Incongruent psychosis in bipolar i disorder: heritability and importance for genetic association studies

Abstract

Introduction

Phenotype homogeneity and heritability are important conditions for identifying the genetic basis of bipolar I disorder (BPI) in association studies. Our objective was to study the heritability of mood-incongruent psychosis (MIP) in BPI in a sample of 504 families ascertained through BPI probands (294 females; 210 males) recruited from consecutive hospital admissions.

Method

There were 402 families with a psychotic proband and 275 families with a proband with MIP. All probands were directly interviewed as well as 79.55% first-degree and 22.59% second-degree relatives. The narrow and the broad sense heritability (h²) of MIP and the effect of sex and age were estimated using S.A.G.E.v.6.01-software (2009).

Results

There was no sex difference for the psychosis prevalence in probands but MIP was two times more frequent in females than in males. In families with MIP probands the narrow-sense h² for MIP was 0.14 (SE = 0.02, P = 0.002) and the broad-sense h² was 0.20 (SE = 0.014, P = 0.0000). Significant but lower heritabilities were found in families with a psychotic proband (narrow-sense h² = 0.12; broad-sense h² = 0.13). In the total sample the narrow-sense h² was 0.06 (P < 0.005) and the broad-sense h² was 0.10 (P < 0.00001). The female sex was more prone to incongruency (χ² = 33.32, P = 0.0000).

Conclusion

The heritability of MIP was significant but not high in families ascertained through BPI probands regardless of familial psychopathology. These finding is in line with GWAS-studies showing that the polygenic score fails to differentiate psychotic BPI from non-psychotic BPI. Is therefore incongruent psychosis a useful dimension for association studies?