Multiplex immunoassay analysis of plasma shows prominent upregulation of growth factor activity pathways linked to GSK3β signaling in bipolar patients

Introduction Stress was described by Cushing and Selye as an adaptation to a foreign stressor by the anterior pituitary increasing ACTH, which stimulates the release of glucocorticoid and mineralocorticoid hormones. The question is raised whether stress can induce additional steroidal hormone cascade changes in severe mental diseases (SMD), since stress is the common denominator. Methods A systematic literature review was conducted in PubMed, where the steroidal hormone cascade of patients with SMD was compared to the impact of increasing stress on the steroidal hormone cascade (a) in healthy amateur marathon runners with no overtraining; (b) in healthy well-trained elite soldiers of a ranger training unit in North Norway, who were under extreme physical and mental stress, sleep deprivation, and insufficient calories for 1 week; and, (c) in soldiers suffering from post traumatic stress disorder (PTSD), schizophrenia (SI), and bipolar disorders (BD). Results (a) When physical stress is exposed moderately to healthy men and women for 3-5 days, as in the case of amateur marathon runners, only few steroidal hormones are altered. A mild reduction in testosterone, cholesterol and triglycerides is detected in blood and in saliva, but there was no decrease in estradiol. Conversely, there is an increase of the glucocorticoids, aldosterone and cortisol. Cellular immunity, but not specific immunity, is reduced for a short time in these subjects. (b) These changes are also seen in healthy elite soldiers exposed to extreme physical and mental stress but to a somewhat greater extent. For instance, the aldosterone is increased by a factor of three. (c) In SMD, an irreversible effect on the entire steroidal hormone cascade is detected. Hormones at the top of the cascade, such as cholesterol, dehydroepiandrosterone (DHEA), aldosterone and other glucocorticoids, are increased. However, testosterone and estradiol and their metabolites, and other hormones at the lower end of the cascade, seem to be reduced. 1) The rate and extent of reduction of the androgen metabolites may cause a decrease of cellular and specific immunity which can lead to viral and bacterial infections; joint and stomach inflammation; general pain; and allergic reactions. 2) The decrease in testosterone, and estradiol in SMD may have detrimental effects in cell repair as the estradiol metabolite, 2-methoxy-estradiol (2ME2), helps to transforms stem cells into functional cells. As dopamine and 2ME2 are inversely metabolized via various forms of catechol-O-methyl transferase (COMT), well-being and hypertension may be related. 2ME2 is related to vascular endothelial growth factor (VEGF), which regulates blood capillary growth and O2 supply. As reduced O2 is a key marker of stress, the increase of glucocorticoids in all forms of mental and physical stress cannot counterbalance the reduced 2ME2 in cellular and mental stress. The increased cholesterol and triglycerides are related to stroke and infarction, contributing to a reduced life expectancy in SMD between 14 and 20 years. The increase of aldosterone leads to increases in anxiety, edema, and lung infections. Discussion Increasing mental and physical stress is related to systematic deviations in the steroidal hormone cascade in the non-psychotic state, which then may cause life threatening co-morbidities in PTSD, SI, and BD.

Model approach for stress induced steroidal hormone cascade changes in severe mental diseases

Bipolar disorder (BD) is a severe mental condition characterized by episodes of elevated mood and depression. Being a heritable condition, it features a complex genetic architecture, and it is not still clear how genes contribute to the onset and course of the disease. In this paper we adopted an evolutionary-genomic approach to this condition, focusing on changes occurring during human evolution as a source of our distinctive cognitive and behavioral phenotype. We show clinical evidence that the BD phenotype can be construed as an abnormal presentation of the human self-domestication phenotype. We further demonstrate that candidate genes for BD significantly overlap with candidates for mammal domestication, and that this common set of genes is enriched in functions that are important for the BD phenotype, especially neurotransmitter homeostasis. Finally, we show that candidates for domestication are differentially expressed in brain regions involved in BD pathology, particularly, the hippocampus and the prefrontal cortex. Overall, this link between domestication and BD should facilitate a better understanding of the BD etiopathology.

https://www.biorxiv.org/content/biorxiv/early/2020/04/28/2020.04.28.065581.full.pdf

Abnormal features of human self-domestication in bipolar disorder

Economics, financial markets are sciences that try to predict the behavior of actors to get the best performance possible,

/pdf/mathematical-formula-of-sex-love-economy-and-happiness-sqb24y4wsf.pdf

Mathematical formula of sex, love, economy and happiness. : Therapy and psychiatric analysis of the economy and the financial markets.

A 40-year-old female patient with bipolar disorder and premenstrual dysphoric disorder did not present any physical evidence of virilization, treated with quetiapine and lithium carbonate. Laboratory testing showed evidence of hyperandrogenism (Testosterone levels 88.5ng/dL). After control, testosterone levels were normal (free testosterone 0.20 pg/ml, total testosterone 27.90ng/dl), as free thyroxine levels decreased (T4 0.83ng/dl) and increased progesterone levels (progesterone 3.80ng/ml). We consider an association between increased androgenic hormone levels in women, quetiapine and lithium carbonate treatment as well as the presence of an affective disorder and premenstrual dysphoric disorder. Some relevant patents are also outlined in this review.

Affective disorder and hyperandrogenism.

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Affective disorder and hyperandrogenism.