A Gene for Risk Taking: Effect of Genotypic Variants on Decision Making, Response Inhibition and Impulsivity in Parkinson’s Disease (P4.325)

Objective: To compare decision making, motor response inhibition and behavioural impulsivity in Parkinson’s disease (PD) patients with single nucleotide polymorphism (SNP) variants of dopamine receptor D3, N-methyl-d-aspartate receptor subunit 2B and serotonin receptor HTR2A genes. Background: SNPs in genes encoding monoamine receptors are associated with impulse control disorders (ICD) in PD. Polymorphisms in the NMDA GRIN2B gene affect risky decision making in healthy volunteers. Whether similar polymorphisms modulate impulsivity in PD is unknown. Methods: We conducted a prospective study including PD patients (n=90) whose DRD3 p.S9G (rs6280), GRIN2B c.2664C>T (rs1806201) and HTR2A c.102T>C (rs6313) genotypic status was known. Genotyping was done using PCR-based assays. All patients were screened for ICD using modified Minnesota Impulsive Disorders Interview. Decision making, response inhibition and self-reported impulsivity were assessed using the Iowa Gambling Task (IGT), Cued Go-NoGo Task (GNG) and Barratt Impulsiveness Scale (BIS). Results: Total IGT score was lower in subjects with ICD (p=0.037). None of the SNPs were significantly associated with IGT total or block scores after adjusting for age, gender, depression and apathy. Subjects with GRIN2B c.2664C>T genotype ‘AG’ preferred the high-frequency-of-gain disadvantageous deck (p=0.009) while those with at least one ‘C’ allele in the DRD3 p.S9G gene preferred the low-frequency-of-gain advantageous deck (p=0.017). For GNG, hit rate (p=0.039), discriminability index (p=0.035) and Go-reaction time (p=0.045) differed according to GRIN2B genotype. No difference was seen in BIS factors among genotypes. Conclusions: SNP variants of monoamine receptor genes are associated with varying constructs of impulsivity in PD patients. GRIN2B polymorphisms seem to be associated with response inhibition and poor choices in the long term where as DRD3 variants confer insensitivity to immediate frequent punishments and lower rewards. Although overall IGT performance is impaired only during active ICD, analysis of deck choice patterns may reveal impairments in PD patients at risk of ICD. Disclosure: Dr. Rajan has nothing to disclose. Dr. Krishnamoorthy has nothing to disclose. Dr. Krishnan has nothing to disclose. Dr. Sarma has nothing to disclose. Dr. Kishore has nothing to disclose.