Neuregulin-1 haplotype HAP(ICE) is associated with lower hippocampal volumes in schizophrenic patients and in non-affected family members

Abstract

The neuregulin-1 (NRG1) gene on chromosome 8p has been suggested as a potential susceptibility gene for schizophrenia. The exact way in which genetic variation in NRG1 might impact on this susceptibility for the disorder is a focus of current research. The present study aimed at investigating the possible relationship between a putative NRG1 at-risk haplotype (HAP(ICE)) and hippocampal volumes in schizophrenic patients and their healthy first-degree relatives. We genotyped 30 schizophrenic patients and 52 non-affected family members with regard to the presence or absence of the NRG1 haplotype HAP(ICE). Structural magnetic resonance imaging was used to determine hippocampal brain volumes in the same subjects. Patients and relatives carrying haplotype HAP(ICE) both had smaller relative hippocampal volumes as compared to patients or relatives who did not carry this haplotype. These findings provide first direct evidence for a link between NRG1 genetic variation and hippocampal volume reductions in schizophrenic patients and non-affected relatives. This preliminary evidence may help to guide further research into the pathophysiological pathways that underlie this genetic susceptibility for schizophrenia.