Disentangling the relationship between psychiatric disorders, cardiometabolic abnormalities, and antipsychotics: A systematic review of genomic studies

Psychiatric disorders are often comorbid with metabolic syndrome (MetS), suggesting shared genetic architecture. This systematic review investigated the genetic connections between psychiatric disorders, antipsychotic use, and MetS through genome-wide association studies and related genetic approaches. We systematically searched PubMed, Scopus, and Web of Science for relevant studies published between January 2005 and August 2025. Seventy-seven studies were included in the systematic review upon meeting the inclusion criteria. Substantial shared genetic architecture was found between psychiatric disorders and metabolic traits, particularly involving major depressive disorder (MDD), schizophrenia (SCZ), and body mass index (BMI). Key implicated pathways included lipid metabolism, glucose homeostasis, and inflammatory processes. Mendelian randomization studies provided evidence for causal relationships, notably a unidirectional effect of MDD on MetS, and bidirectional relationships between SCZ and BMI. Antipsychotic-induced weight gain showed a more specific genetic basis compared to broader psychiatric disorder-related MetS. Future research should focus on diverse populations, refined phenotype definitions, and translating genetic insights into clinical practice. The integration of pharmacogenomic scores with clinical data shows promise for personalizing treatment strategies in psychiatry.