Gamma-Aminobutyric Acid Levels in the Anterior Cingulate Cortex of Perimenopausal Women With Depression: A Magnetic Resonance Spectroscopy Study

Abstract

Objective: The anterior cingulate cortex (ACC) is associated with the processing of negative emotions. Gamma-aminobutyric acid (GABA) metabolism plays an important role in the pathogenesis of mental disorders. We aimed to determine the changes in GABA levels in the ACC of perimenopausal women with depression.

Methods: We recruited 120 perimenopausal women, who were followed up for 18-24 months. After reaching menopause, the participants were divided into a control group (n = 71), an anxiety group (n = 30), and a depression group (n = 19). The participants were examined using proton magnetic resonance spectroscopy (MRS). TARQUIN software was used to calculate the GABA concentrations in the ACC before and after menopause. The relationship of the GABA levels with the patients' scores on the 14-item Hamilton Anxiety Scale and 17-item Hamilton Depression Scale was determined.

Results: GABA decreased with time. The postmenopausal GABA levels were significantly lower in the depression group than in the anxiety group and were significantly lower in both these groups than in the normal group. The postmenopausal GABA levels were significantly lower than the premenopausal levels in the normal, anxiety, and depression groups (P = 0.014, <0.001, and <0.001, respectively). The premenopausal GABA levels did not significantly differ between the normal vs. anxiety group (P = 0.907), normal vs. depression group (P = 0.495), and anxiety vs. depression group. The postmenopausal GABA levels were significantly lower in the depression group than in the anxiety group and were significantly lower in both these groups than in the normal group, normal vs. anxiety group (P = 0.022), normal vs. depression group (P < 0.001), and anxiety vs. depression group (P = 0.047).

Conclusion: Changes in GABA concentrations in the anterior cingulate cortex are related with the pathophysiological mechanism and symptoms of perimenopausal depression.

Keywords: anterior cingulate cortex; anxiety; depression; gamma-aminobutyric acid; magnetic resonance spectroscopy; postmenopausal.

FIGURE 1

Flow chart and comparisons of GABA levels between the normal, anxiety, and depression groups.

FIGURE 2

The region of interest in the anterior cingulate cortex on MEGA-PRESS in the axial, sagittal, and coronal planes. TARQUIN edited spectrum GABA in the normal, anxiety, and depression groups. The edited spectrum of the premenopausal and postmenopausal GABA levels located at 3.0 ppm.

FIGURE 3

Two-way repeated ANOVA was used to compare the difference between normal group, anxiety group and depression group at different times. The ANOVA for repeated measures is used to perform the data analysis. Interaction between group effects and time effects was significant (F = 6.642, p < 0.01), the main effect of the group was significant (F = 4.473, p < 0.05), and the time effect was significant (F = 49.251, p < 0.001). (1) The main effect showed no statistical difference between any two groups in the three groups at the start time point, but there was a statistical difference between the two groups in the follow-up time point (p < 0.05). (2) The time effect shows that there are differences between the two time points in the normal group, there are differences between the two time points of the anxiety group, and there are also differences between the two time points in the depression group. ^∗P < 0.05; ^∗∗P < 0.01; ^∗∗∗P < 0.001.

FIGURE 4

Pearson correlation coefficients for premenopausal GABA levels in the anxiety group and the premenopausal HAMA-14 scores.

FIGURE 5

Pearson correlation coefficients for postmenopausal GABA levels in the anxiety group and the postmenopausal HAMA-14 scores.

FIGURE 6

Pearson correlation coefficients for premenopausal GABA levels in the depression group and premenopausal HAMD-17 scores.

FIGURE 7

Pearson correlation coefficients for postmenopausal GABA levels in the depression group and postmenopausal HAMD-17 scores.

FIGURE 8

Receiver operating characteristic (ROC) curves and area under the curve (AUC) value were calculated to assess the diagnostic performance of GABA in the normal, anxiety, and depression groups.