Attention-deficit hyperactivity disorder (ADHD) is a common, chronic, and impairing disorder, yet presentations of ADHD and clinical course are highly heterogeneous. Despite substantial research efforts, both (a) the secondary co-occurrence of ADHD and complicating additional clinical problems and (b) the developmental pathways leading toward or away from recovery through adolescence remain poorly understood. Resolving these requires accounting for transactional influences of a large number of features across development. Here, we applied a longitudinal cross-lagged panel network model to a multimodal, multilevel dataset in a well-characterized sample of 488 children (nADHD = 296) to test Research Domain Criteria initiative-inspired hypotheses about transdiagnostic risk. Network features included Diagnostic and Statistical Manual of Mental Disorders symptoms, trait-based ratings of emotional functioning (temperament), and performance-based measures of cognition. Results confirmed that ADHD symptom domains, temperamental irritability, and working memory are independent transdiagnostic risk factors for psychopathology based on their direct associations with other features across time. ADHD symptoms and working memory each had direct, independent associations with depression. Results also demonstrated tightly linked co-development of ADHD symptoms and temperamental irritability, consistent with the possibility that this type of anger dysregulation is a core feature that is co-expressed as part of the ADHD phenotype for some children.

High levels of early emotionality (of either negative or positive valence) are hypothesized to be important precursors to early psychopathology, with attention-deficit/hyperactivity disorder (ADHD) a prime early target. The positive and negative affect domains are prime examples of Research Domain Criteria (RDoC) concepts that may enrich a multilevel mechanistic map of psychopathology risk. Utilizing both variable-centered and person-centered approaches, the current study examined whether levels and trajectories of infant negative and positive emotionality, considered either in isolation or together, predicted children's ADHD symptoms at 4 to 8 years of age. In variable-centered analyses, higher levels of infant negative affect (at as early as 3 months of age) were associated with childhood ADHD symptoms. Findings for positive affect failed to reach statistical threshold. Results from person-centered trajectory analyses suggest that additional information is gained by simultaneously considering the trajectories of positive and negative emotionality. Specifically, only when exhibiting moderate, stable or low levels of positive affect did negative affect and its trajectory relate to child ADHD symptoms. These findings add to a growing literature that suggests that infant negative emotionality is a promising early life marker of future ADHD risk and suggest secondarily that moderation by positive affectivity warrants more consideration.

Genetic influences on dopaminergic neurotransmission have been implicated in attention-deficit hyperactivity disorder (ADHD) and are theorized to impact cognitive functioning via alterations in frontal–striatal circuitry. Neuropsychological functioning has been proposed to account for the potential associations between dopamine candidate genes and ADHD. However, to date, this mediation hypothesis has not been directly tested. Participants were 498 youth ages 6–17 years (mean M = 10.8 years, SD = 2.4 years, 55.0% male). All youth completed a multistage, multiple-informant assessment procedure to identify ADHD and non-ADHD cases, as well as a comprehensive neuropsychological battery. Youth provided a saliva sample for DNA analyses; the 480 base pair variable number of tandem repeat polymorphism of the dopamine active transporter 1 gene (DAT1) and the 120 base pair promoter polymorphism of the dopamine receptor D4 gene (DRD4) were genotyped. Multiple mediation analysis revealed significant indirect associations between DAT1 genotype and inattention, hyperactivity–impulsivity, and oppositionality, with specific indirect effects through response inhibition. The results highlight the role of neurocognitive task performance, particularly response inhibition, as a potential intermediate phenotype for ADHD, further elucidating the relationship between genetic polymorphisms and externalizing psychopathology.

The domains of self-regulation, self-control, executive function, inattention, and impulsivity cut across broad swathes of normal and abnormal development. Attention-deficit/hyperactivity disorder is a common syndrome that encompasses a portion of these domains. In the past 25 years research on attention-deficit/hyperactivity disorder has been characterized by dramatic advances in genetic, neural, and neuropsychological description of the syndrome as well as clarification of its multidimensional phenotypic structure. The limited clinical applicability of these research findings poses the primary challenge for the next generation. It is likely that clinical breakthroughs will require further refinement in describing heterogeneity or clinical/biological subgroups, renewed focus on the environment in the form of etiological events as well as psychosocial contexts of development, and integration of both with biological understanding.

