Structural brain change in Attention Deficit Hyperactivity Disorder identified by meta-analysis

Avon and Wiltshire Mental Health Partnership NHS Trust, Salisbury, UK.
BMC Psychiatry (Impact Factor: 2.21). 02/2008; 8(1):51. DOI: 10.1186/1471-244X-8-51
Source: PubMed


The authors sought to map gray matter changes in Attention Deficit Hyperactivity Disorder (ADHD) using a novel technique incorporating neuro-imaging and genetic meta-analysis methods.
A systematic search was conducted for voxel-based structural magnetic resonance imaging studies of patients with ADHD (or with related disorders) in relation to comparison groups. The authors carried out meta-analyses of the co-ordinates of gray matter differences. For the meta-analyses they hybridised the standard method of Activation Likelihood Estimation (ALE) with the rank approach used in Genome Scan Meta-Analysis (GSMA). This system detects three-dimensional conjunctions of co-ordinates from multiple studies and permits the weighting of studies in relation to sample size.
For gray matter decreases, there were 7 studies including a total of 114 patients with ADHD (or related disorders) and 143 comparison subjects. Meta-analysis of these studies identified a significant regional gray matter reduction in ADHD in the right putamen/globus pallidus region. Four studies reported gray matter increases in ADHD but no regional increase was identified by meta-analysis.
In ADHD there is gray matter reduction in the right putamen/globus pallidus region. This may be an anatomical marker for dysfunction in frontostriatal circuits mediating cognitive control. Right putamen lesions have been specifically associated with ADHD symptoms after closed head injuries in children.

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    • "The highest accuracy achieved using structural MRI, 79%, was associated with brain regions which included the caudate, ventral striatum/ putamen, insula, brainstem, thalamus, hypothalamus, precuneus/cuneus , hippocampus, amygdala, cerebellar vermis and inferior, and superior parietal regions [Lim et al., 2013]. Studies using non-prediction group level analysis methods have provided evidence for subtle reductions in total brain volume in ADHD [Castellanos et al., 2002] and consistent evidence for basal ganglia gray matter reductions [Ellison-Wright et al., 2008; Frodl and Skokauskas, 2012; Nakao et al., 2011]. Caudate reductions may normalize as a child matures toward adulthood [Castellanos et al., 2002], which may be clinically relevant as the caudate is associated with motor activity, and there is often a relative reduction in hyperactivity later in development. "
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    • "The release of anonymised image data by a number of research groups allows testing of different image analysis methods. The results of published studies can be combined either by meta-analysis of co-ordinates (e.g. using techniques such as ALE, [93], SDM, [94], or GSMA, [95]) or changes quantified within parcellated brain regions. The latter will require publication of results, as in this study, according to standard white matter atlases. "
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    • "Our own results demonstrating functional connectivity between caudate nucleus and MFG in ADHD children during WM are in agreement with this hypothesis. Additionally, morphometric MRI studies have found larger anatomical differences between ADHD and Controls in a set of regions including the right caudate, although between-study discrepancies make results globally inconsistent [13], [36]. Still, significant reductions in both right and left ventro-striatal volumes provide neuroanatomical evidence of alterations in the ventral striatum of ADHD children [37]. "
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