Autism and Cortical Thickness Deviation From Neurotypical Controls: Evidence for a Spatial Association With Serotonin Receptors.

Overview

1. Psychiatry Unit, Department of Health Sciences University of Florence Florence Italy
2. Division of Psychological and Social Medicine and Developmental Neurosciences, Translational Developmental Neuroscience Section, Faculty of Medicine Technische Universität Dresden Dresden Germany
3. German Center for Child and Adolescent Health (DZKJ), Partner Site Dresden/Leipzig Dresden Germany
4. Neuroscience Department Meyer Children's Hospital IRCCS Florence Italy
5. Department of Child and Adolescent Psychiatry Heidelberg University Hospital Heidelberg Germany

Abstract

Cortical thickness (CT) differences between autistic individuals (AI) and neurotypical controls have been consistently reported, yet the neurochemical mechanisms underlying these differences remain insufficiently understood. Neurotransmitter receptor systems exhibit distinct spatial distributions across the cortex and influence synaptic maturation, plasticity, and cortical organization. Consequently, mapping CT deviations onto these receptor density gradients provides a biologically informed framework for investigating the potential underlying neurochemical architectures of observed structural patterns in autism. A total of 1035 structural MRIs (AI n = 505, neurotypical controls n = 530) were included from Autism Brain Imaging Data Exchange (ABIDE). Group contrasts and individual‐level deviations from age‐predicted CT patterns were computed. These spatial patterns were correlated with neurotransmitter receptors cortical density distributions (D1, D2, 5HT1a, 5HT2a, 5HT4, 5HT6, mGluR5) from previous PET studies. Widespread vertex‐wise deviations in CT were observed in AI in comparison to neurotypical controls. At the group level, CT differences were spatially aligned with the cortical density of serotonin receptors (5HT1a: r = 0.22, FDR‐p = 0.032; 5HT4: r = 0.21, FDR‐p = 0.032). At the individual level, greater deviations from predicted CT, if mapped onto specific neurotransmitter receptor density gradients, correlated with greater difficulties in the social and communication domains. The findings provide novel evidence that serotonin receptors may play a role in shaping cortical structural brain differences between AI and neurotypical controls. The link between CT differences and spatial distributions of the serotoninergic system offers a translational perspective for future targeted support strategies focused on serotonergic pathways.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data Availability Statement

The datasets generated during the current study, as well as the code supporting the analyses, are available from the corresponding author upon reasonable request. The original data can be retrieved from the ABIDE consortium http://preprocessed‐connectomes‐project.org/abide/ (http://preprocessed-connectomes-project.org/abide/).

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 2, 28 September 2026

• Publisher: — → Wiley

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 10 authors, 5 keywords, 10 MeSH terms, 2 funders, 84 references.

Cite

This paper

Tarchi, L., Doose, A., Hennig, J., Bernardoni, F., King, J. A., Pisano, T., Castellini, G., Ricca, V., Kamp‐Becker, I., & Ehrlich, S. (2026). Autism and Cortical Thickness Deviation From Neurotypical Controls: Evidence for a Spatial Association With Serotonin Receptors. Autism research : official journal of the International Society for Autism Research, 19(6), e70243. https://doi.org/10.1002/aur.70243

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