Increased serotonin axons (immunoreactive to 5-HT transporter) in postmortem brains from young autism donors

Imaging studies of serotonin transporter binding or tryptophan retention in autistic patients suggest that the brain serotonin system is decreased. However, treatment with drugs which increase serotonin (5-HT) levels, specific serotonin reuptake inhibitors (SSRIs), commonly produce a worsening of the symptoms. In this study we examined 5-HT axons that were immunoreactive to a serotonin transporter (5-HTT) antibody in a number of postmortem brains from autistic patients and controls with no known diagnosis who ranged in age from 2 to 29 years. Fine, highly branched, and thick straight fibers were found in forebrain pathways (e.g. medial forebrain bundle, stria terminalis and ansa lenticularis). Many immunoreactive varicose fine fibers were seen in target areas (e.g. globus pallidus, amygdala and temporal cortex). Morphometric analysis of the stained axons at all ages studied indicated that the number of serotonin axons was increased in both pathways and terminal regions in cortex from autism donors. Our findings provide morphological evidence to warrant caution when using serotonin enhancing drugs (e.g. SSRIs and receptor agonist) to treat autistic children.This article is part of a Special Issue entitled ‘Trends in Neuropharmacology: In Memory of Erminio Costa’.

► Increased axons reactive to 5-HT transporter in postmortem brain from autism donors. ► Increased axons in autism donors from 2.5 to 29 yr compared to age-matched controls. ► Increased axons in MFB and ansa lenticularis pathways from brainstem to forebrain. ► Increased axons seen in fusiform cortex, superior temporal cortex and amygdala. ► Caution about using drugs that increase 5-HT agonist or uptake blockers in autism.