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

Background: Limited extant research on neurocognitive endophenotypes in obsessive-compulsive disorder (OCD) show inconsistent results. Limitations of this body of literature include small sample sizes, strict exclusion criteria, lack of objective standard normalized test scores, and significant lack of studies utilizing pediatric probands. This study aimed to address these limitations. Methods: A large carefully screened cohort of pediatric OCD (n = 102), their unaffected siblings (n = 78), and parents (n = 164), completed a neuropsychological battery. To compare participants at different ages and developmental stages, standard scores were computed using test norms. Cluster-robust regression with sample size-adjusted sandwich estimates of variance, and interclass correlations were computed. False Discovery Rate procedures were employed to correct for multiplicity. Results: Probands, siblings and parents demonstrated deficient task performance (Z < -0.5) on the 'number of trials to complete first category' on the Wisconsin Card Sorting Test, and on the Stroop color naming trials. Compared to test norms, the three groups exhibited medium to large effect sizes on these outcome measures. No other meaningful familial trends were found. Conclusions: OCD probands, their unaffected siblings and parents exhibited deficiencies in specific subdomains of cognitive flexibility and inhibitory control, namely, initial concept formation and proactive control, which may be valid candidate neurocognitive endophenotypes of OCD. No other meaningful familial effect has been found on other functions, including other executive function indices such as perseverations and interference control. These results highlight the need to carefully examine individual outcomes from executive function tests instead of the tendency to focus largely on major outcome measures.