Nov 2011

Serotonin and the AutismsA Red Flag or a Red Herring?

Author Affiliations

Author Affiliation: Zilkha Neurogenetic Institute, Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles.

Arch Gen Psychiatry. 2011;68(11):1093-1094. doi:10.1001/archgenpsychiatry.2011.98

The struggles to provide mechanistic insight regarding the causes of the autisms (autism spectrum disorder [ASD]) continue as the data mount from the newest population-based studies finding that ASD diagnoses affect 1% to 2% of the population.1,2 Twin and sibling studies support the highly heritable nature of ASD risk, and at-risk younger siblings may have a recurrence risk of 15% to 20%. The newest estimates concur that rare mutations and copy number variants may account for up to 20% of cases.3 What about the other 80%? The genomecentric emphases have resulted in an opacity regarding the idea that through enhanced risk and/or endophenotype modulation, environmental factors are likely to interact with genetic components to participate at some important level in ASD etiology. Yet, the generation of convincing evidence of specific environmental factors remains a struggle, with the few exceptions of medication (eg, valproate sodium) or prenatal infection. Co-occurrence does not impart guilt, so the many candidates identified based on increases of exposures to a variety of agents that parallel an increase in ASD prevalence remain unsubstantiated. The problem is that even benign environmental elements can affect brain development in experimental systems because the building of well-functioning brain architecture is exquisitely sensitive to both genetic and environmental regulation. So, the field is left with basic findings that implicate a variety of genetic and epigenetic factors, together with associated small to modest increases in odds ratios for ASD due to a lengthening list of investigated environmental factors.

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