Susan Mosher Ruiz

Profiles of impaired, spared, and recovered neuropsychologic processes in alcoholism.

Long-term chronic alcoholism is associated with disparate and widespread residual consequences for brain functioning and behavior, and alcoholics suffer a variety of cognitive deficiencies and emotional abnormalities. Alcoholism has heterogeneous origins and outcomes, depending upon factors such as family history, age, gender, and mental or physical health. Consequently, the neuropsychologic profiles associated with alcoholism are not uniform among individuals. Moreover, within and across research studies, variability among subjects is substantial and contributes to characteristics associated with differential treatment outcomes after detoxification. In order to refine our understanding of alcoholism-related impaired, spared, and recovered abilities, we focus on five specific functional domains: (1) memory; (2) executive functions; (3) emotion and psychosocial skills; (4) visuospatial cognition; and (5) psychomotor abilities. Although the entire brain might be vulnerable in uncomplicated alcoholism, the brain systems that are considered to be most at risk are the frontocerebellar and mesocorticolimbic circuitries. Over time, with abstinence from alcohol, the brain appears to become reorganized to provide compensation for structural and behavioral deficits. By relying on a combination of clinical and scientific approaches, future research will help to refine the compensatory roles of healthy brain systems, the degree to which abstinence and treatment facilitate the reversal of brain atrophy and dysfunction, and the importance of individual differences to outcome.

Drinking History Associations with Regional White Matter Volumes in Alcoholic Men and Women

BACKGROUND Alcoholism has been repeatedly associated with gray and white matter pathology. Although neuroimaging has shown alcoholism-related brain volume reductions and axonal compromise, the integrity of white matter volumes in chronic alcoholism has been challenging to measure on a regional level. METHODS We first examined the effects of alcoholism on cerebral white matter volumes by lobar and gyral subdivisions in 42 abstinent alcoholics and 42 control participants (split evenly by gender). We also examined cerebellar white matter and regions of the corpus callosum, as well as ventricular volumes. Next, relationships between white matter and ventricular volumes with measures of drinking patterns were assessed. Finally, an examination of early versus late abstinence was conducted. Within each examination, gender effects were explored. RESULTS Differences in regional white matter volumes between alcoholics and controls were observed primarily in the corpus callosum, with a stronger group difference among men than women. Years of heavy drinking had a strong negative impact on frontal and temporal white matter among alcoholic women, and on the corpus callosum among alcoholic men. Quantity of alcohol consumption was associated with smaller corpus callosum and larger ventricular volumes among alcoholic women, whereas abstinence duration was associated with larger corpus callosum volume among alcoholic men. Preliminary data indicated that alcoholic women showed stronger positive associations between sobriety duration and white matter volume than men within the first year of abstinence, whereas men showed this association more so than women after 1 year of abstinence. CONCLUSIONS Effects of drinking history on white matter and ventricular volumes vary by gender, with alcoholic women showing greatest sensitivity in frontal, temporal, ventricular, and corpus callosum regions, and alcoholic men showing effects mainly in the corpus callosum. Preliminary results indicate that recovery of white matter volume may occur sooner for women than for men.

Brain volumes and neuropsychological performance are related to current smoking and alcoholism history

