Влияние различных гормонов на симптомы шизофрении

The relationship between androgens and mental state seems particularly complicated. Animal evidence suggests that testosterone may be propsychotic, given that administration of testosterone significantly enhanced NMDA antagonist-induced disruptions in prepulse inhibition in OVX rats. There is also limited evidence that high-dose androgenic steroids can induce psychiatric symptoms in humans; however, most of the research to date into androgens and mental state has focused on the testosterone precursors dehydroepiandrosterone and DHEA-sulfate (DHEA-S). DHEA(S) is neuroprotective in the rodent brain, and differences in DHEA(S) blood levels between psychotic patients and healthy controls are widely reported; however, the direction of these differences is far from consistent. Results from clinical studies trialling DHEA(S) as an augmentation strategy have been similarly contradictory, with some studies finding a modest treatment effect and others reporting no superiority over placebo. Further research is needed. Pregnenolone and its metabolites pregnenolone sulfate and allopregnanolone seem more promising. In addition to also possessing neuromodulatory and neuroprotective properties, these neurosteroids exert positive effects in rodent models of cognition and psychosis.Serum levels of pregnenolone have been found to be lower in patients with schizophrenia than in healthy controls, and antipsychotic medications can significantly increase pregnenolone levels in the brain. A review of three small pilot studies investigating pregnenolone as an adjunctive intervention for patients with schizophrenia reports that pregnenolone was able to improve psychotic and cognitive symptoms, paving the way for future research into this compound. Recently, oxytocin has also emerged as possibly having an influence on mental state after one study found that higher peripheral oxytocin levels were associated with decreased symptom severity in women with chronic schizophrenia, and another study demonstrated efficacy of intranasal oxytocin as an adjunctive therapy in a randomized, cross-over sample of 15 schizophrenia patients.

 Hormones and Schizophrenia

Бисфенол А, эндокринная дисфункция и патогенез шизофрении

In recent years, numerous substances have been identified as so-called ‘‘endocrine disruptors’’ because exposure to them results in disruption of normal endocrine function with possible adverse health outcomes. The pathologic and behavioral abnormalities attributed to exposure to endocrine disruptors like bisphenol-A (BPA) have been studied in animals. Mental conditions ranging from cognitive impairment to autism have been linked to BPA exposure by more than one investigation. Concurrent with these developments in BPA research, schizophrenia research has continued to find evidence of possible endocrine or neuroendocrine involvement in the disease. Sufficient information now exists for a comparison of the neurotoxicological and behavioral pathology associated with exposure to BPA and other endocrine disruptors to the abnormalities observed in schizophrenia. This review summarizes these findings and proposes a theory of endocrine disruption, like that observed from BPA exposure, as a pathway of schizophrenia pathogenesis

BPA is a common ingredient of many plastic and resin products including food and drink containers, internal linings of food cans, and dental enamels. Also known as 2,2-bis(4-hydroxyphenyl) propane, BPA was invented in the 20th century and is manufactured by combining acetone and phenol. Emerging research indicates BPA is an estrogenic EDC that alters or interferes with normal endocrine development in various vertebrate and invertebrate species.

Effects of Bisphenol-A and Other Endocrine Disruptors Compared With Abnormalities of Schizophrenia: An Endocrine-Disruption Theory of Schizophrenia

Интраназальный окситоцин в дополнение к эсциталопраму в терапии депрессии

Oxytocin (OT) is, first, a hormone synthesized in the hypothalamus and released by the neurohypophysis, but OT is also involved in the regulation of emotions, and OT receptors are distributed in various brain regions, including the limbic system and amygdala. There is much data suggesting a role for OT as an endogenous antidepressant/anxiolytic hormone and there is support for the idea that stimulation of OT receptors inhibits the hypothalamo-pituitary-adrenal (HPA) axis. The pathophysiology of stress-related diseases, such as depression or anxiety disorders, includes both endogenous/genetic predisposing factors and a dysregulated response to stress, and efficiency of antidepressants involves normalization of HPA-axis abnormalities.

Case Report

RX is a 38-year-old man with a 15-year history of major depressive disorder without psychotic features. His depression severely worsened over a 5-year period despite various antidepressant treatments (tricyclics, serotonin reuptake inhibitors, and serotonin-noradrenaline reuptake inhibitors). He also received benzodiazepines and amisulpride without clinical success. His current treatment involves escitalopram 20 mg. After he gave full informed consent, intranasal synthetic OT (Syntocinon®, 1 puff per nostril each with 4 U.I., twice daily; Novartis Pharmaceuticals Corporation, Switzerland) was added. Initial severity of depression was scored at 17 on the Hamilton Rating Scale for Depression (Ham-D), and anxiety reached 57 on the Spielberger State-Anxiety Inventory (STAI–A). One week after OT initiation, his Ham-D score decreased to 11, and the STAI–A score to 49. At this time, the patient bought a car after several months of hesitancy. He contracted a loan and explained that he was offered good buying conditions. One week later, the patient was very much improved; his HAM-D score dropped to 2, and his STAI–A to 37. Unfortunately, Syntocinon® was stopped after 1 week because the patient missed the visit. After this period, the patient was much worse. Intranasal OT was then delivered at the dose of 36 UI per day in addition to escitalopram, 20 mg. His symptoms improved after 7 days (Ham-D: 5; STAI–A: 48). At the same time, he was very affected by the [bankruptcy] of his [step-]father, who raised him. One week later, he offered to install hardware [electronic equipment] in his parent's house. On The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), he scored at higher levels, going from 1 to 4 by the end of the study.

Discussion

This is the first trial of OT as an adjunct to antidepressant in major depression. Our case report suggests that OT instillation significantly improves mood and anxiety. OT was already shown to reduce responses to social stress,1 to increase trust,2 and improve "mind-reading" in humans.3 It is possible that the efficacy of SSRIs in restoring interest in social interactions is due, in part, to their action on the reward circuit via the OT system.4 Further studies are needed to investigate the effects of OT or OT-receptor selective agonists in additional clinical models to promote the development of psychopharmacology targeting central OT receptors.

Intranasal Oxytocin as an Adjunct to Escitalopram in Major Depression

Окситоцин и негативная симптоматика шизофрении

Oxytocin is a hormone that has been reported to reduce the severity of schizophrenia when administered intra-nasally. Rubin and colleagues from the University of Illinois at Chicago report that women with schizophrenia showed less severe symptoms on the Positive and Negative Syndrome Scale (PANSS) in the mid-luteal phase compared with the follicular phase. Higher oxytocin levels in both men and women were associated with more prosocial behaviors. This lends credence to the potential usefulness of oxytocin in schizophrenia, which also is being studied in autism. As a researcher, I also think this study points to the possibility that PANSS ratings in clinical trials of antipsychotics should control for the menstrual phase to avoid the confounding effects of a decline in severity of psychosis during the mid-luteal phase irrespective of drug treatment.

Oxytocin is a hormone that has been reported to reduce the severity of schizophrenia when administered intra-nasally. Rubin and colleagues from the University of Illinois at Chicago report that women with schizophrenia showed less severe symptoms on the Positive and Negative Syndrome Scale (PANSS) in the mid-luteal phase compared with the follicular phase. Higher oxytocin levels in both men and women were associated with more prosocial behaviors. This lends credence to the potential usefulness of oxytocin in schizophrenia, which also is being studied in autism. As a researcher, I also think this study points to the possibility that PANSS ratings in clinical trials of antipsychotics should control for the menstrual phase to avoid the confounding effects of a decline in severity of psychosis during the mid-luteal phase irrespective of drug treatment.

Peripheral oxytocin is associated with reduced symptom severity in schizophrenia