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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2 Responses to Autism and Serotonin: Is MAOB the missing link?

  1. passionlessDrone says:

    Hi Nestor –

    As far as blood levels go, I sort of thought that increased blood levels had been associated with problems with integrin beta 3; it wasn’t that too much serotonin was being created so much as it just wasn’t getting transported the way it needed to be.

    http://www.eurekalert.org/pub_releases/2008-03/vumc-sbp030408.php

    Do you have any thoughts as to the possible interactions between MAOB and SERT/integrate beta3?

    - pD

  2. RAJ says:

    MOAB studies have already been shown to be associated with ADHD in China.

    http://www.ncbi.nlm.nih.gov/pubmed/17918234?

    5HT2aR disfunctions are also assocated with high risk for infection by JV virus

    http://www.ncbi.nlm.nih.gov/pubmed/18579595?

    It would be interesting to see the rate of ADHD comorbity associated with this study or if any child had a history of early infection.

    The links don't seem to work so I'll post the lengthier abstracts:

    The monoamine oxidase B gene exhibits significant association to ADHD.Li J, Wang Y, Hu S, Zhou R, Yu X, Wang B, Guan L, Yang L, Zhang F, Faraone SV.
    Institute of Mental Health, Peking University (Peking University sixth hospital), China.

    Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatric condition with strong genetic basis. Recent work in China indicated that ADHD may be linked to Xp1-2 in the Han Chinese population. The gene encoding monoamine oxidase B (MAOB), the main enzyme degrading dopamine in the human brain, is located in this region. The current study sequenced the exons and the 5' and 3' flanking regions of the MAOB gene and found four common variants including 2276C>T and 2327C>T in exon 15, rs1799836 in intron 13 and rs1040399 in 3'-UTR. We assessed the association of these variants with ADHD in 548 trios collected from 468 males and 80 females probands. TDT analysis showed that alleles of each polymorphism were preferentially transmitted to probands (rs1799836, P = 3.28E-15; rs1040399, P = 1.87E-6; 2276T>C or 2327T>C, P = 2.20E-6) and haplotype-based TDT analyses also found distorted transmission. In conclusion, this study provides the strongest evidence for the involvement of MAOB gene in the etiology of ADHD to date, at least in Han Chinese population. Copyright 2007 Wiley-Liss, Inc.

    PMID: 17918234 [PubMed - indexed for MEDLINE

    Human embryonic stem cell-derived oligodendrocyte progenitor cells express the serotonin receptor and are susceptible to JC virus infection.Schaumburg C, O'Hara BA, Lane TE, Atwood WJ.
    Department of Molecular Biology and Biochemistry, University of California, Irvine, California, USA.

    We studied the susceptibility of human embryonic stem cell-derived oligodendrocyte progenitor cells to infection with JC virus, the causative agent of progressive multifocal leukoencephalopathy (PML). A human embryonic stem cell line, H7, was used to derive an enriched population of cells expressing the oligodendrocyte progenitor cell-specific marker NG2. These cells expressed the 5HT2a receptor (5HT2aR) for JC virus and were highly susceptible to infection. Infection was reduced by treatment with anti-5HT2aR antibodies and by the 5HT2aR antagonists ritanserin and ketanserin. This is the first demonstration that human embryonic stem cell-derived oligodendrocyte progenitor cells are susceptible to JC virus infection and indicates that cells poised to replenish mature oligodendrocytes in PML lesions may also be a target of viral infection.

    PMID: 18579595 [PubMed - indexed for MEDLINE]

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