Interactive effects of HIV/AIDS, body mass, and substance abuse on the frontal brain: A P300 study

Abstract

In view of the rising prevalence of an overweight body mass among patients living with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), clinicians must now be mindful of possible adverse outcomes resulting from the co-occurrence. The present study was designed to examine the additive and interactive effects of HIV/AIDS and an excess body mass, as well as the additional contributions of substance abuse or dependence. The dependent variable was brain function estimated by the measurement of P300 electroencephalographic potentials. P300 potentials were recorded during a task designed to elicit subcomponents with frontal (P300a) and both frontal and non-frontal (P300b) generators. Analyses revealed greater frontal P300a latencies among the 102 HIV-1 seropositive versus the 68 seronegative participants. In addition, frontal P300a latency was further increased by a synergistic interaction of HIV-1 serostatus with a body mass index (BMI) ≥ 25 kg/m². A history of substance abuse/dependence did not alter these changes. However, it did combine with HIV/AIDS to produce a smaller P300a amplitude than was seen in participants with neither disorder. The findings suggest that white matter changes accompanying an excess BMI may exacerbate those that attend HIV/AIDS and thereby slow down frontal brain function. Substance abuse, likewise, interacts with HIV/AIDS but may impair frontal brain function via a different mechanism.

Introduction

Loss of weight and lean muscle mass are common features of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS; Tang et al., 2005). Many causes have been described, including nausea and fatigue precipitated by the disease and its treatment as well as HIV-related abnormalities in gastrointestinal and hepatic function. If severe, weight loss can be a sign of a poor prognosis, including a more rapid progression to death (Shor-Posner et al., 2000, Tang et al., 2002).

Although weight loss remains problematic for many patients, its incidence and prevalence have declined dramatically in recent years. In the U.S. Multicenter AIDS Cohort Study, for example, incidence declined from a peak of 22.1 per 1000 person-years in 1994–1995 to 13.4 in 1996–1999 (Smit et al., 2002). Similarly, Hodgson and colleagues (Hodgson et al., 2001) reported a 77% decline in the prevalence of wasting as an AIDS-defining event from a survey of 162 HIV/AIDS cases studied between 1992 and 2001 in the United Kingdom. Other surveys have yielded comparable results (Mocroft et al., 1999, Dworkin and Williamson, 2003). The declining occurrence of wasting and weight loss coincides with the increased availability and prescription of Highly Active Antiretroviral Therapy (HAART) and is often attributed to that cause. Across multiple studies, protease-inhibitor-based HAART has been associated with many factors that either promote or accompany weight gain, including insulin resistance (Walli et al., 1998), hyperglycemia (Dever et al., 2000, Tsiodras et al., 2000), new onset Type 2 diabetes mellitus (Justman et al., 2003, Ledergerber et al., 2007), hyperlipidemia (Mulligan et al., 2005, Rimland et al., 2006), lipodystrophy (McDermott et al., 2001), and the metabolic syndrome.

Because of HAART, excess body weight is emerging as a new and unexpected threat to the HIV-1 seropositive community. The results of a recent analysis (Bauer, 2008c) support this assertion. In the analysis, obesity was a prevalent condition, affecting 30.1% of the 159 HIV-1 seropositive patients. This rate is greater than the 9–28% prevalence rates reported in previous studies (Shor-Posner et al., 2000, Hodgson et al., 2001, Amorosa et al., 2005, Jacobson et al., 2006) of HIV/AIDS patients and exceeds the 25.6% rate found in U.S. adults generally (CDC, 2008).

In view of the rising prevalence of overweight/obesity (Amorosa et al., 2005) among seropositive patients, clinicians must now be mindful of possible adverse outcomes resulting from the combination. The most obvious areas for interaction are the heart and vasculature. Both disorders are known to increase risk for atherosclerosis, diabetes, and myocardial infarction.

An additional area for interaction is the white matter of the brain. HIV/AIDS has been shown to demyelinate fronto-striatal white matter tracts in autopsy studies, increase the number of white matter abnormalities or hyperintensities in magnetic resonance imaging (MRI) studies (Pfefferbaum et al., 2007), and slow down the neural processing of auditory, visual, or somatosensory information in evoked electroencephalographic potential studies (Harrison et al., 1998, Chao et al., 2004). Interestingly, within the brain, obesity is also, primarily, a white matter disease. An increased waist-to-hip ratio (Jagust et al., 2005) or body mass index (BMI; Gazdzinski et al., 2008) is associated with an increase in the prevalence of white matter abnormalities in MRI — an increase that can be partially reversed through dieting and weight loss (Haltia et al., 2007). In addition, an overweight body mass increases the latencies of some evoked electroencephalographic potentials (Bauer et al., submitted for publication).

The potential therefore exists for HIV/AIDS and overweight/obesity to act synergistically. The goal of the present study was to evaluate the independent and interactive effects of HIV/AIDS and a BMI ≥ 25 kg/m² on an estimate of white matter integrity. It also evaluated the contribution of a history of substance abuse/dependence — a common disorder among HIV/AIDS patients (Bing et al., 2001, Galvan et al., 2002) — to this relationship. To eliminate the potential confounding effect of childhood Conduct Disorder — a neurodevelopmental disorder which precedes and promotes HIV (Bauer and Shanley, 2006), excess BMI (Anderson et al., 2006), and substance abuse — as well as depression symptoms that also accompany these disorders, the number of Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) childhood Conduct Disorder criteria and the Beck Depression Inventory score were entered as covariates in the analysis.

To assess the effects of HIV/AIDS, excess body mass, and substance abuse/dependence, the study employed simple, non-invasive measures of brain function that could, unlike functional magnetic resonance imaging, be practically used to evaluate participants whose body weights (> 300 lbs) or trunk diameters (> 60 cm) exceed the physical limits of most research scanners. The indices were the P300a and P300b components of the event-related electroencephalographic potential (ERP). The latencies of these components are inversely correlated with the integrity of white matter pathways connecting their generators (Cardenas et al., 2005) whereas their amplitudes are more closely related to the gray matter volumes of the generators themselves (Egan et al., 1994, McCarley et al., 2002). P300a is generated frontally. In contrast, the P300b has a diffuse distribution of frontal and non-frontal generators (Halgren et al., 1998, Clark et al., 2000).