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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Available from: Katya Rubia, Sep 30, 2015
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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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    • "Neuropsychological deficits in executive functions in children with ADHD have been shown to persist into adulthood, with the most consistent findings showing abnormalities in stimulus interference, response interference, and behavioral inhibition. These deficits have most consistently been linked to prefrontal dysfunctions especially in lateral prefrontal regions and the ACC (Cubillo and Rubia, 2010; Hart et al., 2013; Volkow and Swanson, 2013). We will focus in the following sections on adult ADHD but we will also consider findings from childhood ADHD whenever no or too little studies on adult ADHD are available. "
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    ABSTRACT: Disorders such as borderline personality disorder (BPD) or attention-deficit/hyperactivity disorder (ADHD) are characterized by impulsive behaviors. Impulsivity as used in clinical terms is very broadly defined and entails different categories including personality traits as well as different cognitive functions such as emotion regulation or interference reso-lution and impulse control. Impulse control as an executive function, however, is neither cognitively nor neurobehaviorally a unitary function. Recent findings from behavioral and cognitive neuroscience studies suggest related but dissociable components of impulse control along functional domains like selective attention, response selection, motivational control, and behavioral inhibition. In addition, behavioral and neural dissociations are seen for proactive vs. reactive inhibitory motor control.The prefrontal cortex with its sub-regions is the central structure in executing these impulse control functions. Based on these con-cepts of impulse control, neurobehavioral findings of studies in BPD and ADHD were reviewed and systematically compared. Overall, patients with BPD exhibited prefrontal dysfunctions across impulse control components rather in orbitofrontal, dorsomedial, and dorsolateral prefrontal regions, whereas patients with ADHD displayed disturbed activity mainly in ventrolateral and medial prefrontal regions. Prefrontal dysfunctions, however, varied depending on the impulse control component and from disorder to disorder. This suggests a dissociation of impulse control related frontal dysfunctions in BPD and ADHD, although only few studies are hitherto available to assess frontal dysfunctions along differ-ent impulse control components in direct comparison of these disorders.Yet, these findings might serve as a hypothesis for the future systematic assessment of impulse control com-ponents to understand differences and commonalities of prefrontal cortex dysfunction in impulsive disorders.
    Frontiers in Human Neuroscience 09/2014; 8:698. DOI:10.3389/fnhum.2014.00698 · 2.99 Impact Factor
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    • "In addition, one fMRI study conducted in adults with childhood ADHD showed reduced activations in bilateral inferior prefrontal cortices (IFC), left parietal lobe, caudate and thalamus, and reduced inter-regional functional connectivity between right inferior fronto-frontal, fronto-striatal, and fronto-parietal neural networks during a stop and switching task, when compared to controls (Cubillo et al., 2010). Structures of the cingulo-fronto-pariental (CFP) cognitive/attention network, including the fronto-striatal and frontoparietal pathways, are thought to be the primary substrate for most attention and executive functions (Bush, 2011). "
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    ABSTRACT: Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed neurodevelopmental disorder in childhood, which affects more than 5% of the population worldwide. ADHD is characterized by developmentally inappropriate behaviors of inattention, and/or impulsivity and hyperactivity. These behavioral manifestations contribute to diminished academic, occupational and social functioning, and have neurobiological bases. Neuronal deficits, especially in the attention and executive function processing networks, have been implicated in both children and adults with ADHD by using sophisticated structural and functional neuroimaging approaches. These structural and functional abnormalities in the brain networks have been associated with the impaired cognitive, affective, and motor behaviors seen in the disorder. The goal of this review is to summarize and integrate emerging themes from the existing neuroimaging connectivity studies based on advanced imaging techniques, applied in data of structural magnetic resonance imaging (MRI), functional MRI (fMRI), diffusion tensor imaging, electroencephalography and event related potential; and to discuss the results of these studies when considering future directions for understanding pathophysiological mechanisms and developmental trajectories of the behavioral manifestations in ADHD. We conclude this review by suggesting that future research should put more effort on understanding the roles of the subcortical structures and their structural/functional pathways in ADHD.
    Frontiers in Human Neuroscience 05/2013; 7:192. DOI:10.3389/fnhum.2013.00192 · 2.99 Impact Factor
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