Neurochemical alterations in adolescent chronic marijuana smokers: a proton MRS study

Abstract

Converging evidence from neuroimaging and neuropsychological studies indicates that heavy marijuana use is associated with cingulate dysfunction. However, there has been limited human data documenting in vivo biochemical brain changes after chronic marijuana exposure. Previous proton magnetic resonance spectroscopy studies have demonstrated reduced basal ganglia glutamate and dorsolateral prefrontal cortex N-acetyl aspartate levels in adult chronic marijuana users. Similar studies have not been reported in adolescent populations. The present study used proton magnetic resonance spectroscopy to determine whether reductions in glutamate, N-acetyl aspartate and/or other proton metabolite concentrations would be found in the anterior cingulate cortex (ACC) of adolescent marijuana users compared with non-using controls. Adolescent marijuana users (N=17; average age 17.8 years) and similarly aged healthy control subjects (N=17; average age 16.2 years) were scanned using a Siemens 3T Trio MRI system. Proton magnetic resonance spectroscopy data were acquired from a 22.5 mL voxel positioned bilaterally within the ACC. Spectra were fitted using commercial software and all metabolite integrals were normalized to the scaled unsuppressed water integral. Analysis of variance and analysis of covariance were performed to compare between-group metabolite levels. The marijuana-using cohort showed statistically significant reductions in anterior cingulate glutamate (-15%, p<0.01), N-acetyl aspartate (-13%, p=0.02), total creatine (-10%, p<0.01) and myo-inositol (-10%, p=0.03). Within-voxel tissue-type segmentation did not reveal any significant differences in gray/white matter or cerebrospinal fluid content between the two groups. The reduced glutamate and N-acetyl aspartate levels in the adolescent marijuana-using cohort are consistent with precedent human (1)H MRS data, and likely reflect an alteration of anterior cingulate glutamatergic neurotransmission and neuronal integrity within these individuals. The reduced total creatine and myo-inositol levels observed in these subjects might infer altered ACC energetic status and glial metabolism, respectively. These results expand on previous functional MRI data reporting altered cingulate function in individuals with marijuana-abuse.

Copyright © 2011 Elsevier Inc. All rights reserved.

Figures

Figure 1

(a) A single tissue-segmented axial slice extracted from a 3D MPRAGE dataset recorded from a 19 year-old female MJ subject. WM, GM and CSF are represented by white, light gray and dark gray pixels, respectively. (b) The corresponding single tissue-segmented sagital slice extracted from the same MPRAGE dataset. The black rectangle depicts the positioning of the MRS voxel within the ACC, which was obliqued along the sagital dimension. For this subject, GM, WM and CSF tissue fractions were estimated to be 67, 23 and 10%, respectively.

Figure 2

LC-Model fitted PRESS 1H-MRS data recorded from a 13 year-old HC subject (a) and a 19 year-old MJ subject (b). The black line spectra correspond to the ‘raw’ 1H-MRS data with the LC-Model fits overlaid as red line spectra. The residual spectra (raw data minus the LC-Model fit) are displayed below each spectrum. The signal assignments displayed in (a) are based on (Govinduraju et al. 2000) and can be directly translated to spectrum (b).

Figure 3

Metabolite/water ratios measured for 6 metabolites in the HC and MJ cohorts. Group mean values are shown and the error bars represent SD.