Lawford Bruce R, Barnes Mark, Morris C Phillip, Noble Ernest P, Nyst Phillip, Heslop Karen, Young Ross McD, Voisey Joanne, Connor Jason P
Division of Mental Health, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Brisbane, Queensland, Australia
Division of Mental Health, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
Can J Psychiatry. 2016 May;61(5):291-7. doi: 10.1177/0706743716644765. Epub 2016 Apr 6.
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.
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).
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).
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.
2型糖尿病在精神分裂症患者中很常见,是导致该疾病死亡率和发病率的重要因素。多巴胺与糖尿病和精神分裂症的病因均有关联。这两种疾病可能存在共同的遗传易感性。
在一项横断面研究中,我们检测了207例接受抗精神病药物治疗的精神分裂症患者的2种多巴胺D2受体(DRD2)单核苷酸多态性(SNP),即先前与精神分裂症相关的C939T(rs6275)和C957T(rs6277),同时检测了空腹血糖和体重指数(BMI)。所有参与者均符合精神分裂症的DSM-IV标准,排除患有其他精神疾病的患者。在控制已知混杂因素后,采用协方差分析比较不同DRD2基因型的空腹血糖结果。对于显著关联,采用后续的Bonferroni事后检验来检测不同基因型之间空腹血糖水平的差异。还使用方差分析和卡方检验(Fisher精确检验)进行了具体比较。
在控制了BMI、年龄、性别、抗精神病药物的剂量和类型、住院次数以及阴性症状后,两种DRD2风险基因型与血糖显著升高相关(rs6275,F(2, 182) = 5.901,P = 0.003;rs6277 SNP,F(2, 178) = 3.483,P = 0.033)。
这些发现支持DRD2不仅参与精神分裂症的发病,还与接受抗精神病药物治疗的精神分裂症患者中常见的血糖升高有关。我们的数据支持这样一种观点,即糖尿病可能不仅仅是一种共病情况,而是可能与精神分裂症本身的发病机制存在根本关联。