Brain Serotonin and Dopamine Transporter Bindings in Adults With High-Functioning Autism
Abstract
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 ((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. 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.
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Group-level abnormalities of serotonergic and dopaminergic transporter activity have been reported in individuals with ASD, but the results are mixed, presumably due to the spectrum nature of ASD.
“While group-level abnormalities of serotonergic and dopaminergic transporter activity have been reported by previous studies using single-photon emission computed tomography and positron emission tomography in individuals with ASD (119, 120), the results are mixed, presumably due to the spectrum nature of ASD.”
From Can Bayesian Theories of Autism Spectrum Disorder Help Improve Clinical Practice? (2016) · cites this paper as [120]
A PET study reported elevated dopamine transporter levels in orbitalfrontal cortex in high functioning autism subjects.
“In a PET study, elevated dopamine transporter levels were reported in the orbitalfrontal cortex in high functioning autism subjects [182].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [182]
A PET study found reduced serotonin transporter binding in anterior and posterior cingulate cortex in high functioning autistic subjects, associated with impaired social cognition, and in thalamus associated with repetitive/obsessive behavior.
“In a PET imaging study, serotonin transporter binding was reduced in the anterior and posterior cingulate cortex in high functioning autistic subjects associated with impaired social cognition and, in the thalamus associated with repetitive and /or obsessive behavior and interests [182].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [182]
A recent study with a relatively large sample found evidence of higher DAT binding in the orbitofrontal cortex in ASD.
“although a recent study with a relatively large sample found evidence of higher DAT binding in the orbitofrontal cortex in ASD [586].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [586]
These neurotransmitter systems play key roles in neurotransmission, brain maturation, cortical organisation, and behaviours including social and repetitive behaviour.
“These systems play key roles in neurotransmission, brain maturation, cortical organisation and behaviours (including social behaviour and repetitive behaviour) [180,181,182,183,184].”
From Vitamin D and Autism Spectrum Disorder: A Literature Review (2016) · cites this paper as [184]
Binding of brain dopamine transporter was significantly higher in autistic patients than healthy controls.
“While the binding of brain serotonin transporter was significantly lower in adults with high functioning autism than healthy controls, the binding of brain dopamine transporter was significantly higher in autistic patients [184].”
From Vitamin D and Autism Spectrum Disorder: A Literature Review (2016) · cites this paper as [184]
Binding of brain serotonin transporter was significantly lower in adults with high functioning autism than healthy controls.
“While the binding of brain serotonin transporter was significantly lower in adults with high functioning autism than healthy controls, the binding of brain dopamine transporter was significantly higher in autistic patients [184].”
From Vitamin D and Autism Spectrum Disorder: A Literature Review (2016) · cites this paper as [184]
Multiple lines of evidence suggest an involvement of dysregulated neurotransmitter systems (serotonergic, oxytocinergic, and dopaminergic) in autism.
“Multiple lines of evidence suggest an involvement of dysregulated neurotransmitter systems (serotonergic, oxytocinergic and dopaminergic systems) in autism.”
From Vitamin D and Autism Spectrum Disorder: A Literature Review (2016) · cites this paper as [184]
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Consensus Paper: Pathological Role of the Cerebellum in Autism
Fatemi, S. H., Aldinger, K. A., Ashwood, P., Bauman, M. L., Blaha, C. D., Blatt, G. J., Chauhan, A., Chauhan, V., Dager, S. R., Dickson, P. E., et al. (2012) · The Cerebellum · doi:10.1007/s12311-012-0355-9 · Cited by 723 · see citing works
An aberrant precision account of autism
Lawson, R. P., Rees, G., & Friston, K. J. (2014) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2014.00302 · Cited by 641 · see citing works
Cerebellar modulation of the reward circuitry and social behavior
Carta, I., Chen, C. H., Schott, A. L., Dorizan, S., & Khodakhah, K. (2019) · Science · doi:10.1126/science.aav0581 · Cited by 601 · see citing works
The serotonin system in autism spectrum disorder: From biomarker to animal models
Muller, C. L., Anacker, A. M. J., & Veenstra-VanderWeele, J. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2015.11.010 · Cited by 531 · see citing works
Blood serotonin levels in autism spectrum disorder: A systematic review and meta-analysis
Gabriele, S., Sacco, R., & Persico, A. M. (2014) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2014.02.004 · Cited by 346 · see citing works
Dichter, G. S., Damiano, C. A., & Allen, J. A. (2012) · Journal of Neurodevelopmental Disorders · doi:10.1186/1866-1955-4-19 · Cited by 299 · see citing works
Danforth, A. L., Grob, C. S., Struble, C., Feduccia, A. A., Walker, N., Jerome, L., Yazar-Klosinski, B., & Emerson, A. (2018) · Psychopharmacology · doi:10.1007/s00213-018-5010-9 · Cited by 280 · see citing works
Gene × Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms
Tordjman, S., Somogyi, E., Coulon, N., Kermarrec, S., Cohen, D., Bronsard, G., Bonnot, O., Weismann-Arcache, C., Botbol, M., Lauth, B., et al. (2014) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2014.00053 · Cited by 283 · see citing works
Role of microglial m1/m2 polarization in relapse and remission of psychiatric disorders and diseases
Nakagawa, Y., & Chiba, K. (2014) · Pharmaceuticals · doi:10.3390/ph7121028 · Cited by 215 · see citing works
Psychiatric comorbidities in Asperger syndrome and high functioning autism: diagnostic challenges
Mazzone, L., Ruta, L., & Reale, L. (2012) · Annals of General Psychiatry · doi:10.1186/1744-859x-11-16 · Cited by 213 · see citing works
Social “wanting” dysfunction in autism: neurobiological underpinnings and treatment implications
Kohls, G., Chevallier, C., Troiani, V., & Schultz, R. T. (2012) · Journal of Neurodevelopmental Disorders · doi:10.1186/1866-1955-4-10 · Cited by 197 · see citing works
Can Bayesian Theories of Autism Spectrum Disorder Help Improve Clinical Practice?
