Dataset Information

Gray matter alterations in adults with attention-deficit/hyperactivity disorder identified by voxel based morphometry.

ABSTRACT:

Background

Gray and white matter volume deficits have been reported in many structural magnetic resonance imaging (MRI) studies of children with attention-deficit/hyperactivity disorder (ADHD); however, there is a paucity of structural MRI studies of adults with ADHD. This study used voxel based morphometry and applied an a priori region of interest approach based on our previous work, as well as from well-developed neuroanatomical theories of ADHD.

Methods

Seventy-four adults with DSM-IV ADHD and 54 healthy control subjects comparable on age, sex, race, handedness, IQ, reading achievement, frequency of learning disabilities, and whole brain volume had an MRI on a 1.5T Siemens scanner. A priori region of interest hypotheses focused on reduced volumes in ADHD in dorsolateral prefrontal cortex, anterior cingulate cortex, caudate, putamen, inferior parietal lobule, and cerebellum. Analyses were carried out by FSL-VBM 1.1.

Results

Relative to control subjects, ADHD adults had significantly smaller gray matter volumes in parts of six of these regions at p ≤ .01, whereas parts of the dorsolateral prefrontal cortex and inferior parietal lobule were significantly larger in ADHD at this threshold. However, a number of other regions were smaller and larger in ADHD (especially fronto-orbital cortex) at this threshold. Only the caudate remained significantly smaller at the family-wise error rate.

Conclusions

Adults with ADHD have subtle volume reductions in the caudate and possibly other brain regions involved in attention and executive control supporting frontostriatal models of ADHD. Modest group brain volume differences are discussed in the context of the nature of the samples studied and voxel based morphometry methodology.

SUBMITTER: Seidman LJ

PROVIDER: S-EPMC3940267 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Publications

Gray matter alterations in adults with attention-deficit/hyperactivity disorder identified by voxel based morphometry.

Seidman Larry J LJ Biederman Joseph J Liang Lichen L Valera Eve M EM Monuteaux Michael C MC Brown Ariel A Kaiser Jonathan J Spencer Thomas T Faraone Stephen V SV Makris Nikos N

Biological psychiatry 20101223 9

<h4>Background</h4>Gray and white matter volume deficits have been reported in many structural magnetic resonance imaging (MRI) studies of children with attention-deficit/hyperactivity disorder (ADHD); however, there is a paucity of structural MRI studies of adults with ADHD. This study used voxel based morphometry and applied an a priori region of interest approach based on our previous work, as well as from well-developed neuroanatomical theories of ADHD.<h4>Methods</h4>Seventy-four adults wit ...[more]

PMID: 21183160

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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:PurposePresently, research concerning alterations in brain structure among individuals with attention deficit hyperactivity disorder (ADHD) predominantly focuses on entire brain volume and cortical thickness. In this study, we extend our examination to the cortical microstructure of male children with ADHD. To achieve this, we employ the gray-white matter tissue contrast (GWC) metric, allowing for an assessment of modifications in gray matter density and white matter microstructure. Furthermore, we explore the potential connection between GWC and the severity of disorder in male children by ADHD.MethodsWe acquired 3DT1 sequences from the public ADHD-200 database. In this study, we conducted a comparative analysis between 43 male children diagnosed with ADHD and 50 age-matched male controls exhibiting typical development trajectories. Our investigation entailed assessing differences in GWC and cortical thickness. Additionally, we explored the potential correlation between GWC and the severity of ADHD. To delineate the cerebral landscape, each hemisphere was subdivided into 34 cortical regions using freesurfer 7.2.0. For quantification, GWC was computed by evaluating the intensity contrast of non-normalized T1 images above and below the gray-white matter interface.ResultsOur findings unveiled elevated GWC within the bilateral lingual, bilateral insular, left transverse temporal, right parahippocampal and right pericalcarine regions in male children with ADHD when contrasted with their healthy counterparts. Moreover, the cortical thickness in the ADHD group no notable distinctions that of control group in all areas. Intriguingly, the GWC of left transverse temporal demonstrated a negative correlation with the extent of inattention experienced by male children with ADHD.ConclusionUtilizing GWC as a metric facilitates a more comprehensive assessment of microstructural brain changes in children with ADHD. The fluctuations in GWC observed in specific brain regions might serve as a neural biomarker, illuminating structural modifications in male children grappling with ADHD. This perspective enriches our comprehension of white matter microstructure and cortical density in these children. Notably, the inverse correlation between the GWC of the left transverse temporal and inattention severity underscores the potential role of structural and functional anomalies within this region in ADHD progression. Enhancing our insight into ADHD-related brain changes holds significant promise in deciphering potential neuropathological mechanisms.

Project description:Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder, with onset in childhood and a considerable likelihood to persist into adulthood. Our previous work has identified that across adults and adolescents with ADHD, gray matter volume (GMV) alteration in the frontal cortex was consistently associated with working memory underperformance, and GMV alteration in the cerebellum was associated with inattention. Recent knowledge regarding ADHD genetic risk loci makes it feasible to investigate genomic factors underlying these persistent GMV alterations, potentially illuminating the pathology of ADHD persistence. Based on this, we applied a sparsity-constrained multivariate data fusion approach, sparse parallel independent component analysis, to GMV variations in the frontal and cerebellum regions and candidate risk single nucleotide polymorphisms (SNPs) data from 341 unrelated adult participants, including 167 individuals with ADHD, 47 unaffected siblings, and 127 healthy controls. We identified one SNP component significantly associated with one GMV component in superior/middle frontal regions and replicated this association in 317 adolescents from ADHD families. The association was stronger in individuals with ADHD than in controls, and stronger in adults and older adolescents than in younger ones. The SNP component highlights 93 SNPs in long non-coding RNAs mainly in chromosome 5 and 21 protein-coding genes that are significantly enriched in human neuron cells. Eighteen identified SNPs have regulation effects on gene expression, transcript expression, isoform percentage, or methylation level in frontal regions. Identified genes highlight MEF2C, CADM2, and CADPS2, which are relevant for modulating neuronal substrates underlying high-level cognition in ADHD, and their causality effects on ADHD persistence await further investigations. Overall, through a multivariate analysis, we have revealed a genomic pattern underpinning the frontal gray matter variation related to working memory deficit in ADHD.

Dataset Information

Gray matter alterations in adults with attention-deficit/hyperactivity disorder identified by voxel based morphometry.

Background

Methods

Results

Conclusions

Publications

Gray matter alterations in adults with attention-deficit/hyperactivity disorder identified by voxel based morphometry.

Similar Datasets

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