Uwe was right!

It is time for a review. I am collecting scientific papers on a regular basis and since 2016, when Uwe Rohr died, there have been several publications related to his hypotheses. Most of them confirm what he stated, so it is safe to say: "Uwe was right!"

Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap
http://science.sciencemag.org/content/359/6376/693

Gandal et al. performed meta-analyses of transcriptomic studies covering five major psychiatric disorders and compared cases and controls to identify coexpressed gene modules. From this, they found that some psychiatric disorders share global gene expression patterns.

This is exactly what Uwe said: Severe mental diseases, no matter whether it is schizophrenia, bipolar disorder or other diseases such as autism, are induced by stress. Stress affects the steroidal hormone cascade, and this effectively alters gene expression.

Meditation and vacation effects have an impact on disease-associated molecular phenotypes
https://www.ncbi.nlm.nih.gov/pubmed/27576169

More recent systems biology approaches have identified gene regulatory networks associated with a diversity of biological processes, including immune and stress responses, and objectively linked them with disease or salutary states. [...] Chronic stress is associated with higher inflammation, shorter telomeres, and lower activity levels of telomerase, the cellular enzyme that elongates telomeric DNA. [...] One found that mindfulness-based and supportive expressive therapies were associated with telomere maintenance, compared with a ‘treatment as usual’ control group. A second study found that mindfulness-based stress reduction was associated with increases in telomerase after 3 months. Long-term mind–body interventions, including tai chi, yoga and meditation, have been associated with gene expression (GE) changes associated with inflammatory pathways as reviewed elsewhere. [...] One study compared GE changes in experienced versus novice meditators after one session. They found changes in both groups in inflammation, energy metabolism, mitochondrial function and telomere maintenance, but experienced meditators had greater changes. Another study comparing experienced meditators to novices after 8 hours of meditation examined GE changes specific to epigenetic regulatory enzymes. Changes were found only in the experienced meditators. Another study found threefold changes in GE in the immune cells after yoga versus a control movement program.

Chronic stress is associated with higher inflammation - that's exactly what Uwe said. Inflammation is the bad thing that the immune system uses to thwart infectious agents. However, it is a mistake to conclude that patients would benefit from suppressing the immune system altogether! That's the mistake Carl Djerassi made, according to Uwe. Djerassi synthesized cortisone which suppresses inflammation but also the immune system as such. By contrast, the adiols (androstanediol and androstenediol) only suppress inflammation, while they keep the immune system intact and even boost it. So said Uwe.

The role of glucocorticoid receptors in metabolic syndrome and psychiatric illness
https://www.ncbi.nlm.nih.gov/pubmed/27002803

Glucocorticoids (GCs) are involved in a large number of the physiological changes associated with metabolic syndrome and certain psychiatric illness. Although significance is often given to the concentration of GC, its biological action is determined by the activation of intracellular GC receptors (GR). Genetic polymorphisms of the GR and the large array of GR related cofactors can directly or indirectly affect the pathophysiology and evolution of these conditions. This review will discuss the effects of GR mutations on metabolic syndrome and psychotic depression. [...] Glucocorticoids (GCs) play an integral role in a wide array of physiological systems in the body, affecting lipid and glucose metabolism, immunosuppressive and anti-inflammatory reactions, growth, reproduction and brain function. [...] The resemblance of the symptoms and biochemical findings between Cushing’s syndrome and metabolic syndrome suggest that cortisol plays a central role in the pathogenesis and the evolution of both of these medical conditions. [...] It has long been hypothesized that the development of psychotic symptoms in Psychotic Depression (PD) is related to increased or dysregulated systemic cortisol levels, leading to increased dopamine levels and changes to dopamine metabolism, which potentially induce psychotic symptoms in susceptible individuals. Biologic findings in patients with PD related to elevated and dysregulated cortisol levels include high rates of nonsuppression on the DST, reduced diurnal fluctuation of cortisol, high plasma cortisol and ACTH levels, and increased excretion of 24 h urinary free cortisol. [...] A higher incidence of the 9b polymorphism has been linked with a lower frequency of hypomanic episodes in patients with bipolar disorder, suggesting a protective effect of this polymorphism. [...] FKBP5 SNPs have been linked to a variety of psychiatric disorders including dissociative symptoms after trauma, a predictor of PTSD development in children and adult. In addition, FKBP5 SNPs have been linked to recurrence of major depression and the response to antidepressants.

One of Uwe's stances was also that metabolic syndrome is not caused by obesity but by stress, or stress combined with obesity, but not by obesity alone. Stress is the thing that makes you sick, not a few extra pounds. This view is confirmed by this paper.

Impact of stress response in development of first-episode psychosis in schizophrenia: An overview of systematic reviews
https://www.ncbi.nlm.nih.gov/pubmed/2829196

In this paper our publication "Model approach for stress induced steroidal hormone cascade changes in severe mental diseases" (https://www.ncbi.nlm.nih.gov/pubmed/26812880) is cited. However, it was not evaluated since we dealt with various types of severe mental diseases, while this paper focused on schizophrenia only, so our publication was not considered relevant.

The role of stress-regulation genes in moderating the association of stress and daily-life psychotic experiences
https://www.ncbi.nlm.nih.gov/pubmed/28865405

Results: Unlike genetic variants, distal and proximal stressors were associated with PEs in both samples and were more strongly associated with PEs in the early-psychosis than in the non-clinical group. The RGS4 TA and FKBP5 CATT haplotypes interacted with distal stress, whereas the A allele of OXTR (rs2254298) interacted with proximal stress, increasing momentary levels of PEs in the early-psychosis group. No interactions emerged with COMT or BDNF variants. 

Conclusion: Individual differences in relevant stress-regulation systems interact with both distal and proximal psychosocial stressors in shaping the daily-life manifestation of PEs across the psychosis continuum.

All in all, one may conclude that we were obviously on the best way to uncovering the truth about severe mental diseases! Uwe was right!