Sulcal Depth and Genetic Susceptibility Influence Initial Treatment Response in Adults With...

As neurobiological markers gain prominence in guiding personalized treatments, sulcal depth (SD) remains an underexplored yet pivotal factor in neural processing and therapeutic efficacy. While genetic influences shape cortical architecture, their role in modulating the relationship between SD and treatment outcomes remains unclear. In this study, we investigated whether pretreatment SD predicts symptom alleviation in adults with attention-deficit/hyperactivity disorder (ADHD) and explored moderating effects of genetic susceptibility for ADHD and cross-disorder influences.

Using structural neuroimaging data from COMPAS (Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study), we examined associations between SD and treatment response following a 12-week intervention involving either group psychotherapy or clinical management with methylphenidate or placebo. Pretreatment SD was derived from 119 T1-weighted anatomical scans and analyzed using linear regression models to assess its predictive value for posttreatment symptom severity. Subsequently, we explored the moderating role of polygenic scores for ADHD and cross-disorder susceptibility. Structural analyses were performed using the threshold-free cluster enhancement approach in CAT, with moderation analyses conducted in SPSS.

Results revealed that SD in parietal, temporal, and occipital regions significantly predicted symptom alleviation, linking deeper sulci with greater treatment efficacy. Moreover, genetic predisposition to ADHD and cross-disorder traits influenced these relationships, highlighting an interaction between cortical structure and genetic susceptibility in determining treatment outcomes.

These findings highlight SD as a promising neurobiological marker of ADHD treatment response and emphasize the importance of integrating neurobiological and genetic factors into predictive models of therapeutic efficacy in psychiatry.