Ersche KD, Barnes A, Jones PS, Morein-Zamir S, Robbins TW, Bullmore ET. Abnormal structure of frontostriatal brain systems is associated with aspects of impulsivity and compulsivity in cocaine dependence. Brain 134(Pt 7): 2013-2024

University of Cambridge, Department of Psychiatry, Herchel Smith Building for Brain and Mind Sciences, Cambridge Biomedical Campus, Cambridge CB20SZ, UK.
Brain (Impact Factor: 9.2). 07/2011; 134(Pt 7):2013-24. DOI: 10.1093/brain/awr138
Source: PubMed


A growing body of preclinical evidence indicates that addiction to cocaine is associated with neuroadaptive changes in frontostriatal brain systems. Human studies in cocaine-dependent individuals have shown alterations in brain structure, but it is less clear how these changes may be related to the clinical phenotype of cocaine dependence characterized by impulsive behaviours and compulsive drug-taking. Here we compared self-report, behavioural and structural magnetic resonance imaging data on a relatively large sample of cocaine-dependent individuals (n = 60) with data on healthy volunteers (n = 60); and we investigated the relationships between grey matter volume variation, duration of cocaine use, and measures of impulsivity and compulsivity in the cocaine-dependent group. Cocaine dependence was associated with an extensive system of abnormally decreased grey matter volume in orbitofrontal, cingulate, insular, temporoparietal and cerebellar cortex, and with a more localized increase in grey matter volume in the basal ganglia. Greater duration of cocaine dependence was correlated with greater grey matter volume reduction in orbitofrontal, cingulate and insular cortex. Greater impairment of attentional control was associated with reduced volume in insular cortex and increased volume of caudate nucleus. Greater compulsivity of drug use was associated with reduced volume in orbitofrontal cortex. Cocaine-dependent individuals had abnormal structure of corticostriatal systems, and variability in the extent of anatomical changes in orbitofrontal, insular and striatal structures was related to individual differences in duration of dependence, inattention and compulsivity of cocaine consumption.

