title: Cognitive and neural correlates of the 5-repeat allele of the dopamine D4 receptor gene in a population lacking the 7-repeat allele.
abstract: The 5-repeat allele of a common length polymorphism in the gene that encodes the dopamine D4 receptor (DRD4) is robustly associated with the risk of attention deficit hyperactivity disorder (ADHD) and substantially exists in Asian populations, which have a lower ADHD prevalence. In this study, we investigated the effect of this allele on microstructural properties of the brain and on its functional activity during externally directed attention-demanding tasks and creative performance in the 765 Asian subjects. For this purpose, we employed diffusion tensor imaging, N-back functional magnetic resonance imaging paradigms, and a test to measure creativity by divergent thinking. The 5-repeat allele was significantly associated with increased originality in the creative performance, increased mean diffusivity (the measure of how the tissue includes water molecules instead of neural and vessel components) in the widespread gray and white matter areas of extensive areas, particularly those where DRD4 is expressed, and reduced task-induced deactivation in the areas that are deactivated during the tasks in the course of both the attention-demanding working memory task and simple sensorimotor task. The observed neural characteristics of 5-repeat allele carriers may lead to an increased risk of ADHD and behavioral deficits. Furthermore, the increased originality of creative thinking observed in the 5-repeat allele carriers may support the notion of the side of adaptivity of the widespread risk allele of psychiatric diseases.
authors: Division of Developmental Cognitive Neuroscience, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan. Electronic address: takehi@idac.tohoku.ac.jp.
authors: Hikaru
authors: H
authors: Takeuchi
authors: Department of Disaster Psychiatry, International Research Institute of Disaster Science, Tohoku University, Sendai, Japan.
authors: Hiroaki
authors: H
authors: Tomita
authors: Division of Developmental Cognitive Neuroscience, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; Division of Medical Neuroimage Analysis, Department of Community Medical Supports, Tohoku Medical Megabank Organization, Tohoku University, Japan; Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer, Tohoku University, Japan.
authors: Yasuyuki
authors: Y
authors: Taki
authors: Department of Disaster Psychiatry, International Research Institute of Disaster Science, Tohoku University, Sendai, Japan.
authors: Yoshie
authors: Y
authors: Kikuchi
authors: Department of Disaster Psychiatry, International Research Institute of Disaster Science, Tohoku University, Sendai, Japan.
authors: Chiaki
authors: C
authors: Ono
authors: Department of Disaster Psychiatry, International Research Institute of Disaster Science, Tohoku University, Sendai, Japan.
authors: Zhiqian
authors: Z
authors: Yu
authors: Division of Medical Neuroimage Analysis, Department of Community Medical Supports, Tohoku Medical Megabank Organization, Tohoku University, Japan; Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors: Atsushi
authors: A
authors: Sekiguchi
authors: Human and Social Response Research Division, International Research Institute of Disaster Science, Tohoku University, Sendai, Japan.
authors: Rui
authors: R
authors: Nouchi
authors: Smart Ageing International Research Center, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors: Yuka
authors: Y
authors: Kotozaki
authors: Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors: Seishu
authors: S
authors: Nakagawa
authors: Graduate School of Arts and Sciences, Department of General Systems Studies, The University of Tokyo, Tokyo, Japan.
authors: Carlos Makoto
authors: CM
authors: Miyauchi
authors: Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; Department of Psychiatry, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Kunio
authors: K
authors: Iizuka
authors: Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; Japan Society for the Promotion of Science, Tokyo, Japan.
authors: Ryoichi
authors: R
authors: Yokoyama
authors: Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors: Takamitsu
authors: T
authors: Shinada
authors: Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors: Yuki
authors: Y
authors: Yamamoto
authors: Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors: Sugiko
authors: S
authors: Hanawa
authors: Smart Ageing International Research Center, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors: Tsuyoshi
authors: T
authors: Araki
authors: Division of Developmental Cognitive Neuroscience, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors: Hiroshi
authors: H
authors: Hashizume
authors: Faculty of Medicine, Tohoku University, Sendai, Japan.
authors: Keiko
authors: K
authors: Kunitoki
authors: Division of Developmental Cognitive Neuroscience, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors: Yuko
authors: Y
authors: Sassa
authors: Division of Developmental Cognitive Neuroscience, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; Smart Ageing International Research Center, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors: Ryuta
authors: R
authors: Kawashima
mesh_terms: D000483:Alleles; D001288:Attention / Q000502:physiology; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics / Q000523:psychology; D003071:Cognition / Q000502:physiology*; D003405:Creativity; D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic / Q000235:genetics; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D055815:Young Adult
chemical_list: D050638:Receptors, Dopamine D4; D004247:DNA