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Impaired insulin signaling in unaffected siblings and patients with first-episode psychosis.

Abstract：

:Patients with psychotic disorders are at high risk for type 2 diabetes mellitus, and there is increasing evidence that patients display glucose metabolism abnormalities before significant antipsychotic medication exposure. In the present study, we examined insulin action by quantifying insulin sensitivity in first-episode psychosis (FEP) patients and unaffected siblings, compared to healthy individuals, using a physiological-based model and comprehensive assessment battery. Twenty-two unaffected siblings, 18 FEP patients, and 15 healthy unrelated controls were evaluated using a 2-h oral glucose tolerance test (OGTT), with 7 samples of plasma glucose and serum insulin concentration measurements. Insulin sensitivity was quantified using the oral minimal model method. Lipid, leptin, free fatty acids, and inflammatory marker levels were also measured. Anthropometric, nutrient, and activity assessments were conducted; total body composition and fat distribution were determined using whole-body dual-energy X-ray absorptiometry. Insulin sensitivity significantly differed among groups (F = 6.01 and 0.004), with patients and siblings showing lower insulin sensitivity, compared to controls (P = 0.006 and 0.002, respectively). Body mass index, visceral adipose tissue area (cm2), lipids, leptin, free fatty acids, inflammatory markers, and activity ratings were not significantly different among groups. There was a significant difference in nutrient intake with lower total kilocalories/kilogram body weight in patients, compared to siblings and controls. Overall, the findings suggest that familial abnormal glucose metabolism or a primary insulin signaling pathway abnormality is related to risk for psychosis, independent of disease expression and treatment effects. Future studies should examine underlying biological mechanisms of insulin signaling abnormalities in psychotic disorders.

journal_name

Mol Psychiatry

journal_title

Molecular psychiatry

authors

Chouinard VA,Henderson DC,Dalla Man C,Valeri L,Gray BE,Ryan KP,Cypess AM,Cobelli C,Cohen BM,Öngür D

doi

10.1038/s41380-018-0045-1

subject

Has Abstract

pub_date

2019-10-01 00:00:00

pages

1513-1522

issue

eissn

1359-4184

issn

1476-5578

pii

10.1038/s41380-018-0045-1

journal_volume

pub_type

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Impaired insulin signaling in unaffected siblings and patients with first-episode psychosis.