Higher schizotypy predicts better metabolic profile in unaffected siblings of patients with schizophrenia
Type 2 diabetes (T2D) is more frequent in schizophrenia (Sz) than in the general population. This association is partly accounted for by shared susceptibility genetic variants.
We tested the hypotheses that a genetic predisposition to Sz would be associated with higher likelihood of insulin resistance (IR), and that IR would be predicted by subthreshold psychosis phenotypes.
Unaffected siblings of Sz patients (n = 101) were compared with a nonclinical sample (n = 305) in terms of IR, schizotypy (SzTy), and a behavioural experiment of “jumping to conclusions”. The measures, respectively, were the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Structured Interview for Schizotypy-Revised (SIS-R), and the Beads Task (BT). The likelihood of IR was examined in multiple regression models that included sociodemographic, metabolic, and cognitive parameters alongside group status, SIS-R scores, and BT performance.
Insulin resistance was less frequent in siblings (31.7%) compared to controls (43.3%) (p < 0.05), and negatively associated with SzTy, as compared among the tertile groups for the latter (p < 0.001). The regression model that examined all relevant parameters included the tSzTy tertiles, TG and HDL-C levels, and BMI, as significant predictors of IR. Lack of IR was predicted by the highest as compared to the lowest SzTy tertile [OR (95%CI): 0.43 (0.21–0.85), p = 0.015].
Higher dopaminergic activity may contribute to both schizotypal features and a favourable metabolic profile in the same individual. This is compatible with dopamine’s regulatory role in glucose metabolism via indirect central actions and a direct action on pancreatic insulin secretion. The relationship between dopaminergic activity and metabolic profile in Sz must be examined in longitudinal studies with younger unaffected siblings.
KeywordsDopamine Genetics Insulin resistance Schizophrenia Schizotypy Type 2 diabetes mellitus
This work was supported by the Scientific and Technological Research Council of Turkey (Program 1001, Project No: 112S475) and the 7th Frame Work Programme of the European Union (Grant Agreement No. HEALTH-F2-2009-241909, Project EU-GEI).
Compliance with ethical standards
The complete details of the entire study and procedures were in accordance with the Declaration of Helsinki. Written informed consent was obtained from each participant. This study was approved by the Medical Ethics Committee of Ankara University, Ankara, Turkey (approval #33-720).
Conflict of interest
The authors declare that they have no conflict of interest.
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