European archives of psychiatry and clinical neuroscience · 2026
Dissecting immune-psychiatric links: a Mendelian randomization analysis of antibody-mediated responses and mental health disorders.
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Liu Zeyu, Li Zixi, Zhu Keyu, Gao Sheng, Hua Chunyan, Hong Yanggang
Аннотация
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.
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.