EPA-0460 – Effects of comt val158/met polymorphism on sensory-motor gating and blood monoamines level in russian schizophrenia patients and healthy persons

Abstract

Catechol-O-methyltransferase (COMT) is candidate gene for schizophrenia, as it encodes enzyme involved in dopamine and noradrenaline methabolism. However, data concerning association of COMT polymorphism with schizophrenia onset in different ethnic groups are controversial. Impaired acoustic startle prepulse inhibition (PPI) is potential hallmark of vulnerability to schizophrenia, but a few investigations of COMT polymorphism effects on PPI revealed controversial results (Liu et al., 2013). To estimate effects of COMT polymorphism on PPI and blood monoamines level in Russian populations of schizophrenia patients and healthy persons. (males 22–55 years old): 39 schizophrenia patients and 32 healthy persons. PPI was estimated according to standard protocol (Calkins et al., 2007). Blood monoamnes estimated using HPLC with electrochemical detection. COMT polymorphism was detected by real-time PCR. There were significantly (p<0,05) lower heterozygotes frequency, impaired PPI, increased baseline startle latency, decreased plasma DOPAC in patients relatively to controls. Group x Genotype interaction was revealed for PPI and startle latency. In controls VAL/VAL carriers displayed the lowest PPI. In patients the lowest PPI showed VAL/ME T and the longest startle latency - MET/MET carriers. In controls PPI positively correlated with dopamine turnover ratio whereas in patients - with plasma adrenaline level. In Russian population effects of COMT VAL158/MET polymorphism on PPI significantly differ at healthy and schizophrenia persons. One can propose that PPI level in healthy subjects more strictly depends on dopamine turnover than in schizophrenia patients. Further investigations are needed to clear this problem. Supported by RHF grant 12-06-00809a