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SHARE00REPORTAbnormal Brain Structure Implicated inStimulant Drug Addiction1.Karen D. Ersche1,*,2.P. Simon Jones1,3.Guy B. Williams1,2,4.Abigail J Turton1,5.Trevor W. Robbins1,6.Edward T. Bullmore1,3,4+See all authors and affiliationsScience03 Feb 2012:Vol. 335, Issue 6068, pp. 601-604DOI: 10.1126/science.1214463ArticleFigures & DataInfo & MetricseLettersPDFAbstractAddiction to drugs is a major contemporary public health issue, characterized bymaladaptive behavior to obtain and consume an increasing amount of drugs at theexpense of the individual’s health and social and personal life. We discoveredabnormalities in fronto-striatal brain systems implicated in self-control in bothstimulant-dependent individuals and their biological siblings who have no history ofchronic drug abuse; these findings support the idea of an underlying neuro-cognitiveendophenotype for stimulant drug addiction.Drug dependence is increasingly recognized as a “relapsing brain disorder” (1) and, insupport of this view, marked structural changes in striatal and prefrontal brain regionshave been reported in people dependent on stimulant drugs (2). These reports,however, raise the question of whether these brain abnormalities may have predateddrug-taking, rendering individuals vulnerable for the development of dependence.Individuals at risk for drug dependence typically have deficits in self-control (3,4),which may reflect a diminished ability to recruit prefrontal networks for regulatingbehavior (5). Stimulant drugs are highly reinforcing, because they directly affect brainsystems implicated in motivated behavior, such as the basal ganglia and the limbicsystem (6), and they modulate control systems in the prefrontal cortex (7).
Malfunction of these circuitries may increase the susceptibility for stimulant-inducedneuroadaptive changes and facilitate the development of drug dependence.As brain structure is, to a large extent, inherited (8) and drug dependence runs infamilies (9), a genetic or epigenetic influence on addictive behaviors seems plausible.Yet, we know very little about the mechanisms through which risks for drugdependence might be inherited. Endophenotypes are quantitative traits, mediatingbetween the predisposing genes (genotypes) and the clinical symptoms (phenotypes)in complex disorders (10). As heritable traits, endophenotypes can be measuredobjectively in both patients and their unaffected first-degree relatives. We comparedbrain structure and the ability to regulate behavior in 50 biological sibling pairs;within each pair, one sibling satisfied theDiagnostic and Statistical Manual of MentalDisorders(DSM-IV) criteria for dependence on stimulant drugs and the other had nohistory of chronic drug or alcohol abuse (11). The sib-pairs were also compared with50 unrelated healthy volunteers matched for age and intelligence quotient (table S1).

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