Chronic active heavy drinking and family history of problem drinking modulate regional brain tissue volumes

https://doi.org/10.1016/j.pscychresns.2005.01.002Get rights and content

Abstract

The goals of this study were to measure if chronic active heavy drinking is associated with brain volume loss in non-treatment seeking men and women, and to assess the effect of positive family history of problem drinking on brain structure in heavy drinkers. Automated image processing was used to analyze high-resolution T1-weighted magnetic resonance images from 49 active heavy drinkers and 49 age- and sex-matched light drinkers, yielding gray matter, white matter and cerebrospinal fluid (CSF) volumes within the frontal, temporal, parietal and occipital lobes. Regional brain volume measures were compared as a function of group, sex and their interaction. Within heavy drinkers, volumes were correlated with measures of alcohol consumption and compared as a function of family history of problem drinking. Deformation morphometry explored localized patterns of atrophy associated with heavy drinking or severity of drinking. We found significant gray matter volume losses, but no white matter losses, in active heavy drinkers compared with light drinkers. Women had greater gray matter and smaller white matter and CSF volumes as a percentage of intracranial vault than men. Within heavy drinkers, smaller gray matter volumes were associated with higher current levels of drinking and older age, while a positive family history of problem drinking was associated with smaller CSF volumes. Community-dwelling heavy drinkers who are not in alcoholism treatment have dose-related gray matter volume losses, and family history of problem drinking ameliorates some structural consequences of heavy drinking.

Introduction

Magnetic resonance imaging (MRI) has been used to study the effects of chronic alcohol consumption on the brain in alcoholics (for reviews, cf. Rosenbloom et al., 1995, Sullivan et al., 2000b). Enlarged ventricles and sulci are commonly seen in alcoholics (Jernigan et al., 1991b, Hayakawa et al., 1992, Pfefferbaum et al., 1992), and studies have demonstrated loss of volume in localized regions of cortical gray matter (GM: frontal-parietal and temporal cortex), white matter (WM: frontal-parietal, corpus callosum), cerebellum (Shear et al., 1996, Sullivan et al., 2000a) and subcortical structures including thalamus, hypothalamus and caudate (Jernigan et al., 1991a, Jernigan et al., 1991b, Pfefferbaum et al., 1992, Charness, 1993, Hommer et al., 1995, Sullivan et al., 1995b, Pfefferbaum et al., 1996, Sullivan et al., 1996). The greater the age (older), the more severe the GM and WM losses (Pfefferbaum et al., 1992). It has been suggested that women's brains are more vulnerable to the effects of alcohol than men's, but findings have been inconsistent (Jacobson, 1986, Mann et al., 1992, Hommer et al., 2001, Pfefferbaum et al., 2001).

Most previous studies examined individuals in substance abuse treatment programs who were abstinent from alcohol for several weeks at the time of study (recovering alcoholics). Previously, we reported that structural brain changes in treatment-naïve, heavily drinking men were less severe than those found in alcoholics receiving treatment (Fein et al., 2002). In contrast to previous studies of alcoholics in treatment, we found GM atrophy in the frontal and parietal lobes but did not observe WM loss in any region. Because this study focused on cortical regions of interest defined by Brodmann areas, WM effects may have been underestimated. Also, because this earlier study only included men, it did not address gender effects on brain tissue loss in active heavy drinkers.

Children and adolescents with a positive family history of problem drinking and thus at higher risk of developing alcoholism later in life have been extensively studied using a variety of techniques. A wide range of cognitive deficits have been reported in these populations (Drejer et al., 1985, Knop et al., 1985, Berman et al., 1993, Hill and Steinhauer, 1993, Polich et al., 1994), and structural and metabolic brain changes may underlie these cognitive deficits. Because heavy drinkers with a positive family history of problem drinking may have reduced brain volumes before the onset of drinking (Hill et al., 2001), they may continue to have smaller brain volumes than heavy drinkers without a family history of problem drinking. This is particularly true if such premorbid brain structure abnormalities in family-history-positive (FHP) heavy drinkers render the brain vulnerable to the effects of alcohol because of limited reserve capacity.

