Neurocognitive endophenotypes in pediatric OCD probands, their unaffected parents and siblings

Area of Science:

• Neuroscience
• Psychiatry
• Genetics

Background:

• Existing research on neurocognitive endophenotypes in obsessive-compulsive disorder (OCD) is limited and shows inconsistent findings.
• Previous studies suffered from small sample sizes, strict exclusion criteria, lack of normalized test scores, and few studies on pediatric probands.
• This study aimed to overcome these limitations by examining a large cohort of pediatric OCD patients and their families.

Purpose of the Study:

• To investigate neurocognitive endophenotypes in pediatric obsessive-compulsive disorder (OCD).
• To assess cognitive flexibility and inhibitory control in individuals with OCD, their unaffected siblings, and parents.
• To identify potential familial transmission of cognitive deficits associated with OCD.

Main Methods:

• A large cohort including pediatric OCD probands (n=102), unaffected siblings (n=78), and parents (n=164) underwent a comprehensive neuropsychological assessment.
• Standardized scores were calculated using established test norms to account for age and developmental differences.
• Statistical analyses included cluster-robust regression and interclass correlations, with False Discovery Rate procedures for multiple comparisons.

Main Results:

• Pediatric OCD probands, siblings, and parents demonstrated significant deficits (Z < -0.5) in initial concept formation (Wisconsin Card Sorting Test) and inhibitory control (Stroop color naming).
• These deficits were consistent across the three groups, with medium to large effect sizes compared to normative data.
• No other significant familial cognitive trends were observed in other executive functions, such as perseveration or interference control.

Conclusions:

• Individuals with OCD, their unaffected siblings, and parents exhibit shared deficits in specific aspects of cognitive flexibility and inhibitory control.
• These findings suggest that difficulties in initial concept formation and proactive control may represent valid neurocognitive endophenotypes for OCD.
• The study underscores the importance of examining individual executive function test outcomes rather than relying solely on global measures to understand OCD's cognitive underpinnings.