Elevated striatal γ-aminobutyric acid in youth with major depressive disorder

Abstract

Background: Alterations in γ-aminobutyric acid (GABA) have been hypothesized to play a role in the pathogenesis of psychiatric illness. Our previous work has specifically linked anterior cingulate cortex (ACC) GABA deficits with anhedonia in youth with major depressive disorder (MDD). As anhedonia reflects alterations within the reward circuitry, we sought to extend this investigation and examine GABA levels in another key reward-related region, the striatum, in the same adolescent population.

Methods: Thirty-six youth [20 with MDD and 16 healthy controls; (HC)], ages 12 to 21 years old, underwent J-edited proton magnetic resonance spectroscopy (¹H MRS) whereby GABA levels were measured in striatal and ACC voxels. GABA levels were compared between groups and between voxel positions and were examined in relation to clinical symptomatology, such as depression severity, anhedonia, anxiety, and suicidality.

Results: Depressed youth had unexpectedly higher GABA levels in the striatum compared to HC. In both depressed and healthy youth, GABA levels were higher in the striatum than in the ACC, while the differences in depressed youth were greater. Moreover, in depressed youth, higher striatal GABA above the mean of HCs was correlated with lower ACC GABA below the mean of HCs. Striatal GABA was not correlated with clinical symptomatology in this small sample.

Conclusions: Together, these findings suggest that higher striatal GABA levels may serve some compensatory function as a result of lower ACC GABA in depressed adolescents. It is also possible that, like lower ACC GABA, higher striatal GABA might simply be another pathological feature of adolescent depression.

Keywords: Adolescence; Depression; GABA; J-edited magnetic resonance spectroscopy; Striatum.

Fig. 1. ACC and striatal GABA levels.

Depressed youth had higher striatal GABA than HC (p = .001). GABA was significantly higher in the striatum than the ACC in both depressed youth (p < .0005) and HC (p < .0005), although this difference was greater in MDD.

Fig. 2

A) Line graphs of individual ACC and striatal GABA levels for all depressed participants. B) Significant correlation between the deviations from the average HC levels for striatal GABA and ACC GABA in depressed youth. Higher striatal GABA above the HC mean was correlated with lower ACC GABA below the HC mean.