Neuroimaging of Gender Differences in Alcohol Dependence: Are Women More Vulnerable?

Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
Alcoholism Clinical and Experimental Research (Impact Factor: 3.21). 06/2005; 29(5):896-901. DOI: 10.1097/01.ALC.0000164376.69978.6B
Source: PubMed

ABSTRACT Alcoholic brain damage has been demonstrated in numerous studies using neuropathology and brain imaging techniques. However, gender differences were addressed only in a few studies. Recent research has shown that development, course, and consequences of alcohol dependence may differ between female and male patients. Our investigation was built upon earlier research where we hypothesized that women develop alcoholic brain damage more readily than men do. To further compare the impact of alcohol dependence between men and women, we examined brain atrophy in female and male alcoholics by means of computed tomography (CT).
The study group consisted of a total of 158 subjects (76 women: 42 patients, 34 healthy controls; 82 age-matched men: 34 patients, 48 healthy controls). All patients had a DSM-IV and ICD-10 diagnosis of alcohol dependence. CT with digital volumetry was performed twice in patients (at the beginning and end of the 6-week inpatient treatment program) and once in controls.
Patients of both genders had consumed alcohol very heavily. Although the average alcohol consumption in the year before the study was significantly lower in female alcoholics, this gender difference disappeared when controlled for weight. However, women had a significantly shorter duration of alcohol dependence. Despite this fact, both genders developed brain atrophy to a comparable extent. Brain atrophy was reversible in part after 6 weeks of treatment; it did not reach the level in the control groups.
Gender-specific differences in the onset of alcohol dependence were confirmed. This is in line with the telescoping effect, where a later onset and a more rapid development of dependence in women were described. Under the assumption of a gradual development of consequential organ damage, brain atrophy seems to develop faster in women. As shown in other organs (i.e., heart, muscle, liver), this may confirm a higher vulnerability to alcohol among women.

