Novel genome-wide associations for effort valuation and psychopathology in children and adults.

The Research Domain Criteria (RDoC) initiative was established by the US National Institute of Mental Health as a multilevel, disorder-agnostic framework for analysis of human psychopathology through designated domains and constructs, including the "Positive Valence Systems" domain focused on reward-related behavior. This study investigates the reward valuation subconstruct of "effort" and its association with genetic markers, functional neurobiological pathways, and polygenic risk scores for psychopathology in 1215 children aged 6-12 and their parents (n = 1044). All participants completed the effort expenditure for rewards task (EEfRT), which assesses "effort" according to two quantitative measures: hard-task choice and reward sensitivity. Genetic association analyses were undertaken in MAGMA, utilizing EEfRT outcome variables as genome-wide association studies phenotypes to compute SNP and gene-level associations. Genome-wide association analyses found two distinct genetic loci that were significantly associated with measures of reward sensitivity and a separate genetic locus associated with hard task choice. Gene-set enrichment analysis yielded significant associations between "effort" and multiple gene sets involved in reward processing-related pathways, including dopamine receptor signaling, limbic system and forebrain development, and biological response to cocaine. These results serve to establish "effort" as a relevant construct for understanding reward-related behavior at the genetic level and support the RDoC framework for assessing disorder-agnostic psychopathology.

From Structural Disparities to Neuropharmacology: A Review of Adult Attention-Deficit/Hyperactivity Disorder Medication Treatment.

Adult attention-deficit/hyperactivity disorder (ADHD) is an early-onset disorder with many functional impairments and psychiatric comorbidities. Although no treatment fully mitigates impairments associated with ADHD, effective management is possible with pharmacologic and nonpharmacologic treatments. The etiology and pathophysiology of ADHD are remarkably complex and the disorder is continuously distributed in the population. While these findings have been well documented in studies with predominantly white samples, ADHD may affect racial and ethnic minorities differentially, given diagnostic and treatment disparities. This review provides an updated overview of the epidemiology, etiology, neurobiology, and neuropharmacology of ADHD, addressing racial and ethnic disparities whereby data are available.

Gene co-expression networks in peripheral blood capture dimensional measures of emotional and behavioral problems from the Child Behavior Checklist (CBCL).

The U.S. National Institute of Mental Health (NIMH) introduced the research domain criteria (RDoC) initiative to promote the integration of information across multiple units of analysis (i.e., brain circuits, physiology, behavior, self-reports) to better understand the basic dimensions of behavior and cognitive functioning underlying normal and abnormal mental conditions. Along those lines, this study examined the association between peripheral blood gene expression levels and emotional and behavioral problems in school-age children. Children were chosen from two age- and sex-matched groups: those with or without parental reports of any prior or current psychiatric diagnosis. RNA-sequencing was performed on whole blood from 96 probands aged 6-12 years who were medication-free at the time of assessment. Module eigengenes were derived using weighted gene co-expression network analysis (WGCNA). Associations were tested between module eigengene expression levels and eight syndrome scales from parent ratings on the Child Behavior Checklist (CBCL). Nine out of the 36 modules were significantly associated with at least one syndrome scale measured by the CBCL (i.e., aggression, social problems, attention problems, and/or thought problems) after accounting for covariates and correcting for multiple testing. Our study demonstrates that variation in peripheral blood gene expression relates to emotional and behavioral profiles in children. If replicated and validated, our results may help in identifying problem or at-risk behavior in pediatric populations, and in elucidating the biological pathways that modulate complex human behavior.

Initial Responsiveness to Reward Attainment and Psychopathology in Children and Adults: An RDoC Study.

The Research Domain Criteria (RDoC) initiative of the National Institute of Mental Health (NIMH) established a dimensional framework for understanding psychiatric constructs. Initial Responsiveness to Reward Attainment (IRRA) was identified as a dimensional construct relevant to several psychiatric disorders. The current study aimed to (1) examine IRRA as a predictor of psychopathology and impairment in children and their parents, and (2) examine the potential effects of sex and ancestry on the relationship between IRRA and psychopathology. Participants included 1127 children ages 6 to 12, and 1018 of their parents. Parents and children completed self-report measures of IRRA. Psychopathology and impairment were measured using self-report for adults, and parent-report and semi-structured interview for children. In adults, IRRA was significantly, but modestly, related to adaptive functioning. In children, IRRA was significantly, but modestly, related to overall, school, spare time, home, and peer functioning. Findings suggest IRRA may be a helpful construct for understanding adaptive functioning in adults and children, however it may be less helpful for understanding specific dimensions of psychopathology. Additionally, ancestry should be taken into consideration when examining how IRRA relates to psychopathology and functioning.

