Severe mental disorders, hormones and the immune system: A Review

The following text, generated by ChatGPT, is a structured synthesis of the relationship between severe mental disorders (SMD), hormones, and the immune system, integrating Dr. Uwe Rohr’s work with subsequent and newer research in psychoneuroimmunology and psychoneuroimmunoendocrinology. 

1. Core idea in Dr. Uwe Rohr’s research

Dr. Uwe Rohr approached severe mental disorders (e.g. major depression, bipolar disorder, schizophrenia, PTSD) not primarily as isolated “brain diseases”, but as systemic disorders of stress regulation, involving endocrine and immune dysregulation.

1.1 Stress as the central trigger

Building on Selye’s stress concept, Rohr emphasized that chronic or extreme stress is the common denominator in SMD. Stress activates the hypothalamic–pituitary–adrenal (HPA) axis, leading to altered ACTH and cortisol signaling .

1.2 Steroidal hormone cascade model

Rohr proposed that stress does not only elevate cortisol but distorts the entire steroid hormone cascade, including:

  • Glucocorticoids (cortisol)

  • Mineralocorticoids

  • Androgens (testosterone)

  • Estrogens and progesterone derivatives

These hormonal shifts can persist and become maladaptive, especially in SMD, resulting in long-term endocrine imbalance rather than a simple “high cortisol” state .

1.3 Hormones as immune modulators

A central and somewhat underappreciated insight in Rohr’s work is that steroid hormones are immune-regulating molecules:

  • Cortisol is immunosuppressive but, when dysregulated, may paradoxically promote chronic low-grade inflammation.

  • Sex hormones (testosterone, estrogens) directly influence cytokine production, T-cell differentiation, and antibody responses.

Rohr therefore framed SMD partly as immune-modulated endocrine disorders, not purely psychiatric entities.

1.4 Example: testosterone and depression

In earlier work, Rohr demonstrated that both low and high testosterone levels are associated with depressive symptoms, particularly in women, supporting a U-shaped hormone–mood relationship rather than a simple deficiency model .

2. Immune dysfunction in severe mental disorders

2.1 From psychoneuroimmunology to psychoneuroimmunoendocrinology

Later research broadly confirmed Rohr’s systemic view. Modern psychoneuroimmunology (PNI) and psychoneuroimmunoendocrinology (PNIE) show that:

  • The brain, endocrine system, and immune system form a bidirectional regulatory network

  • Cytokines influence neurotransmission and mood

  • Hormones shape immune responsiveness and inflammatory tone .

2.2 Inflammation and mental illness

Large-scale studies now consistently show that many SMD are associated with:

  • Elevated pro-inflammatory cytokines (IL-6, TNF-α, CRP)

  • Altered immune cell profiles (e.g. reduced NK cells, altered T-cell balance)

Chronic inflammation is increasingly seen as a causal or maintaining factor, not merely a consequence, of mental illness .

2.3 Autoimmunity and psychiatric risk

Recent population data demonstrate that autoimmune diseases nearly double the risk of affective disorders, particularly in women. Proposed mechanisms include:

  • Chronic systemic inflammation

  • Sex hormone–immune interactions

  • Immune-mediated effects on the brain .

This strongly aligns with Rohr’s early hypothesis that some severe mental disorders may have immune-disease characteristics.

3. Hormones as the missing link between psyche and immunity

Modern research largely validates Rohr’s intuition that hormones are the critical interface:

  • Stress hormones (cortisol) alter immune thresholds

  • Sex hormones modulate inflammatory and antibody responses

  • Immune cytokines feed back into the brain, affecting mood, cognition, and motivation

This creates self-reinforcing loops:

Stress → hormonal dysregulation → immune imbalance → neuroinflammation → worsening mental symptoms → more stress

Such loops help explain:

  • Chronicity of SMD

  • Partial treatment resistance

  • High comorbidity with autoimmune and inflammatory diseases

4. Current consensus vs. Rohr’s original position

AspectRohr’s positionCurrent research
StressCentral causal factorConfirmed
HormonesSystemic steroid cascade dysfunctionConfirmed & expanded
Immune systemKey modulator of mental illnessStrongly confirmed
Mental illness modelSystemic diseaseIncreasingly accepted

What was once considered “non-mainstream” in Rohr’s time is now embedded in mainstream research under PNIE frameworks.

5. Summary in one sentence

Dr. Uwe Rohr anticipated today’s psychoneuroimmunoendocrine model by viewing severe mental disorders as stress-driven systemic illnesses in which hormonal dysregulation and immune imbalance interact bidirectionally with the brain—an idea that has since been strongly supported by modern inflammation, hormone, and immune research.

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