Dataset Information

Brain gray matter deficits at 33-year follow-up in adults with attention-deficit/hyperactivity disorder established in childhood.

ABSTRACT: Volumetric studies have reported relatively decreased cortical thickness and gray matter volumes in adults with attention-deficit/hyperactivity disorder (ADHD) whose childhood status was retrospectively recalled. We present, to our knowledge, the first prospective study combining cortical thickness and voxel-based morphometry in adults diagnosed as having ADHD in childhood.To test whether adults with combined-type childhood ADHD exhibit cortical thinning and decreased gray matter in regions hypothesized to be related to ADHD and to test whether anatomic differences are associated with a current ADHD diagnosis, including persistent vs remitting ADHD.Cross-sectional analysis embedded in a 33-year prospective follow-up at a mean age of 41.2 years.Research outpatient center.We recruited probands with ADHD from a cohort of 207 white boys aged 6 to 12 years. Male comparison participants (n = 178) were free of ADHD in childhood. We obtained magnetic resonance images in 59 probands and 80 comparison participants (28.5% and 44.9% of the original samples, respectively).Whole-brain voxel-based morphometry and vertexwise cortical thickness analyses.The cortex was significantly thinner in ADHD probands than in comparison participants in the dorsal attentional network and limbic areas (false discovery rate < 0.05, corrected). In addition, gray matter was significantly decreased in probands in the right caudate, right thalamus, and bilateral cerebellar hemispheres. Probands with persistent ADHD (n = 17) did not differ significantly from those with remitting ADHD (n = 26) (false discovery rate < 0.05). At uncorrected P < .05, individuals with remitting ADHD had thicker cortex relative to those with persistent ADHD in the medial occipital cortex, insula, parahippocampus, and prefrontal regions.Anatomic gray matter reductions are observable in adults with childhood ADHD, regardless of the current diagnosis. The most affected regions underpin top-down control of attention and regulation of emotion and motivation. Exploratory analyses suggest that diagnostic remission may result from compensatory maturation of prefrontal, cerebellar, and thalamic circuitry.

SUBMITTER: Proal E

PROVIDER: S-EPMC3554238 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Brain gray matter deficits at 33-year follow-up in adults with attention-deficit/hyperactivity disorder established in childhood.

Proal Erika E Reiss Philip T PT Klein Rachel G RG Mannuzza Salvatore S Gotimer Kristin K Ramos-Olazagasti Maria A MA Lerch Jason P JP He Yong Y Zijdenbos Alex A Kelly Clare C Milham Michael P MP Castellanos F Xavier FX

Archives of general psychiatry 20111101 11

<h4>Context</h4>Volumetric studies have reported relatively decreased cortical thickness and gray matter volumes in adults with attention-deficit/hyperactivity disorder (ADHD) whose childhood status was retrospectively recalled. We present, to our knowledge, the first prospective study combining cortical thickness and voxel-based morphometry in adults diagnosed as having ADHD in childhood.<h4>Objectives</h4>To test whether adults with combined-type childhood ADHD exhibit cortical thinning and de ...[more]

PMID: 22065528

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Project description:BackgroundMagnetic resonance imaging (MRI) is able to provide detailed insights into the structural organization of the brain, e.g., by means of mapping brain anatomy and white matter microstructure. Understanding interrelations between MRI modalities, rather than mapping modalities in isolation, will contribute to unraveling the complex neural mechanisms associated with neuropsychiatric disorders as deficits detected across modalities suggest common underlying mechanisms. Here, we conduct a multimodal analysis of structural MRI modalities in the context of attention-deficit/hyperactivity disorder (ADHD).MethodsGray matter volume, cortical thickness, surface areal expansion estimates, and white matter diffusion indices of 129 participants with ADHD and 204 participants without ADHD were entered into a linked independent component analysis. This data-driven analysis decomposes the data into multimodal independent components reflecting common inter-subject variation across imaging modalities.ResultsADHD severity was related to two multimodal components. The first component revealed smaller prefrontal volumes in participants with more symptoms, co-occurring with abnormal white matter indices in prefrontal cortex. The second component demonstrated decreased orbitofrontal volume as well as abnormalities in insula, occipital, and somato-sensory areas in participants with more ADHD symptoms.ConclusionsOur results replicate and extend previous unimodal structural MRI findings by demonstrating that prefrontal, parietal, and occipital areas, as well as fronto-striatal and fronto-limbic systems are implicated in ADHD. By including multiple modalities, sensitivity for between-participant effects is increased, as shared variance across modalities is modeled. The convergence of modality-specific findings in our results suggests that different aspects of brain structure share underlying pathophysiology and brings us closer to a biological characterization of ADHD.

Project description:OBJECTIVE:Disruptive mood dysregulation disorder (DMDD), characterized by severe irritability, and attention-deficit/hyperactivity disorder (ADHD) are highly comorbid. This is the first study to characterize neural and behavioral similarities and differences in attentional functioning across these disorders. METHOD:Twenty-seven healthy volunteers, 31 patients with DMDD, and 25 patients with ADHD (8 to 18 years old) completed a functional magnetic resonance imaging attention task. Group differences in intra-subject variability in reaction time (RT) were examined. The present functional magnetic resonance imaging analytic approach precisely quantified trial-wise associations between RT and brain activity. RESULTS:Group differences manifested in the relation between RT and brain activity (all regions: p < .01, F > 2.54, partial eta-squared [?p2] > 0.06). Patients with DMDD showed specific alterations in the right paracentral lobule, superior parietal lobule, fusiform gyrus, and cerebellar culmen. In contrast, patients with DMDD and those with ADHD exhibited blunted compensatory increases in activity on long RT trials. In addition, youth with DMDD exhibited increased activity in the postcentral gyrus, medial frontal gyrus, and cerebellar tonsil and declive (all regions: p < .05, F > 2.46, ?p2 > 0.06). Groups in the imaging sample did not differ significantly in intra-subject variability in RT (F2,79 = 2.664, p = .076, ?p2 = 0.063), although intra-subject variability in RT was significantly increased in youth with DMDD and ADHD when including those not meeting strict motion and accuracy criteria for imaging analysis (F2,96 = 4.283, p = .017, ?p2 = 0.083). CONCLUSION:Patients with DMDD exhibited specific alterations in the relation between pre-stimulus brain activity and RT. Patients with DMDD and those with ADHD exhibited similar blunting of compensatory neural activity in frontal, parietal, and other regions. In addition, patients with DMDD showed increased RT variability compared with healthy youth. This work is the first to identify common and unique behavioral and neural signatures of DMDD and ADHD.

Dataset Information

Brain gray matter deficits at 33-year follow-up in adults with attention-deficit/hyperactivity disorder established in childhood.

Publications

Brain gray matter deficits at 33-year follow-up in adults with attention-deficit/hyperactivity disorder established in childhood.

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