Causal role of immune cells in schizophrenia: Mendelian randomization (MR) study.

BACKGROUND: Complex immune-brain interactions that affect neural development, survival and function might have causal and therapeutic implications for psychiatric illnesses. However, previous studies examining the association between immune inflammation and schizophrenia (SCZ) have yielded inconsistent findings. METHODS: Comprehensive two-sample Mendelian randomization (MR) analysis was performed to determine the causal association between immune cell signatures and SCZ in this study. Based on publicly available genetic data, we explored causal associations between 731 immune cell signatures and SCZ risk. A total of four types of immune signatures (median fluorescence intensities (MFI), relative cell (RC), absolute cell (AC), and morphological parameters (MP)) were included. Comprehensive sensitivity analyses were used to verify the robustness, heterogeneity, and horizontal pleiotropy of the results. RESULTS: After FDR correction, SCZ had no statistically significant effect on immunophenotypes. It was worth mentioning some phenotypes with unadjusted low P-values, including FSC-A on NKT (ß = 0.119, 95% CI = 0.044 ~ 0.194, P = 0.002), DN (CD4-CD8-) NKT %T cell (ß = 0.131, 95% CI = 0.054 ~ 0.208, P = 9.03 × 10- 4), and SSC-A on lymphocytes (ß = 0.136, 95% CI = 0.059 ~ 0.213, P = 5.43 × 10- 4). The causal effect of SCZ IgD on transitional was estimated to 0.127 (95% CI = 0.051 ~ 0.203, P = 1.09 × 10- 3). SCZ also had a causal effect on IgD+ %B cell (ß = 0.130, 95% CI = 0.054 ~ 0.207, P = 8.69 × 10- 4), and DP (CD4+CD8+) %T cell (ß = 0.131, 95% CI = 0.054 ~ 0.207, P = 8.05 × 10- 4). Furthermore, four immunophenotypes were identified to be significantly associated with SCZ risk: naive CD4+ %T cell (OR = 0.986, 95% CI = 0.979 ~ 0.992, P = 1.37 × 10- 5), HLA DR on CD14- CD16- (OR = 0.738 (95% CI = 0.642 ~ 0.849, P = 2.00 × 10- 5), CD33dim HLA DR+ CD11b- AC (OR = 0.631, 95% CI = 0.529 ~ 0.753, P = 3.40 × 10- 7) and activated & resting Treg % CD4 Treg (OR = 0.937, 95% CI = 0.906 ~ 0.970, P = 1.96 × 10- 4). CONCLUSIONS: Our study has demonstrated the close connection between immune cells and SCZ by genetic means, thus providing guidance for future clinical research.

Empathy deficit in male patients with schizophrenia and its relationships with impulsivity and premeditated violence.

Objective: To explore the pattern of empathy characteristics in male patients with schizophrenia (SCH) and to examine whether empathy deficit is associated with impulsivity and premeditated violence. Methods: One hundred and fourteen male SCH patients were enrolled in this study. The demographic data of all patients were collected and the subjects were divided into two groups, namely, the violent group, including 60 cases, and the non-violent group, comprising 54 cases, according to the Modified Overt Aggression Scale (MOAS). The Chinese version of the Interpersonal Reactivity Index-C (IRI-C) was used to evaluate empathy and the Impulsive/Predicted Aggression Scales (IPAS) was employed to assess the characteristics of aggression. Results: Among the 60 patients in the violent group, 44 patients had impulsive aggression (IA) and 16 patients had premeditated aggression (PM) according to the IPAS scale. In the violent group, the scores of the four subfactors of the IRI-C, i.e., perspective taking (PT), fantasy (FS), personal distress (PD), and empathy concern (EC), were significantly lower than in the non-violent group. Stepwise logistic regression showed that PM was independent influencing factor for violent behaviors in SCH patients. Correlation analysis revealed that EC of affective empathy was positively correlated with PM but not with IA. Conclusion: SCH patients with violent behavior had more extensive empathy deficits compared with non-violent SCH patients. EC, IA and PM are independent risk factors of violence in SCH patients. Empathy concern is an important index to predict PM in male patients with SCH.