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.
Aynekulu Mersha. Daniël G DG; Fromme. Sarah E SE; van Boven. Frank F; Arteaga-Henríquez. Gara G; Wijkhuijs. Annemarie A; van der Ent. Marianne M; Bergmans. Raf R; Baune. Bernard T BT; Drexhage. Hemmo A HA; Dalm. Virgil V
Key Findings
- All five CVID patients showed a ~52% reduction in HDRS depression scores after 8 weeks of thymosin‑alpha‑1, compared to a 36% drop in a larger usual‑care depression group.
- Naïve/memory CD4+ and CD8+ T‑cell ratios increased in every treated patient, indicating enhanced thymic output.
- IL‑6 levels fell in four of five patients, while standard‑care patients showed no immune changes.
Practical Outcomes
- For most biohackers, the data are not ready for direct use: the study is very small, involves a rare disease, and lacks a placebo control. The dosing used (1.6 mg subcutaneously daily for one week, then twice weekly) could serve as a reference if someone chooses to experiment, but safety, efficacy, and long‑term effects remain unproven. Larger, controlled trials are needed before recommending thymosin‑alpha‑1 as a general anti‑depressive or immune‑boosting supplement.
Summary
A tiny open‑label study gave five people with a rare immune disorder (CVID) and depression daily thymosin‑alpha‑1 injections for a week, then twice a week for seven weeks. Their depression scores dropped about half, and their immune cells (naïve T‑cells) improved. When the drug stopped, the two worst patients got depressed again. The results hint that thymosin‑alpha‑1 might lift mood by fixing immune problems, but the study is tiny and only in a special patient group.
Abstract
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. To treat CVID patients with a comorbid depressive episode with Tα1 to increase naïve T cells and thereby improve mood. 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)). 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<sup>+</sup> and CD8<sup>+</sup> 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. This preliminary small study suggests thymus hormone treatment to have antidepressive and related immune correcting effects. Data urge for larger placebo-controlled trials.
Study Information
pubmed
2025
2025-01-02T00:00:00.000Z
10.1016/j.bbih.2024.100934
2
43