Testosterone is related to GABA+ levels in the posterior-cingulate in unmedicated depressed women during reproductive life

Abstract

Background: The role of testosterone (T) in the pathophysiology of affective disorders and anxiety is broadly supported. Evidence suggests that T has anxiolytic and antidepressant properties. One proposed route for the central effects of T is its interaction with the gamma-aminobutyric acid (GABA) system. We explored the relationship between T levels and GABA+ levels in anterior-cingulate (ACC) and the posterior-cingulate (PCC) regions in depressed women, using magnetic resonance spectroscopy (¹H-MRS).

Methods: Twenty-one depressed patients with regularly cycling who were not taking hormonal or psychotropic drugs were recruited. We assessed severity of depression using the Hamilton Depression Rating Scale (HDRS). Blood samples were taken for quantification of free (FT) and total testosterone (TT) on the day of the magnetic resonance (MR) scan. We evaluated GABA+ levels in the PCC and ACC, using the Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy (HERMES) sequence. Pearson correlations were used to evaluate the association between FT, TT, GABA+ concentrations, and HDRS scores.

Results: TT and FT levels were positively correlated with GABA+ levels in the PCC. No correlation was observed between T levels and GABA+ levels in the ACC. The HDRS total scores correlated negatively with FT levels.

Limitations: Limitations include the cross-sectional evaluation and the lack of a comparative healthy group.

Conclusions: Our findings suggest that the potential anxiolytic and antidepressant properties of T are related to increased GABA+ levels in the PCC. This observation may contribute to increased understanding of the role of T in depressive and anxiety symptoms in women.

Keywords: GABA; MR spectroscopy; Major depressive disorder; Testosterone; Women.

Fig. 1.

Location of MRS voxels in the anterior (A) and posterior (B) cingulate regions.

Fig. 2.

GABA+ edited difference spectrum from one subject. The GABA+ signal being quantified is marked at 3 ppm.

Fig. 3.

(A) GABA+ levels in PCC are correlated with total testosterone (r = 0.64; p = 0.009). (B) GABA+ levels in PCC are correlated with free testosterone (r = 0.53; p = 0.039). (C) HDRS total scores showed a negative relationship to FT (r = −0.50, p = 0.02).