Individual Differences in Autistic Traits are Associated with Serotonin Transporter Gene Polymorphism Through Medial...

Area of Science:

• Neuroscience
• Genetics
• Psychology

Background:

• Autism spectrum disorder (ASD) is a heritable neurodevelopmental condition with variable severity.
• Autistic traits exist on a continuum in the general population, including sub-clinical individuals.
• The serotonin transporter gene (5-HTTLPR) has been inconsistently linked to ASD, despite its role in medial prefrontal cortex (mPFC) function, a region implicated in ASD-related social deficits.

Purpose of the Study:

• To investigate the mediating role of mPFC function in the relationship between 5-HTTLPR genotype and autistic traits.
• To examine mPFC activation during a facial affect-labeling task in individuals with ASD compared to typically developing individuals.
• To explore the association between autistic traits, 5-HTTLPR genotype, and mPFC function in sub-clinical populations.

Main Methods:

• Near-infrared spectroscopy (NIRS) was used to measure mPFC activation during a facial affect-labeling task.
• Participants included individuals with ASD and a typically developing group, as well as sub-clinical individuals.
• Correlation and structural equation analyses were employed to examine genetic and neural mediation effects.

Main Results:

• Individuals with ASD exhibited significantly lower mPFC activation compared to controls during the facial affect-labeling task.
• In sub-clinical participants, a higher number of 5-HTTLPR L-alleles correlated with increased autistic social traits and reduced right mPFC activation.
• Right mPFC activation was negatively correlated with autistic social traits.
• Structural equation modeling confirmed that 5-HTTLPR genotype indirectly affects autistic traits via right mPFC activation.

Conclusions:

• Right mPFC function mediates the association between the 5-HTTLPR genotype and autistic social traits in the general population.
• These findings provide insight into the neurogenetic underpinnings of social skill variations related to autism.
• The study highlights the role of 5-HTTLPR and mPFC in the continuous distribution of autistic traits.