The Effect of ANKK1 Taq1A Polymorphism on Cognition in Recent-Onset Psychosis: A Controlled Study

Background The T allele of rs1800497 SNP of ANKK1 gene has been linked to a poorer performance on prefrontal cognitive processes. There is the lack of studies investigating the effect of this variant on cognition in schizophrenia. Our main aim therefore was to investigate its impact on cognition in a sample of subjects with a recent diagnosis of psychosis Methods We included 128 patients with recent –onset psychosis (ROP) and 70 healthy controls (HC) with both complete neuropsychological assessment by MATRICS Consensus Cognitive Battery (MCCB) and blood specimen drawn for DNA analysis. Genotypes were grouped following an additive model. We explored main effects of disease (ROP and HC) and genetics (T+ and T-) and their interaction term on cognition. Results Two-way ANOVAs showed a significant genetic and disease interaction effect in WMS –SS (non-verbal working memory) (F=10.32, p=0.002, partial eta squared =0.05) and on MCCB total score (F=5.02, p=0.02, partial eta squared =0.03). When sample was stratified by allele status, ROP- T+ performed poorly than HC-T+ in WMS-SS, while that difference was not found among T-. Within ROP, T carriers presented a worse cognitive profile than non-carriers but within HC, cognitive profile did not differ as a function of allele status. When adjusting for clinical confounders both WMS-SS (F=9.53, p=0.003, partial eta squared =0.09) and total MCBB scores (F=7.09, p=0.009, partial eta squared=0.08) continued to be lower in ROP-T+ compared with ROP-T–. Conclusion This is the first study to report an association of the vulnerability allele of Taq1A with cognitive impairment in psychosis assessed by a standardized instrument as the MCCB battery. Our study therefore, provides preliminary evidence for the potential role of the ANNK1 gene in modulating cognitive performance in psychosis.