Dataset Information

Genotype and neuropsychological response inhibition as resilience promoters for attention-deficit/hyperactivity disorder, oppositional defiant disorder, and conduct disorder under conditions of psychosocial adversity.

ABSTRACT: Whereas child personality, IQ, and family factors have been identified as enabling a resilient response to psychosocial adversity, more direct biological resilience factors have been less well delineated. This is particularly so for child attention-deficit/hyperactivity disorder (ADHD), which has received less attention from a resilience perspective than have associated externalizing disorders. Children from two independent samples were classified as resilient if they avoided developing ADHD, oppositional defiant disorder (ODD), or conduct disorder (CD) in the face of family adversity. Two protective factors were examined for their potential relevance to prefrontal brain development: neuropsychological response inhibition, as assessed by the Stop task, and a composite catecholamine genotype risk score. Resilient children were characterized in both samples by more effective response inhibition, although the effect in the second sample was very small. Genotype was measured in Sample 1, and a composite high risk genotype index was developed by summing presence of risk across markers on three genes expressed in prefrontal cortex: dopamine transporter, dopamine D4 receptor, and noradrenergic alpha-2 receptor. Genotype was a reliable resilience indicator against development of ADHD and CD, but not ODD, in the face of psychosocial adversity. Results illustrate potential neurobiological protective factors related to development of prefrontal cortex that may enable children to avoid developing ADHD and CD in the presence of psychosocial adversity.

SUBMITTER: Nigg J

PROVIDER: S-EPMC2291356 | biostudies-literature | 2007

REPOSITORIES: biostudies-literature

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Genotype and neuropsychological response inhibition as resilience promoters for attention-deficit/hyperactivity disorder, oppositional defiant disorder, and conduct disorder under conditions of psychosocial adversity.

Nigg Joel J Nikolas Molly M Friderici Karen K Park Leeyoung L Zucker Robert A RA

Development and psychopathology 20070101 3

Whereas child personality, IQ, and family factors have been identified as enabling a resilient response to psychosocial adversity, more direct biological resilience factors have been less well delineated. This is particularly so for child attention-deficit/hyperactivity disorder (ADHD), which has received less attention from a resilience perspective than have associated externalizing disorders. Children from two independent samples were classified as resilient if they avoided developing ADHD, op ...[more]

PMID: 17705902

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Project description:In this study, we aimed to expand on our prior research into the relative efficacy of combining parent training, stimulant medication, and placebo (Basic therapy) versus parent training, stimulant, and risperidone (Augmented therapy) by examining treatment effects for attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) symptoms and peer aggression, symptom-induced impairment, and informant discrepancy.Children (6-12 years of age; N = 168) with severe physical aggression, ADHD, and co-occurring ODD/CD received an open trial of parent training and stimulant medication for 3 weeks. Participants failing to show optimal clinical response were randomly assigned to Basic or Augmented therapy for an additional 6 weeks.Compared with Basic therapy, children receiving Augmented therapy experienced greater reduction in parent-rated ODD severity (p = .002, Cohen's d = 0.27) and peer aggression (p = .02, Cohen's d = 0.32) but not ADHD or CD symptoms. Fewer children receiving Augmented (16%) than Basic (40%) therapy were rated by their parents as impaired by ODD symptoms at week 9/endpoint (p = .008). Teacher ratings indicated greater reduction in ADHD severity (p = .02, Cohen's d = 0.61) with Augmented therapy, but not for ODD or CD symptoms or peer aggression. Although both interventions were associated with marked symptom reduction, a relatively large percentage of children were rated as impaired for at least 1 targeted disorder at week 9/endpoint by parents (Basic 47%; Augmented 27%) and teachers (Basic 48%; Augmented 38%).Augmented therapy was superior to Basic therapy in reducing severity of ADHD and ODD symptoms, peer aggression, and symptom-induced impairment, but clinical improvement was generally context specific, and effect sizes ranged from small to moderate. Clinical trial registration information-Treatment of Severe Childhood Aggression (The TOSCA Study); http://clinicaltrials.gov/; NCT00796302.

Project description:IntroductionThe externalizing disorders of attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) are common in adolescence and are strong predictors of adult psychopathology. While treatable, substantial diagnostic overlap complicates intervention planning. Understanding which factors predict the onset of each disorder and disambiguating their different predictors is of substantial translational interest.Materials and methodsWe analyzed 5,777 multimodal candidate predictors from children aged 9-10 years and their parents in the ABCD cohort to predict the future onset of ADHD, ODD, and CD at 2-year follow-up. We used deep learning optimized with an innovative AI algorithm to jointly optimize model training, perform automated feature selection, and construct individual-level predictions of illness onset and all prevailing cases at 11-12 years and examined relative predictive performance when candidate predictors were restricted to only neural metrics.ResultsMultimodal models achieved ~86-97% accuracy, 0.919-0.996 AUROC, and ~82-97% precision and recall in testing in held-out, unseen data. In neural-only models, predictive performance dropped substantially but nonetheless achieved accuracy and AUROC of ~80%. Parent aggressive and externalizing traits uniquely differentiated the onset of ODD, while structural MRI metrics in the limbic system were specific to CD. Psychosocial measures of sleep disorders, parent mental health and behavioral traits, and school performance proved valuable across all disorders. In neural-only models, structural and functional MRI metrics in subcortical regions and cortical-subcortical connectivity were emphasized. Overall, we identified a strong correlation between accuracy and final predictor importance.ConclusionDeep learning optimized with AI can generate highly accurate individual-level predictions of the onset of early adolescent externalizing disorders using multimodal features. While externalizing disorders are frequently co-morbid in adolescents, certain predictors were specific to the onset of ODD or CD vs. ADHD. To our knowledge, this is the first machine learning study to predict the onset of all three major adolescent externalizing disorders with the same design and participant cohort to enable direct comparisons, analyze >200 multimodal features, and include many types of neuroimaging metrics. Future study to test our observations in external validation data will help further test the generalizability of these findings.

Dataset Information

Genotype and neuropsychological response inhibition as resilience promoters for attention-deficit/hyperactivity disorder, oppositional defiant disorder, and conduct disorder under conditions of psychosocial adversity.

Publications

Genotype and neuropsychological response inhibition as resilience promoters for attention-deficit/hyperactivity disorder, oppositional defiant disorder, and conduct disorder under conditions of psychosocial adversity.

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