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    • "Although not all studies agree (Hommer, 2003), women appear more vulnerable than men to the widespread damaging effects of alcohol on the brain, including volumetric loss in frontolimbic regions that subserve affective processing despite, on average, having fewer years of drinking and consuming less alcohol in their lifetimes (Mann et al., 1992; Medina et al., 2008). On par, both men and women with AD demonstrate atrophy following years of chronic drinking, however, atrophy appears to develop faster in women, suggesting an increased vulnerability (Mann et al., 2005). However, Pfefferbaum and colleagues (2010) did not find a gender vulnerability to the effects of alcohol when examining white matter bundles, nor were there gender differences in gray or white matter volumes in recently detoxified individuals with AD (Demirakca et al., 2011). "
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    ABSTRACT: Background Alcohol dependence (AD) has global effects on brain structure and function, including frontolimbic regions regulating affective processing. Preliminary evidence suggests alcohol blunts limbic response to negative affective stimuli and increases activation to positive affective stimuli. Subtle gender differences are also evident during affective processing.Methods Fourteen abstinent AD individuals (8 F, 6 M) and 14 healthy controls (9 F, 5 M), ages 23 to 60, were included in this facial affective processing functional magnetic resonance imaging pilot study. Whole-brain linear regression analyses were performed, and follow-up analyses examined whether AD status significantly predicted depressive symptoms and/or coping.ResultsFearful Condition—The AD group demonstrated reduced activation in the right medial frontal gyrus, compared with controls. Gender moderated the effects of AD in bilateral inferior frontal gyri. Happy Condition—AD individuals had increased activation in the right thalamus. Gender moderated the effects of AD in the left caudate, right middle frontal gyrus, left paracentral lobule, and right lingual gyrus. Interactive AD and gender effects for fearful and happy faces were such that AD men activated more than control men, but AD women activated less than control women. Enhanced coping was associated with greater activation in right medial frontal gyrus during fearful condition in AD individuals.Conclusions Abnormal affective processing in AD may be a marker of alcoholism risk or a consequence of chronic alcoholism. Subtle gender differences were observed, and gender moderated the effects of AD on neural substrates of affective processing. AD individuals with enhanced coping had brain activation patterns more similar to controls. Results help elucidate the effects of alcohol, gender, and their interaction on affective processing.
    Alcoholism Clinical and Experimental Research 02/2015; 39(2). DOI:10.1111/acer.12626 · 3.21 Impact Factor
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    • "Gender telescoping has been observed among users of nicotine (Oncken et al., 2004), cannabis (Hernandez-Avila et al., 2004), cocaine (Haas and Peters, 2000), and both heroin and prescription opioids (Sartor et al., 2014) as well as non-treatment seeking prescription opioid users (Back et al., 2011a). Findings are equivocal among alcoholdependent populations: some studies replicated the Piazza et al. (1989) findings of gender telescoping (Bravo et al., 2013; Diehl et al., 2007; Johnson et al., 2005; Mann et al., 2005; Piazza et al., 1989; Randall et al., 1999) whereas others did not (Alvanzo et al., 2011; "
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    ABSTRACT: Background: Addiction research literature suggests some demographic groups exhibit a later age of substance use initiation, more rapid escalation to dependence, and worse substance use-related outcomes. This 'telescoping' effect has been observed more often in females but has not yet been examined in not-in-treatment heroin users or racial subgroups. Methods: Not-in-treatment, intensive heroin-using adults screened for laboratory-based research studies (N=554; range 18-55 yr; mean age: 42.5 yr; 60.5% African American [AA]; 70.2% male) were included in this secondary analysis. A comprehensive drug history questionnaire assessed heroin-use characteristics and lifetime adverse consequences. We examined telescoping effects by racial and gender groups: Caucasian males and females; AA males and females. Results: Caucasian males initiated heroin use significantly later than AA males but this difference was not observed for age at intensive heroin use (≥3 times weekly). Caucasian males reported significantly more lifetime heroin use-related consequences, were more likely to inject heroin, and reported more-frequent past-month heroin use, but did not differ from AA males in lifetime heroin quit attempts or prior heroin treatment. Females, compared to males, reported later onset of initial and intensive use, but there was no gender-telescoping effect from initial to intensive heroin-use. Conclusions: In this not-in-treatment sample, Caucasian males exhibited more rapid heroin-use progression and adverse consequences than AA males, i.e., within-gender, racial-group telescoping. Despite later-onset heroin use among females, there was no evidence of gender-related telescoping. Given the resurgence of heroin use, differential heroin-use trajectories across demographic groups may be helpful in planning interventions.
    Drug and Alcohol Dependence 01/2015; 148. DOI:10.1016/j.drugalcdep.2015.01.010 · 3.42 Impact Factor
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    • "For instance, males use illicit substances more frequently and in greater quantities than females (Berkowitz and Perkins, 1987; Thomas, 1995). Although female substance users typically begin using substances later than males do, they demonstrate an accelerated transition to addiction (Brady and Randall, 1999; Mann et al., 2005). Furthermore, imaging studies also supported gender differences in the influence of cocaine use on cerebral responses (Adinoff et al., 2001, 2006; Andersen et al., 2012; Ernst et al., 2000; Li et al., 2005b, 2005c; Levin et al., 1994; Luo et al., 2013; Tucker et al., 2004; Volkow et al., 2011). "
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    ABSTRACT: Error processing is a critical component of cognitive control, an executive function that has been widely implicated in substance misuse. In previous studies we showed that error related activations of the thalamus predicted relapse to drug use in cocaine addicted individuals (Luo et al., 2013). Here, we investigated whether error-related functional connectivity of the thalamus is altered in cocaine dependent patients (PCD, n = 54) as compared to demographically matched healthy individuals (HC, n = 54). The results of a generalized psychophysiological interaction analysis showed negative thalamic connectivity with the ventral medial prefrontal cortex (vmPFC), in the area of perigenual and subgenual anterior cingulate cortex, in HC but not PCD (p < 0.05, corrected, two-sample t test). This difference in functional connectivity was not observed for task-residual signals, suggesting that it is specific to task-related processes during cognitive control. Further, the thalamic-vmPFC connectivity is positively correlated with the amount of cocaine use in the prior month for female but not for male PCD. These findings add to recent literature and provide additional evidence for circuit-level biomarkers of cocaine dependence.
    Clinical neuroimaging 02/2014; 4. DOI:10.1016/j.nicl.2014.01.015 · 2.53 Impact Factor
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