Dopamine 2 Receptor Genes Are Associated with Raised Blood Glucose in Schizophrenia.

OBJECTIVE: Type 2 diabetes is commonly found in schizophrenia and is an important contributor to mortality and morbidity in this condition. Dopamine has been implicated in the aetiology of both diabetes and schizophrenia. It is possible that both disorders share a common genetic susceptibility. METHODS: In a cross-sectional study, we examined 2 dopamine D2 receptor (DRD2) single-nucleotide polymorphisms (SNPs) previously associated with schizophrenia (C939 T, rs6275 and C957 T, rs6277) along with fasting blood glucose and body mass index (BMI) in 207 antipsychotic-treated patients with schizophrenia. All participants met DSM-IV criteria for schizophrenia, and those with other psychiatric disorders were excluded. Analysis of covariance was used to compare fasting glucose results by DRD2 genotypes, after controlling for known confounds. For significant associations, follow-up Bonferroni post hoc tests examined differences in fasting glucose levels between genotypes. Specific comparisons were also made using analysis of variance and chi-square (Fisher's exact test). RESULTS: The 2 DRD2 risk genotypes were associated with significant increases in blood glucose, after controlling for BMI, age, sex, dosage and type of antipsychotic medication, number of hospitalisations, and negative symptoms (rs6275, F(2, 182) = 5.901, P = 0.003; rs6277 SNP, F(2, 178) = 3.483, P = 0.033). CONCLUSIONS: These findings support the involvement of DRD2 not only in schizophrenia but also in elevated levels of blood glucose commonly found in antipsychotic-treated patients with schizophrenia. Our data support the notion that diabetes may not merely be a comorbid condition but could be fundamentally associated with the pathogenesis of schizophrenia itself.

Alcohol Use Disorders Identification Test (AUDIT) scores are elevated in antipsychotic-induced hyperprolactinaemia.

Hyperprolactinaemia in antipsychotic treated patients with schizophrenia is a consequence of D2 receptor (DRD2) blockade. Alcohol use disorder is commonly comorbid with schizophrenia and low availability of striatal DRD2 may predispose individuals to alcohol use. In this pilot study we investigated whether hyperprolactinaemia secondary to pharmacological DRD2 blockade was associated with alcohol use disorder in 219 (178 males and 41 females) patients with schizophrenia. Serum prolactin determinations were made in patients diagnosed with schizophrenia and maintained on antipsychotic agents. Clinical assessment included demographics, family history and administration of the AUDIT (Alcohol Use Disorders Identification Test). Higher AUDIT scores were associated with prolactin-raising antipsychotic medication (n=106) compared with prolactin-sparing medication (n=113). Risperidone (n=63) treated patients had higher AUDIT scores and prolactin levels than those on other atypical antipsychotics (n = 113). Across the entire sample, patients with a prolactin greater than 800 mIU/L had higher AUDIT scores and were more likely to exceed the cut-off score for harmful and hazardous alcohol use. These differences were not explained by potential confounds related to clinical features and demographics, comorbidity or medication side-effects. These data suggest that by lowering dosage, or switching to another antipsychotic agent, the risk for alcohol use disorder in those with schizophrenia may be reduced. This hypothesis requires testing using a prospective methodology.