Effort valuation and psychopathology in children and adults.

BACKGROUND: The Research Domain Criteria initiative was launched by the US National Institute of Mental Health to establish a multi-level framework for understanding psychological constructs relevant to human psychiatric disorders, and identified 'effort valuation/willingness to work' as a clinically useful construct worthy of further study. This construct encompasses the processes by which the cost(s) of obtaining an outcome are calculated, and the tendency to overcome response costs to obtain a reinforcer. The current study aims to examine effort valuation as a correlate of psychopathology in children and adults, and the moderating effects of sex on this relationship. METHODS: Participants were 1215 children aged 6-12 and their parents (n = 1044). All participants completed the Effort Expenditure for Rewards Task as a measure of effort expenditure. Child psychopathology was measured via the Child Behavior Checklist, while adult psychopathology was measured via the Adult Self Report. Additionally, the Social Adjustment Inventory for Children and Adolescents and Injury Behavior Checklist were used to examine child social impairments/problem behaviors. RESULTS: In children, significant interactions between reward sensitivity and sex were observed in association with anxiety and thought problems, specifically at low reward sensitivity levels. In adults, main effects of effort expenditure were seen in drug and alcohol abuse, where higher effort was associated with higher degrees of abuse. CONCLUSIONS: These results establish effort valuation as a relevant psychological construct for understanding psychopathology, but with different profiles of associated psychopathology across sex in children and adults.

Childhood Executive Functioning Predicts Young Adult Outcomes in 22q11.2 Deletion Syndrome.

OBJECTIVE: While individuals with 22q11.2 deletion syndrome (22q11DS) are at increased risk for a variety of functional impairments and psychiatric disorders, including psychosis, not all individuals with 22q11DS experience negative outcomes. Efforts to further understand which childhood variables best predict adult functional outcomes are needed, especially those that investigate childhood executive functioning abilities. METHODS: This longitudinal study followed 63 individuals with 22q11DS and 43 control participants over 9 years. Childhood executive functioning ability was assessed using both rater-based and performance-based measures and tested as predictors of young adult outcomes. RESULTS: Childhood global executive functioning abilities and parent report of child executive functioning abilities were the most consistent predictors of young adult outcomes. The study group moderated the relationship between child executive functioning and young adult outcomes for several outcomes such that the relationships were stronger in the 22q11DS sample. CONCLUSION: Rater-based and performance-based measures of childhood executive functioning abilities predicted young adult outcomes in individuals with and without 22q11DS. Executive functioning could be a valuable target for treatment in children with 22q11DS for improving not only childhood functioning but also adult outcomes. (JINS, 2018, 24, 905-916).

A schoolwide approach to promoting student bystander behavior in response to the use of the word "retard".

BACKGROUND AND AIMS: The use of the word retard ("the r-word") among adolescents sheds light on societal views about individuals with intellectual disability and the need to address the colloquial use of this word and its underlying stigma. Schools provide an important platform for intervening to promote social change among youth. The present study examined the impact of a schoolwide social inclusion program on students' bystander behavior against the use of the r-word. METHODS AND PROCEDURES: 1233 students from 5 high schools were surveyed about the prevalence of the r-word in their school, the contexts in which it is used, and their bystander behavior in response to the word. Approximately 40% of surveyed students participated in an R-word Campaign, Unified Sports team, and/or Unified Club as part of the Special Olympics Unified Champion Schools (UCS) program. OUTCOMES AND RESULTS: Students' prosocialness, the context in which the r-word was used, and participation in UCS activities significantly predicted active bystander behavior in response to the r-word. CONCLUSIONS AND IMPLICATIONS: By empowering students to be active bystanders against the use of the r-word in school, school-based interventions provide a promising avenue for addressing both the use of the r-word and its underlying stigma.

Sticks, Stones, and Stigma: Student Bystander Behavior in Response to Hearing the Word "Retard".

The present study explored the prevalence of the r-word in schools and students' bystander behavior in response to hearing the word. In total, 2,297 students from 12 high schools across the country participated in this study. Results revealed the r-word was used frequently among high school students, most often toward individuals without intellectual disability (ID). Students were more likely to take an active bystander role when hearing the r-word used toward students with ID than when hearing it used toward students without ID. Students' gender and prosocialness also played a role in determining their bystander behavior in response to the r-word. This study has implications for reducing the use of the r-word and the stigma associated with ID.