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Autism and Serotonin: Is MAOB the missing link?

Posted Feb 25 2009 4:27pm
A review of: Dubravka Hranilović, Zorana Bujas-Petković, Maja Tomičić, Tatjana Bordukalo-Nikšić, Sofia Blažević, Lipa Čičin-Šain (2009). Hyperserotonemia in autism: activity of 5HT-associated platelet proteins Journal of Neural Transmission DOI: 10.1007/s00702-009-0192-2

Although dysregulation of serotonin has been associated with several psychiatric disorders, there is evidence suggesting that disruption in serotonin systems may be implicated in autism. Specifically, serotonin is a critical component of the regulation of the growth and maturation of key areas of the Brain. This is relevant to autism research as numerous studies suggest that autism is associated with impaired cell pruning during development. But not all individuals with autism show dysregulation of serotonin systems. For example, only about 30% of individuals with autism show hyperserotonemia, or elevated blood serotonin levels (see for example Hranilovic et al., 2007 DOI: 10.1007/s10803-006-0324-6 ).

In this study the authors wanted to examine 3 proteins associated with serotonin functioning (5HTT,MAOB, and 5HT2Ar) in 3 groups of people: 15 individuals with autism and elevated serotonin blood levels (10 male, between 19 and 36 years, mean age 29.6), 17 individuals with autism but normal serotonin levels (12 male, between 21 and 42 years, mean age 30.3), and 15 non-autistic individuals (12 male, between 22 and 54 years, mean age 41.7).

The most surprising finding is that the authors observed altered kinetics of one protein (MAOB) in both groups of individuals with autism. That is, even those with non-elevated blood serotonin levels displayed dysregulation of MAOB when compared with non-autistic individuals. Although it is possible that this difference is due to medications being taken by the participants with autism, the authors indicate that there is no evidence that the type of medications reported by the participants would affect MAOB functioning. Therefore, the examination of simple blood serotonin levels may not fully reflect differences between individuals with autism and non-autistics in their serotonin functioning.

Original Abstract:
Disturbances in serotonin (5HT) neurotransmission have been indicated as biological substrates in several neuropsychiatric disorders including autism. Blood 5HT concentrations, elevated in about one-third of autistic subjects, are regulated through the action of peripheral 5HT-associated proteins. We have measured the activity of two platelet 5HT-associated proteins: 5HT transporter (5HTT) and monoamine oxidase B (MAOB), and indirectly studied the activity of 5HT2A receptor (5HT2Ar) in 15 hyper-serotonemic (HS) and 17 normoserotonemic (NS) autistic subjects, and 15 healthy controls (C).While mean velocities of 5HTT kinetics did not significantly differ among the groups, significant elevation in the mean velocity of MAOB kinetics was observed in NS subjects and was even more pronounced in HS subjects in comparison to controls. Also, a decrease in adenosine 50 -diphosphate-induced platelet aggregation of borderline significance was observed in NS subjects, compared to C subjects. The results suggest a possibility of upregulation of monoaminergic synthesis/ degradation and, probably consequential, downregulation of 5HT2Ar in autistic subjects.

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