The COMT Val158Met polymorphism is associated with novelty seeking in Czech methamphetamine abusers: preliminary results.

OBJECTIVES: Measurable traits of human personality may mark the predisposition to psychopathology. Increased novelty seeking plays an important role in the pathogenesis of substance abuse. Novelty seeking, one of the fundamental traits of the human temperament, is related to dopamine. Catechol-O-methyltransferase (COMT) is essential for dopamine inactivation. The aim of our study was to assess whether the COMT gene Val158Met functional polymorphism in patients dependent on methamphetamine is related to their novelty seeking score.

METHODS: Patients dependent on methamphetamine who had been treated at the Addiction Treatment Unit in Nechanice in 2004 and 2005 agreed to participate in the investigation. We administered the Temperament and Character Inventory (TCI) questionnaire, assessed their novelty seeking score and analysed their DNA samples for COMT Val158Met genotype.

RESULTS: The subjects were thirty-seven Czech Caucasians (women N=10) dependent on methamphetamine with an average age of 23.6+/-3.8 years. We found a significantly higher mean novelty seeking score among the patients with the Met allele (Met/Met homozygotes+Val/Met heterozygotes; N=28) than in nine Val/Val homozygotes (27.4 vs 24.1; p=0.042, Two-Sample T-Test).

CONCLUSION: The Met allele of the COMT gene Val158Met polymorphism is associated with low COMT enzyme activity and high endogenous dopamine synaptic levels in the prefrontal cortex. This leads to a decrease in dopaminergic neurotransmission in nucleus accumbens and a need for an increased activity to stimulate it. Novelty seeking behavior corresponds with this need.