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COMT and DAT1 polymorphisms moderate the indirect effect of parenting behavior on youth ADHD symptoms through neurocognitive functioning.

ABSTRACT: Although gene × environment interactions contribute to youth attention-deficit/hyperactivity disorder (ADHD) symptoms, the pathways mediating these influences are unknown. We tested genetic moderation of indirect effects from parenting behavior to youth ADHD symptoms through multiple neurocognitive factors. Two hundred and twenty-nine youth with and without ADHD were assessed at baseline (Wave 1; ages 5-10) and at a 2-year follow-up (Wave 2; ages 7-13). At Wave 1, youth completed a neurocognitive battery including measures of response inhibition, visuospatial working memory, and fluid reasoning, and a standardized parent-child interaction task yielding observational measures of positive and negative parenting. At Wave 2, youth psychopathology was rated by parents and teachers using multiple methods (i.e., structured interview, rating scale). We employed moderated multiple mediation and compared conditional indirect effects across youth genotypes at two biologically plausible genetic loci. Controlling for parent ADHD symptoms as well as youth demographic factors and co-occurring externalizing symptoms, these genetic factors moderated the indirect effect from Wave 1 parenting to multi-method/informant Wave 2 ADHD symptoms through Wave 1 neurocognitive functioning. This preliminary study is the first to identify genetic moderation of mediated effects underlying ADHD symptoms and suggests that specific gene × parenting interactions may underlie neurocognitive functioning deficits and subsequent ADHD.

SUBMITTER: Morgan JE

PROVIDER: S-EPMC6179434 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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COMT and DAT1 polymorphisms moderate the indirect effect of parenting behavior on youth ADHD symptoms through neurocognitive functioning.

Morgan Julia E JE Caplan Barbara B Tung Irene I Noroña Amanda N AN Baker Bruce L BL Lee Steve S SS

Child neuropsychology : a journal on normal and abnormal development in childhood and adolescence 20170704 6

Although gene × environment interactions contribute to youth attention-deficit/hyperactivity disorder (ADHD) symptoms, the pathways mediating these influences are unknown. We tested genetic moderation of indirect effects from parenting behavior to youth ADHD symptoms through multiple neurocognitive factors. Two hundred and twenty-nine youth with and without ADHD were assessed at baseline (Wave 1; ages 5-10) and at a 2-year follow-up (Wave 2; ages 7-13). At Wave 1, youth completed a neurocognitiv ...[more]

PMID: 28675949

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Project description:Parental cognitive functioning is thought to play a key role in parenting behavior and may inform response to behavioral intervention. This open-label pilot study examined the extent to which parent and child cognition impacted response to behavioral parent training for children with ADHD. Fifty-four participants (27 parent-child dyads; Mages?=?10.6 and 45.2 for children and parents, respectively) completed tasks assessing visuospatial and phonological working memory, inhibitory control, and choice-reaction speed at pre-treatment. Drift diffusion modeling decomposed choice-reaction time data into indicators of processing speed (drift rate) and response caution (boundary separation). Parents completed a 10-week manualized behavioral parent training program. Primary outcomes were pre- and post-treatment child ADHD and conduct problem severity, and parent-reported relational frustration and parenting confidence. Bayesian multiple regressions assessed parent and child cognitive processes as predictors of post-treatment outcomes, controlling for pre-treatment behavior. Better child visuospatial and phonological WM and higher parental response caution were associated with greater reductions in inattention. For conduct problems, better parental self-regulation (stronger inhibitory control and greater response caution) predicted fewer post-treatment conduct problems. Higher parental response caution also predicted lower post-treatment relational frustration and higher parental confidence. Bayesian evidence supported no relation between parent and child cognitive functions and treatment-related changes in hyperactivity. This pilot study demonstrates that cognitive processes central to etiologic theories of ADHD and models of parenting behavior can be successfully integrated into treatment outcome research to inform which families are most likely to benefit from behavioral interventions. This study demonstrates the feasibility of bridging the translational research gap between basic and applied clinical science and facilitates research on the role of cognition in psychosocial interventions.

Project description:BACKGROUND:Although there are extensive data on clinical psychopathology in youth with suicidal ideation, data are lacking regarding their neurocognitive function. AIMS:To characterise the cognitive profile of youth with suicidal ideation in a community sample and evaluate gender differences and pubertal status effects. METHOD:Participants (N = 6151, age 11-21 years, 54.9% females) from the Philadelphia Neurodevelopmental Cohort, a non-help-seeking community sample, underwent detailed clinical evaluation. Cognitive phenotyping included executive functioning, episodic memory, complex reasoning and social cognitive functioning. We compared participants with suicidal ideation (N = 672) and without suicidal ideation (N = 5479). Regression models were employed to evaluate differences in cognitive performance and functional level, with gender and pubertal status as independent variables. Models controlled for lifetime depression or general psychopathology, and for covariates including age and socioeconomic status. RESULTS:Youth with suicidal ideation showed greater psychopathology, poorer level of function but better overall neurocognitive performance. Greater functional impairment was observed in females with suicidal ideation (suicidal ideation × gender interaction, t = 3.091, P = 0.002). Greater neurocognition was associated with suicidal ideation post-puberty (suicidal ideation × puberty interaction, t = 3.057, P = 0.002). Exploratory analyses of specific neurocognitive domains showed that suicidal ideation-associated cognitive superiority was more prominent in post-pubertal males compared with females (Cohen's d = 0.32 and d = 0.11, respectively) across all cognitive domains. CONCLUSIONS:Suicidal ideation was associated with poorer functioning yet better cognitive performance, especially in post-pubertal males, as measured by a comprehensive cognitive battery. Findings point to gender and pubertal-status specificity in the relationship between suicidal ideation, cognition and function in youth. DECLARATION OF INTEREST:R.B. serves on the scientific board and reports stock ownership in 'Taliaz Health', with no conflict of interest relevant to this work. M.A.O. receives royalties for the commercial use of the Columbia-Suicide Severity Rating Scale from the Research Foundation for Mental Hygiene. Her family owns stock in Bristol-Myers Squibb. All other authors declare no potential conflict of interest.

Dataset Information

COMT and DAT1 polymorphisms moderate the indirect effect of parenting behavior on youth ADHD symptoms through neurocognitive functioning.

Publications

COMT and DAT1 polymorphisms moderate the indirect effect of parenting behavior on youth ADHD symptoms through neurocognitive functioning.

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