Substance dependence is associated with executive function deficits, but the nature of these executive defects and the effect that different drugs and sex have on these defects has not been fully clarified. Therefore, we compared the performance of alcohol-(n = 33; 18 women), cocaine-(n = 27; 14 women), and methamphetamine-dependent individuals (n = 38; 25 women) with sex-matched healthy comparisons (n = 36; 17 women) on complex decision-making as measured with the Iowa Gambling Task, working memory, cognitive flexibility, and response inhibition. Cocaine-and methamphetamine-dependent individuals were impaired on complex decision-making, working memory, and cognitive flexibility, but not on response inhibition. The deficits in working memory and cognitive flexibility were milder than the decision-making deficits and did not change as a function of memory load or task switching. Interestingly, decision-making was significantly more impaired in women addicted to cocaine or methamphetamine than men addicted to these drugs. Together, these findings suggest that drug of choice and sex have different effects on executive functioning, which, if replicated, may help tailor intervention.

ObjectiveThe huntingtin gene is critical for the formation and differentiation of the CNS, which raises questions about the neurodevelopmental effect of CAG expansion mutations within this gene (mHTT) that cause Huntington disease (HD). We sought to test the hypothesis that child and adolescent carriers of mHTT exhibit different brain growth compared to peers without the mutation by conducting structural MRI in youth who are at risk for HD. We also explored whether the length of CAG expansion affects brain development.MethodsChildren and adolescents (age 6–18) with a parent or grandparent diagnosed with HD underwent MRI and blinded genetic testing to confirm the presence or absence of mHTT. Seventy-five individuals were gene-expanded (GE) and 97 individuals were gene-nonexpanded (GNE). The GE group was estimated to be on average 35 years from clinical onset. Following an accelerated longitudinal design, age-related changes in brain regions were estimated.ResultsAge-related striatal volume changes differed significantly between the GE and GNE groups, with initial hypertrophy and more rapid volume decline in GE. This pattern was exaggerated with CAG expansion length for CAG > 50. A similar age-dependent group difference was observed for the globus pallidus, but not in other major regions.ConclusionOur results suggest that pathogenesis of HD begins with abnormal brain development. An understanding of potential neurodevelopmental features associated with mHTT may be needed for optimized implementation of preventative gene silencing therapies, such that normal aspects of neurodevelopment are preserved as neurodegeneration is forestalled.

Despite the assumed prevalence of risk-taking behavior in adolescence, the laboratory evidence of risk taking remains scarce, and the individual variation poorly understood. Drawing from neuroscience studies, we tested whether risk and reward orientation are influenced by the perspective that adolescents take when making risky decisions. Perspective taking was manipulated by cuing participants prior to each choice whether the decision was made for "self," or from the perspective of an "other" (the experimenter in Experiment 1; a hypothetical peer in Experiment 2). In Experiment 1, we show a developmental decrease in risk-taking behavior across different stages of adolescence. In addition, all age groups made fewer risky choices for the experimenter, but the difference between self and other was larger in early adolescence. In Experiment 2, we show that high sensation-seeking (SS) adolescents make more risky choices than low SS adolescents, but both groups make a similar differentiation for other individuals (low risk-taking or high risk-taking peers). Together, the results show that younger adolescents and high SS adolescents make more risky choices for themselves, but can appreciate that others may make fewer risky choices. The developmental change toward more rational decisions versus emotional, impulsive decisions may reflect, in part, more efficient integration of others' perspectives into one's decision making. These developmental results are discussed regarding brain systems important for risk taking and perspective taking.

Research into the neural underpinnings of fear and fear-related pathology has highlighted the role of the amygdala. For instance, bilateral damage to the amygdaloid complex is associated with decreased appreciation of danger and recognition of fear in humans, whereas enlarged amygdala volume is associated with internalizing syndromes. It is unknown whether amygdala volume and fearfulness are related in the absence of pathology. We examined the correlation between normal fearfulness and amygdala morphology in 116 healthy children and adolescents (60 boys, 56 girls, age 7-17 years). Fearfulness was measured using the parent ratings on the Pediatric Behavior Scale and amygdala volumes were determined by manual tracing. We found a positive correlation between right amygdala volume in girls (r = 0.29). This relationship was more robust and present bilaterally when analyses were limited to girls with a positive nuclear family history of depression (for left r = 0.63; for right r = 0.58). In boys there was no significant relationship which may suggest that biological mechanisms differ between sexes. Given the role of enlarged amygdala volume in pathology, these findings may indicate that variation in amygdala morphology marks susceptibility to internalizing disorders.

Background The purpose was to examine associations between treatment and chronic health conditions with neurocognitive impairment survivors of acute lymphoblastic leukemia (ALL) treated with chemotherapy only. Methods This cross-sectional study included 1,207 ALL survivors (54.0% female; mean age 30.6 years) and 2,273 siblings (56.9% female; mean age 47.6 years), who completed the CCSS Neurocognitive Questionnaire. Multivariable logistic regression compared prevalence of neurocognitive impairment between survivors and siblings by sex. Associations between neurocognitive impairment with treatment exposures and chronic conditions (graded according to Common Terminology Criteria for Adverse Events) were also examined. Statistical tests were two-sided. Results Relative to same-sex siblings, male and female ALL survivors reported increased prevalence of impaired task efficiency (males: 11.7% vs. 16.9%; adjusted odds ratio [OR]=1.89, 95% confidence interval [CI]=1.31 to .74; females: 12.5% vs. 17.6%; OR = 1.50, 95% CI = 1.07to2.14), as well as impaired memory (males: 11.6% vs. 19.9%, OR = 1.89, CI = 1.31to2.74; females: 14.78% vs. 25.4%, OR = 1.96, 95% CI = 1.43 to 2.70, respectively). Among male survivors, impaired task efficiency was associated with 2-4 neurologic conditions (OR = 4.33, 95% CI = 1.76 to 10.68) and with pulmonary conditions (OR = 4.99, 95% CI = 1.51 to 16.50), while impaired memory was associated with increased cumulative dose of intrathecal methotrexate (OR = 1.68, 95% CI = 1.16 to 2.46) and with exposure to dexamethasone (OR = 2.44, 95% CI = 1.19 to 5.01). In female survivors, grade 2-4 endocrine conditions were associated with higher risk of impaired task efficiency (OR = 2.19, 95% CI = 1.20 to 3.97) and memory (OR = 2.26, 95% CI = 1.31 to 3.92). Conclusion Neurocognitive impairment is associated with methotrexate, dexamethasone and chronic health conditions in a sex-specific manner, highlighting the need to investigate physiological mechanisms and monitor impact through survivorship.