Autism: Serotonin susceptibility 5/1/06. By Ian Jones The nature of the genetic influence on autism is unclear. Now, a possible susceptibility gene links the condition to the brain's serotonin pathways.

Serotonin metabolism is disturbed in some conditions with abnormal behaviour patterns similar to autism. The serotonin transporter (SERT) – the target of the serotonin reuptake inhibitor (SSRI) class of antidepressant drugs – is a candidate autism susceptibility gene, but no convincing links have been established.

Nevertheless, a susceptibility locus does exist on chromosome 17, right by the SERT gene. Changes at this position mainly seem to affect boys, so researchers at Vanderbilt University in Tennessee undertook a detailed analysis of the DNA around the SERT gene just in affected males.

In several cases of autism and rigid-compulsive behaviour, the group found changes to DNA at the SERT locus (SLC6A4). They suggest that a range of rare mutations at this position may underlie some cases of autism.

The serotonin transporter was also implicated by Bernie Devlin and colleagues in Pittsburgh, who looked at the inheritance of SERT alleles of different lengths in families with autism. They discovered a higher than expected incidence of a 'short' allele.

While these studies implicate disrupted serotonin signalling in autism, the results need to be interpreted with caution. Other studies have found no linkage to SLC6A4, and several other genes have been identified recently as possible susceptibility loci.

Together, the studies emphasise the complexity of autism genetics. The real benefit of genetic studies is that they can lead to a better understanding of the mechanisms of disease – which, in turn, will provide leads to novel therapies.

Further reading

Sutcliffe JS et al. Allelic heterogeneity at the serotonin transporter locus (SLC6A4) confers susceptibility to autism and rigid-compulsive behaviors. Am J Hum Genet 2005;77(2):265-79. Abstract

Devlin B et al. Autism and the serotonin transporter: the long and short of it. Mol Psychiatry 2005;10(12):1110-6. Abstract