Dopamine 2 receptor genes are associated with raised blood glucose in schizophrenia

Lawford, Bruce R., Barnes, Mark, Morris, C. Phillip, Noble, Ernest P., Nyst, Phillip, Heslop, Karen, Young, Ross McD., Voisey, Joanne and Connor, Jason P. (2016) Dopamine 2 receptor genes are associated with raised blood glucose in schizophrenia. The Canadian Journal of Psychiatry, 61 5: 291-297. doi:10.1177/0706743716644765

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Author Lawford, Bruce R.
Barnes, Mark
Morris, C. Phillip
Noble, Ernest P.
Nyst, Phillip
Heslop, Karen
Young, Ross McD.
Voisey, Joanne
Connor, Jason P.
Title Dopamine 2 receptor genes are associated with raised blood glucose in schizophrenia
Journal name The Canadian Journal of Psychiatry   Check publisher's open access policy
ISSN 0706-7437
1497-0015
Publication date 2016-05-01
Sub-type Article (original research)
DOI 10.1177/0706743716644765
Open Access Status File (Publisher version)
Volume 61
Issue 5
Start page 291
End page 297
Total pages 7
Place of publication Thousand Oaks, CA, United States
Publisher Sage Publications
Language eng
Subject 2738 Psychiatry and Mental health
Abstract 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.
Formatted abstract
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.
Keyword Dopamine 2 receptor
Schizophrenia
Genetics
Type 2 diabetes
Hyperglycaemia
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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