GABAergic dysfunction in Parkinson’s disease: Insights from in vivo proton magnetic resonance spectroscopy

The pathogenesis of Parkinson’s disease (PD) includes neurotransmitters beyond dopamine with suggestions of serotonergic, noradrenergic, cholinergic and GABAergic involvement. In this context advanced methods of magnetic resonance spectroscopy (MRS) permit the in-vivo quantification of GABA. This article aims to systematically review the existing literature on GABAergic alterations in PD as quantified by in-vivo proton MRS with a focus on ascertaining the influence of GABA on motor and non-motor symptoms, motor subtypes, effect of medication status and methodological variations across studies. A systematic search of PubMed and Scopus was carried out in April 2025 with a relevant Boolean phrase. A total of 22 studies met the inclusion criteria. From a methodological perspective, there was variability in magnetic field strengths, pulse sequences, voxel location, voxel size, quantification reference, and methods of processing. Review of reported GABA levels revealed a very heterogenous set of alterations, with gross variations in GABA observed across studies, regions of interest and clinical phenotypes. These observations suggest a multifaceted dysregulation of GABA related neurotransmission that extends the concepts of PD pathogenesis beyond the traditionally implicated canonical dopaminergic framework. GABA plays a definite modulatory role in the pathogenesis of PD, and complex, distinct regional alterations contribute to the development of motor and non-motor symptoms in PD. Standardisation of GABA spectroscopy methods and ideal patient selection is crucial to identify definite patterns of alterations.