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Striatal dysfunction marks preexisting risk and medial prefrontal dysfunction is related to problem drinking in children of alcoholics.

ABSTRACT: Parental alcoholism substantially raises risk for offspring alcoholism, an effect thought to be mediated by a dysregulation in impulse control. Adult alcoholics have alterations in the frontostriatal system involved in regulating impulsive responses. However, it remains controversial whether these alterations reflect preexisting traits predisposing to problem alcohol use or are secondary to alcohol involvement.Sixty-one 16 to 22 year olds were tested using a go/no-go task during functional magnetic resonance imaging. Forty-one were family history positive (FH+), having at least one parent with a diagnosis of alcohol use disorder (AUD), and 20 were family history negative (FH-). Two FH+ subgroups were created to disentangle alcohol involvement from preexisting risk: the FH+ control group (n = 20) had low alcohol problems, differing from the FH- group only by family history. The FH+ problem group (n = 21) had high alcohol problems.The ventral caudate deactivated during successful inhibition in the FH- but not the FH+ groups, regardless of problem alcohol involvement. Regression analyses showed that ventral caudate deactivation was related to fewer externalizing problems as well as to family history. Orbital and left medial prefrontal regions were deactivated in both the FH- and FH+ control groups but not the FH+ problem group. Activation in these regions was associated with alcohol and other drug use.These findings suggest a preexisting abnormality in ventral striatal function in youth at risk for AUD, which may lead to inappropriate motivational responding, and suggest that with alcohol use, the prefrontal "control" mechanism loses efficiency, further dysregulating the frontostriatal motivational circuitry.

SUBMITTER: Heitzeg MM

PROVIDER: S-EPMC2907458 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Striatal dysfunction marks preexisting risk and medial prefrontal dysfunction is related to problem drinking in children of alcoholics.

Heitzeg Mary M MM Nigg Joel T JT Yau Wai-Ying Wendy WY Zucker Robert A RA Zubieta Jon-Kar JK

Biological psychiatry 20100422 3

<h4>Background</h4>Parental alcoholism substantially raises risk for offspring alcoholism, an effect thought to be mediated by a dysregulation in impulse control. Adult alcoholics have alterations in the frontostriatal system involved in regulating impulsive responses. However, it remains controversial whether these alterations reflect preexisting traits predisposing to problem alcohol use or are secondary to alcohol involvement.<h4>Methods</h4>Sixty-one 16 to 22 year olds were tested using a go ...[more]

PMID: 20416863

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Project description:ObjectiveAlcohol use disorder (AUD) is associated with neuroadaptations in brain stress and reward circuits. It is not known whether such neuroadaptations are affected by number of days of alcohol abstinence and whether they influence heavy drinking during the early treatment phase. The authors used a novel functional MRI (fMRI) approach to assess brain responses during sustained exposure to standardized visual stimuli of stressful, alcohol cue, and neutral control images combined with prospective assessment of drinking outcomes during early outpatient treatment, in two related studies.MethodsIn study 1, 44 treatment-entering patients with AUD and 43 demographically matched healthy control subjects participated in the fMRI experiment to identify dysfunctional responses associated with chronic alcohol abuse. In study 2, 69 treatment-entering patients with AUD were assessed for whether fMRI responses at treatment initiation were influenced by alcohol abstinence and were prospectively predictive of early heavy drinking outcomes.ResultsRelative to control subjects, patients with AUD showed significant hyperreactivity in the ventromedial prefrontal cortex (vmPFC) in response to neutral images, but significant hypoactivation in the vmPFC and ventral striatum in response to stress images and to alcohol cues relative to response to neutral images. In study 2, this specific prefrontal-ventral striatal dysfunction was associated with fewer days of alcohol abstinence and also predicted greater number heavy drinking days during the subsequent 2 weeks of treatment engagement.ConclusionsNumber of days of alcohol abstinence at treatment initiation significantly affected functional disruption of the prefrontal-striatal responses to stress images and to alcohol cues in patients with AUD, and the severity of this disruption in turn predicted greater heavy drinking during early treatment. Treatments that target this functional prefrontal-striatal pathology could improve early treatment outcomes in AUD.

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Striatal dysfunction marks preexisting risk and medial prefrontal dysfunction is related to problem drinking in children of alcoholics.

Publications

Striatal dysfunction marks preexisting risk and medial prefrontal dysfunction is related to problem drinking in children of alcoholics.

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