GABAergic dysfunction in Parkinson's disease: insights from in vivo proton magnetic resonance spectroscopy

Parkinson's disease (PD) pathogenesis extends beyond dopamine with evidence of serotonergic, noradrenergic, cholinergic and involvement of γ-aminobutyric acid (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 and 22 studies met the inclusion criteria. Considerable methodological variability was observed across studies in magnetic field strengths, pulse sequences, voxel location and size, quantification reference and processing methods. Review of reported GABA levels revealed a heterogeneous pattern of alterations across studies, regions of interest and clinical phenotypes, precluding meta-analysis. These observations suggest a multifaceted, region-specific dysregulation of GABAergic neurotransmission extending beyond the 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 appropriate patient stratification is crucial to identify definite patterns of alterations.