GABAergic imbalance in Parkinson's disease-related depression determined with MEGA-PRESS

The pathogenesis of depression in patients with Parkinson's disease (PD) is poorly understood. Therefore, this study aimed to explore the changes in γ-aminobutyric acid (GABA) and glutamate plus glutamine (Glx) levels in patients with PD with or without depression determined using MEscher-GArwood Point Resolved Spectroscopy (MEGA-PRESS).

A total of 83 patients with primary PD and 24 healthy controls were included. Patients with PD were categorized into depressed PD (DPD, n = 19) and nondepressed PD (NDPD, n = 64) based on the 17-item Hamilton Depression Rating Scale. All participants underwent T1-weighted imaging and MEGA-PRESS sequence to acquire GABA+ and Glx values. The MEGA-PRESS sequence was conducted using 18.48 mL voxels in the left thalamus and medial frontal cortex. The GABA+, Glx, and creatine values were quantified using Gannet 3.1 software.

The GABA+ and Glx values were not significantly disparate between patients with PD and controls in the thalamus and medial frontal cortex. However, the levels of N-acetyl aspartate/creatine and choline/creatine in the left thalamus were significantly lower in patients with PD than in controls (P = .031, P = .009). The GABA+/Water and GABA+/Creatine in the medial frontal cortex were higher in DPD than in NDPD (P = .001, P = .004). The effects of depression on Glx or other metabolite levels were not evident, and no significant difference in metabolite values was noted in the left thalamus among all groups (P > .05).

GABA+ levels increased in the medial frontal cortex in DPD, which may be more closely related to depressive pathology. Thus, alterations in GABAergic function in special brain structures may be related to the clinical manifestations of PD symptoms, and hence mediating this function might help in treating depression in PD.