Serotonergic paradoxes of autism replicated in a simple mathematical model.
The biological causes of autism are unknown. Since the early 1960s, the most consistent pathophysiological finding in autistic individuals has been their statistically elevated blood 5-hydroxytryptamine (5-HT, serotonin) levels. However, many autistic individuals have normal blood 5-HT levels, so this finding has been difficult to interpret. The serotonin transporter (SERT) controls 5-HT uptake by blood platelets and has been implicated in autism, but recent studies have found no correlation between SERT polymorphisms and autism. Finally, autism is considered a brain disorder, but studies have so far failed to find consistent serotonergic abnormalities in autistic brains. A simple mathematical model may account for these paradoxes, if one assumes that autism is associated with the failure of a molecular mechanism that both regulates 5-HT release from gut enterochromaffin cells and mediates 5-HT signaling in the brain. Some 5-HT receptors may play such a dual role. While the failure of such a mechanism may lead to consistent abnormalities of synaptic transmission with no alteration of brain 5-HT levels, its effects on blood 5-HT levels may appear paradoxical.
Janusonis
Skirmantas
S
Department of Neurobiology, Yale University School of Medicine, P.O. Box 208001, New Haven, CT 06520-8001, USA. skirmantas.janusonis@yale.edu
D001321:Autistic Disorder / Q000097:blood / Q000503:physiopathology*; D001921:Brain / Q000002:abnormalities; D006801:Humans; D008962:Models, Theoretical; D012701:Serotonin / Q000097:blood / Q000502:physiology*
D012701:Serotonin