Background Dual dependence on alcohol and nicotine is common, with many reports suggesting that more than 80% of alcoholics also smoke cigarettes. Even after cessation of alcohol consumption, many recovering alcoholics continue to smoke. In this exploratory study, we examined how current smoking and a history of alcoholism interacted in relation to brain volumes and neuropsychological performance. Methods Participants were 14 abstinent long-term alcoholics (seven current smokers and seven nonsmokers), and 13 nonalcoholics (six current smokers and seven nonsmokers). The groups were equivalent in age, gender, education, and intelligence quotient. Two multiecho magnetization-prepared rapid acquisition with gradient echo (MP-RAGE) scans were collected for all participants using a 3T magnetic resonance imaging scanner with a 32 channel head coil. Brain volumes for each gray and white matter region of interest were derived using FreeSurfer. Participants completed a battery of neuropsychological tests measuring intelligence quotient, memory, executive functions, personality variables, and affect. Results Compared to nonsmoking nonalcoholics, alcoholics who smoke (the comorbid group) had volumetric abnormalities in: pre- and para-central frontal cortical areas and rostral middle frontal white matter; parahippocampal and temporal pole regions; the amygdala; the pallidum; the ventral diencephalic region; and the lateral ventricle. The comorbid group performed worse than nonsmoking nonalcoholics on tests of executive functioning and on visually-based memory tests. History of alcoholism was associated with higher neuroticism scores among smokers, and current smoking was associated with higher sensation seeking scores and lower extraversion scores among nonalcoholics. Conclusion Results from this exploratory study support and extend prior reports showing that alcoholism and smoking, alone and in combination, are associated with structural brain abnormalities and poorer performance on neuropsychological tests. Therefore, it is important to consider smoking status in alcoholism studies and vice versa.

Social cognition deficits and associations with drinking history in alcoholic men and women.

BACKGROUND Previous studies have demonstrated the presence of a social cognition factor as an element of general cognition in healthy control and clinical populations. Recently developed measures of social cognition include the social perception and faces subtests of the Wechsler Advanced Clinical Solutions (ACS) Social Cognition module. While these measures have been validated on various clinical samples, they have not been studied in alcoholics. Alcoholism has been associated with emotional abnormalities and diminished social cognitive functioning as well as neuropathology of brain areas underlying social processing abilities. We used the ACS Social Perception and Faces subtests to assess alcoholism-related impairments in social cognition. METHODS Social cognitive functioning was assessed in 77 abstinent alcoholic individuals (37 women) and 59 nonalcoholic control participants (29 women), using measures of the ACS Social Cognition module and subtests of the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) that contain a social cognition component (Picture Completion and Comprehension). Group and gender differences in ACS and WAIS-IV performance were assessed, as well as relationships between measures of alcoholism severity and social cognitive functioning. RESULTS Alcoholics performed significantly worse than nonalcoholics on the ACS measures of Affect Naming and Faces Content. Alcoholic men were impaired relative to alcoholic women on Prosody Face Matching and Faces Content scores. Among alcoholics, longer durations of heavy drinking were associated with poorer performance on Affect Naming, and a greater number of daily drinks were associated with lower Prosody Face Matching performance. For alcoholic women, a longer duration of abstinence was associated with better performance on Affect Naming. CONCLUSIONS Alcoholic men and women showed different patterns of associations between alcoholism indices and clinically validated social cognition assessments. These findings extend into the social cognition domain, previous literature demonstrating the presence of cognitive deficits in alcoholism, their association with alcoholism severity, and variability by gender. Moreover, because impairments in social cognition can persist despite extended abstinence, they have important implications for relapse prevention.

Closing the Gender Gap: The Case for Gender-Specific Alcoholism Research

As the number of women who use alcohol increases, so does the number of women who engage in alcohol abuse and develop alcohol dependence. The recent increased focus on women and gender differences in alcoholism research has largely come about following recognition that the face of alcoholism is changing, with alcoholism rates among men remaining stable and rising among women, particularly in younger women. As such, the need to understand gender differences in both acute and long-term effects of alcohol abuse has never been more critical. Gender differences in the long-term effects of chronic alcoholism on the brain and other systems are currently under debate, often with a focus on proclaiming whether men or women suffer the most impact. However, the story appears to be more complex than that. The issue of how alcoholism interacts with gender is complicated, as gender differences in many factors including alcohol metabolism, alcoholism progression, problematic drinking patterns, neurobiology, hormones, and psychiatric comorbidities will contribute to the differences in structural and functional outcomes observed experimentally across domains of inquiry. While women are now much more commonly included in studies of alcohol’s effects on the brain, there remains a need for more explicit examinations of gender effects.

