Reduced serotonin receptor subtypes in a limbic and a neocortical region in autism

Autism Res. 2013 Dec;6(6):571-83. doi: 10.1002/aur.1317. Epub 2013 Jul 24.


Autism is a behaviorally defined, neurological disorder with symptom onset before the age of 3. Abnormalities in social-emotional behaviors are a core deficit in autism, and are characterized by impaired reciprocal-social interaction, lack of facial expressions, and the inability to recognize familiar faces. The posterior cingulate cortex (PCC) and fusiform gyrus (FG) are two regions within an extensive limbic-cortical network that contribute to social-emotional behaviors. Evidence indicates that changes in brains of individuals with autism begin prenatally. Serotonin (5-HT) is one of the earliest expressed neurotransmitters, and plays an important role in synaptogenesis, neurite outgrowth, and neuronal migration. Abnormalities in 5-HT systems have been implicated in several psychiatric disorders, including autism, as evidenced by immunology, imaging, genetics, pharmacotherapy, and neuropathology. Although information is known regarding peripheral 5-HT in autism, there is emerging evidence that 5-HT systems in the central nervous system, including various 5-HT receptor subtypes and transporters, are affected in autism. The present study demonstrated significant reductions in 5-HT1A receptor-binding density in superficial and deep layers of the PCC and FG, and in the density of 5-HT(2A) receptors in superficial layers of the PCC and FG. A significant reduction in the density of serotonin transporters (5-HTT) was also found in the deep layers of the FG, but normal levels were demonstrated in both layers of the PCC and superficial layers of the FG. This study provides potential substrates for decreased 5-HT modulation/innervation in the autism brain, and implicate two 5-HT receptor subtypes as potential neuromarkers for novel or existing pharmacotherapies.

Keywords: 5-HT transporters; 5-HT1A receptors; 5-HT2A receptors; autism; pharmacotherapy; selective serotonin reuptake inhibitors (SSRI); serotonin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Autistic Disorder / genetics
  • Autistic Disorder / metabolism*
  • Autopsy
  • Brain / metabolism*
  • Female
  • Gyrus Cinguli / metabolism
  • Humans
  • In Vitro Techniques
  • Male
  • Receptors, Serotonin / genetics
  • Receptors, Serotonin / metabolism*
  • Serotonin / genetics
  • Serotonin / metabolism*
  • Serotonin Plasma Membrane Transport Proteins / genetics
  • Serotonin Plasma Membrane Transport Proteins / metabolism
  • Young Adult


  • Receptors, Serotonin
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin