Faculty Bibliography

The authors examined the neuropsychological status of 22 preschoolers at risk for attention-deficit/hyperactivity disorder (ADHD) and 50 matched control children, using measures of nonverbal working memory, perceptual and motor inhibition, and memory for relative time. All tasks included paired control conditions, which allowed for the isolation of discrete executive function constructs. Group differences were evident on several measures of neuropsychological functioning; however, after accounting for nonexecutive abilities, no deficits could be attributed to specific functions targeted by the tasks. Performance on executive measures was not related to objective indices of activity level or ratings of ADHD symptoms. Yet, the fact that at-risk preschoolers were highly symptomatic casts doubt on whether executive function deficits and/or frontostriatal networks contribute etiologically to early behavioral manifestations of ADHD.

CONTEXT: While numerous magnetic resonance imaging (MRI) studies have evaluated adults with bipolar disorder (BPD), few have examined MRI changes in children with BPD. OBJECTIVE: To determine volume alterations in children with BPD using voxel-based morphometry, an automated MRI analysis method with reduced susceptibility to various biases. A priori regions of interest included amygdala, accumbens, hippocampus, dorsolateral prefrontal cortex (DLPFC), and orbitofrontal cortex. DESIGN: Ongoing study of the pathophysiology of pediatric BPD. SETTING: Intramural National Institute of Mental Health; approved by the institutional review board.Patients Pediatric subjects with BPD (n = 20) with at least 1 manic or hypomanic episode meeting strict DSM-IV criteria for duration and elevated, expansive mood. Controls (n = 20) and their first-degree relatives lacked psychiatric disorders. Groups were matched for age and sex and did not differ in IQ. MAIN OUTCOME MEASURES: With a 1.5-T MRI machine, we collected 1.2-mm axial sections (124 per subject) with an axial 3-dimensional spoiled gradient recalled echo in the steady state sequence. Image analysis was by optimized voxel-based morphometry. RESULTS: Subjects with BPD had reduced gray matter volume in the left DLPFC. With a less conservative statistical threshold, additional gray matter reductions were found in the left accumbens and left amygdala. No difference was found in the hippocampus or orbitofrontal cortex. CONCLUSIONS: Our results are consistent with data implicating the prefrontal cortex in emotion regulation, a process that is perturbed in BPD. Reductions in amygdala and accumbens volumes are consistent with neuropsychological data on pediatric BPD. Further study is required to determine the relationship between these findings in children and adults with BPD

In this event-related functional magnetic resonance imaging (fMRI) study, we provide evidence that the role of the anterior cingulate cortex (ACC) in cognitive control may not be unitary, as the responses of different ACC subregions vary depending upon the nature of task-irrelevant information. More specifically, using the color-word Stroop task (congruent, incongruent, and neutral trial types), we examined the degree to which increases in neural activity within ACC are specific to conditions of conflict, as posited by the conflict monitoring theory (Botvinick et al. [1999]: Rev Neurosci 10:49-57; Carter et al. [1998]: Science 280:747-749). Although incongruent and congruent trials both involve two competing sources of color information (color word and ink color), only incongruent trials involve a direct conflict between task-relevant and task-irrelevant information. Although the anterior division of the ACC rostral zone exhibited conflict specific increases in neural activity (i.e., incongruent > congruent = neutral), the posterior division exhibited a more generalized pattern, increasing whenever the task-irrelevant information was color related, regardless of whether it was conflicting (i.e., incongruent and congruent > neutral). Our data thus suggest a possible functional differentiation within the ACC. As such, it is unlikely that the role of the ACC in cognitive control will be able to be accommodated by a single unifying theory

The purpose of this study was to understand the impact of community-level stressors (particularly violence), coping strategies, and resources to prevent exposure to violence or to mitigate its effects in an inner-city community. Parents and children participated in focus groups, and children also completed standardized instruments. In the focus groups, parents and children identified several areas of concern related to "helpers," schools, community safety, and emotional distress. They identified protective resources including intensive monitoring and social supports. Fifty percent of the children met criteria for Posttraumatic Stress Disorder (PTSD), and another 21% met criteria for partial PTSD. The mental health issues in children living with ongoing community violence necessitate that researchers use a qualitative approach to inform future interventions.

In the present study, we examined the role of the auditory thalamus [medial division of the medial geniculate nucleus and the adjacent posterior intralaminar nucleus (MGm/PIN)] in auditory pavlovian fear conditioning using pharmacological manipulation of intracellular signaling pathways. In the first experiment, rats were given intrathalamic infusions of the MEK (mitogen-activated protein kinase-kinase) inhibitor 1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto) butadiene (U0126) before fear conditioning. Findings revealed that long-term memory (assessed at 24 h) was impaired, whereas short-term memory (assessed at 1-3 h) of fear conditioning was intact. In the second experiment, rats received immediate posttraining intrathalamic infusion of U0126, the mRNA synthesis inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), or infusion of the protein synthesis inhibitor anisomycin. Posttraining infusion of either U0126 or DRB significantly impaired long-term retention of fear conditioning, whereas infusion of anisomycin had no effect. In the final experiment, rats received intrathalamic infusion of U0126 before long-term potentiation (LTP)-inducing stimulation of thalamic inputs to the lateral nucleus of the amygdala (LA). Findings revealed that thalamic infusion of U0126 impaired LTP in the LA. Together, these results suggest the possibility that MGm/PIN cells that project to the LA contribute to memory formation via ERK (extracellular signal-regulated kinase)-mediated transcription, but that they do so by promoting protein synthesis-dependent plasticity locally in the LA

BACKGROUND: Despite growing interest in adult attention-deficit/hyperactivity disorder (ADHD), little is known about predictors of persistence of childhood cases into adulthood. METHODS: A retrospective assessment of childhood ADHD, childhood risk factors, and a screen for adult ADHD were included in a sample of 3197 18-44 year old respondents in the National Comorbidity Survey Replication (NCS-R). Blinded adult ADHD clinical reappraisal interviews were administered to a sub-sample of respondents. Multiple imputation (MI) was used to estimate adult persistence of childhood ADHD. Logistic regression was used to study retrospectively reported childhood predictors of persistence. Potential predictors included socio-demographics, childhood ADHD severity, childhood adversity, traumatic life experiences, and comorbid DSM-IV child-adolescent disorders (anxiety, mood, impulse-control, and substance disorders). RESULTS: Blinded clinical interviews classified 36.3% of respondents with retrospectively assessed childhood ADHD as meeting DSM-IV criteria for current ADHD. Childhood ADHD severity and childhood treatment significantly predicted persistence. Controlling for severity and excluding treatment, none of the other variables significantly predicted persistence even though they were significantly associated with childhood ADHD. CONCLUSIONS: No modifiable risk factors were found for adult persistence of ADHD. Further research, ideally based on prospective general population samples, is needed to search for modifiable determinants of adult persistence of ADHD

Before assigning full etiologic validity to a psycopathologic disorder, disease theory suggests that a causal dysfunction in a mechanism within the affect individuals must be identified. Existing theories on attention-deficit/hyperactivity disorder (ADHD) suggest such dysfunctions in cognitive, neuropsychological, or motivational processes in the child. To date, researchers have tested these theories by comparing groups with DSM-defined ADHD to children without ADHD. Using executive functioning as an illustration of an issue that exists across all such theories, this article describes substantial overlaps in the group performance data. Thus only a subgroup may have executive deficits. Noted are other supportive data suggesting multiple pathways to ADHD. The article explores implications and recommends that future theory and research give more consideration to the probability that only a subset of behaviorally defined children will have a deficit in a given neurocognitive mechanism believed to contribute to the disorder. Creation of a provisional set of criteria in DSM-V for defining an 'executive deficit type' could stimulate research to validate the first etiologic subtype of ADHD and spur the development of more sophisticated causal models, which in the longer term may give clinicians ways to target and tailor treatments