Lower glutamate levels in rostral anterior cingulate of chronic cocaine users - A (1)H-MRS study using TE-averaged PRESS at 3 T with an optimized quantification strategy - PubMed (original) (raw)

Lower glutamate levels in rostral anterior cingulate of chronic cocaine users - A (1)H-MRS study using TE-averaged PRESS at 3 T with an optimized quantification strategy

Shaolin Yang et al. Psychiatry Res. 2009.

Abstract

Previous studies have shown significantly lower metabolism and functional activity in the anterior cingulate cortex (ACC) of human cocaine addicts. The present study examined whether this ACC hypoactivity is associated with altered glutamate (Glu), the primary excitatory neurotransmitter in the central nervous system (CNS), which has been recently implicated in drug addiction. Participants comprised 14 chronic cocaine addicts and 14 matched healthy volunteers who were examined using (1)H magnetic resonance spectroscopy at 3 T. A new quantification strategy for echo time (TE)-averaged point-resolved spectroscopy (PRESS) was applied to disentangle relaxation effects from J-evolution of coupled spin systems such as Glu. The concentrations of Glu as well as N-acetyl aspartate (NAA), total creatine (tCr), choline-containing compounds (tCho), and myo-inositol (Ins) were estimated from both groups. Glu/tCr was significantly lower in chronic cocaine users compared to control subjects and was significantly correlated with years of cocaine use. Glu/tCr was also positively correlated with NAA/tCr. NAA/tCr significantly decreased with age but was not significantly different between the two groups. These findings suggest a metabolic/neurotransmitter dysregulation associated with cocaine addiction and support a possible therapeutic intervention strategy aimed at normalizing the Glu transmission and function in the treatment of cocaine addiction.

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Figures

Fig. 1

Fig. 1

Simulated PRESS spectra of tCr and Glu at multiple TEs (TE = 35 ms, 85 ms, 135 ms, 185 ms, and 235 ms, respectively), in which relaxation was not considered in the simulation. The singlet resonances of tCr at 3.02 ppm and 3.92 ppm remain unchanged through different TEs. In contrast, due to _J_-evolution of coupled spins, the C4 proton resonance of Glu at 2.35 ppm (Glu4), the C3 proton resonance of Glu around 2.08 ppm (Glu3), and the C2 proton resonance of Glu at 3.75 ppm (Glu2) demonstrate complex variation with TE.

Fig. 2

Fig. 2

TE-averaged PRESS spectrum acquired from a single voxel (white box) encompassing the rACC of a healthy volunteer (NAA = _N_-acetyl aspartate, tCr = total creatine, tCho = choline-containing compounds, Glu = glutamate, and Ins = _myo_-inositol).

Fig. 3

Fig. 3

Metabolite levels (in ratio to tCr) in the rACC of chronic cocaine users (red) and healthy controls (yellow) (NAA = _N_-acetyl aspartate, tCr = total creatine, tCho = choline-containing compounds, Glu = glutamate, and Ins = _myo_-inositol). Glu/tCr is significantly lower (15.88%) (F1,25=10.2; p < 0.005) in the cocaine-user group compared to the control group, after correcting for age. The thick light-green lines mark the mean values and the thin black lines mark the median values. Bars indicate the 5th/95th percentiles.

Fig. 4

Fig. 4

Significant positive correlation between Glu/tCr and NAA/tCr (Glu = glutamate, NAA = _N_-acetyl aspartate, and tCr = total creatine) (partial R = 0.503; p < 0.01), accounting for age, in the rACC of chronic cocaine users (red) and healthy controls (yellow).

Fig. 5

Fig. 5

Significant positive correlation between Glu/tCr and years of cocaine use (Glu = glutamate and tCr = total creatine) (partial R = 0.579; p<0.05), accounting for age and current cocaine use, in the rACC of chronic cocaine users (red). The mean and standard deviation of Glu/tCr in the control group (blue) are also shown for comparison.

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