Serotonin Transporter Gene Polymorphisms and Processing of Fearful Faces in Autism

Background: The characteristic social impairments found in Autistic Spectrum Disorders(ASD) may be influenced by alterations in the processing of facial emotions. Functional MRI imaging studies of people with ASD show neural hypoactivation in brain regions supporting social cognition such as the amygdala (Deeley et al. 2007). The amygdala plays an important role in the processing of fearful faces (Blair 2003). This neural activity in the amygdala is affected by the allelic variation of the serotonin transporter gene (5-HTT). The presence of one or two copies of the short allele of 5-HTT shows greater amygdalar activity when processing fearful face than in the presence of two of the long allele. Serotonin and the serotonin transporter gene are reportedly involved in he pathophysiology of ASD (Huang 2008).

Objectives: The objective of this study is to examine the influence of serotonin transporter polymorphisms on the role of the amygdala when controls and subjects with Austism process fearful faces.

Methods: 13 adults with ASD and 11 matched controls performed an event-related functional Magnetic Resonance implicit fear processing task on a GE 1.5T Signa Scanner. All participants were male, right-handed, with an IQ >70. All individuals with ASD met algorithm cut-offs for autism on the ADI or ADOS. Subjects viewed expressions of fear contrasted with a cross hair baseline condition. The BOLD signal was extracted from the left amygdala for both groups of subjects. Genotyping was performed to ascertain the allelic varation of the 5-HTT for either the short containing (SS+SL) or long (LL). Self-reporting psychiatric inventories and neuropsychological tests were performed.

Results: Genotyping revealed that the controls had 2 subjects with LL and 9 subjects with SS+SL, while the ASD group had 3 subjects with LL and 10 subjects with SS+SL. For the controls, there was a significant linear increase in amygdalar activation for the SS+SL group compared to the LL group. In contrast, subjects with ASD showed no difference dependant on 5-HTT variation.

Conclusions: These results suggest that there are variations in the influence of 5-HTT variation on the activity of the amygdale between people with ASD and controls.