The Effects of HIV on P300 are Moderated by Familial Risk for Substance Dependence: Implications for a Theory of Brain Reserve

Abstract Background The goal of the study was to test the validity of additive versus synergistic versus underadditive versions of brain reserve theory within the context of HIV/AIDS. In addition, it tested the convergent validity of 2 operational definitions of premorbid reserve: verbal IQ (VIQ) and a family history (FH) of substance abuse or dependence. Methods Seventy HIV-1 seronegative and 115 HIV-1 seropositive male and female volunteers were assigned to 4 subgroups defined by the crossing of a VIQ score \u3c versus ≥ 90 with the presence versus absence of a paternal history of alcohol, cocaine, or opiate abuse or dependence. The principal dependent measure was the P300 event related brain potential elicited during the Stroop color-word interference task. Results The principal finding was an underadditive effect of FH plus HIV/AIDS on P300 area over the frontal region: FH reduced frontal scalp P300 to such a degree that the additional effects of HIV/AIDS were blunted. The alternate operational definition of brain reserve, VIQ, had no effect on P300 and did not alter the effects of HIV/AIDS. Conclusions Familial risk for substance dependence and low VIQ compromise different aspects of brain structure and/or function and therefore differ in their relationship to HIV/AIDS and P300. Genetic differences associated with familial risk may reduce brain reserve to such a degree that the neurophysiological effects of HIV/AIDS can no longer be measured