Increased cardiometabolic dysfunction in first-degree relatives of patients with psychotic disorders

Abstract

Introduction Elevated prevalence of comorbid cardio-vascular and metabolic dysfunction (CMD) is consistently reported in patients with severe psychotic disorders such as schizophrenia (SZ), schizoaffective (SZA) and bipolar disorder (BP-P). Since both psychosis and CMD are substantively heritable in nature, we attempted to investigate the occurrence of CMD disorders in first degree relatives of probands with psychosis. Methods Our sample included 861 probands with a diagnoses of SZ (n=354), SZA (n=212) and BP-P (n=295), 776 first-degree relatives of probands and 416 healthy controls. Logistic regression was used to compare prevalence of any CMD disorders (diabetes, hypertension, hyperlipidaemia or coronary artery disease) across groups. Post-hoc tests of independence checked for CMD prevalence across psychosis diagnosis (SZ, SZA and BP-P), both in relatives of probands and within probands themselves. Results After controlling for potential confounders, first degree relatives with (p<0.001) and without (p=0.03) Axis I non-psychotic or Axis- II cluster disorders were at a significant risk for CMD compared to controls. No significant difference (p=0.42) was observed in prevalence of CMD between relatives of SZ, SZA and BP-P, or between psychosis diagnoses for probands (p=0.25). Discussion Prevalence of CMD was increased in the first degree relatives of psychosis subjects. This finding suggests the possibility of overlapping genetic contributions to CMD and psychosis. Increased somatic disease burden in relatives of psychotic disorder probands points to need for early detection and preventive efforts in this population.

Polygenic risk for type 2 diabetes mellitus among individuals with psychosis and their relatives

“…In this study, we found an elevated prevalence of self-reported diabetes in probands with psychotic disorders and their relatives compared to controls, in concordance with previously published data (Bushe and Holt, 2004, Dixon et al, 2000, Fernandez-Egea et al, 2008, Mothi et al, 2015, Mukherjee et al, 1989). Prevalence of self-reported diabetes was also elevated in African-American probands in comparison with Caucasian probands, corroborating findings in the general population, in which incidence (Brancati et al, 2000) and prevalence of T2D (Carter et al, 1996) are also higher in African-Americans.…”

“…However, other studies have not confirmed these findings (Sengupta et al, 2008). In addition, some studies have noted increased rates of T2D among relatives of people with schizophrenia (Fernandez-Egea et al, 2008, Mothi et al, 2015, Mukherjee et al, 1989), and a clustering of diabetes mellitus and psychosis in family histories of people with psychosis (Foley et al, 2015). These family data raise the possibility of shared genetic and environmental risk factors between T2D and psychosis.…”

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

“…Several lines of evidence also suggest that patients with psychotic disorders have an endogenous risk for developing T2DM. Prevalence of diabetes is elevated in unaffected family members 17 , 18 , and genetic association and pathway analysis studies point to shared genetic risk factors between psychotic disorders and T2DM 19 , 20 , including the association of well-established T2DM gene variants with schizophrenia 21 . In this convergence of genetic and environmental risk factors for T2DM, the underlying physiology of impaired glucose metabolism in patients with psychosis remains to be elucidated.…”

Esquizofrenia y su asociación con enfermedades médicas crónicas

“…Esto es sugerente de la existencia de un contexto genético común de las condiciones cardiometabólicas y los desórdenes psicóticos 30 .…”