The type 2 diabetes mellitus susceptibility gene CDKAL1 polymorphism is associated with depressive symptom in first-episode drug-naive schizophrenic patients.

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Patients with schizophrenia have an increased prevalence of type 2 diabetes mellitus that has shown a significant association with the rs7754840 polymorphism in the gene encoding the cyclin-dependent kinase 5 (CDK5) regulatory subunit-associated protein 1-like 1 (CDKAL1). To examine whether this polymorphism was involved in the susceptibility in first-episode drug-naive schizophrenic patients (FDSP), and further influenced their clinical symptoms. This polymorphism was genotyped in 239 FDSP and 368 healthy controls. The clinical symptoms in FDSP were assessed using the Positive and Negative Syndrome Scale (PANSS) five-factor models. There was no significant difference in the allelic and genotypic frequencies of this polymorphism between two groups (both p>0.05) after adjusting for covariates. However, the PANSS depressive score significantly differed by genotype in FDSP after adjusting for covariates (F=5.25, p=0.006). This significant difference also persisted after Bonferroni correction (p<0.05). FDSP with C/C genotype had significantly higher PANSS depressive score than those with C/G genotype (p=0.007) and those with G/G genotype (p=0.005). Moreover, further stepwise multivariate regression analysis showed the significant association between the rs7754840 polymorphism and PANSS depressive score in FDSP (β=-1.07, t=-2.75, p=0.007). Our findings demonstrated that although the CDKAL1 rs7754840 polymorphism did not contribute to the susceptibility to FDSP, it might be implicated in depressive symptoms in this patient group.