Additive effects of HIV and chronic methamphetamine use on brain metabolite abnormalities

Abstract

Objective: Proton magnetic resonance spectroscopy (1H-MRS) showed decreased neuronal marker N-acetylaspartate and increased glial marker myo-inositol in subjects with chronic methamphetamine use and in subjects infected with HIV. The authors sought to determine whether HIV and a history of chronic methamphetamine use might have additive or interactive effects on brain metabolite abnormalities.

Method: 1H-MRS was performed in 68 HIV-positive subjects (24 with a history of chronic methamphetamine use with a lifetime exposure of a mean of 2,167 g [SD=2,788] and last use a mean of 4.9 months earlier [SD=6.0]; 44 with no history of drug abuse) and 75 HIV-negative subjects (36 with a history of chronic methamphetamine use with a lifetime exposure of a mean of 8,241 g [SD=16,850] and last use a mean of 6.3 months earlier [SD=7.8]; 39 with no history of drug abuse). Concentrations of N-acetylaspartate, creatine, choline, and myo-inositol were measured in the frontal cortex, frontal white matter, and basal ganglia.

Results: HIV-negative subjects with a history of chronic methamphetamine use showed lower concentrations of the neuronal marker N-acetylaspartate in the frontal white matter and basal ganglia and higher concentrations of choline compounds and the glial marker myo-inositol in the frontal cortex, relative to subjects with no history of drug abuse. HIV-positive status was associated with lower concentrations of N-acetylaspartate and creatine in the frontal cortex and higher concentrations of myo-inositol in the white matter, compared with HIV-negative status. Compared to the mean concentrations of metabolites in HIV-negative subjects with no history of drug abuse, the mean concentrations in subjects with HIV and chronic methamphetamine use showed additive effects on N-acetylaspartate in all three regions (-9% in the basal ganglia, -7% in the frontal white matter, and -6% in the frontal gray matter), on creatine in the basal ganglia (-7%), and on myo-inositol in the frontal white matter (+11%).

Conclusions: The combined effects of HIV and chronic methamphetamine use were consistent with an additive model, suggesting additional neuronal injury and glial activation due to the comorbid conditions.

FIGURE 1

Sagittal T₁-Weighted MRI Scan Showing the Locations of Center Slices and Axial Inversion Recovery Images Showing Voxels in Three Brain Regions Examined With Proton Magnetic Resonance Spectroscopy

FIGURE 2

Concentrations of N-Acetylaspartate, Creatine, Choline, and myo-Inositol in Three Brain Regions in HIV-Positive and HIV-Negative Subjects With and Without a History of Chronic Methamphetamine Use ^a Significant −6% difference between groups (t=2.37, df=57, p=0.02). ^b Significant −4% difference between groups (t=1.92, df=70, p=0.05). ^c Significant −6% difference between groups (t=2.21, df=60, p=0.03). ^d Significant −5% difference between groups (t=2.39, df=66, p=0.02). ^e Significant −5% difference between groups (t=2.59, df=57, p=0.01). ^f Significant −5% difference between groups (t=2.35, df=57, p=0.02). ^g Significant −9% difference between groups (t=4.16, df=60, p=0.0001). ^h Significant −4% difference between groups (t=2.21, df=70, p=0.03). ⁱ Significant −6% difference between groups (t=2.23, df=75, p=0.02). ^j Significant −5% difference between groups (t=2.11, df=55, p=0.04). ^k Significant −6% difference between groups (t=2.51, df=66, p=0.01). ^l Significant −7% difference between groups (t=2.80, df=60, p=0.007). ^mSignificant 15% difference between groups (t=3.51, df=57, p=0.0009). ⁿ Significant 11% difference between groups (t=2.45, df=56, p<0.02). ^o Significant 14% difference between groups (t=3.49, df=72, p=0.0008). ^p Significant 14% difference between groups (t=3.20, df=63, p=0.002). ^q Significant 12% difference between groups (t=2.41, df=56, p=0.02). ^r Significant 8% difference between groups (t=1.96, df=75, p=0.05). ^s Significant 10% difference between groups (t=2.27, df=72, p=0.02). ^t Significant 10% difference between groups (t=2.37, df=62, p=0.02).