Association between the COMT gene and neurological abnormalities and poorer executive function in psychosis

Objective: Motor and sensory neurological dysfunctions, and executive dysfunction, present in excess in psychosis, could reflect the same pathophysiological process possibly involving the prefrontal cortex. The COMT Val158Met may influence these impairments by affecting the function of prefrontal regions. We tested in a large cohort of Caucasian patients with psychosis whether subjects homozygous for the Val158 allele had greater neurological impairments and worse executive performance. Method: We evaluated 211 individuals with psychosis from four different cohorts recruited in Italy and UK. All patients underwent neurological and neuropsychological evaluations, and were genotyped for the COMT Val158Met (rs4680) polymorphism. Results: Patients with higher motor sequencing scores exhibited a worse block design performance (ANCOVA, p=0.002). Individuals with high motor sequencing signs and poorer executive function were significantly more likely to be homozygotes for the Met158 allele (Chi Square, p=0.016). Conclusion: Our finding of an association between the Met158 allele and both neurological and executive deficits was not predicted and needs to be replicated.