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Kazuhiko Nakamura, MD, PhD; Yoshimoto Sekine, MD, PhD; Yasuomi Ouchi, MD, PhD; Masatsugu Tsujii, MA; Etsuji Yoshikawa, BS; Masami Futatsubashi, BS; Kenji J. Tsuchiya, MD, PhD; Genichi Sugihara, MD, PhD; Yasuhide Iwata, MD, PhD; Katsuaki Suzuki, MD, PhD; Hideo Matsuzaki, MD, PhD; Shiro Suda, MD, PhD; Toshiro Sugiyama, MD, PhD; Nori Takei, MD, PhD; Norio Mori, MD, PhD

Arch Gen Psychiatry. 2010;67(1):59-68.

Context  Autism is a neurodevelopmental disorder that is characterized by repetitive and/or obsessive interests and behavior and by deficits in sociability and communication. Although its neurobiological underpinnings are postulated to lie in abnormalities of the serotoninergic and dopaminergic systems, the details remain unknown.

Objective  To determine the occurrence of changes in the binding of serotonin and dopamine transporters, which are highly selective markers for their respective neuronal systems.

Design  Using positron emission tomography, we measured the binding of brain serotonin and dopamine transporters in each individual with the radioligands carbon 11 (¹¹C)–labeled trans-1,2,3,5,6,10-β-hexahydro-6-[4-(methylthio)phenyl]pyrrolo-[2,1-a]isoquinoline ([¹¹C](+)McN-5652) and 2β-carbomethoxy-3-β-(4-fluorophenyl)tropane ([¹¹C]WIN-35,428), respectively. Statistical parametric mapping was used for between-subject analysis and within-subject correlation analysis with respect to clinical variables.

Setting  Participants recruited from the community.

Participants  Twenty men (age range, 18-26 years; mean [SD] IQ, 99.3 [18.1]) with autism and 20 age- and IQ-matched control subjects.

Results  Serotonin transporter binding was significantly lower throughout the brain in autistic individuals compared with controls (P < .05, corrected). Specifically, the reduction in the anterior and posterior cingulate cortices was associated with the impairment of social cognition in the autistic subjects (P < .05, corrected). A significant correlation was also found between repetitive and/or obsessive behavior and interests and the reduction of serotonin transporter binding in the thalamus (P < .05, corrected). In contrast, the dopamine transporter binding was significantly higher in the orbitofrontal cortex of the autistic group (P < .05, corrected in voxelwise analysis). In the orbitofrontal cortex, the dopamine transporter binding was significantly inversely correlated with serotonin transporter binding (r = –0.61; P = .004).

Conclusions  The brains of autistic individuals have abnormalities in both serotonin transporter and dopamine transporter binding. The present findings indicate that the gross abnormalities in these neurotransmitter systems may underpin the neurophysiologic mechanism of autism. Our sample was not characteristic or representative of a typical sample of adults with autism in the community.

Author Affiliations: Department of Psychiatry and Neurology (Drs Nakamura, Sekine, Iwata, Suzuki, Suda, and Mori), Laboratory of Human Imaging Research, Molecular Imaging Frontier Research Center (Dr Ouchi), and Osaka-Hamamatsu Joint Research Center for Child Mental Development (Mr Tsujii and Drs Tsuchiya, Sugihara, Matsuzaki, Takei, and Mori), Hamamatsu University School of Medicine, Positron Medical Center, Hamamatsu Medical Center (Dr Ouchi), and Central Research Laboratory, Hamamatsu Photonics K.K. (Messrs Yoshikawa and Futatsubashi), Hamamatsu, Japan; Faculty of Sociology, Chukyo University, Toyota, Japan (Mr Tsujii); and Aichi Children's Health and Medical Center, Obu, Japan (Dr Sugiyama).

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