Serotonin transporter gene polymorphism implicates reduced orbito-frontal cortex in obsessive-compulsive disorder.

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Obsessive-compulsive disorder (OCD) research has explored magnetic resonance imaging (MRI) and genetic factors separately.
• Limited studies have concurrently investigated genetic variations and neuroanatomical differences in OCD.

Purpose of the Study:

• To investigate the association between 5-HTT gene promoter region variation (5-HTTLPR) and brain structure volumes in OCD.
• To compare the influence of 5-HTTLPR genotypes on the orbito-frontal cortex (OFC), thalamus, and anterior cingulate in OCD patients versus healthy controls.

Main Methods:

• Genotyping for 5-HTT (SS, SL, LL) in 40 OCD patients and 40 controls.
• MRI volumetric analysis of OFC, thalamus, and anterior cingulate using T1-weighted images.
• Statistical analysis including ANCOVA to assess genotype-diagnosis interactions.

Main Results:

• OCD patients exhibited reduced OFC volume, increased thalamus and white matter volumes compared to controls.
• No significant differences in allelic frequencies were found between groups.
• 5-HTT polymorphism showed stronger effects on OFC and thalamus morphology in OCD patients, with short variants linked to smaller right OFC volumes.

Conclusions:

• A significant genotype-diagnosis interaction was observed, indicating that 5-HTT gene variations impact key brain structures in OCD.
• The 5-HTT polymorphism influences OFC and thalamus morphology more significantly in individuals with OCD than in healthy individuals.