Longitudinal trajectories of childhood and adolescent attention deficit hyperactivity disorder diagnoses in three cohorts.

Background: Attention deficit/hyperactivity disorder (ADHD) is usually conceptualized as a childhood-onset neurodevelopmental disorder, in which symptoms either decrease steadily into adulthood or remain stable. A recent study challenged this view, reporting that for most with ADHD, diagnostic status fluctuates with age. We ask if such a 'fluctuating' ADHD symptom trajectory subgroup is present in other population-based and clinic-based cohorts, centered on childhood and adolescence.

Mapping the cortico-striatal transcriptome in attention deficit hyperactivity disorder.

Despite advances in identifying rare and common genetic variants conferring risk for ADHD, the lack of a transcriptomic understanding of cortico-striatal brain circuitry has stymied a molecular mechanistic understanding of this disorder. To address this gap, we mapped the transcriptome of the caudate nucleus and anterior cingulate cortex in post-mortem tissue from 60 individuals with and without ADHD. Significant differential expression of genes was found in the anterior cingulate cortex and, to a lesser extent, the caudate.

A Longitudinal Study of Resting-State Connectivity and Response to Psychostimulant Treatment in ADHD.

Objective: Psychostimulants are first-line pharmacological treatments for attention deficit hyperactivity disorder (ADHD), although symptom reduction varies widely between patients and these individual differences in treatment response are poorly understood. The authors sought to examine whether the resting-state functional connectivity within and between cingulo-opercular, striato-thalamic, and default mode networks was associated with treatment response to psychostimulant medication, and whether this relationship changed with development.

Methods: Patients with ADHD (N=110; 196 observations; mean age at first observation, 10.

An examination of the relationships between attention/deficit hyperactivity disorder symptoms and functional connectivity over time.

Previous cross-sectional work has demonstrated resting-state connectivity abnormalities in children and adolescents with attention/deficit hyperactivity disorder (ADHD) relative to typically developing controls. However, it is unclear to what extent these neural abnormalities confer risk for later symptoms of the disorder, or represent the downstream effects of symptoms on functional connectivity. Here, we studied 167 children and adolescents (mean age at baseline = 10.

Predicting the course of ADHD symptoms through the integration of childhood genomic, neural, and cognitive features.

Childhood attention deficit hyperactivity disorder (ADHD) shows a highly variable course with age: some individuals show improving, others stable or worsening symptoms. The ability to predict symptom course could help individualize treatment and guide interventions. By studying a cohort of 362 youth, we ask if polygenic risk for ADHD, combined with baseline neural and cognitive features could aid in the prediction of the course of symptoms over an average period of 4.

Estimating the Heritability of Developmental Change in Neural Connectivity, and Its Association With Changing Symptoms of Attention-Deficit/Hyperactivity Disorder.

Background: Twin studies show that age-related change in symptoms of attention-deficit/hyperactivity disorder (ADHD) is heritable. However, we do not know the heritability of the development of the neural substrates underlying the disorder. Here, we estimated the heritability of developmental change in white matter tracts and the brain's intrinsic functional connectivity using longitudinal data.

Using virtual reality to define the mechanisms linking symptoms with cognitive deficits in attention deficit hyperactivity disorder.

The mechanisms underpinning attentional deficits are only partially understood. Here we ask if shifts in a child's field of view (FOV) act as a mediator between symptoms of attention deficit hyperactivity disorder (ADHD) and associated cognitive anomalies, particularly in attentional processes. Real time measurement of shifts in FOV were obtained on 85 children (mean age 9.

Associations between neighborhood, family factors and symptom change in childhood attention deficit hyperactivity disorder.

Transactional theories view development as partly shaped by processes proximal to a child, which in turn interact with more distal neighborhood and societal contexts. Here we apply this theory to parse the interplay between neighborhood and familial factors on age-related change in symptoms of inattention and hyperactivity-impulsivity (ADHD). A cohort of 190 children (96 with ADHD) had a range of neighborhood and familial factors ascertained and had repeated clinical assessments over an average of 2.

Mapping associations between polygenic risks for childhood neuropsychiatric disorders, symptoms of attention deficit hyperactivity disorder, cognition, and the brain.

