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. Objectif: Le diabete de type 2 s'observe souvent dans la schizophrenie et est un important contributeur a la mortalite et la morbidite de cette affection. La dopamine est impliquee dans l'etiologie du diabete et de la schizophrenie. Il est possible que ces deux troubles aient en commun une susceptibilite genetique. Methodes: Dans une etude transversale, nous avons examine deux polymorphismes mononucleotidiques (SNP) d'un recepteur de la dopamine D2 (DRD2) precedemment associes a la schizophrenie (C939T, rs6275 et C957T, rs6277) ainsi que la glycemie a jeun et l'indice de masse corporelle (IMC) chez 207 patients souffrant de schizophrenie traites aux antipsychotiques. Tous les participants satisfaisaient aux criteres du DSM-IV pour la schizophrenie et ceux qui souffraient d'autres troubles psychiatriques ont ete exclus. L'analyse de covariance (ANCOVA) a ete utilisee pour comparer les resultats de la glycemie a jeun par genotypes DRD2, apres controle pour les facteurs de confusion connus. Pour les associations significatives, des tests post hoc de Bonferroni ont examine les differences des taux de glycemie a jeun entre les genotypes. Des comparaisons specifiques ont aussi ete effectuees a l'aide d'ANOVA et du chi-carre (Fisher's exact test). Resultats: Les deux genotypes a risque DRD2 etaient associes a des augmentations significatives de la glycemie, apres controle de l'IMC, l'age, le sexe, le dosage et le type de medicament antipsychotique, le nombre d'hospitalisations et de symptomes negatifs (rs6275, F(2, 182) = 5.901, P = 0,003, rs6277 SNP, F(2, 178) = 3.483, P = 0,033). Conclusions: Ces resultats soutiennent la participation de DRD2 non seulement a la schizophrenie mais aussi a des taux eleves de glycemie souvent observes chez les patients souffrant de schizophrenie traites aux antipsychotiques. Nos donnees appuient la notion que le diabete n'est peut-etre pas seulement une affection comorbide, mais qu'il pourrait fondamentalement etre associe a la pathogenese de la schizophrenie meme.