Oestrogen--a new treatment approach for schizophrenia?

Alfred Psychiatry Research Centre, Monash University and Alfred Hospital, Melbourne, VIC.
The Medical journal of Australia (Impact Factor: 3.79). 03/2009; 190(4 Suppl):S37-8.
Source: PubMed

ABSTRACT 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.

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    ABSTRACT: There is now a growing appreciation that estrogen is capable of rapidly activating a number of signaling cascades within the central nervous system. In addition, there are an increasing number of studies reporting that 17β-estradiol, the major biologically active estrogen, can modulate cognition within a rapid time frame. Here we review recent studies that have begun to uncover the molecular and cellular framework which contributes to estrogens ability to rapidly modulate cognition. We first describe the mechanisms by which estrogen receptors (ERs) can couple to intracellular signaling cascades, either directly, or via the transactivation of other receptors. Subsequently, we review the evidence that estrogen can rapidly modulate both neuronal function and structure in the hippocampus and the cortex. Finally, we will discuss how estrogens may influence cognitive function through the modulation of neuronal structure, and the implications this may have on the treatment of a range of brain disorders.
    Frontiers in Neuroendocrinology 08/2014; 36. DOI:10.1016/j.yfrne.2014.08.001 · 7.58 Impact Factor
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    ABSTRACT: Objective: To better understand premenstrual exacerbations of schizophrenia in women and weigh treatment options. Method: A PubMed literature search was conducted, using the search terms “schizophrenia”, “psychosis” “menstrual exacerbation”, “hormones” and assessing relevance to premenstrual exacerbation of schizophrenia symptoms. Results: Exacerbations are usually distinguishable from periodic or menstrual psychosis, a relatively rare condition. Controversy continues about whether low estrogen periods of the month lead to an increase in schizophrenia symptoms among women of reproductive age or whether some women suffer from both schizophrenia and premenstrual dysphoric disorder (PMDD). No treatment trials of specific interventions have been conducted so that physicians must decide on a case by case basis whether to raise antipsychotic doses premenstrually, try estrogens or estrogen/progesterone combinations or selective estrogen receptor modulators, or target PMDD symptoms. Conclusion: Clinicians need to be aware of premenstrual symptom aggravation in a large minority of women with schizophrenia. Treatment strategies will depend on the nature of the symptoms that are exacerbated. Optimal treatment needs to be adjusted to the individual woman.
    Acta Psychiatrica Scandinavica 05/2012; 125(5):363-371. DOI:10.1111/j.1600-0447.2011.01822.x · 5.55 Impact Factor
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    ABSTRACT: Hippocampal memory formation is highly regulated by post-translational histone modifications and DNA methylation. Accordingly, these epigenetic processes play a major role in the effects of modulatory factors, such as sex steroid hormones, on hippocampal memory. Our laboratory recently demonstrated that the ability of the potent estrogen 17β-estradiol (E2) to enhance hippocampal-dependent novel object recognition memory in ovariectomized female mice requires ERK-dependent histone H3 acetylation and DNA methylation in the dorsal hippocampus. Although these data provide valuable insight into the chromatin modifications that mediate the memory-enhancing effects of E2, epigenetic regulation of gene expression is enormously complex. Therefore, more research is needed to fully understand how E2 and other hormones employ epigenetic alterations to shape behavior. This review discusses the epigenetic alterations shown thus far to regulate hippocampal memory, briefly reviews the effects of E2 on hippocampal function, and describes in detail our work on epigenetic regulation of estrogenic memory enhancement.
    Frontiers in Neuroendocrinology 05/2014; DOI:10.1016/j.yfrne.2014.05.001 · 7.58 Impact Factor

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