Difficulty with selective attention is a frequent complaint of adult patients with ADHD, but selective attention tasks have not provided robust evidence of attentional dysfunction in this group. Two experiments examine this puzzle by distinguishing between failures of spatial selection and problems due to sensitivity to perceptual interference. In Experiment 1, we measured the level of perceptual interference generated by targets in crowded displays with nearby distractors by comparing luminance thresholds in both distractor-present (noise) and distractor-absent (clean) displays. ADHD and control participants had comparable thresholds for clean displays, but ADHD individuals had elevated thresholds to crowded displays. These effects could be explained in two distinct ways. Deficits may have arisen from amplified visual interference in the noise condition, or from abnormalities in top-down attentional processes that reduce visual interference. Experiment 2 adjusted for individual perceptual differences with clean and noise displays, before measuring visual interference resolution at attended versus unattended locations. ADHD and control groups had comparable interference resolution at attended locations. These results suggest that perceptual interference rather than spatial attention deficits may account for some deficits in ADHD. This putative deficit in sensory function highlights a potential early-stage perceptual processing deficit in ADHD distinct from selective attention. (JINS, 2012, 18, 511–520)

This study first examined the respective relations of resiliency and reactive control with executive functioning. It then examined the relationship of these different domains to the development of academic and social outcomes, and to the emergence of internalizing and externalizing problem behavior in adolescence. Resiliency and reactive control were assessed from preschool to adolescence in a high-risk sample of boys and girls (n = 498) and then linked to component operations of neuropsychological executive functioning (i.e., response inhibition, interference control, fluency, working memory/set-shifting, planning, and alertness), assessed in early and late adolescence. Consistent, linear relations were found between resiliency and executive functions (average r = .17). A curvilinear relationship was observed between reactive control and resiliency, such that resiliency was weaker when reactive control was either very high or very low. In multivariate, multilevel models, executive functions contributed to academic competence, whereas resiliency and interference control jointly predicted social competence. Low resiliency, low reactive control, and poor response inhibition uniquely and additively predicted internalizing problem behavior, whereas low reactive control and poor response inhibition uniquely predicted externalizing problem behavior. Results are discussed in relation to recent trait models of regulation and the scaffolded development of competence and problems in childhood and adolescence.This work was supported by NIAAA Grant R01-AA12217 to Robert Zucker and Joel Nigg, NIAAA Grant R37-AA07065 to Robert Zucker and Hiram Fitzgerald, and NIMH Grant R01-MH59105 to Joel Nigg. We are indebted to the families and staff who made the study possible.

Attention-deficit/hyperactivity disorder (ADHD) is associated with impairments in occupational, social, and educational functioning in adults. This study examined relations of adaptive impairment to ADHD symptom domains (inattentive–disorganized and hyperactive–impulsive) and to deficits in executive functioning (EF) in 195 well-characterized adults (105 ADHD, 90 non-ADHD, between ages 18 and 37). Participants completed a battery of EF measures as well as assessments of adaptive functioning. Confirmatory factor analyses were used to validate latent factors for adaptive functioning and EF. In a measurement model, weaker EF was associated with poorer adaptive functioning (r = −.30). When multi-informant composite variables for current inattentive–disorganized and hyperactive–impulsive ADHD symptoms were included in the structural model, EF no longer predicted adaptive functioning. While both symptom composites were similarly related to EF (inattentive–disorganized r = .36; hyperactive–impulsive r = .29), inattentive–disorganized symptoms accounted for more variance in adaptive functioning (67.2% vs. 3.6%). Furthermore, for retrospectively reported childhood symptoms of ADHD, only the inattentive–disorganized symptom domain was related to EF or adaptive impairment. These results suggest that, in adults with ADHD, inattentive–disorganized symptoms may be the primary contributor to key aspects of poorer adaptive function and may be the behavioral path through which EF deficits lead to adaptive impairment. (JINS, 2007, 13, 324–334.)

We review different conceptions of inhibitory control that may be relevant to the regulatory problems featured in borderline personality disorder (BPD). These conceptions have often been framed with regard to personality traits of inhibitory control, but can also be related to cognitive measures of response suppression as well as affect regulation. Reactive behavioral inhibition is relatively unstudied in relation to BPD. A substantial amount of literature links executive function problems with BPD, but that literature has not isolated executive response inhibition nor been controlled for other personality disorder symptoms of antisociality, attention-deficit/hyperactivity disorder (ADHD), or depression, anxiety, or posttraumatic symptoms. We therefore conducted a study of this question looking at BPD symptoms in an adult sample with a small number of BPD subjects and other disorders. Results indicated that symptoms of BPD were correlated with response inhibition (measured by stop signal reaction time) even after controlling for the overlap of stop inhibition with ADHD, antisociality, and other Axis II disorder symptoms. We conclude by hypothesizing discrete developmental routes to BPD, based on different mechanism breakdowns, which would be amenable to empirical investigation at the cognitive or trait level of analysis.Portions of this work were supported by National Institute of Mental Health Grant R01-MH63146 (J.N., PI).

