Neurosteroid and Neuroinflammatory Markers of Therapeutic Dynamics in Unipolar Depression in Women of Reproductive Age

Background: Chronic stress can disrupt the adaptive mechanism consisting of negative regulation of the hypothalamicpituitary-adrenal (HPA) axis by endogenous neurosteroids, thereby contributing to the development of stress-related affective disorders. However, the dynamics of neurosteroid status during treatment has not been sufficiently studied. The aim was to evaluate the relationship between the therapeutic dynamics of patients with unipolar depression and changes in their neurohormonal status. Patients and Methods: the study included 42 females of reproductive age with unipolar depression (39; 93% completed the study). Average age of patients was 33.5 ± 2.1 years. A diagnosis of depressive episode within recurrent depressive disorder was established in 17 patients (43.6%), a single depressive episode in 10 (25.6%), and dysthymia in 12 (32.4%). The patients' condition was assessed before the start of therapy in the hospital and three months later using a battery of psychometric tests (MADRS, HAM-A, Holmes-Ray Stress Rating Scale) and laboratory tests (progesterone, cortisol, total cholesterol, and C-reactive protein in blood). Results: the average total MADRS score decreased from 22.82 ± 1.2 at the beginning to 9.13 ± 1.4 (p < 0.001) at the end point. The severity of anxiety according to the HAM-A scale decreased from 17.91 ± 0.792 to a level comparable to the population level — 6.13 ± 0.766 (p < 0.001). 30 patients (76.9%) achieved a response. Complete remission was registered in 19 (48.7%) after treatment. Concerning the laboratory data, the cortisol level changed signi cantly -— from 409 nmol/l to 273 nmol/l (p = 0.005), the cortisol to progesterone ratio decreased from 48.5 to 16.06 (p = 0.006). Changes in progesterone indicators from 8.50 nmol/l to 17.51 nmol/l (p = 0.118), total cholesterol (p = 0.801), CRP (p = 0.945) did not reach statistical signi cance. Cortisol levels were significantly lower in responders (242.5 ± 38.9) than in non-responders (315.2 ± 43.2), (Exp(B) = 0.413, p = 0.008). Progesterone levels were higher in responders (19.8 ± 2.3) than in non-responders (15.6 ± 3.3), (Exp(B) = 1.314, p = 0.044). Differences in total cholesterol levels between the responder and nonresponder groups (Exp(B) = 0.618, p = 0.036) are significant predictors of therapeutic response. Differences in CRP levels between responders and non-responders were not statistically signifi cant. High Holmes-Rey Depression Inventory scores (260.86 ± 12) did not associate with other psychometric and laboratory parameters. Conclusions: peripheral markers of neuroin ammation, endogenous neurosteroid system activity, and the HPA axis demonstrate signi cant changes during treatment of unipolar depression in women of reproductive age. Evaluating the ef cacy of neurosteroid analogs in antidepressive therapy is a promising direction.

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