Glutathione S-Transferase Deletion Polymorphisms in Early-Onset Psychotic and Bipolar Disorders: A Case-Control Study

Objective: To examine glutathione S-transferase (GST) deletion polymorphisms in development of early-onset severe mental disorders, with the hypothesis that patients with GSTM1-null and GSTT1-null genotypes will develop psychotic disorders at a younger age. Methods: We identified GSTM1 and GSTT1 deletion polymorphisms by multiplex polymerase chain reaction (PCR) in 93 patients with early onset severe mental disorders and 278 control individuals. The diagnoses were confirmed by Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version and Schedule for Affective Disorders and Schizophrenia–Life-Time Version (K-SADS-PL) interviews. Results: Individuals with the GSTM1-null genotype were at 3.36-fold higher risk of developing early-onset severe mental disorders than carriers of a corresponding active genotype. The risk of those disorders was increased by 6.59-fold in patients with GSTM1-null/GSTT1-active genotype. Patients with the GSTM1-null genotype were at approximately 2-fold increased risk for developing early-onset schizophrenia-spectrum disorder (EOS), early-onset bipolar disorder (EOBD) with psychotic symptoms, or early-onset first-episode psychosis (EOFEP), compared with patients with the GSTM1-active genotype. Conclusion: The GSTM1-null genotype might be associated with higher risk for early onset severe mental disorders. * Abbreviations : EOS : early-onset schizophrenia EOFEP : early-onset first-episode psychosis EOBPs : early-onset bipolar disorders GSH : glutathione GST : glutathione S-transferase ROSs : reactive oxygen species MAPEG : membrane-associated proteins in eicosanoid and glutathione metabolism K-SADS-PL : Schedule for Affective Disorders and Schizophrenia for School-Age Children–Present and Lifetime Version ICD-10 : International Classification of Diseases, Revision 10 DSM-IV : Diagnostic and Statistical Manual of Mental Disorders , 4th Edition DSM-III-R : Diagnostic and Statistical Manual of Mental Disorders , 3rd Edition–Revised SADS-L : Schedule for Affective Disorders and Schizophrenia Lifetime PCR : polymerase chain reaction ORs : odds ratios CIs : confidence intervals CNV : copy number variation NA : not applicable