There are now large-scale data on which common genetic variants confer risk for attention deficit hyperactivity disorder (ADHD). Here, we use mediation analyses to explore how cognitive and neural features might explain the association between common variant (polygenic) risk for ADHD and its core symptoms. In total, 544 participants participated (mean 21 years, 212 (39%) with ADHD), most with cognitive assessments, neuroanatomic imaging, and imaging of white matter tract microstructure.

Mapping the neuroanatomic substrates of cognition in familial attention deficit hyperactivity disorder.

Background: While the neuroanatomic substrates of symptoms of attention deficit hyperactivity disorder (ADHD) have been investigated, less is known about the neuroanatomic correlates of cognitive abilities pertinent to the disorder, particularly in adults. Here we define the neuroanatomic correlates of key cognitive abilities and determine if there are associations with histories of psychostimulant medication.

Methods: We acquired neuroanatomic magnetic resonance imaging data from 264 members of 60 families (mean age 29.

Genetic associations with childhood brain growth, defined in two longitudinal cohorts.

Genome-wide association studies (GWASs) are unraveling the genetics of adult brain neuroanatomy as measured by cross-sectional anatomic magnetic resonance imaging (aMRI). However, the genetic mechanisms that shape childhood brain development are, as yet, largely unexplored. In this study we identify common genetic variants associated with childhood brain development as defined by longitudinal aMRI.

Multimodal mapping of the brain's functional connectivity and the adult outcome of attention deficit hyperactivity disorder.

We have a limited understanding of why many children with attention deficit hyperactivity disorder do not outgrow the disorder by adulthood. Around 20-30% retain the full syndrome as young adults, and about 50% show partial, rather than complete, remission. Here, to delineate the neurobiology of this variable outcome, we ask if the persistence of childhood symptoms into adulthood impacts on the brain's functional connectivity.

Defining the Neural Substrate of the Adult Outcome of Childhood ADHD: A Multimodal Neuroimaging Study of Response Inhibition.

Objective: Understanding the neural processes tied to the adult outcome of childhood attention deficit hyperactivity disorder (ADHD) could guide novel interventions to improve its clinical course. It has been argued that normalization of prefrontal cortical activity drives remission from ADHD, while anomalies in subcortical processes are "fixed," present even in remission. Using multimodal neuroimaging of inhibitory processes, the authors tested these hypotheses in adults followed since childhood, contrasting remitted against persistent ADHD.

Estimating the Heritability of Structural and Functional Brain Connectivity in Families Affected by Attention-Deficit/Hyperactivity Disorder.

Importance: Despite its high heritability, few risk genes have been identified for attention-deficit/hyperactivity disorder (ADHD). Brain-based phenotypes could aid gene discovery. There is a myriad of structural and functional connections that support cognition.

White matter microstructure and the variable adult outcome of childhood attention deficit hyperactivity disorder.

Changes in cerebral cortical anatomy have been tied to the clinical course of attention deficit hyperactivity disorder (ADHD). We now ask if alterations in white matter tract microstructure are likewise linked with the adult outcome of childhood ADHD. Seventy-five young adults, 32 with ADHD persisting from childhood and 43 with symptom remission were contrasted against 74 never-affected comparison subjects.

Mapping the development of the basal ganglia in children with attention-deficit/hyperactivity disorder.

Objective: The basal ganglia are implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD), but little is known of their development in the disorder. Here, we mapped basal ganglia development from childhood into late adolescence using methods that define surface morphology with an exquisite level of spatial resolution.

Method: Surface morphology of the basal ganglia was defined from neuroanatomic magnetic resonance images acquired in 270 youth with DSM-IV-defined ADHD and 270 age- and sex-matched typically developing controls; 220 individuals were scanned at least twice.

Trajectories of cerebral cortical development in childhood and adolescence and adult attention-deficit/hyperactivity disorder.

Background: Childhood attention-deficit/hyperactivity disorder (ADHD) persists into adulthood in around half of those affected, constituting a major public health challenge. No known demographic, clinical, or neuropsychological factors robustly explain the clinical course, directing our focus to the brain. Herein, we link the trajectories of cerebral cortical development during childhood and adolescence with the severity of adult ADHD.

Development of cortical surface area and gyrification in attention-deficit/hyperactivity disorder.