Attention-deficit/hyperactivity disorder (ADHD) is a behavioral syndrome that arises in early childhood, often co-occurs with conduct disorder and leads, developmentally, to antisocial behavior and substance abuse. Models from cognitive and affective neuroscience have been invoked in an effort to understand the development of ADHD, leading to a broad array of interrelated theories and hypothesized mechanisms. In this paper, we highlight core mechanisms that may cut across several theories and constructs, and thus provide some leverage for further study and conceptualization from a neuroscience perspective. We emphasize the joint operations of frontostriatal and frontocerebellar neural loops in detecting and predicting what and when important events in the environment will occur and their interaction with frontoamygdala loops in assigning emotional significance to these events. We note that weaknesses in the development of these basic operations could lead to decrement in the development of cognitive and affective control and other mental operations mediated by prefrontal cortex during development. In turn, such decrement could lead to many of the phenotypic cognitive and neuropsychological features seen in children with ADHD.This work was supported by National Institute of Mental Health Grants R01-MH59105 and R01-MH63146 to J.T.N. and NIMH R01 MH63255 and NIDA R21 DA15882 to B.J.C.

Inattention/hyperactivity and aggressive behavior problems were measured in 335 children from school entry throughout adolescence, at 3-year intervals. Children were participants in a high-risk prospective study of substance use disorders and comorbid problems. A parallel process latent growth model found aggressive behavior decreasing throughout childhood and adolescence, whereas inattentive/hyperactive behavior levels were constant. Growth mixture modeling, in which developmental trajectories are statistically classified, found two classes for inattention/hyperactivity and two for aggressive behavior, resulting in a total of four trajectory classes. Different influences of the family environment predicted development of the two types of behavior problems when the other behavior problem was held constant. Lower emotional support and lower intellectual stimulation by the parents in early childhood predicted membership in the high problem class of inattention/hyperactivity when the trajectory of aggression was held constant. Conversely, conflict and lack of cohesiveness in the family environment predicted membership in a worse developmental trajectory of aggressive behavior when the inattention/hyperactivity trajectories were held constant. The implications of these findings for the development of inattention/hyperactivity and for the development of risk for the emergence of substance use disorders are discussed.This work was supported by National Institute on Alcohol Abuse and Alcoholism grants (RO1 AA12217 to R.A.Z. and J.T.N. and R37 AA07065 to R.A.Z. and H.E.F.). We are indebted to Bengt Muthén for his advice on the statistical analyses for this study.

Although a role for family and parent factors in the development of behavioral problems in childhood is often acknowledged, the roles of specific parental characteristics in relation to specific child actions need further elucidation. We studied parental “Big Five” personality traits and psychiatric diagnoses in relation to their children's antisocial diagnoses and naturalistically observed antisocial behaviors, in boys with and without the diagnosis of Attention-Deficit Hyperactivity Disorder (ADHD). First, regardless of comorbid antisocial diagnosis, boys with ADHD, more often than comparison boys, had mothers with a major depressive episode and/or marked anxiety symptoms in the past year, and fathers with a childhood history of ADHD. Second, compared to the nondiagnosed group, boys with comorbid ADHD+Oppositional Defiant or Conduct Disorder (ODD/CD) had fathers with lower Agreeableness, higher Neuroticism, and more likelihood of having Generalized Anxiety Disorder. Third, regarding linkages between parental characteristics and child externalizing behaviors, higher rates of child overt antisocial behaviors observed in a naturalistic summer program were associated primarily with maternal characteristics, including higher Neuroticism, lower Conscientiousness, presence of Major Depression, and absence of Generalized Anxiety Disorder. The association of maternal Neuroticism with child aggression was larger in the ADHD than in the comparison group. In contrast, higher rates of observed child covert antisocial behaviors were associated solely with paternal characteristics, including history of substance abuse and higher Openness. Results provide external validation in parent data for a distinction between overt and covert antisocial behaviors and support inclusion of parent personality traits in family studies. The interaction of maternal Neuroticism and child ADHD in predicting child aggression is interpreted in regard to a conceptualization of child by parent “fit.”

Abbreviations: ADHD: Attention-Deficit Hyperactivity Disorder; CBCL: Child Behavior Checklist; CD: Conduct Disorder; DBD: Disruptive Behaviors Checklist; DIS-3-R: Diagnostic Interview Schedule for DSM-III-R; MMPI: Minnesota Multiphasic Personality Inventory; NEO-FFI: Neuroticism, Extraversion, Openness Five Factor Inventory; ODD: Oppositional Defiant Disorder; WURS: Wender Utah Rating Scale.