Dissecting immune-psychiatric links: a Mendelian randomization analysis of antibody-mediated responses and mental health disorders.

BACKGROUND

The relationship between antibody-mediated immune responses and psychiatric disorders remains incompletely understood. We characterized the relationship between antibody-mediated immune responses and 10 typical psychiatric disorders to ultimately achieve prevention or treatment.

METHODS

We obtained summary data from published genome-wide association studies, including those concerning antibody-mediated immune responses and 10 psychiatric disorders. Bidirectional two-sample Mendelian randomization (MR) analysis was used to assess the potential causal relationships between genetically proxied antibody-mediated immune responses and 10 psychiatric disorders.

RESULTS

We identified a total of 4 prioritized MR associations and 17 suggestive MR associations. Specifically, Epstein‒Barr virus EBNA-1 antibody levels showed an inverse association with attention deficit hyperactivity disorder (ADHD), varicella zoster virus (VZV) glycoprotein E and I antibody levels were associated with a lower risk of anorexia nervosa, and Epstein‒Barr virus ZEBRA antibody levels were associated with a higher risk of anorexia nervosa. Furthermore, VZV glycoprotein E and I antibody levels were inversely associated with posttraumatic stress disorder (PTSD), and there was no strong evidence of pleiotropy, heterogeneity, or reverse causality.

CONCLUSION

This study provides genetic evidence supporting potential links between antibody-mediated immune responses and psychiatric disorders, as well as the pathogenesis and treatment strategies for psychiatric disorders. Our results suggest a potential relationship between VZV glycoproteins E/I antibody levels and anorexia nervosa, warranting further functional and epidemiological studies to confirm this potential neuroimmune relationship.