Brain structure differences in autism map onto serotonin receptor locations

A neuroimaging study found that autistic individuals whose cortical thickness deviated most from that of neurotypical peers tended to experience greater social and communication difficulties. In autistic individuals, the cortical regions showing the greatest differences in thickness relative to neurotypical individuals also tended to have a higher density of serotonin receptors. The research provides evidence linking brain structure, neurochemistry, and behavioral traits in autism. The paper was published in Autism Research.

Autism is a neurodevelopmental condition that affects how a person communicates, interacts with others, processes sensory information, and experiences the world. It is called a spectrum because its characteristics and level of support needs vary widely between individuals.

Some autistic people have difficulty interpreting social cues, maintaining conversations, or understanding unwritten social rules. Others are able to communicate fluently but still find social interaction tiring, confusing, or overwhelming. Repetitive movements, strong preferences for routines, intense interests, and unusual responses to sounds, lights, textures, or smells are also common.

Autism begins early in development, although it may not be recognized until later in childhood or adulthood. It is a lifelong form of neurological difference that may bring both difficulties and strengths. Many autistic people show beneficial qualities such as strong attention to detail, deep knowledge in areas of interest, logical thinking, creativity, or exceptional memory.

Study author Livio Tarchi and his colleagues note that previous research indicates consistent structural differences between the brains of individuals with autism and their neurotypical peers. The authors suggest these differences might be connected to the brain’s neurotransmitter systems. Neurotransmitters are chemical messengers that carry signals between brain cells. The researchers specifically focused on systems using serotonin, dopamine, and glutamate.

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The scientists investigated how structural differences in the brain might map onto the spatial distribution of these chemical messengers. They analyzed data from the Autism Brain Imaging Data Exchange. This public dataset contains physical measurements, behavioral assessments, and brain scans collected across twenty different sites.

The data used in this analysis came from 1,035 participants. The sample included 505 autistic individuals and 530 neurotypical individuals. The average age of participants was about 17 years old. Both groups were predominantly male, reflecting historical diagnosis patterns.

The study authors used structural magnetic resonance imaging (MRI) data to calculate deviations from expected cortical thickness. Cortical thickness refers to the depth of the brain’s outer layer of gray matter, which is responsible for complex thought and sensory processing. They measured this thickness across thousands of individual points, called vertices, on the surface of the brain. These measurements were adjusted for both the sex and age of each participant.

Next, the researchers compared these structural measurements against reference maps of neurotransmitter receptor density. Receptors are protein structures on cells that receive chemical messages. These reference maps were derived from separate, previously published imaging studies. This allowed the authors to see if areas with unusual thickness in autistic individuals aligned with regions known to have high concentrations of specific neurotransmitters.

The results showed widespread deviations in cortical thickness in the brains of autistic participants compared to neurotypical participants. The structural differences tended to be larger in areas of the brain with a higher density of serotonin receptors. The researchers did not find a similar spatial link for dopamine or glutamate receptors. At the individual level, greater deviations in cortical thickness were associated with greater difficulties in social and communication domains.

These findings provide evidence for a neurobiological link between autism, brain structure, and serotonin. However, the participants in this study were mostly male. Because brain development and cortical thickness can vary by sex, studies involving more female participants might yield different results. Future research could help clarify these connections and guide tailored support strategies for autistic individuals.

The paper, “Autism and Cortical Thickness Deviation From Neurotypical Controls: Evidence for a Spatial Association With Serotonin Receptors,” was authored by Livio Tarchi, Arne Doose, Julius Hennig, Fabio Bernardoni, Joseph A. King, Tiziana Pisano, Giovanni Castellini, Valdo Ricca, Inge Kamp-Becker, and Stefan Ehrlich.