Associations Between Cerebellar Subregional Morphometry and Alcoholism History in Men and Women

BACKGROUND Alcoholism has been linked to deficits in cognitive, behavioral, and emotional functions, and the cerebellum is important for optimal functioning of these abilities. However, little is known about how individual differences such as gender and drinking history might influence regional cerebellar abnormalities. METHODS Volumetric analyses of the cerebellum and its subregions were performed in relation to the interaction of gender and measures of drinking history. Structural magnetic resonance imaging scans of 44 alcoholic individuals (23 men) and 39 nonalcoholic controls (18 men) were obtained. In addition to measuring total cerebellar gray and white matter volumes, we measured 64 individual cerebellar parcellation units, as well as functionally defined a priori regions of interest that have been shown to correspond to functions impaired in alcoholism. RESULTS Total cerebellar white matter volume was smaller in alcoholic relative to nonalcoholic participants. Moreover, volumes of parcellation units varied with drinking history, showing negative associations between years of heavy drinking and the anterior lobe, the vestibulocerebellar lobe, and the spinocerebellar subdivision. The negative association between anterior volume and years of heavy drinking was driven primarily by alcoholic men. Additionally, we observed larger white and gray matter volumes for alcoholic women than for alcoholic men. CONCLUSIONS The identification of drinking-related abnormalities in cerebellar subregions lays a foundation that can be utilized to inform how cerebro-cerebellar networks are perturbed in this pathological condition. These results also provide estimates of how gender and individual differences in drinking history can predict cerebellar volumes.

Measures of skin conductance and heart rate in alcoholic men and women during memory performance

We examined abnormalities in physiological responses to emotional stimuli associated with long-term chronic alcoholism. Skin conductance responses (SCR) and heart rate (HR) responses were measured in 32 abstinent alcoholic (ALC) and 30 healthy nonalcoholic (NC) men and women undergoing an emotional memory task in an MRI scanner. The task required participants to remember the identity of two emotionally-valenced faces presented at the onset of each trial during functional magnetic resonance imaging (fMRI) scanning. After viewing the faces, participants saw a distractor image (an alcoholic beverage, nonalcoholic beverage, or scrambled image) followed by a single probe face. The task was to decide whether the probe face matched one of the two encoded faces. Skin conductance measurements (before and after the encoded faces, distractor, and probe) were obtained from electrodes on the index and middle fingers on the left hand. HR measurements (beats per minute before and after the encoded faces, distractor, and probe) were obtained by a pulse oximeter placed on the little finger on the left hand. We expected that, relative to NC participants, the ALC participants would show reduced SCR and HR responses to the face stimuli, and that we would identify greater reactivity to the alcoholic beverage stimuli than to the distractor stimuli unrelated to alcohol. While the beverage type did not differentiate the groups, the ALC group did have reduced skin conductance and HR responses to elements of the task, as compared to the NC group.

Associations Between Personality and Drinking Motives Among Abstinent Adult Alcoholic Men and Women

Aims Men and women differ in personality characteristics and may be motivated to use alcohol for different reasons. The goals of the present study were to characterize personality and drinking motives by gender and alcoholism status in adults, and to determine how alcoholism history and gender are related to the associations between personality traits and drinking motivation. Methods Personality characteristics were assessed with the Eysenck Personality Questionnaire, which includes Extraversion, Neuroticism, Psychoticism and Lie (Social Conforming) scales. To evaluate drinking motivation, we asked abstinent long-term alcoholic men and women, and demographically similar nonalcoholic participants to complete the Drinking Motives Questionnaire, which includes Conformity, Coping, Social and Enhancement scales. Results Patterns of personality scale scores and drinking motives differed by alcoholism status, with alcoholics showing higher psychopathology and stronger motives for drinking compared with controls. Divergent gender-specific relationships between personality and drinking motives also were identified, which differed for alcoholics and controls. Conclusion Alcoholic and control men and women differed with respect to the associations between personality traits and motives for drinking. A better understanding of how different personality traits affect drinking motivations for alcoholic men and women can inform individualized relapse prevention strategies. Short Summary Men and women differed in their personality traits and their motivations for drinking, and these relationships differed for abstinent alcoholic and control groups. Additionally, alcoholics scored higher on Neuroticism and Psychoticism personality traits, and had lower Enhancement and Social Conformity drinking motives than nonalcoholic controls.

