High cortisol, cortisol/DHEA, cortisol/testosterone ratios may drive schizophrenia
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The connection between chronic stress and schizophrenia is well-established but medicine continues to vehemently deny that stress on its own can cause psychotic states such as schizophrenia. To this day, the most commonly used drugs for schizophrenia are so-called dopamine antagonists, yet recent studies have demonstrated that they all have anti-serotonin effects as well. Serotonin is the primary central control mechanism behind cortisol production and anti-serotonin drugs have been successfully used to treat hyper-cortisol states such as Cushing disease/syndrome. Thus, it would be plausible to conclude that elevated cortisol is a causative factor in schizophrenia, likely downstream from elevated serotonin. On a side, but related note, this suggests that SSRI drugs at the very least exacerbate psychotic states such as schizophrenia, if not outright cause it. Yet, SSRI drugs are widely prescribed to patients with schizophrenia to “prevent” them from developing depression or “treat” already established one. Now, measuring cortisol levels in blood is tricky and more often than not patients with mental health conditions do not present with consistently elevated cortisol levels. However, even if cortisol levels are normal in serum, one can still be in a state of relative cortisol dominance. How so? Well, multiple human and animal studies have demonstrated that it is not absolute cortisol levels that matter most for health, but the ratio of cortisol to anti-cortisol steroids such as DHEA and testosterone. In fact, the serum cortisol/DHEA ratio has been consistently shown to be one of the most reliable biomarkers of all-cause mortality and morbidity, regardless of sex, age, health history, diet, genetics, etc. Thus, ideally one would want to not only measure cortisol, the cortisol/DHEA and the cortisol/testsoterone ratio, but do the measurement in a way that presents a long-term picture that can smooth out any outliers that often occur on single blood tests. Hair/nail steroid analysis is perfectly suited for such tasks, and the study below demonstrated that hair cortisol, cortisol/DHEA and cortisol/testosterone ratios are all strongly associated with schizophrenia severity, likely being causative factors for this condition.
https://doi.org/10.1016/j.psyneuen.2024.107049
“…Hair samples were taken from 137 SCZ patients and 73 controls. The SCZ patients were diagnosed by their attending physician according to the Diagnostic and Statistical Manual of Mental Disorders IV and were clinically stable after treatment. Gender, age, BMI, frequency of hair washing, marital status, education level, family history of mental illness and clozapine dosage were concurrently collected as covariates. The 10-item perceived stress scale (PSS-10) and the social readjustment rating scale were used to assess chronic stress status in SCZ patients. Eight hair biomarkers, cortisol, cortisone, dehydroepiandrosterone (DHEA), testosterone, progesterone, cortisol/cortisone, cortisol/DHEA and cortisol/testosterone, were measured by high performance liquid chromatography tandem mass spectrometer. Among them, cortisol, cortisone, DHEA and cortisol/DHEA reflected the functional activity of the HPA axis, and testosterone and progesterone reflected the functional activity of the HPG axis, and cortisol/cortisone reflected the activity of 11_β_-hydroxysteroid dehydrogenase types 2 (11_β_-HSD 2), and cortisol/testosterone reflected the HPA-HPG interaction. SCZ patients showed significantly higher cortisone and cortisol/testosterone than controls (p<0.001, η²_p=0.180 and p=0.015, η²__p=0.031),_ lower testosterone (p=0.009, η²__p=0.034), progesterone (p<0.001, η²__p=0.069) and cortisol/cortisone (p=0.001, _η²_p=0.054). There were significant intergroup differences in male and female progesterone (p=0.003, _η²_p=0.088 and _p=_0.030, _η²_p=0.049) and female testosterone (p=0.028, _η²_p=0.051). In SCZ patients, cortisol, cortisol/cortisone, cortisol/DHEA and cortisol/testosterone were positively associated with PSS-10 score (_p_s<0.05, 0.212<_r_s< 0.265).”