Hemmo A. Drexhage, MD, PhD

Professor emeritus Medical Immunology, Department of Immunology
Research on Immuno-Psychiatry and Immuno-Neuro-Endocrinology
Coordinator EU consortium MOODSTRATIFICATION (former: MOODINFLAME, PSYCH-AID) PROMETEO UCE Ecuador

h.drexhage@erasmusmc.nl

Studies on Immunopsychiatry since 1990 on the department

Since 1990, research led by Drexhage HA has demonstrated that many psychiatric disorders are linked to disturbances in the T cell and monocyte/macrophage/microglia system. These immune imbalances affect the growth and function of the frontal limbic regions of the brain and increase susceptibility to inflammation. Microglia, T cells, and macrophages are essential for neuronal regulation, infection control, and the prevention of autoimmune reactions.

Patients with these immune disturbances are also more prone to infections and autoimmune diseases, such as Hashimoto’s thyroiditis, type 1 diabetes, Sjögren’s syndrome, and rheumatoid arthritis. These conditions are demonstrably more common in individuals with psychiatric disorders.

Through European projects (MOODINFLAME, PSYCH-AID, MOODSTRATIFICATION), multidisciplinary teams have developed new diagnostic and therapeutic approaches for depression, bipolar disorder, postpartum psychosis/depression, and schizophrenia. The focus has been on identifying immune abnormalities and creating simple blood tests for clinical application.

Outcomes of these EU projects show (after studies of more than 15 years) that severe mood disorders are the result of  a combination of shortages of mono-amines (serotonin, adrenalin), a reduced  neuro resilience (low BDNF) and deviant immune reactions, the latter caused by one or a combination of the following issues:

  1. (Inborn and virus acquired) T cell imbalances which result in
  2. mal development and malfunctioning of the fronto-limbic systems in the brain,
  3. flares of chronic low grade inflammation, due to monocyte/macrophages senescence and inflammaging, further impacting functioning of brain systems; and
  4. Childhood trauma, obesity and metabolic syndrome leading to an even higher inflammatory state of the immune system.

In particular females are more prone to these latter higher inflammatory states.

Clinical studies on immune-modulating therapies—including COX-2 inhibitors, low-dose IL2, thymus hormone, spinning, and statins—have shown that these treatments not only correct above described immune abnormalities but also significantly reduce psychiatric symptoms.

More details can be found on the websites of the EU projects MOODINFLAME (2008–2012), PSYCH-AID (2013-2017) and MOODSTRATIFICATION, the last project, has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 754740, www.moodstratification.eu

Status in 2026

Currently, initiatives are underway to establish specialized outpatient clinics for patients with complex psychiatric and somatic issues. These clinics will screen for metabolic, endocrinological, and immunological comorbidities to provide targeted treatment and improve overall health. The use of experimental immune modulators is also being considered for treatment-resistant depression.

Selected publications over the past 5 years focusing on those with impact for immune treatment and on practical reviews in Dutch.

Simon MS, Burger B, Weidinger E, Arteaga-Henríquez G, Zill P, Musil R, Drexhage HA, Müller N. Front Psychiatry. 2021 Sep 27;12:615261. doi: 10.3389/fpsyt.2021.615261. eCollection 2021. Efficacy of Sertraline Plus Placebo or Add-On Celecoxib in Major Depressive Disorder: Macrophage Migration Inhibitory Factor as a Promising Biomarker for Remission After Sertraline-Results From a Randomized Controlled Clinical Trial. PMID: 34646168

Aichholzer M, Gangadin SS, Sommer IEC, Wijkhuis A, de Witte LD, Kahn RS, Bahn S, Drexhage HA, Schiweck C. Inflammatory monocyte gene signature predicts beneficial within group effect of simvastatin in patients with schizophrenia spectrum disorders in a secondary analysis of a randomized controlled trial. Brain Behav Immun Health. 2022 Nov 8;26:100551. doi: 10.1016/j.bbih.2022.100551. eCollection 2022 Dec. PMID: 36405425 Free PMC article.

Drexhage HA. [Stress, the immune system and depression]. Ned Tijdschr Geneeskd. 2023 Dec 20;168:D7984. PMID: 38175575 Dutch.

Poletti S, Zanardi R, Mandelli A, Aggio V, Finardi A, Lorenzi C, Borsellino G, Carminati M, Manfredi E, Tomasi E, Spadini S, Colombo C, Drexhage HA, Furlan R, Benedetti F. Low-dose interleukin 2 antidepressant potentiation in unipolar and bipolar depression: Safety, efficacy, and immunological biomarkers. Brain Behav Immun. 2024 Feb 15;118:52-68. doi: 10.1016/j.bbi.2024.02.019. Online ahead of print. PMID: 38367846 Free article.

Verhoeven M, Drexhage HA. De invloed van chronische stress. Nurse Academy, 2:4-10, 2024

Drexhage HA, Bergink V, Poletti S, Benedetti F, Osborne LM. Conventional and new immunotherapies for immune system dysregulation in postpartum mood disorders: comparisons to immune system dysregulations in bipolar disorder, major depression, and postpartum autoimmune thyroid disease. Expert Rev Clin Immunol. 2025 Feb;21(2):113-135. doi: 10.1080/1744666X.2024.2420053. Epub 2024 Oct 29. PMID: 39441185 Free article. Review.

Aynekulu Mersha DG, Fromme SE, van Boven F, Arteaga-Henríquez G, Wijkhuijs A, van der Ent M, Bergmans R, Baune BT, Drexhage HA, Dalm V. 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. Brain Behav Immun Health. 2025 Jan 2;43:100934. doi: 10.1016/j.bbih.2024.100934. eCollection 2025 Feb. PMID: 39867848

Fromme SE, Arteaga-Henríquez G, Haarman BCM, Wijkhuijs A, Berghmans R, Munk-Olsen T, Drexhage H, Baune BT. One treatment does not fit all: Indications that spinning therapy benefits only a subgroup of patients with depression characterized by a T memory cell inflation profile. Brain Behav Immun. 2025 Dec 18;133:106228. doi: 10.1016/j.bbi.2025.106228. Online ahead of print. PMID: 41421730 Free article

Drexhage H, Verhoeven M, Huizer K, Megen van K, Gelderman K, Haarman B, Beveren van N. Unipolaire depressie, de immunopsychiatrische benadering. Nurse Academy, 4, 16-22, 2025