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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.
Mechanistic endophenotypes can inform process models of psychopathology and aid interpretation of genetic risk factors. Smaller total brain and subcortical volumes are associated with attention-deficit hyperactivity disorder (ADHD) and provide clues to its development. This study evaluates whether common genetic risk for ADHD is associated with total brain volume (TBV) and hypothesized subcortical structures in children.
Children 7–15 years old were recruited for a case–control study (N = 312, N = 199 ADHD). Children were assessed with a multi-informant, best-estimate diagnostic procedure and motion-corrected MRI measured brain volumes. Polygenic scores were computed based on discovery data from the Psychiatric Genomics Consortium (N = 19 099 ADHD, N = 34 194 controls) and the ENIGMA + CHARGE consortium (N = 26 577).
ADHD was associated with smaller TBV, and altered volumes of caudate, cerebellum, putamen, and thalamus after adjustment for TBV; however, effects were larger and statistically reliable only in boys. TBV was associated with an ADHD polygenic score [β = −0.147 (−0.27 to −0.03)], and mediated a small proportion of the effect of polygenic risk on ADHD diagnosis (average ACME = 0.0087, p = 0.012). This finding was stronger in boys (average ACME = 0.019, p = 0.008). In addition, we confirm genetic variation associated with whole brain volume, via an intracranial volume polygenic score.
Common genetic risk for ADHD is not expressed primarily as developmental alterations in subcortical brain volumes, but appears to alter brain development in other ways, as evidenced by TBV differences. This is among the first demonstrations of this effect using molecular genetic data. Potential sex differences in these effects warrant further examination.
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
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