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. 2016 May;61(5):291-7.
doi: 10.1177/0706743716644765. Epub 2016 Apr 6.

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

Bruce R Lawford  1 , Mark Barnes  2 , C Phillip Morris  3 , Ernest P Noble  4 , Phillip Nyst  2 , Karen Heslop  5 , Ross McD Young  3 , Joanne Voisey  3 , Jason P Connor  6
Affiliations

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

Bruce R Lawford et al. Can J Psychiatry. 2016 May.

Abstract
in English, French

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 diabète de type 2 s’observe souvent dans la schizophrénie et est un important contributeur à la mortalité et la morbidité de cette affection. La dopamine est impliquée dans l’étiologie du diabète et de la schizophrénie. Il est possible que ces deux troubles aient en commun une susceptibilité génétique.

Méthodes:: Dans une étude transversale, nous avons examiné deux polymorphismes mononucléotidiques (SNP) d’un récepteur de la dopamine D2 (DRD2) précédemment associés à la schizophrénie (C939T, rs6275 et C957T, rs6277) ainsi que la glycémie à jeun et l’indice de masse corporelle (IMC) chez 207 patients souffrant de schizophrénie traités aux antipsychotiques. Tous les participants satisfaisaient aux critères du DSM-IV pour la schizophrénie et ceux qui souffraient d’autres troubles psychiatriques ont été exclus. L’analyse de covariance (ANCOVA) a été utilisée pour comparer les résultats de la glycémie à jeun par génotypes DRD2, après contrôle pour les facteurs de confusion connus. Pour les associations significatives, des tests post hoc de Bonferroni ont examiné les différences des taux de glycémie à jeun entre les génotypes. Des comparaisons spécifiques ont aussi été effectuées à l’aide d’ANOVA et du chi-carré (Fisher’s exact test).

Résultats:: Les deux génotypes à risque DRD2 étaient associés à des augmentations significatives de la glycémie, après contrôle de l’IMC, l’âge, le sexe, le dosage et le type de médicament antipsychotique, le nombre d’hospitalisations et de symptômes négatifs (rs6275, F(2, 182) = 5.901, P = 0,003, rs6277 SNP, F(2, 178) = 3.483, P = 0,033).

Conclusions:: Ces résultats soutiennent la participation de DRD2 non seulement à la schizophrénie mais aussi à des taux élevés de glycémie souvent observés chez les patients souffrant de schizophrénie traités aux antipsychotiques. Nos données appuient la notion que le diabète n’est peut-être pas seulement une affection comorbide, mais qu’il pourrait fondamentalement être associé à la pathogenèse de la schizophrénie même.

Keywords: dopamine 2 receptor; genetics; hyperglycaemia; schizophrenia; type 2 diabetes.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Mean blood glucose levels in schizophrenia patients for dopamine D2 receptor single-nucleotide polymorphisms rs6277 and rs6275. Error bars are standard error of the mean. *P < 0.05.
See this image and copyright information in PMC

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