Association of frontal and posterior cortical gray matter volume with time to alcohol relapse: a prospective study

Abstract

Objective: Alcoholism is associated with gray matter volume deficits in frontal and other brain regions. Whether persistent brain volume deficits in abstinence are predictive of subsequent time to alcohol relapse has not been established. The authors measured gray matter volumes in healthy volunteers and in a sample of treatment-engaged, alcohol-dependent patients after 1 month of abstinence and assessed whether smaller frontal gray matter volume was predictive of subsequent alcohol relapse outcomes.

Method: Forty-five abstinent alcohol-dependent patients in treatment and 50 healthy comparison subjects were scanned once using high-resolution (T(1)-weighted) structural MRI, and voxel-based morphometry was used to assess regional brain volume differences between the groups. A prospective study design was used to assess alcohol relapse in the alcohol-dependent group for 90 days after discharge from 6 weeks of inpatient treatment.

Results: Significantly smaller gray matter volume in alcohol-dependent patients relative to comparison subjects was seen in three regions: the medial frontal cortex, the right lateral prefrontal cortex, and a posterior region surrounding the parietal-occipital sulcus. Smaller medial frontal and parietal-occipital gray matter volumes were each predictive of shorter time to any alcohol use and to heavy drinking relapse.

Conclusions: These findings are the first to demonstrate that gray matter volume deficits in specific medial frontal and posterior parietal-occipital brain regions are predictive of an earlier return to alcohol use and relapse risk, suggesting a significant role for gray matter atrophy in poor clinical outcomes in alcoholism. Extent of gray matter volume deficits in these regions could serve as useful neural markers of relapse risk and alcoholism treatment outcome.

FIGURE 1. Schedule of Procedures for Alcohol-Dependent Patients and Healthy Comparison Subjects in a Study of Gray Matter Volume and Time to Alcohol Relapse^a

^aAlcohol-dependent patients had been in inpatient treatment and abstinent for at least 1 month at the time of MRI scanning. Comparison subjects were assessed within 2 weeks after a research hospital stay. Alcohol-dependent patients were prospectively followed after treatment and participated in face-to-face interviews 14, 30, and 90 days after discharge to assess alcohol relapse outcomes.

FIGURE 2. Significant Clusters of Gray Matter Volume Deficit in Alcohol-Dependent Patients Relative to Healthy Comparison Subjects^a

^aFamily-wise error p<0.025. Panel A shows the right lateral prefrontal cortex with crosshairs at Montreal Neurological Institute (MNI) coordinates x=51, y=40, z=19 (Brodmann’s area 46; dorsolateral prefrontal cortex). Panel B shows the medial frontal cortex with crosshairs at MNI coordinates x=−5, y=1, z=50 (Brodmann’s area 24; anterior cingulate gyrus). Panel C shows the posterior region, including the area surrounding the parietal-occipital sulcus, with the crosshairs at MNI coordinates x=8, y=−58, z=18 (Brodmann’s area 31; posterior cingulate). These results were overlaid on the SPM template single_subj_T1 in MNI space. Only statistically significant clusters are displayed.

FIGURE 3. Estimated Survival Risk Functions and Receiver Operating Characteristic Curves for Gray Matter Volumes in Specific Significant Brain Regions in Alcohol-Dependent Patients (N=44)^a

^aPanels A and B present estimated survival risk functions (with mean age, IQ, and baseline total amount of alcohol consumed held constant) for mean gray matter volumes as well as for volumes one and two standard deviations above and below the mean for the medial frontal cluster (panel A; cluster χ²=6.7, p<0.009; hazard ratio=0.52, 95% CI=0.31–0.85) and the parietal-occipital cluster (panel B; χ²=9.28, p<0.002; hazard ratio=0.52, 95% CI=0.34-0.79). Although the survival function was a 90-day analysis, the graphs are cut off at day 60 because all alcohol-dependent patients with gray matter volumes two standard deviations below the mean for each of the two regions relapsed by day 60. For patients with volumes two standard deviations above the mean in the medial frontal cluster, the estimated survival function at day 60 spans a 0.68 (68%) proportion of surviving relapse, and for those with volumes two standard deviations above the mean in the parietal-occipital cluster, a 0.66 (66%) proportion, whereas for patients with volumes two standard deviations below the mean, the estimated survival function at day 60 for both regions spans only a 0.02% chance of surviving relapse. Panel C shows receiver operating characteristic (ROC) curves for the medial frontal (area under the curve=0.83; 95% CI=0.65–0.96), lateral frontal (area under the curve=0.75, 95% CI=0.55–0.89), and parietal-occipital clusters (area under the curve=0.70, 95% CI=0.49–0.86). The optimal gray matter volume cutoff values are circled in the ROC curves for each of the three regions that best differentiated between those who relapsed and those who did not (medial frontal cluster: χ²=7.04, df=1, 44, p<0.008; odds ratio=0.25, 95% CI=0.09–0.70; correctly classified 80% of relapsers at a 93.3% sensitivity and 50% specificity; optimal cutoff value=8.41; lateral frontal cluster: χ²=4.23, df=1, 44, p<0.04; odds ratio=0.56, 95% CI=0.32–0.97; correctly classified 71% of relapsers at a 83.3% sensitivity and 42.9% specificity; optimal cutoff value=10.6; parietal-occipital cluster: χ²=3.86, df=1, 44, p<0.05; odds ratio=0.47, 95% CI=0.22–0.99; correctly classified 66% of relapsers at a 90% sensitivity and 14.3% specificity; optimal cutoff value=10.4).