This article presents results from two interrelated studies. The first study conducted a meta-analysis of the published literature since 1990 to determine the magnitude of achievement problems associated with attention-deficit/hyperactivity disorder (ADHD). Effect sizes were significantly different between participants with and without ADHD (sample weighted r = .32, sample weighted d = . 71; p = .001). Effects were also examined according to the moderators of age, gender, achievement domain (reading, math, spelling), measurement method (standardized tests vs. grades, parent/teacher ratings, etc.), sample type (clinical vs. nonclinical), and system used to identify ADHD (DSM-III-R vs. DSM-IV). Significant differences emerged from the moderator comparisons. The second study, using averaged effect sizes from the first study as a baseline for comparison, investigated achievement levels for an understudied age group with ADHD, namely, college students. Unlike previous studies at the college level, the sample incorporated both student and parent ratings (N = 380 dyads). The results were comparable to outcomes from the meta-analysis for college students and adults. Analyses demonstrated modest (R = .21) but meaningful predictive validity across 1 year to end-of-first-year grades. However, unlike earlier studies with children and adolescents, student ratings were as predictive as parent ratings. Findings are discussed in terms of the impact of moderator variables on ADHD and achievement.

PTEN is a tumor suppressor associated with an inherited cancer syndrome and an important regulator of ongoing neural connectivity and plasticity. The present study examined molecular and phenotypic characteristics of individuals with germline heterozygous PTEN mutations and autism spectrum disorder (ASD) (PTEN-ASD), with the aim of identifying pathophysiologic markers that specifically associate with PTEN-ASD and that may serve as targets for future treatment trials. PTEN-ASD patients (n=17) were compared with idiopathic (non-PTEN) ASD patients with (macro-ASD, n=16) and without macrocephaly (normo-ASD, n=38) and healthy controls (n=14). Group differences were evaluated for PTEN pathway protein expression levels, global and regional structural brain volumes and cortical thickness measures, neurocognition and adaptive behavior. RNA expression patterns and brain characteristics of a murine model of Pten mislocalization were used to further evaluate abnormalities observed in human PTEN-ASD patients. PTEN-ASD had a high proportion of missense mutations and showed reduced PTEN protein levels. Compared with the other groups, prominent white-matter and cognitive abnormalities were specifically associated with PTEN-ASD patients, with strong reductions in processing speed and working memory. White-matter abnormalities mediated the relationship between PTEN protein reductions and reduced cognitive ability. The Pten^m3m4 murine model had differential expression of genes related to myelination and increased corpus callosum. Processing speed and working memory deficits and white-matter abnormalities may serve as useful features that signal clinicians that PTEN is etiologic and prompting referral to genetic professionals for gene testing, genetic counseling and cancer risk management; and could reveal treatment targets in trials of treatments for PTEN-ASD.