Genetic and clinical characteristics associated with antidepressant-induced mania in depression patients

Antidepressant-induced mania (AIM) is a significant clinical concern, primarily studied in bipolar disorder patients. Limited research exists on AIM in unipolar depression, with reported incidence rates of 3.0-8.2 %.

Using data from the Taiwan's National Health Insurance Research Database merged with Taiwan Biobank (2001-2017), we analyzed 772 depression patients who were prescribed antidepressants and had available genotype data. A genome-wide association study (GWAS) was performed to investigate potential genetic factors associated with AIM. Single-marker association analysis and polygenic risk scores were calculated using PLINK.

AIM developed in 145 (19.65 %) of depressive patients within 28 days of medication use or discontinuation. Significant associated clinical characteristics included female gender, postpartum depression, comorbid obsessive-compulsive disorder, severe depression, substance use disorders, and other non-organic psychosis. Eight single nucleotide polymorphisms were identified as potential genetic markers associated with AIM in this GWAS, and higher polygenic risk scores for bipolar disorder were associated with increased AIM risk.

AIM was observed in one-fifth of depressive patients of the Han Chinese origin, with female gender and psychiatric comorbidities as significant clinical characteristics. This GWAS of AIM in depressive patients identified potential genetic markers and suggested that a genetic predisposition to bipolar disorder may increase the likelihood of developing AIM, although this association did not reach statistical significance. Future research should aim to increase sample size and further investigate genotype-AIM associations.