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: 9.47). 08/2010; 68(3):287-95. DOI: 10.1016/j.biopsych.2010.02.020
Source: PubMed

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.

Download full-text


Available from: Robert A Zucker, Sep 04, 2015
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: 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. 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). 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. The current results highlight altered proactive control that may serve as an additional behavioral and neural marker of alcohol dependence.
    Clinical neuroimaging 12/2015; 8:39-50. DOI:10.1016/j.nicl.2015.03.008 · 2.53 Impact Factor
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Adolescence is usually the time when individuals first drink alcohol and this has been associated with relatively weak or immature inhibitory control. This review examines the changes on brain development and inhibitory function that take place during adolescence and youth as well as the relationship between inhibitory control and alcohol use at this early age. Narrative review of the chief studies related to (a) the development of inhibitory control during adolescence, (b) the deficits in the inhibitory ability in alcohol use disorders and (c) the effects of acute alcohol intake and binge drinking on inhibitory control in adolescents and young adults. Inhibitory control processes are developing during adolescence and youth. Poor inhibitory functions may predispose the individual to alcohol misuse. Likewise, acute and binge alcohol drinking may impair the inhibitory control and compromise the ability to prevent or stop behaviour related to alcohol use. Poor inhibitory control can be both the cause and the consequence of excessive alcohol use. Adolescence and young adulthood may be a particularly vulnerable period due to (a) the weak or immature inhibitory functioning typical of this stage may contribute to the inability of the individual to control alcohol use and (b) alcohol consumption per se may alter or interrupt the proper development of inhibitory control leading to a reduced ability to regulate alcohol intake. Further longitudinal research is needed to evaluate the interaction between inhibitory control dysfunction and alcohol use in both situations.
    Alcohol and Alcoholism 11/2013; 49(2). DOI:10.1093/alcalc/agt168 · 2.09 Impact Factor
  • Source
    • "In agreement with Kamarajan and colleagues' (2004) model, which postulates that disturbances in prefrontal network systems are involved in AD, our findings suggest that impulsivity and EF impairment may be important factors underlying the pathogenesis of AD. Accordingly, recent studies using functional neuroimaging among adolescent and young adult AD offspring (Cservenka and Nagel, 2012; Heitzeg et al., 2010; Silveri et al., 2011) revealed a significant influence of AD family history status on brain activation during inhibition or decision-making tasks, suggesting a preexisting abnormality in functions depending on frontal lobe in youths at risk of alcohol use disorders. However, it is important to emphasize that, in our study, the EF factor was not correlated with self-reported impulsiveness. "
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Executive function (EF) impairment in alcohol dependence (AD) has been related to the toxic effects of alcohol on frontal lobes. However, this impairment could be partially present before the onset of the disease and might constitute a vulnerability factor. Although a considerable body of research has investigated executive functioning among AD patients, much less attention has been directed toward high-risk individuals. Most studies were carried out among children or adolescents, and very few were conducted in adults. The aim of this study was to examine EF in a group of adult offspring of AD individuals. METHODS: One hundred and fifty-five nonalcoholic adults with (family history positive [FHP]) or without (family history negative [FHN]) family history of AD were included in the study. All participants were screened for past and current psychiatric diagnoses, and alcohol, tobacco, and other substance use. They were compared on self-rated impulsiveness using the Barratt Impulsiveness Scale-11 (BIS-11) and EF using a neuropsychological test battery. RESULTS: Group comparison revealed that FHP participants had significantly higher BIS-11 scores than the FHN participants, while neuropsychological examination revealed lower EF scores for FHP participants. Hierarchical regression analysis revealed that the number of AD family members was a predictor of EF results, whereas impulsiveness was not. CONCLUSIONS: Nonalcoholic adult offspring of AD individuals showed increased impulsiveness and decreased EF, suggesting weakness of 2 distinct neurobehavioral decision systems. Findings support evidence that EF weaknesses may qualify as a suitable endophenotype candidate for AD.
    Alcoholism Clinical and Experimental Research 12/2012; 37. DOI:10.1111/j.1530-0277.2012.01903.x · 3.31 Impact Factor
Show more