Reduced Serotonin Receptor Subtypes in a Limbic and a Neocortical Region in Autism

Abstract

Autism is a behaviorally defined, neurological disorder with symptom onset before the age of three. 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 (5HT) is one of the earliest expressed neurotransmitters, and plays an important role in synaptogenesis, neurite outgrowth, and neuronal migration. Abnormalities in 5HT 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 5HT in autism, there is emerging evidence that 5HT systems in the CNS, including various 5HT receptor subtypes and transporters, are affected in autism. The present study demonstrated significant reductions in 5HT1A receptor binding density in superficial and deep layers of the PCC and FG, and in the density of 5HT2A receptors in superficial layers of the PCC and FG. 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. These studies provide 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.

The serotonin system in autism spectrum disorder: From biomarker to animal models

“…Paralleling platelet binding studies, two neuroimaging studies have found decreased 5-HT 2 receptor binding: a SPECT study in adults with Asperger’s syndrome (Murphy et al, 2006) and a PET study in parents of children with autism (Goldberg et al, 2009). A postmortem study found decreases in both 5-HT 2A and 5-HT 1A binding in ASD (Oblak et al, 2013). Consistent findings showing decreased 5-HT 2 receptor binding in platelet, neuroimaging, and post-mortem studies support the idea that peripheral alterations in the serotonin system may be an important marker of central abnormalities in autism.…”

“…Another report found no changes in a PET study of SERT binding in adults with Asperger’s disorder (Girgis et al, 2011). One postmortem study found decreased SERT binding in deep layers of the fusiform gyrus but no difference in superficial layers or in the posterior cingulate cortex (Oblak et al, 2013). In contrast, the Azmitia laboratory described an increase in axons showing SERT immunoreactivity in postmortem tissue from individuals with autism spectrum disorder, spanning two to twenty-nine years old (Azmitia et al, 2011).…”

Synaptic proteins and receptors defects in autism spectrum disorders

“…In addition, reduction in the density of serotonin transporters (5-HTT) was also found in the deep layers of the fusiform gyrus in autistic subjects (Oblak et al, 2013). Transcriptome analyses showed that genes involved in synaptic function were downregulated in the ASDs post-mortem brain.…”

Autism Spectrum Disorder

“…There is evidence of significant reductions in 5-HT 1A receptor binding density in superficial and deep layers of the posterior cingulate cortex and fusiform gyrus, and in the density of 5-HT 2A receptors in superficial layers of the posterior cingulate cortex and fusiform gyrus. 46 In contrast to serotonin, evidence for dopamine and norepinephrine is less compelling. Levels of homovanillic acid, the primary dopamine metabolite, in blood, urine, and cerebrospinal fluid, were not significantly different between people with ASD and controls.…”