Contribution of alcoholism to brain dysmorphology in HIV infection: effects on the ventricles and corpus callosum.

Nonrigid registration and atlas-based parcellation methods were used to compare the volume of the ventricular system and the cross-sectional area of the midsagittal corpus callosum on brain MRIs from 272 subjects in four groups: patients with HIV infection, with and without alcoholism comorbidity, alcoholics, and controls. Prior to testing group differences in regional brain metrics, each measure was corrected by regression analysis for significant correlations with supratentorial cranial volume and age, observed in 121 normal control men and women, whose age spanned six decades. Disregarding HIV disease severity, we observed a graded pattern of modest enlargement of the total ventricular system (0.28 SD for uncomplicated HIV, 0.65 SD for HIV comorbid with alcoholism, and 0.72 SD for the alcoholism group). The pattern of callosal thinning showed a similar but small ( approximately 0.5 SD) graded effect. A different pattern emerged, however, when HIV severity in the context of alcoholism comorbidity was factored into the analysis. Substantially greater volume abnormalities were present in individuals with a history of an AIDS-defining event or low CD4+ T cell counts (<or=200 mm(3)) irrespective of alcoholism comorbidity, and the effect of HIV severity was disproportionately exacerbated by alcoholism comorbidity, with 1 SD size deficit in the genu of corpus callosum and nearly 2 SD greater volume of the frontal and body regions of the ventricles for the AIDS + alcohol comorbid group. The differences in brain volumes between the AIDS groups with vs. without alcoholism could not be attributed to differences in HIV disease severity, defined by CD4+ count, viral load, or Karnofsky score. The substantial effect of the alcoholism-AIDS interaction on ventricular and callosal dysmorphology, in the context of the modest changes observed in non-AIDS, nonalcohol abusing HIV-infected individuals, highlight the need to consider alcohol use disorders as a major risk factor for neuropathology among HIV-infected persons.