Alcoholism and sexual dimorphism in the middle longitudinal fascicle: a pilot study.

Alcoholism can lead to a complex mixture of cognitive and emotional deficits associated with abnormalities in fronto-cortico-striatal-limbic brain circuitries. Given the broad variety of neurobehavioral symptoms, one would also expect alterations of postrolandic neocortical systems. Thus, we used diffusion tensor imaging (DTI) to study the integrity of the middle longitudinal fascicle (MdLF), a major postrolandic association white matter tract that extends from the superior temporal gyrus to the parietal and occipital lobes, in individuals with a history of chronic alcohol abuse. DTI data were acquired on a 3 Tesla scanner in 30 abstinent alcoholics (AL; 9 men) and 25 nonalcoholic controls (NC; 8 men). The MdLF was determined using DTI-based tractography. Volume of the tract, fractional anisotropy (FA), radial (RD), and axial (AD) diffusivity, were compared between AL and NC, with sex and hemispheric laterality as independent variables. The association of DTI measures with neuropsychological performance was evaluated. Men showed bilateral reduction of MdLF volume and abnormal diffusion measurements of the left MdLF. Analyses also indicated that the left MdLF diffusion measurements in AL men were negatively associated with Verbal IQ and verbal fluency test scores. Abstinent alcoholic men display macrostructural abnormalities in the MdLF bilaterally, indicating an overall white matter deficit. Additionally, microstructural deficits of the left MdLF suggest more specific alterations associated with verbal skills in men.

Gender dimorphism of white matter integrity assessed by diffusion tensor magnetic resonance imaging in abstinent alcoholic men and women

Background Alcoholism is a debilitating disorder associated with widespread cognitive and neurological abnormalities. However, there is limited scientific literature evaluating gender-specific similarities and differences in microstructural white matter pathology associated with alcoholism. In our prior work, we used diffusion tensor magnetic resonance imaging to examine the integrity of white matter fiber tracts in the brains of abstinent alcoholic (ALC) men compared with nonalcoholic (NC) men. We found that ALC men had decreased fractional anisotropy (FA) within white matter fiber tracts connecting to frontal and limbic networks, primarily of the right hemisphere (Harris et al., 2008). In the current project, we sought to confirm our prior findings in abstinent ALC men and, additionally, examine whether different white matter abnormalities were present in abstinent ALC women. Methods As determined by our manual inspection, 60-direction high-quality diffusion tensor imaging images were acquired from 30 abstinent (at least 4 weeks) ALC participants (21 women) and 25 NC controls (17 women). Tract-based spatial statistics tools included in FSL 5.0 were used to analyze a tensor model that yielded regional FA values for each participant. To examine the effects of gender, we built a 2 X 2 ANOVA design with three planned comparisons of primary interest: ALC group-by-gender interaction, ALC women versus NC women, and ALC men versus NC men. Results We observed FA deficits in ALC men relative to NC men, with a similar effect size and variability as observed in our prior study. In contrast, ALC women displayed strikingly greater FA values compared to NC women in widespread white matter regions, including most principal long-association fiber tracts. Also, they had greater FA for local white matter architecture in the dorsolateral and ventral prefrontal regions, as well as the sublenticular extended amygdala. When controlling for multiple comparisons, the higher FA observed in ALC women remained significant. For many regions, groupby-gender interaction effects were observed. However, likely due to the small sample sizes for men, the interaction effects did not survive threshold-free cluster enhancement, the correction procedure for multiple comparisons used in these analyses. Conclusions These results suggest antithetical gender abnormalities in white matter tracts of ALC brains. Whereas abstinent ALC men displayed deficits consistent with our prior study, our new findings for abstinent ALC women demonstrated increased FA values. These distinct patterns of white matter abnormalities point toward a differential underlying neural basis for gender-specific propensity and/or sequelae to long-term alcoholism, and suggest implications for further investigation of possible gender-specific approaches to prevention and treatment.