Cubillo A, Rubia K. Structural and functional brain imaging in adult attention-deficit/hyperactivity disorder. Expert Rev Neurother 10: 603-620

Department of Child Psychiatry/SGDP, P046, Institute of Psychiatry, 16 De Crespigny Park, London, SE5 8AF, UK.
Expert Review of Neurotherapeutics (Impact Factor: 2.78). 04/2010; 10(4):603-20. DOI: 10.1586/ern.10.4
Source: PubMed


Attention-deficit/hyperactivity disorder (ADHD) is a childhood disorder that persists into adulthood. Nevertheless, there are far fewer imaging studies in adult compared with childhood ADHD. Here we review the imaging literature on brain structure, function and structural and functional connectivity in adult ADHD, as well as the effects of psychostimulants on brain dysfunctions. Importantly, we discuss similarities and differences between these deficit findings and those in childhood ADHD to address the key question of continuity of brain abnormalities into adulthood. Findings show strikingly similar but more inconsistent abnormalities in adult ADHD in key childhood ADHD deficit areas of frontostriatal, temporoparietal and cerebellar regions, presumably due to highly prevalent confounding factors in adult ADHD of elevated rates of comorbidity and medication history.

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    • "Conversely, there are other studies in adults that show increased activation throughout the frontal, parietal and occipital lobes during tasks of executive function (Hale et al. 2007, Banich et al. 2009, Dibbets et al. 2010). It has been hypothesized that inconsistencies across studies of adult ADHD, as compared to child/adolescent ADHD, may be due to confounding factors such as the need for retrospective diagnoses, medication effects, symptom remission and comorbid disorders (Cubillo and Rubia 2010). "
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    ABSTRACT: An important characteristic of childhood attention-deficit/hyperactivity disorder (ADHD) is a bias towards small immediate versus larger delayed rewards, but it is not known if this symptom is also a feature of adult ADHD. A delay-discounting task was administered to participants with adult ADHD and a comparison group in conjunction with functional magnetic resonance imaging. Participants responded to a series of questions that required judgments between small sums of money available immediately and larger sums obtained after a temporal delay. Question parameters were adjusted by an adaptive algorithm designed to converge on each participant’s discounting indifference point, an individual set point at which there is equal valuation of both choices. In all participants, robust task activation was observed in regions previously identified in functional imaging studies of delay discounting. However, adults with ADHD showed less task activation in a number of regions including the dorsolateral prefrontal cortex, superior frontal gyrus, anterior cingulate, caudate nucleus and declive of the cerebellum. Additionally, the degree to which a participant discounted delayed rewards was inversely related to task activation in the cerebellum. The results suggest that the bias towards immediate rewards in childhood ADHD may not persist behaviorally, but instead present in adulthood as alterations in frontostriatal and frontocerebellar networks.
    Acta neurobiologiae experimentalis 10/2015; 75(3):2015. · 1.29 Impact Factor
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    • "These reports also reveal reduced grey matter volume in the caudate nucleus (Almeida Montes et al. 2010) and, specifically in women, reduced grey matter density in the right cerebellum (Almeida Montes et al. 2011) in these individuals. Other studies have found decreased volume and/or cortical thickness in the orbitofrontal, dorsolateral, and anterior and posterior cingulate regions (Cubillo and Rubia 2010; Makris et al. 2007). "
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    ABSTRACT: Response inhibition deficits are widely believed to be at the core of Attention-Deficit Hyperactivity Disorder (ADHD). Several studies have examined neural architectural correlates of ADHD, but research directly examining structural correlates of response inhibition is lacking. Here we examine the relationship between response inhibition as measured by a Go/No Go task, and cortical surface area and thickness of the caudal inferior frontal gyrus (cIFG), a region implicated in functional imaging studies of response inhibition, in a sample of 114 young adults with and without ADHD diagnosed initially during childhood. We used multiple linear regression models to test the hypothesis that Go/No Go performance would be associated with cIFG surface area or thickness. Results showed that poorer Go/No Go performance was associated with thicker cIFG cortex, and this effect was not mediated by ADHD status or history of substance use. However, independent of Go/No Go performance, persistence of ADHD symptoms and more frequent cannabis use were associated with thinner cIFG. Go/No Go performance was not associated with cortical surface area. The association between poor inhibitory functioning and thicker cIFG suggests that maturation of this region may differ in low performing participants. An independent association of persistent ADHD symptoms and frequent cannabis use with thinner cIFG cortex suggests that distinct neural mechanisms within this region may play a role in inhibitory function, broader ADHD symptomatology, and cannabis use. These results contribute to Research Domain Criteria (RDoC) by revealing novel associations between neural architectural phenotypes and basic neurobehavioral processes measured dimensionally.
    Brain Imaging and Behavior 09/2015; DOI:10.1007/s11682-015-9453-x · 4.60 Impact Factor
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    • "We specified our regions of interest using the WFU pickatlas (Maldjian et al. 2003). These regions included the frontal lobe, caudate nucleus and the cerebellum selected based on information on FBXO33 gene expression in combination with knowledge of brain regions implicated in ADHD (Cubillo and Rubia, 2010). "
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    ABSTRACT: Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with high heritability. At least 30% of patients diagnosed in childhood continue to suffer ADHD during adulthood and genetic risk factors may play an essential role in the persistence of the disorder throughout lifespan. To date, Genome-Wide Association Studies (GWAS) of ADHD have been completed in seven independent datasets, six of which were pediatric samples and one on persistent ADHD using a DNA-pooling strategy, but none of them reported genome-wide significant associations. In an attempt to unravel novel genes for the persistence of ADHD into adulthood, we conducted the first two-stage GWAS in adults with ADHD. The discovery sample included 607 ADHD cases and 584 controls. Top signals were subsequently tested for replication in three independent follow-up samples of 2,104 ADHD patients and 1,901 controls. None of the findings exceeded the genome-wide threshold for significance (PGC<5e-08), but we found evidence for the involvement of the FBXO33 gene in combined ADHD in the discovery sample (P=9.02e-07) and in the joint analysis of both stages (P=9.7e-03). Additional evidence for a FBXO33 role in ADHD was found through gene-wise and pathway enrichment analyses in our genomic study. Risk alleles were associated with lower FBXO33 expression in lymphoblastoid cell lines and with reduced frontal grey matter volume in a sample of 1,300 adult subjects. Our findings point for the first time at the ubiquitination machinery as a new disease mechanism for adult ADHD and establish a rationale for searching for additional risk variants in ubiquitination-related genes.Neuropsychopharmacology accepted article preview online, 06 October 2014. doi:10.1038/npp.2014.267.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 10/2014; 40(4). DOI:10.1038/npp.2014.267 · 7.05 Impact Factor
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