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The Journal of Neuroscience, July 6, 2005, 25(27):6460-6466; doi:10.1523/JNEUROSCI.5261-04.2005

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Behavioral/Systems/Cognitive
A Variant C178T in the Regulatory Region of the Serotonin Receptor Gene HTR3A Modulates Neural Activation in the Human Amygdala

Tetsuya Iidaka,^1,5 Norio Ozaki,² Atsushi Matsumoto,¹ Junpei Nogawa,¹ Yoko Kinoshita,³ Tatsuyo Suzuki,³ Nakao Iwata,³ Yukiko Yamamoto,⁴ Tomohisa Okada,⁴ and Norihiro Sadato^4,5

¹Department of Psychology, Graduate School of Environmental Studies, and ²Department of Psychiatry, Graduate School of Medicine, Nagoya University, Nagoya, Aichi 464-8601, Japan, ³Department of Psychiatry, School of Medicine, Fujita Health University, Toyoake 470-1192, Japan, ⁴Department of Cerebral Research, National Institute for Physiological Sciences, Okazaki 444-8585, Japan, and ⁵Japan Science and Technology Corporation/Research Institute of Science and Technology for Society, Kawaguchi 332-0012, Japan

Converging evidence in neurophysiological and neuroimaging studies has suggested that the limbic and prefrontal systems play important roles in emotion and cognition. These structures are activated when we see a human face, assuming that we automatically evaluate the biological significance of the stimuli. The serotonin (5-HT) system within the brain has been tied to various behaviors such as mood and anxiety and to the biology of neuropsychiatric disorders. To investigate the link between the 5-HT system and limbic/prefrontal activity, normal subjects (n = 26) who underwent functional magnetic resonance imaging and faced recognition tasks were genotyped for the single nucleotide polymorphism C178T in the regulatory region of the serotonin receptor type 3 gene (HTR3A). We found that the subjects with C/C alleles had greater activity in the amygdala and dorsal and medial prefrontal cortices than those with C/T alleles. The C/C group also showed a faster reaction time during the task than the C/T group. The temperamental predisposition of the subjects had a significant correlation with brain activity in the C/C group. The genotype effect in the right amygdala and prefrontal cortex was largest during the first run of the experiment. These results indicate that the C178T variation in the HTR3A has a critical influence on the amygdaloid activity and on human face processing, probably through regulation of the receptor expression. The present study may contribute to elucidating a possible link among genes, the brain, and behavior in normal populations and may help reveal the biological basis of neuropsychiatric disorders.

Key words: fMRI; face; limbic system; reaction time; personality; habituation

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Received May 16, 2004; revised May 16, 2005; accepted May 31, 2005.

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