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

Влияние возраста приёма терапии эстрогеном на когнитивное снижение пожилом возрасте

Specifically, taking estrogen around the time of menopause is linked to a lowered risk of dementia for women as they enter old age, but estrogen therapy in late life is associated with a higher risk for dementia, according to a retrospective study led by Dr. Kristine Yaffe, chief of geriatric psychiatry at the San Francisco VA Medical Center.

Age During Estrogen Therapy May Impact Later Dementia

Гормонотерапия при депрессиях

Extensive preclinical studies demonstrate that estrogen can, in many ways, modulate molecular pathways involved in monoaminergic neurotransmission (serotonin [5-hydroxy-tryptamine receptors or 5-HT], norepinephrine [NE]); these systems are critical for mood and behavior regulation. Estradiol (E2) administration decreases the activity of monoamine oxidases (MAO-A and MAO-B), which are enzymes involved in 5-HT degradation; E2 also increases both isoforms of tryptophan hydroxylase, the rate-limiting enzyme of serotonin synthesis. Thus, E2 administration results in an overall increase in 5-HT synthesis and availability. E2 also regulates the 5-HT transporter, which plays an integral role in 5-HT reuptake from the synaptic cleft to the pre-synaptic neuron. Furthermore, by downregulating 5-HT1a autoreceptors and upregulating 5-HT2a receptors, E2 increases the amount of serotonin found in the synapse and increases the amount available for postsynaptic transmission. E2 is capable of inducing antidepressant effects in ovariectomized rats when administered in combination with subdoses of fluoxetine, which suggests that E2 can also augment antidepressant agents. In sum, estrogen appears to work via different pathways that ultimately result in increased serotonin production and transmission. Similarly, estrogens increase NE availability by decreasing expression of MAOs and increasing the activity of tyrosine hydroxylase, the rate-limiting enzyme in the synthetic pathway of catecholamine.

Clinically, E2 administration to depressed perimenopausal and early postmenopausal women demonstrated antidepressant effects of similar magnitude to that observed with antidepressant agents. Randomized, double-blind, placebo-controlled studies reported significantly greater reduction in depressive symptoms with the use of transdermal estradiol (17β-estradiol, 50-100 µg), compared to placebo.[3] In some studies, the antidepressant effects of estrogen were observed even in the absence of concomitant vasomotor symptoms.[4] Notably, studies on E2 therapy for older, postmenopausal women suffering from depression resulted in small, nonsignificant reduction in depressive symptoms. Taken together, these observations suggest that: 1) estrogen’s antidepressant effect may have a “critical window” or optimal timing, possibly during the menopause transition and early postmenopausal years; and 2) the potential benefits of E2 therapy for the improvement of mood symptoms may occur independent from changes or improvement of vasomotor symptoms. In sum, preclinical and clinical evidence suggest that estrogen-based therapies can contribute to greater therapeutic responses and potentially boost the response to traditional antidepressant agents, along with well-established benefits for vasomotor, sexual, and other menopause-related symptoms.

HT in Managing Depression in a Patient Using SSRIs

Трансдермальный эстрадиол для лечения послеродовой депрессии

Transdermal estradiol for postpartum depression: A promising treatment option

Estrogen in the Fight Against Schizophrenia

Many American women are prescribed estrogen to combat the negative effects of menopause, such as bone loss and mood swings. Now, new evidence from a Tel Aviv University study suggests that hormone replacement therapy might also protect them -- and younger women -- from schizophrenia as well.


Prof. Ina Weiner of Tel Aviv University's Department of Psychology and her doctoral student Michal Arad have reported findings suggesting that restoring normal levels of estrogen may work as a protective agent in menopausal women vulnerable to schizophrenia. Their work, based on an animal model of menopausal psychosis, was recently reported in the journal Psychopharmacology.

"We've known for some time that when the level of estrogen is low, vulnerability to psychotic symptoms increases and anti-psychotic drugs are less likely to work. Now, our pre-clinical findings show why this might be happening," says Prof. Weiner.

A hormonal treatment to address a behavioral condition

In their study, Weiner and Arad removed the ovaries of female rats to induce menopause-like low levels of estrogen and showed that this led to schizophrenia-like behavior. The researchers then tried to eliminate this abnormal behavior with an estrogen replacement treatment or with the antipsychotic drug haloperidol. Estrogen replacement therapy effectively alleviated schizophrenia-like behavior but haloperidol had no effect on its own. Haloperidol regained its effect in these rats when supplemented by estrogen.

"When the level of estrogen was low, we could see psychotic-like behavior in the animals. Moreover, the sensitivity to psychosis-inducing drugs went up, while the sensitivity to anti-psychotic drugs went down," Prof. Weiner says. This is exactly what we observe in women with low estrogen levels," she says. "But we also found that estrogen, all by itself, combats psychosis in both male and female rats." Furthermore, in low amounts estrogen increases the effectiveness of anti-psychotic drugs.

