Indications for an antidepressive effect of thymosin alpha-1 in a small open-label proof of concept study in common variable immune deficiency patients with depression

Abstract

Background: A considerable proportion (21%) of patients with common variable immunodeficiency (CVID) suffers from depression. These subjects are characterized by reduced naïve T cells and a premature T cell senescence similar to that of patients with major depressive disorder (MDD). It is known that T cells are essential for limbic system development/function. Treatment with thymosin α1 (Tα1) is capable to increase the thymus output of naïve T cells.

Objective: To treat CVID patients with a comorbid depressive episode with Tα1 to increase naïve T cells and thereby improve mood.

Design: A small open-label, proof of concept trial. Five depressed CVID patients (Hamilton Depression Rating Scale, HDRS >12) could be treated with Tα1 (8 weeks, 1.6 mg daily subcutaneously, 1st week, thereafter 1.6 mg twice weekly). At the start, at 8 weeks and 8 weeks after the last injection, the HDRS was recorded and blood samples drawn for measuring naïve and memory T cells, Th17 and Treg cells, hsCRP, IL-6 and IL-7. Outcomes were compared to those of a contrast group (42 MDD patients, same severity but treated as usual (TAU)).

Results: In all 5 depressed CVID patients HDRS decreased during Tα1 treatment (with average 52%, TAU decreased scores with 36% in MDD patients). All 5 CVID patients showed an increase in naïve/memory CD4⁺ and CD8⁺ T cell ratios, and in 4 of the 5 patients with detectable IL-6 levels reductions were recorded. TAU did not show such immune improvements. In the 8-week wash-out, depression recurred in the 2 most severe patients, while continued to improve in the others. Immune effects were not sustained in the wash-out.

Conclusion: This preliminary small study suggests thymus hormone treatment to have antidepressive and related immune correcting effects. Data urge for larger placebo-controlled trials.

Keywords: CVID; Depression; Improvement; Therapy; Thymalfasin.

Fig. 1

The treatment schedule of the 5 depressed CVID patients. (Created in BioRender. 4, V (2024) https://BioRender.com/a16k591).

Fig. 2

The baseline (T = 0) and 8 week (after treatment) HAMD-17 scores in the 5 depressed CVID patients treated with Thymalfasin (Tα1) given as before-after plot (left panel) and box plots (right panel) with standard deviations (white = baseline, grey = 8 week values). The box plot data for the major depressed (MDD) contrast group treated as usual (TAU) and for the healthy controls (HC) are also given. Significances are as indicated.

Fig. 3

The baseline (T = 0) and 8 week (after treatment) naïve/memory CD4⁺ ratio's in the 5 depressed CVID patients treated with Thymalfasin (Tα1) given as before-after plot (left panel) and box plots (right panel) with standard deviations (white = baseline, grey = 8 week values). The box plot data are also given for the major depressed (MDD) contrast group treated as usual (TAU) and for the healthy controls (HC) (right panel). Significances are as indicated.

Fig. 4

The baseline (T = 0) and 8 week (after treatment) naïve/memory CD8⁺ ratio's in the 5 depressed CVID patients treated with Thymalfasin (Tα1) given as before-after plot (left panel) and box plots (right panel) with standard deviations (white = baseline, grey = 8 week values). The box plot data are also given for the major depressed (MDD) contrast group treated as usual (TAU) and for the healthy controls (HC) (right panel). Significances are as indicated.