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Original Article
March 7, 2011

Reduced Acetylcholinesterase Activity in the Fusiform Gyrus in Adults With Autism Spectrum Disorders

Author Affiliations

Author Affiliations: Research Center for Child Mental Development (Drs Suzuki, Sugihara, Tsuchiya, Takebayashi, Suda, and Takei and Ms Matsumoto), Molecular Imaging Frontier Research Center (Dr Ouchi), and the Departments of Psychiatry and Neurology (Drs Nakamura, Iwata, Wakuda, and Mori), and Child Psychiatry (Dr Sugiyama), Hamamatsu University School of Medicine, Hamamatsu; Positron Medical Center, Hamamatsu Medical Center, Hamamatsu (Dr Ouchi and Mr Futatsubashi); Department of Psychiatry and Neurobiology, Graduate School of Medical Science, Kanazawa University, Kanazawa (Dr Kikuchi); Faculty of Sociology, Chukyo University, Toyota (Mr Tsujii); Koujin Hospital, Nagoya (Dr Yoshihara); and Advanced Technology for Medical Imaging, National Institute of Radiological Sciences, Chiba (Dr Irie), Japan.

Arch Gen Psychiatry. 2011;68(3):306-313. doi:10.1001/archgenpsychiatry.2011.4
Abstract

Context  Both neuropsychological and functional magnetic resonance imaging studies have shown deficiencies in face perception in subjects with autism spectrum disorders (ASD). The fusiform gyrus has been regarded as the key structure in face perception. The cholinergic system is known to regulate the function of the visual pathway, including the fusiform gyrus.

Objectives  To determine whether central acetylcholinesterase activity, a marker for the cholinergic system, is altered in ASD and whether the alteration in acetylcholinesterase activity, if any, is correlated with their social functioning.

Design  Using positron emission tomography and a radiotracer, N -[11C]methyl-4-piperidyl acetate ([11C]MP4A), regional cerebrocortical acetylcholinesterase activities were estimated by reference tissue–based linear least-squares analysis and expressed in terms of the rate constant k3. Current and childhood autism symptoms in the adult subjects with ASD were assessed by the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview–Revised, respectively. Voxel-based analyses as well as region of interest–based methods were used for between-subject analysis and within-subject correlation analysis with respect to clinical variables.

Setting  Participants recruited from the community.

Participants  Twenty adult subjects with ASD (14 male and 6 female; age range, 18-33 years; mean [SD] intelligence quotient, 91.6 [4.3]) and 20 age-, sex-, and intelligence quotient–matched healthy controls.

Results  Both voxel- and region of interest–based analyses revealed significantly lower [11C]MP4A k3 values in the bilateral fusiform gyri of subjects with ASD than in those of controls (P < .05, corrected). The fusiform k3 values in subjects with ASD were negatively correlated with their social disabilities as assessed by Autism Diagnostic Observation Schedule as well as Autism Diagnostic Interview–Revised.

Conclusions  The results suggest that a deficit in cholinergic innervations of the fusiform gyrus, which can be observed in adults with ASD, may be related to not only current but also childhood impairment of social functioning.

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