Prof. Weiner points out that the medical community is hotly debating the pros and cons of estrogen replacement as an add-on to conventional treatment in schizophrenia. Detractors point to higher chances of cervical cancer and heart attacks in those who receive estrogen supplements. But according to her study, which looked at very specific factors possibly related to schizophrenia, estrogen replacement therapy could have positive behavioral effects, she concludes.

Assessing the possibility for prevention

During the course of a woman's lifetime, estrogen levels do not remain constant. During her reproductive years, these levels are affected by the menstrual cycle. There are also dramatic changes in the levels of estrogen just after a woman gives birth -- a change, which can trigger "post-partum blues," and in extreme cases lead to clinical depression and psychosis.

As a preventative therapy, estrogen could be given to women at certain points in time when they are most at risk for schizophrenia, Prof. Weiner suggests: in their mid-twenties and later during the menopausal years.

"Antipsychotic drugs are less effective during low periods of estrogen in the body, after birth and in menopause," says Prof. Weiner. "Our research links schizophrenia and its treatment to estrogen levels. Men seem less likely to begin schizophrenia after their 40s, which also suggests that estrogen is the culprit."


http://www.sciencedaily.com/releases/2010/01/100120112212.htm

эндокринные эффекты нормотимиков

Both seizures and antiepileptic drugs may induce disturbances in hormonal system. Regarding endocrine effects of anticonvulsants, an interaction of these drugs with gonadal, thyroid, and adrenal axis deserves attention. Since majority of antiepileptic drugs block voltage dependent sodium and calcium channels, enhance GABAergic transmission and/or antagonize glutamate receptors, one may expect that similar neurochemical mechanisms are engaged in the interaction of these drugs with synthesis of hypothalamic neurohormones such as gonadotropin-releasing hormone (GnRH), thyrotropin-releasing hormone (TRH), corticotropin-releasing hormone (CRH) and growth hormone releasing hormone (GHRH). Moreover some antiepileptic drugs may affect hormone metabolism via inhibiting or stimulating cytochrome P-450 iso-enzymes. An influence of antiepileptic drugs on hypothalamic-pituitary-gonadal axis appears to be sex-dependent. In males, valproate decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) but elevated dehydroepiandrosterone sulfate (DHEAS) concentrations. Carbamazepine decreased testosterone/sex-hormone binding globulin (SHBG) ratio, whereas its active metabolite--oxcarbazepine--had no effect on androgens. In females, valproate decreased FSH-stimulated estradiol release and enhanced testosterone level. On the other hand, carbamazepine decreased testosterone level but enhanced SHBG concentration. It has been reported that carbamazepine, oxcarbazepine or joined administration of carbamazepine and valproate decrease thyroxine (T4) level in patients with no effect on thyrotropin (TSH). While valproate itself has no effect on T4, phenytoin, phenobarbital and primidone, as metabolic enzyme inducers, can decrease the level of free and bound thyroxine. On the other hand, new antiepileptics such as levetiracetam, tiagabine, vigabatrine or lamotrigine had no effect on thyroid hormones. With respect to hormonal regulation of metabolic processes, valproate was reported to enhance leptin and insulin blood level and increased body weight, whereas topiramate showed an opposite effect. In contrast to thyroid and gonadal hormones, only a few data concern antiepileptic drug action in HPA axis. To this end, no effect of antiepileptic drugs on adrenocorticotropic hormone (ACTH)/cortisol circadian rhytmicity was found. Valproate decreased CRH release in rats, whereas lamotrigine stabilized ACTH/cortisol secretion. Moreover, felbamate was found to inhibit stress-induced corticosterone release in mice. Interestingly, recent data suggest that felbamat and some other new antiepileptic drugs may inhibit transcriptional activity of glucocorticoid receptors. Summing up, the above data suggest that traditional antiepileptic drugs may cause endocrine disturbances, especially in gonadal hormones.
Endocrine effects of antiepileptic drugs

+ Effects of antiepileptic drugs on immune system

Шизофрения и эстрогены

The oestrogen protection hypothesis proposes that oestrogen has a protective effect against onset of schizophrenia. In support of this: Epidemiological studies have shown that young women are less likely to develop schizophrenia than men of the same age, and women are more likely to develop late-onset schizophrenia after menopause. Clinical studies have shown higher psychotic symptoms in perimenopausal women, and women at the low oestrogen phase of the menstrual cycle. Animal studies provide further evidence in support of the oestrogen protection hypothesis. Three randomised double-blind placebo-controlled trials and an open-label study showed that adding oestradiol to women's usual antipsychotic medications was associated with significant abatement of schizophrenia symptoms. A small study of men with schizophrenia who received oral oestradiol valerate also showed a significant abatement in psychotic symptoms. Although oestrogen appears to be a useful treatment for schizophrenia, further research is required to determine the correct dose and duration of use of oestradiol. New types of oestrogen compounds may provide a safer, non-feminising approach for the treatment of schizophrenia.
Oestrogen--a new treatment approach for schizophrenia?