There are now large-scale data on which common genetic variants confer risk for attention deficit hyperactivity disorder (ADHD). Here, we use mediation analyses to explore how cognitive and neural features might explain the association between common variant (polygenic) risk for ADHD and its core symptoms. In total, 544 participants participated (mean 21 years, 212 [39%] with ADHD], most with cognitive assessments, neuroanatomic imaging and imaging of white matter tract microstructure. We found that polygenic risk for ADHD was associated with symptoms of hyperactivity-impulsivity but not inattention. This association was mediated across multiple PRS thresholds by white matter microstructure, specifically by axial diffusivity of the right corona radiata, (maximum indirect effect β = −0.034 [CI. −0.065 to −0.01), by thickness of the left dorsomedial prefrontal [β = −0.029; CI −0.061 to −0.0047]) and area of the right lateral temporal cortex [β = 0.024; CI 0.0034 to 0.054]). Additionally, modest serial mediation was found, mapping a pathway from polygenic risk, to white matter microstructure of the anterior corona radiata, then cognition (working memory, focused attention), and finally to hyperactivity-impulsivity (working memory β = −0.014 [CI. −0.038 to −0.0026]; focused attention β = −0.011 [CI. −0.033 to −0.0017]). These mediation pathways were diagnostically specific and were not found for polygenic risk for ASD or schizophrenia. In conclusion, using a deeply phenotyped cohort, we delineate a pathway from polygenic risk for ADHD to hyperactive-impulsive symptoms through white matter microstructure, cortical anatomy and cognition.

Intervention scientists have published more than 600 randomized controlled trials (RCTs) of youth psychotherapies. Four decades of meta-analyses have been used to synthesize the RCT findings and identify scientifically and clinically significant patterns. These meta-analyses have limitations, noted herein, but they have advanced our understanding of youth psychotherapy, revealing ( a) mental health problems for which our interventions are more and less successful (e.g., anxiety and depression, respectively); ( b) the benefits of single-session interventions, interventions delivered remotely, and interventions tested in low- and middle-income countries; ( c) the association of societal sexism and racism with reduced treatment benefit in majority-girl and majority-Black groups; and, importantly, ( d) the finding that average youth treatment benefit has not increased across five decades of research, suggesting that new strategies may be needed. Opportunities for the future include boosting relevance to policy and practice and using meta-analysis to identify mechanisms of change and guide personalization of treatment. Expected final online publication date for the Annual Review of Clinical Psychology, Volume 19 is May 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

This publication is intended to provide accurate and authoritative information regarding the subject matter covered. It is sold with the understanding that the publisher is not engaged in rendering medical, psychological, financial, legal, or other professional services. The recommended doses of medications cited in this newsletter are not meant to serve as a guide for prescribing of medications. Physicians, please check the manufacturer's product information sheet or the PHYSICIAN'S DESK REFERENCE for further information and contraindications. 1 • CAPN 21(1) Educational Objectives Upon completion of this activity, participants should be able to: • Evaluate treatment approaches to pediatric OCD. • Review traditional medications useful in treating pediatric OCD with comorbidity and for specific subtypes, such as tic-related OCD. Target Audience This CME activity is intended for child and adult psychiatrists, pediatricians and other healthcare professionals with an interest in the psychopharmacology and treatment practices for child and adolescent psychiatric disorders.

No abstract