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Available from: Anna Barnes, Oct 01, 2015
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    • "However, regions of gray matter loss in probands, including the OFC and anterior insula, did not show any change in the relatives. These changes may well occur as a consequence of stimulant drug taking, especially as some of the changes (e.g., in the OFC) were related to duration of drug use as well as to measures of compulsive behavior (Ersche et al. 2011a). This is consistent with longitudinal findings in rhesus monkeys exposed to cocaine self-administration (Porrino et al. 2010). "
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    ABSTRACT: A decade ago, we hypothesized that drug addiction can be viewed as a transition from voluntary, recreational drug use to compulsive drug-seeking habits, neurally underpinned by a transition from prefrontal cortical to striatal control over drug seeking and taking as well as a progression from the ventral to the dorsal striatum. Here, in the light of burgeoning, supportive evidence, we reconsider and elaborate this hypothesis, in particular the refinements in our understanding of ventral and dorsal striatal mechanisms underlying goal-directed and habitual drug seeking, the influence of drug-associated Pavlovian-conditioned stimuli on drug seeking and relapse, and evidence for impairments in top-down prefrontal cortical inhibitory control over this behavior. We further review animal and human studies that have begun to define etiological factors and individual differences in the propensity to become addicted to drugs, leading to the description of addiction endophenotypes, especially for cocaine addiction. We consider the prospect of novel treatments for addiction that promote abstinence from and relapse to drug use. Expected final online publication date for the Annual Review of Psychology Volume 67 is January 03, 2016. Please see for revised estimates.
    Annual Review of Psychology 08/2015; 67(1). DOI:10.1146/annurev-psych-122414-033457 · 21.81 Impact Factor
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    • "Consequently, animals and patients, with lesioned or dysfunction of the frontostriatal pathway, have impairments on prefrontally dependent learning, memory and reward performance (Meyer-Lindenberg et al., 2007; Heller et al., 2009). And the abnormalities are characteristic of the emotional and cognitive deficits found in conditions such as schizophrenia, depression and drug addiction (Alexopoulos, 2002; Harrison et al., 2009; Ersche et al., 2011). The dopaminergic functions in the frontostriatal circuit are controlled by two important proteins: brain-derived neurotrophic factor (BDNF) and catechol-Omethyltransferase (COMT). "
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    ABSTRACT: The frontostriatal system plays a critical role in emotional and cognitive control. Brain-derived neurotrophic factor (BDNF) influences the release of dopamine in the ventral striatum, while catechol-O-methyltransferase (COMT) impacts dopamine availability in the prefrontal cortex (PFC). Behavioral studies have already shown a genetic interaction of BDNF Val66Met and COMT Val158Met, but the interaction on the dopamine-related neural circuit has not been previously studied. Here we show, using functional magnetic resonance imaging in a sample of healthy human subjects, that BDNF and COMT epistatically interacted on the functional connectivity between the bilateral ventral striatum (VST) and the anterior cingulate cortex. Specifically, BDNF Val66Met impacted the VST-PFC functional connectivity in an inverted U-relationship in COMT Met carriers, while COMT Val homozygotes displayed a U-relationship. These data may be helpful elucidating the mechanism of the interaction between BDNF and COMT on the cognitive functions that are based in the frontostriatal system. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
    Neuroscience 04/2015; 298. DOI:10.1016/j.neuroscience.2015.04.014 · 3.36 Impact Factor
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    • "All these conditions may also influence brain morphometry and should ideally be considered in future studies of both treatment-naïve and treatment-seeking individuals with welldefined dependence on alcohol and illicit substances. To address the issue of regional specificity of volume changes within the relatively large lobes and to increase the functional relevance of such measures, reliable segmentation and examination of small brain regions or of the cortical ribbon may be needed, such as provided by whole-brain voxel-based morphometry and cortical thickness measures (see e.g., Cardenas et al., 2011; Durazzo et al., 2011; Ersche et al., 2011). These limitations notwithstanding, our neuroimaging study reveals gross brain structural differences between PSU and ALC that may have implications for different treatment approaches of polysubstance dependence and alcohol dependence. "
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    ABSTRACT: Background Over 50% of individuals with alcohol use disorders (AUD) also use other substances; brain structural abnormalities observed in alcohol dependent individuals may not be entirely related to alcohol consumption. This MRI study assessed differences in brain regional tissue volumes between short-term abstinent alcohol dependent individuals without (ALC) and with current substance use dependence (polysubstance users, PSU) Methods Nineteen, one-month-abstinent PSU and 40 ALC as well as 27 light-drinkers (LD) were studied on a 1.5 Tesla MR system. Whole brain T1-weighted images were segmented automatically into regional gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) volumes. MANOVA assessed group differences of intracranial volume-normalized tissue volumes of the frontal, parietal, occipital, and temporal lobes and regional subcortical GM volumes. The volumetric measures were correlated with neurocognitive measures to assess their functional relevance. Results Despite similar lifetime drinking and smoking histories, PSU had significantly larger normalized WM volumes than ALC in all lobes. PSU also had larger frontal and parietal WM volumes than LD, but smaller temporal GM volumes and smaller lenticular and thalamic nuclei than LD. ALC had smaller frontal, parietal, and temporal GM, thalamic GM and cerebellar volumes than LD. ALC had more sulcal CSF volumes than both PSU and LD Conclusion One-month-abstinent ALC and PSU exhibited different patterns of gross brain structural abnormalities. The larger lobar WM volumes in PSU in the absence of widespread GM volume loss contrast with widespread GM atrophy in ALC. These structural differences may demand different treatment approaches to mitigate specific functionally relevant brain abnormalities
    Drug and Alcohol Dependence 09/2014; 144. DOI:10.1016/j.drugalcdep.2014.09.010 · 3.42 Impact Factor
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