Neurocognitive endophenotypes of obsessive-compulsive disorder

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Endophenotypes offer a way to understand genetic risk for complex brain disorders like obsessive-compulsive disorder (OCD).
• Identifying intermediate phenotypes can clarify diagnostic classification and etiological understanding of OCD.

Purpose of the Study:

• To investigate potential endophenotypes for OCD by examining brain structure and response inhibition.
• To determine if brain structural variations associated with inhibitory control show familial patterns in OCD.

Main Methods:

• Magnetic resonance imaging (MRI) was used to measure brain structure in 31 OCD patients, 31 unaffected first-degree relatives, and 31 controls.
• A response inhibition task (Stop-Signal) assessed behavioral performance.
• Partial least squares analysis identified brain systems associated with response inhibition performance, with permutation testing for familial effects.

Main Results:

• Both OCD patients and their relatives exhibited delayed response inhibition compared to controls.
• Impaired response inhibition was linked to reduced grey matter in orbitofrontal and right inferior frontal regions.
• Increased grey matter was observed in cingulate, parietal, and striatal regions, with significant familial effects on these MRI markers.

Conclusions:

• Structural variations in brain systems related to motor inhibitory control may mediate genetic risk for OCD.
• These findings provide the first evidence for a neurocognitive endophenotype of OCD.
• The identified brain structural systems show familial effects, supporting their candidacy as OCD endophenotypes.