Striatal Dysfunction Marks Preexisting Risk and Medial Prefrontal Dysfunction Is Related to Problem Drinking in Children of Alcoholics

Department of Psychiatry, University of Michigan, Ann Arbor, Michigan, USA.
Biological psychiatry (Impact Factor: 10.26). 08/2010; 68(3):287-95. DOI: 10.1016/j.biopsych.2010.02.020
Source: PubMed


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.

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    • "For instance, children with a family history of alcoholism showed altered activations in a number of cortical structures, including the ventral caudate, OFC, middle frontal gyrus, posterior cingulate cortex/ precuneus, and mPFC in a go/no-go task as compared to the control group. This finding suggested preexisting functional aberrations of impulse control that may increase risk of cognitive impairment and vulnerability to developing alcohol use disorder (Acheson et al., 2014; Anderson et al., 2005; Heitzeg et al., 2010; Schweinsburg et al., 2004). "
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    ABSTRACT: Background Our previous work characterized altered cerebral activations during cognitive control in individuals with alcohol dependence (AD). A hallmark of cognitive control is the ability to anticipate changes and adjust behavior accordingly. Here, we employed a Bayesian model to describe trial-by-trial anticipation of the stop signal and modeled fMRI signals of conflict anticipation in a stop signal task. Our goal is to characterize the neural correlates of conflict anticipation and its relationship to response inhibition and alcohol consumption in AD. Methods Twenty-four AD and 70 age and gender matched healthy control individuals (HC) participated in the study. fMRI data were pre-processed and modeled with SPM8. We modeled fMRI signals at trial onset with individual events parametrically modulated by estimated probability of the stop signal, p(Stop), and compared regional responses to conflict anticipation between AD and HC. To address the link to response inhibition, we regressed whole-brain responses to conflict anticipation against the stop signal reaction time (SSRT). Results Compared to HC (54/70), fewer AD (11/24) showed a significant sequential effect — a correlation between p(Stop) and RT during go trials — and the magnitude of sequential effect is diminished, suggesting a deficit in proactive control. Parametric analyses showed decreased learning rate and over-estimated prior mean of the stop signal in AD. In fMRI, both HC and AD responded to p(Stop) in bilateral inferior parietal cortex and anterior pre-supplementary motor area, although the magnitude of response increased in AD. In contrast, HC but not AD showed deactivation of the perigenual anterior cingulate cortex (pgACC). Furthermore, deactivation of the pgACC to increasing p(Stop) is positively correlated with the SSRT in HC but not AD. Recent alcohol consumption is correlated with increased activation of the thalamus and cerebellum in AD during conflict anticipation. Conclusions The current results highlight altered proactive control that may serve as an additional behavioral and neural marker of alcohol dependence.
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    • "We also found abnormal ventral striatal modulation in vulnerable (FH +, high problem) adolescents during the response inhibition (go–no go) task (Heitzeg et al. 2010). These vulnerable 18–22-year-olds failed to deactivate the ventral caudate compared with controls; regression analysis showed that ventral caudate deactivation was related to having fewer externalizing problems. "
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    ABSTRACT: Addiction science largely has individual behavior as its focus, albeit at increasingly differentiated levels of analysis, ranging from behavior to brain to genes. Context is rarely brought into the causal matrix, although without the addictive object, addiction could not occur. Moreover, although the emergence of addiction is a developmental process, developmental changes in these relationships are rarely examined. Findings that address these issues are reported from a 28-year-long prospective high risk for alcoholism family study, the Michigan Longitudinal Study, which was designed to evaluate these cross-development linkages from early childhood to early adulthood, across multiple levels of analysis involving genes, neural circuitry, behavior, and social context. Analyses focus on the network of GABA2 relationships with externalizing behavior and with nucleus accumbens responsivity, as they relate to problems of alcohol use over the course of adolescence. They illustrate the moderating effect of social relationships—but only in specific portions of adolescence.
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    • "Studies of offspring of alcoholics have shown a lower response in the inhibition performance in subjects with family history of alcohol use disorders (Nigg et al., 2004; Schweinsburg et al., 2004). Consistent with this, children and adolescents with a positive family history for alcohol use disorders also show anomalies in the anatomical and functional structure of some regions involved in inhibitory control (Schweinsburg et al., 2004; Hill et al., 2009; Heitzeg et al., 2010). These anomalies might predispose the children to develop alcohol misuse during adolescence (Norman et al., 2011). "
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