Psychological, Neuroimaging, and Biochemical Studies on Functional Association between Impulsive Behavior and the 5-HT 2A Receptor Gene Polymorphism in Humans MICHIO NOMURA a AND YASUYUKI NOMURA b a Department of Psychology, Tokai Women’s University, Nakakirino-cho, Kakamigahara, Gifu 504-8511, Japan b Department of Pharmacotherapy, Yokohama College of Pharmacy, Matano-cho 601, Totuka-ku, Yokohama 245-0066, Japan ABSTRACT: It has been suggested that impulsive behavior is caused by dysfunctional serotonergic 5-HT neurotransmission in the central ner- vous system (CNS). Brain neuroimaging studies have shown that behav- ioral inhibition is linked to the activation of cortex sites such as the ven- tral frontal cortex. Positron emission tomography (PET) imaging with [ 18 F]altanserin to characterize 5-HT 2A receptor binding revealed a re- duction in 5-HT 2A binding in the ventral frontal cortex in women who had recovered from impulsive diseases. These clinical, neuroimaging, and pharmacological studies appear to support the hypothesis that func- tional alteration of neurotransmission due to genetic polymorphisms of the 5-HT receptors may be involved in impulsive behavior modulation. Following evaluation by a self-reporting measure, it was proposed that a polymorphism in the promoter of the 5-HT 2A receptor gene is the un- derlying cause of impulsive behavior; however, this hypothesis is not con- vincing. We examined whether the polymorphism in the 5-HT 2A receptor gene promoter is involved in impulsive aggression by evaluating a behav- ioral task (Go/No-go task) in normal volunteers. The polymorphism of the 5-HT 2A receptor gene promoter in lymphocytes from 71 volunteers was analyzed by using PCR. Impulsivity was defined as the number of commission errors (responding when one should not) recorded during a Go/No-go task; a larger number of commission errors indicate greater difficulty in inhibiting impulsive behavior. The subjects of the A-1438A allele group for the 5-HT 2A receptor gene made more commission er- rors under the punishment-reward (PR)condition in a Go/No-go task than those in the G-1438G group. In the present review, we discuss and Address for correspondence: Michio Nomura, Ph.D., Department of Psychology, Tokai Women’s University, Nakakirino-cho, Kakamigahara, Gifu 504-8511, Japan. Voice: +81-583-89-2220; fax: +81- 586-24-8310. e-mail: michan900@yahoo.co.jp Ann. N.Y. Acad. Sci. 1086: 134–143 (2006). C  2006 New York Academy of Sciences. doi: 10.1196/annals.1377.004 134