The brain serotonin system in autism

Rev Neurosci. 2023 Jul 10;35(1):1-20. doi: 10.1515/revneuro-2023-0055. Print 2024 Jan 29.

Abstract

Autism spectrum disorders (ASDs) are among the most common neurodevelopmental diseases. These disorders are characterized by lack of social interaction, by repetitive behavior, and often anxiety and learning disabilities. The brain serotonin (5-HT) system is known to be crucially implicated in a wide range of physiological functions and in the control of different kinds of normal and pathological behavior. A growing number of studies indicate the involvement of the brain 5-HT system in the mechanisms underlying both ASD development and ASD-related behavioral disorders. There are some review papers describing the role of separate key players of the 5-HT system in an ASD and/or autistic-like behavior. In this review, we summarize existing data on the participation of all members of the brain 5-HT system, namely, 5-HT transporter, tryptophan hydroxylase 2, MAOA, and 5-HT receptors, in autism in human and various animal models. Additionally, we describe the most recent studies involving modern techniques for in vivo regulation of gene expression that are aimed at identifying exact roles of 5-HT receptors, MAOA, and 5-HT transporter in the mechanisms underlying autistic-like behavior. Altogether, results of multiple research articles show that the brain 5-HT system intimately partakes in the control of some types of ASD-related behavior, and that specific changes in a function of a certain 5-HT receptor, transporter, and/or enzyme may normalize this aberrant behavior. These data give hope that some of clinically used 5-HT-related drugs have potential for ASD treatment.

Keywords: ASD; SSRI; autism spectrum disorder; autistic-like behavior; brain 5-HT system; serotonin receptors.

Publication types

  • Review

MeSH terms

  • Animals
  • Autism Spectrum Disorder* / metabolism
  • Autistic Disorder*
  • Brain / metabolism
  • Humans
  • Membrane Transport Proteins / metabolism
  • Receptors, Serotonin / metabolism
  • Serotonin / metabolism

Substances

  • Serotonin
  • Receptors, Serotonin
  • Membrane Transport Proteins