Quantifying GABA in Addiction: A Review of Proton Magnetic Resonance Spectroscopy Studies

Abstract

Gamma-aminobutyric acid (GABA) signaling plays a crucial role in drug reward and the development of addiction. Historically, GABA neurochemistry in humans has been difficult to study due to methodological limitations. In recent years, proton magnetic resonance spectroscopy (1H-MRS, MRS) has emerged as a non-invasive imaging technique that can detect and quantify human brain metabolites in vivo. Novel sequencing and spectral editing methods have since been developed to allow for quantification of GABA. This review outlines the clinical research utilization of 1H-MRS in understanding GABA neurochemistry in addiction and summarizes current literature that reports GABA measurements by MRS in addiction. Research on alcohol, nicotine, cocaine, and cannabis addiction all suggest medications that modulate GABA signaling may be effective in reducing withdrawal, craving, and other addictive behaviors. Thus, we discuss how improvements in current MRS techniques and design can optimize GABA quantification in future studies and explore how monitoring changes to brain GABA could help identify risk factors, improve treatment efficacy, further characterize the nature of addiction, and provide crucial insights for future pharmacological development.

Recent advances in microfluidics-based bioNMR analysis

“…6,8 Currently, this technology has made a profound impact on a wide range of fields such as chemistry, 9,10 biology, 11 medicine, 12 agriculture 13 and industry. 14 Among these research fields, biochemical NMR (bioNMR) is a major part of NMR studies. It has been playing an important role in molecular structure analysis, 3,11 proteomics 15 and metabolomics, 16,17 biomarker detection, 18 and in vivo imaging.…”

Impact of acquisition and modeling parameters on test-retest reproducibility of edited GABA+

“…Prior work has reported differences in brain GABA levels across the healthy lifespan [1][2][3] , as well as in various psychiatric 4,5 and neurodegenerative conditions [6][7][8] .…”

“…Reports of intrasubject variability in MRS-measured GABA+ vary widely. Reported testretest within-subject coefficients of variation (CVs) vary from 1% to almost 30% 3,[11][12][13][14][15] . Specific reasons for this wide range of reproducibility remain unclear.…”

“…However, due to its low concentration within the brain and overlapping spectral signatures of higher concentration metabolites, spectral editing is required for accurate in vivo quantification of GABA at 3 Tesla. Prior work has reported differences in brain GABA levels across the healthy lifespan 1–3 , as well as in various psychiatric 4,5 and neurodegenerative conditions 6–8 .…”

Impact of acquisition and modeling parameters on the test–retest reproducibility of edited GABA+

“…GABA levels can be quantified in vivo noninvasively using proton magnetic resonance spectroscopy ( 1 H MRS). However, because of its low concentration within the brain and overlapping spectral signatures of higher concentration metabolites, spectral editing is required for accurate in vivo quantification of GABA at 3 T. Prior work has reported differences in brain GABA levels across the healthy lifespan, 1,2 as well as in various psychiatric [3][4][5] and neurodegenerative conditions. [6][7][8] One common spectral editing technique for GABA is MEscher-GArwood Point RESolved Spectroscopy (MEGA-PRESS 9 ), which requires a relatively lengthy (e.g., 10-min) acquisition to target one metabolite (e.g., GABA).…”