Haker, H., Schneebeli, M., & Stephan, K. E. (2016) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2016.00107 · Cited by 130 · see citing works
Tordjman, S., Najjar, I., Bellissant, E., Anderson, G., Barburoth, M., Cohen, D., Jaafari, N., Schischmanoff, O., Fagard, R., Lagdas, E., et al. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms141020508 · Cited by 132 · see citing works
Tordjman, S., Anderson, G. M., Bellissant, E., Botbol, M., Charbuy, H., Camus, F., Graignic, R., Kermarrec, S., Fougerou, C., Cohen, D., et al. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.04.013 · Cited by 129 · see citing works
Veenstra-VanderWeele, J., & Blakely, R. D. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2011.185 · Cited by 128 · see citing works
Nousen, E. K., Franco, J. G., & Sullivan, E. L. (2013) · Neuroendocrinology · doi:10.1159/000355632 · Cited by 123 · see citing works
Vitamin D and Autism Spectrum Disorder: A Literature Review
Mazahery, H., Camargo, C., Conlon, C., Beck, K., Kruger, M., & Von Hurst, P. (2016) · Nutrients · doi:10.3390/nu8040236 · Cited by 110 · see citing works
Azmitia, E. C., Singh, J. S., & Whitaker-Azmitia, P. M. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.02.002 · Cited by 107 · see citing works
The combined role of serotonin and interleukin-6 as biomarker for autism
Yang, C.-J., Liu, C.-L., Sang, B., Zhu, X.-M., & Du, Y.-J. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2014.10.011 · Cited by 80 · see citing works
Chantiluke, K., Barrett, N., Giampietro, V., Santosh, P., Brammer, M., Simmons, A., Murphy, D. G., & Rubia, K. (2015) · Psychopharmacology · doi:10.1007/s00213-014-3837-2 · Cited by 63 · see citing works
Chantiluke, K., Barrett, N., Giampietro, V., Brammer, M., Simmons, A., Murphy, D. G., & Rubia, K. (2015) · Cerebral Cortex · doi:10.1093/cercor/bht365 · Cited by 59 · see citing works
Walsh, J. J., Llorach, P., Cardozo Pinto, D. F., Wenderski, W., Christoffel, D. J., Salgado, J. S., Heifets, B. D., Crabtree, G. R., & Malenka, R. C. (2021) · Neuropsychopharmacology · doi:10.1038/s41386-021-01091-6 · Cited by 56 · see citing works
Kinast, K., Peeters, D., Kolk, S. M., Schubert, D., & Homberg, J. R. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00072 · Cited by 57 · see citing works
Emerging drugs for the treatment of symptoms associated with autism spectrum disorders
Wink, L. K., Plawecki, M. H., Erickson, C. A., Stigler, K. A., & McDougle, C. J. (2010) · Expert Opinion on Emerging Drugs · doi:10.1517/14728214.2010.487860 · Cited by 36 · see citing works
Developing new pharmacotherapies for autism
Ecker, C., Spooren, W., & Murphy, D. (2013) · Journal of Internal Medicine · doi:10.1111/joim.12113 · Cited by 31 · see citing works
Aberrant neural mediation of verbal fluency in autism spectrum disorders
Kenworthy, L., Wallace, G. L., Birn, R., Milleville, S. C., Case, L. K., Bandettini, P. A., & Martin, A. (2013) · Brain and Cognition · doi:10.1016/j.bandc.2013.08.003 · Cited by 26 · see citing works
Wiggins, J. L., Peltier, S. J., Bedoyan, J. K., Carrasco, M., Welsh, R. C., Martin, D. M., Lord, C., & Monk, C. S. (2013) · NeuroImage Clinical · doi:10.1016/j.nicl.2012.10.008 · Cited by 17 · see citing works
- Authors
- Nakamura, K., Sekine, Y., Ouchi, Y., Tsujii, M., Yoshikawa, E., Futatsubashi, M., Tsuchiya, K. J., Sugihara, G., Iwata, Y., Suzuki, K., Matsuzaki, H., Suda, S., Sugiyama, T., Takei, N., & Mori, N.
- Affiliations
- Hamamatsu University School of Medicine (JP)
- ORCID
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2010-01-01
- Volume
- 67
- Issue
- 1
- Pages
- 59
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W1976644675
- Cited by
- 352
- References
- 81
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 20 · 2023: 18 · 2022: 22 · 2021: 35 · 2020: 24 · 2019: 19 · 2018: 19 · 2017: 15 · 2016: 13 · 2015: 29 · 2014: 31 · 2013: 28 · 2012: 26
- FWCI
- 16.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- autism spectrum disorder, serotonin transporter binding, dopamine transporter binding, high-functioning autism, serotonergic system, dopaminergic system, social cognition, cingulate cortex, thalamus, orbitofrontal cortex, neuroimaging biomarkers, autistic adults, positron emission tomography, neurobiology of autism
- MeSH terms
- Adolescent, Adult, Autistic Disorder, Brain, Brain Mapping, Carbon Radioisotopes, Dopamine, Humans, Isoquinolines, Male, Serotonin, Biomarkers, Membrane Transport Proteins, Positron-Emission Tomography, Dopamine Plasma Membrane Transport Proteins, Serotonin Plasma Membrane Transport Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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