T66 - The Neuregulin-1 Gene Is Associated With Schizotypy In The General Population

Abstract

Background It is believed that the personality characteristics and symptoms observed in schizophrenia lie on a continuum, with subclinical symptoms referred to as schizotypy. The continuum theory of schizophrenia recognises schizotypy as a suitable model for investigating schizophrenia: individuals with high levels of schizotypy demonstrate similar symptoms, cognitive profiles and neuroimaging findings to schizophrenia, albeit in a more subtle manner, without the potential confounding factors associated with schizophrenia. Both schizophrenia and schizotypy have been shown to be influenced by genetic factors. Neuregulin-1 (NRG1), involved in neuronal development, migration, myelination and synaptic plasticity, has been identified as a promising candidate gene for schizophrenia risk. Several NRG1 single nucleotide polymorphisms (SNPs) have been associated with schizophrenia and cognitive deficits, though only one SNP has been previously associated with schizotypy. The aim of this study was to examine the link between NRG1 and schizotypy across the schizotypy/schizophrenia continuum. Methods Participants were 200 adults (83 patients with schizophrenia and 117 healthy controls) who were assessed for schizotypy factors using the Oxford-Liverpool Inventory of Feelings and Experience (O-LIFE). The factors assessed were unusual experiences (UnEx), introvertive anhedonia (InAn) and cognitive disorganisation (CogDis), which are thought to reflect the positive, negative and cognitive symptoms of schizophrenia respectively. Participants were also genotyped for five NRG1 SNPs; rs10503929, rs3924999, rs2466058, rs35753505 and rs6994992. A MANOVA was conducted with schizotypy factors as dependent variables and participant group as independent variables to observe differences between patients and controls. Another MANOVA was conducted with schizotypy factors as dependent variables and NRG1 SNPs as independent variables to observe differences and interactions of the NRG1 SNPs on schizotypy across the continuum. Results Confirming previous findings, schizotypy scores were significantly higher in the patient group as compared to controls (p Discussion This is the first study to demonstrate an association between NRG1 and schizotypy across the continuum, in particular CogDis. From this, it can be inferred that genetic variation in NRG1 may be a contributing factor to cognitive deficits in the clinical population, consistent with previous findings. As individual SNPs were not significantly associated with schizotypy but significant interactions were observed, this study also demonstrates the heterogeneity of schizophrenia. This finding contributes to the literature associating NRG1 with cognitive deficits in schizophrenia and supports the use of schizotypy as a model for schizophrenia.