Background: Delineation of the cortical anomalies underpinning attention-deficit/hyperactivity disorder (ADHD) can powerfully inform pathophysiological models. We previously found that ADHD is characterized by a delayed maturation of prefrontal cortical thickness. We now ask if this extends to the maturation of cortical surface area and gyrification.

Developmental trajectories of the corpus callosum in attention-deficit/hyperactivity disorder.

Background: It was recently found that the development of typical patterns of prefrontal, but not posterior, cortical asymmetry is disrupted in right-handed youth with attention-deficit/hyperactivity disorder (ADHD). Using longitudinal data, we tested the hypothesis that there would be a congruent disruption in the growth of the anterior corpus callosum, which contains white matter tracts connecting prefrontal cortical regions.

Methods: Areas of five subregions of the corpus callosum were quantified using a semiautomated method from 828 neuroanatomic magnetic resonance scans acquired from 236 children and adolescents with ADHD (429 scans) and 230 typically developing youth (399 scans), most of whom had repeated neuroimaging.

Cortical development in typically developing children with symptoms of hyperactivity and impulsivity: support for a dimensional view of attention deficit hyperactivity disorder.

Objective: There is considerable epidemiological and neuropsychological evidence that attention deficit hyperactivity disorder (ADHD) is best considered dimensionally, lying at the extreme end of a continuous distribution of symptoms and underlying cognitive impairments. The authors investigated whether cortical brain development in typically developing children with symptoms of hyperactivity and impulsivity resembles that found in the syndrome of ADHD. Specifically, they examined whether a slower rate of cortical thinning during late childhood and adolescence, which they previously found in ADHD, is also linked to the severity of symptoms of hyperactivity and impulsivity in typically developing children.

Development of cortical asymmetry in typically developing children and its disruption in attention-deficit/hyperactivity disorder.

Context: Just as typical development of anatomical asymmetries in the human brain has been linked with normal lateralization of motor and cognitive functions, disruption of asymmetry has been implicated in the pathogenesis of neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD). No study has examined the development of cortical asymmetry using longitudinal neuroanatomical data.

Objective: To delineate the development of cortical asymmetry in children with and without ADHD.

Psychostimulant treatment and the developing cortex in attention deficit hyperactivity disorder.

Objective: While there has been considerable concern over possible adverse effects of psychostimulants on brain development, this issue has not been examined in a prospective study. The authors sought to determine prospectively whether psychostimulant treatment for attention deficit hyperactivity disorder (ADHD) was associated with differences in the development of the cerebral cortex during adolescence.

Method: Change in cortical thickness was estimated from two neuroanatomic MRI scans in 43 youths with ADHD.

Dynamic mapping of cortical development before and after the onset of pediatric bipolar illness.

Background: There are, to date, no pre-post onset longitudinal imaging studies of bipolar disorder at any age. We report the first prospective study of cortical brain development in pediatric bipolar illness for 9 male children, visualized before and after illness onset.

Method: We contrast this pattern with that observed in a matched group of healthy children as well as in a matched group of 8 children with 'atypical psychosis' who had similar initial presentation marked by mood dysregulation and transient psychosis (labeled as 'multi-dimensionally impaired' (MDI)) as in the bipolar group, but have not, to date, developed bipolar illness.

Polymorphisms of the dopamine D4 receptor, clinical outcome, and cortical structure in attention-deficit/hyperactivity disorder.

Context: Attention-deficit/hyperactivity disorder (ADHD) is one of the most heritable neuropsychiatric disorders, and a polymorphism within the dopamine D4 receptor (DRD4) gene has been frequently implicated in its pathogenesis.

Objective: To examine the effects of the 7-repeat microsatellite in the DRD4 gene on clinical outcome and cortical development in ADHD. We drew comparisons with a single nucleotide polymorphism in the dopamine D1 receptor (DRD1) gene, which was associated with ADHD within our cohort, and a polymorphism within the dopamine transporter (DAT1) gene, reported to have additive effects with the DRD4 7-repeat allele.

Cortical brain development in nonpsychotic siblings of patients with childhood-onset schizophrenia.

Context: Cortical gray matter (GM) loss is marked and progressive in childhood-onset schizophrenia (COS) during adolescence but becomes more circumscribed by early adulthood. Nonpsychotic siblings of COS probands could help evaluate whether the cortical GM abnormalities are familial/trait markers.

Objective: To map cortical development in nonpsychotic siblings of COS probands.