Association study of 45 SNPs in a non-help seeking cohort sample with at-risk mental state for psychosis

Abstract

Background: At-risk mental state for psychosis (ARMS) samples are highly heterogeneous and non-epidemiological, as most of the studies recruit help-seeking patients from specialized clinics. Transition-to-psychosis rates differ among them, ranging from 7.4% to 54%, raising a question on the real power of clinical ARMS`s criteria alone to predict transition. Finding a biomarker for transition would improve the prediction rates when associated with clinical high-risk criteria.Methods: We genotyped 45 single nucleotide polymorphisms (SNPs) among a control sample and a non-help seeking ARMS sample and compared their frequencies. Then, we followed up this ARMS cohort of 90 individuals for 2.5 years and compared the genotype frequencies between non-converters and psychotic converters and non-psychotic converters.Results: We found a trend for a higher frequency of the TT genotype of rs6277, a dopamine receptor D2 gene (DRD2) SNP, among those who transitioned to psychosis (p=0.004) and among those who converted to any psychiatric diagnose (p=0.003), which did not remain significant after correction with Benjamini-Hochberg procedure (critical value=0.001). Converters and non-converters could not be differentiated from one another by any other characteristic. There were no significant differences between the genotype frequencies in the control group and the ARMS group in the initial cross section evaluation. Transition rates in our non-help-seeking ARMS sample were 3.33% for psychosis and 13.33% for non-psychotic disorders, a total of 16.66% for psychiatric disorders in general. Conclusions: Our findings suggest that rs6277 should be investigated in a larger ARMS sample to better assess its possible relation to transition to psychosis and other psychiatric disorders.