Individual Differences in Autistic Traits are Associated with Serotonin Transporter Gene Polymorphism Through Medial Prefrontal Function: A Study Using NIRS.

Autism spectrum disorder (ASD) is a heritable neurodevelopmental disorder that can vary considerably in severity. Autistic traits are distributed continuously across populations, even in sub-clinical individuals. Serotonin transporter-gene polymorphic region (5-HTTLPR) has been studied as a candidate genetic factor related to ASD, however results have been inconsistent. 5-HTTLPR is implicated in the function of medial prefrontal cortex (mPFC), a region associated with the social abnormalities found in ASD. Here we hypothesize that autistic traits are affected by the 5-HTTLPR genotype indirectly through mPFC mediation. Using near-infrared spectroscopy (NIRS), we first examined mPFC activation in people with ASD when they performed a facial affect-labeling task. Compared with a typical development group, the ASD group showed significantly lower mPFC activation during the task. Using the same task paradigm, we next investigated the relationship between autistic traits and 5-HTTLPR in sub-clinical participants, and whether associations were mediated by mPFC function. Correlation analyses indicated that participants with a large number of 5-HTTLPR L-alleles had high-level autistic traits related to social skills and low right mPFC activation. We also observed a significant negative correlation between autistic traits related to social skills and right mPFC activation. Structural equation analysis suggested a significant indirect effect of 5-HTTLPR on Autism-Spectrum Quotients, with right mPFC activation acting as a mediator. These results suggest that the diverse autistic traits related to social skills seen in the general population are associated with the 5-HTTLPR genotype, and that this association is mediated by right mPFC function.

Reduced brain activation during imitation and observation of others in children with pervasive developmental disorder: a pilot study.

BACKGROUND: Children with pervasive developmental disorder (PDD) are thought to have poor imitation abilities. Recently, this characteristic has been suggested to reflect impairments in mirror neuron systems (MNS). We used near-infrared spectroscopy (NIRS) to examine the brain activity of children with PDD during tasks involving imitation and observations of others. FINDINGS: The subjects were 6 male children with PDD (8-14 years old) and 6 age- and gender-matched normal subjects (9-13 years old). A video in which a woman was opening and closing a bottle cap was used as a stimulus. Hemoglobin concentration changes around the posterior part of the inferior frontal gyrus and the adjacent ventral premotor cortex were measured with a 24-channel NIRS machine during action observation and action imitation tasks. Regional oxygenated hemoglobin concentration changes were significantly smaller in the PDD group than in the control group. Moreover, these differences were clearer in the action observation task than in the action imitation task. CONCLUSIONS: Dysfunction in the MNS in children with PDD was suggested by the reduced activation in key MNS regions during tasks involving observations and imitations of others. These preliminary results suggest that further studies are needed to verify MNS dysfunction in children with PDD.