EXPLORATORY FINDINGS MAY IMPLICATE GENE'S VARIANTS, RELATED TO ANTIPSYCHOTIC MECHANISMS OF ACTION, WITH SCHIZOPHRENIA PSYCHOPATHOLOGICAL FEATURES

Background Schizophrenia (SCZ) is a common and severe mental disorder. The involvement of genetic factors in the disease is well known. In the present paper, we investigated the effects of several SNPs within 9 candidate genes involved with Antipsychotics (APs) mechanisms of action and APs response in SCZ. Methods Two independent samples were investigated in the present study. 176 subjects diagnosed with SCZ and 326 healthy controls of Korean ancestry, and 83 SCZ subjects and 194 healthy controls of Italian ancestry were used to test association with AP response (measured as PANSS scores). Secondary analyses were also performed on SCZ risk. Exploratory analyses were also performed on symptoms clusters response (PANSS subscales), Age of onset and other parameters. Results Only nominal associations were found for APs response: the analyses showed associations for rs11071511, rs2337980(CHRNA7) and rs6740584(CREB1) in the Korean sample. Allelic analyses in the Italian sample evidenced a nominal association of rs12144159(PLA2G4A). None of the above associations survived to the FDR correction. Interesting data was found on exploratory analyses, which evidenced a correlation of the genes under investigation with several parameters. In particular, fairly indicative data was found for rs11071511 (CHRNA7), rs10798069 (PLAG2G4A) in relation to Positive symptoms (Korean Sample); rs10814130 (SIGMAR1) in relation to Negative symptoms (Korean Sample); rs1719895 and rs2037547 (GSK3B), rs2186358 and rs2839364 (S100B) in relation to Age of Onset (Korean sample); rs10737276 (PLA2G4A) in relation to Age of onset (Italian sample). Discussion Our results did not support a primary role for the genes investigated in APs response as a whole. However, our exploratory data suggests that these genes may be involved in symptoms clusters response. In particular, these variants may determine a higher genetic loading, resulting in an anticipation of the disorder onset (age of onset of the pathology).