Nearly all of the previous MRI studies of the effects of alcohol on the brain, including our previous studies (Di Sclafani et al., 1995, Fein et al., 2002), used computer segmentation of relatively low-resolution images into GM, WM and cerebrospinal fluid (CSF), often combined with manual or automated tracing of regions of interest (ROIs). Recent image-processing innovations have improved methodology for tissue segmentation of high resolution T1-weighted images (Wells et al., 1996, Van Leemput et al., 1999, Ashburner and Friston, 2000, Shattuck et al., 2001) and automated atlas-based identification of ROIs using nonlinear registration techniques (Gee et al., 1993, Collins et al., 1995, Iosifescu et al., 1997, Dawant et al., 1999). Probabilistic segmentation of high-resolution images should reduce partial volume errors and lead to more valid tissue volume estimates, and automated ROI delineation removes human error. Combined use of these MRI analyses may reveal subtle structural brain volume differences between groups that were obscured by cruder image-processing methods. Deformation tensor morphometry (Davatzikos et al., 1996, Machado et al., 1998, Gaser et al., 1999, Studholme et al., 2001a) is a relatively new method that quantifies shape differences between brains without a priori definitions of ROIs. This method should be more sensitive to focal effects of heavy drinking that may be obscured by examination of large ROIs.

The goals of this study were to replicate our previous finding (Fein et al., 2002) of regional brain volume differences due to active heavy drinking and severity of drinking, estimate gender effects of active heavy drinking, and examine the effects of family history of problem drinking on brain structure. These goals were achieved by using a high resolution and atlas-based probabilistic segmentation method, and deformation tensor morphometry. Specifically, we tested the following a priori hypotheses: (1) long-term heavy drinking is associated with reductions of cortical gray matter and white matter, with greatest reductions in the frontal and parietal lobes; (2) at comparable levels of drinking, active heavily drinking women have greater gray matter and white matter reductions than men; (3) lobar gray and white matter volumes within heavy drinkers are negatively correlated with severity of drinking; and (4) FHP heavy drinkers have smaller brain volumes compared to family-history-negative (FHN) heavy drinkers.

Section snippets

Subjects

Light drinkers (LD) and heavy drinkers (HD) were recruited into a study examining the effects of HIV (human immunodeficiency virus) and chronic alcohol consumption on central nervous system morbidity. The study received institutional review board approval, and patient informed consent was obtained. Here we describe a subset of 49 LD (40 men and 9 women) and 49 HD (40 men and 9 women) matched for age and sex drawn from HIV-seronegative subjects. Table 1 lists demographic and alcohol use

Effects of heavy drinking

Table 2 shows the CSF, WM and GM volumes for each lobar ROI for male and female LDs and HDs as % of ICV. Within the GM, there were overall significant main effects of age [F(4,91)=9.93, P<0.0001], heavy drinking [F(4,91)=3.17, P=0.02] and gender [F(4,91)=6.51, P=0.0001], but the heavy drinking×age and heavy drinking×gender interactions were not significant, despite much larger %GM reductions in women than men (see Table 2). The individual ANCOVAs showed that %GM volumes decreased with age in

Discussion

We used atlas-based ROI identification together with high resolution tissue segmentation and deformation morphometry to measure structural brain changes in active HDs. Our major findings were (1) HD men and women have less cortical GM than LD men and women, with quantitatively similar reductions in the temporal, parietal and occipital lobes, but not the frontal lobe; (2) reductions of GM due to heavy drinking were not statistically greater in women than men, although all women had more GM (and

Acknowledgments

This manuscript is dedicated to the memory of Linda Rogers, Ph.D. (1946–2003), for valuable discussions and advice on statistical data analysis. This work was funded by grant number P01 AA11493 (M.W.W.), and in part by R01 AA10788 (D.J.M.), R01 MH65392 (C.S.) and Whitaker foundation award RG-01-0115 (C.S.). We thank George Fein, PhD, the initial PI of the program project grant, John Kornak, PhD for help with statistics, and Diana Truran and her staff for scanning all of our highly appreciated

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