Brain serotonin and dopamine transporter bindings in adults with high-functioning autism.
BACKGROUND
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.


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


METHODS
Participants recruited from the community.


METHODS
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.
Nakamura
Kazuhiko
K
Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Sekine
Yoshimoto
Y
Ouchi
Yasuomi
Y
Tsujii
Masatsugu
M
Yoshikawa
Etsuji
E
Futatsubashi
Masami
M
Tsuchiya
Kenji J
KJ
Sugihara
Genichi
G
Iwata
Yasuhide
Y
Suzuki
Katsuaki
K
Matsuzaki
Hideo
H
Suda
Shiro
S
Sugiyama
Toshiro
T
Takei
Nori
N
Mori
Norio
N
D000293:Adolescent; D000328:Adult; D001321:Autistic Disorder / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D006801:Humans; D007546:Isoquinolines; D008297:Male; D026901:Membrane Transport Proteins; D049268:Positron-Emission Tomography / Q000706:statistics & numerical data; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*
D015415:Biomarkers; D002250:Carbon Radioisotopes; D050483:Dopamine Plasma Membrane Transport Proteins; D007546:Isoquinolines; D026901:Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; C058079:McN 5652; D004298:Dopamine