its re-stimulation, which partially recapitulated the impaired immune function in schizophrenia. In conclusion, we delineated the molecular and cellular landscape of impaired immune function in schizophrenia, and proposed a mutual interplay between innate immune impairment, reduced pathogen clearance, increased MDP translocation along schizophrenia development, and blunted innate immune response. These findings provide new insights into the pathogenic mechanisms that drive systemic immune activation, neuroinflammation, and brain abnormalities in schizophrenia.

The cost of obsessive-compulsive disorder (OCD) in China: a multi-center cross-sectional survey based on hospitals.

BACKGROUND: Obsessive-compulsive disorder (OCD) is considered a very debilitating disorder with severe loss of quality of life and income. AIMS: This study estimates the quality of life and economic consequences of OCD in China. METHODS: The research team interviewed 639 patients with OCD in 13 hospitals in 12 cities in China. The direct method was used to get the direct cost of OCD. Indirect costs associated with OCD were estimated using the human capital approach. Linear regression analysis was conducted for quality of life and generalised linear model analysis was conducted for total cost. Sensitivity analysis was used to analyse the uncertainty of total cost. RESULTS: The mean quality of life score for OCD was 52.78 (20.46). The annual total cost of OCD per capita was 24 503.78 (95% CI: 22 621.53 to 26 386.03) renminbi (RMB) (US$3465.88 (95% CI: US$3199.65 to US$3732.11)). The annual cost of OCD in China was estimated to be 37.74 billion (95% CI: 34.95 billion to 40.53 billion) RMB (equal to US$5.34 billion (95% CI: US$4.94 billion to US$5.73 billion)). Sensitivity analysis showed that the total annual cost of OCD in China was between 23.15 billion RMB (US$3.27 billion) and 370.00 billion RMB (US$52.33 billion). Worse social function status, more psychiatric symptoms and higher Yale Brown Obsessive-Compulsive Scale (Y-BOCS) score were associated with worse quality of life. The numbers of clinic visits and hospitalisations, socioeconomic status, education, Y-BOCS scores and age were found to be significantly associated with total cost. CONCLUSIONS: OCD is associated with low quality of life and high costs in China. The findings call for concerted efforts to improve services for patients with OCD.Improvements may include early detection and diagnosis, the provision of evidence-based treatments and relapse prevention strategies.

Association Between MKP-1, BDNF, and Gonadal Hormones with Depression on Perimenopausal Women.

BACKGROUND: Studies suggest that brain-derived neurotrophic factor (BDNF) exerts effects on the neuronal function of hippocampal neurons and increases hippocampal mitogen-activated protein kinase phosphatase-1 (MKP-1) expression, which causes depressive behaviors in rat or mouse. Here we focus on the change of serum MKP-1, BDNF, testosterone (T), and estradiol (E2) levels, in order to test the hypothesis that dysregulation of MKP-1, BDNF, T, and E2 are associated with depression in perimenopausal women. METHODS: Women with depression, after meeting criteria in the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, for mental and behaviural disorders and the 17-item Hamilton Depression Rating Scale (HDRS), were included in the study. Psychosocial data and blood samples were obtained from the subjects in the study, including 38 perimenopausal and 32 young women with depression, 26 healthy control perimenopausal women, and 34 young women. RESULTS: Serum MKP-1 levels were higher and T was lower in the women with depression compared to controls (p<0.05), and depressed perimenopausal women exhibited the highest serum MKP-1 levels and lowest T levels. Logistic regression analyses showed that MKP-1 levels were positively correlated with HDRS scores in the women, and T levels were inversely correlated with HDRS scores in the perimenopausal women (p<0.05). CONCLUSIONS: This study suggests that high serum MKP-1 levels are associated with depression in women, and this association did not appear to be confounded by age. Further, the results provide evidence of association between depressive symptom severity and increasing serum MKP-1 levels in women, and decreasing T levels in perimenopausal women.