Serum estradiol as a blood-based biomarker predicting hormonal treatment outcomes in women with schizophrenia.

Patients diagnosed with schizophrenia display substantial heterogeneity in terms of their clinical presentations, and treatment response. Accumulating research suggests that such high diversity may reflect distinct biological subtypes with differentially affected underlying neurobiology. Novel treatments, including sex hormone estradiol treatments, provide alternative efficacious treatment avenues but also should be studied within the context of potential heterogeneity. This repeated-measures study characterised the association between hormone levels (estrogen, progesterone, testosterone, prolactin, FSH, LH, DHEA) and symptom treatment outcomes (defined by The Positive and Negative Syndrome Scale (PANSS)) across a 56-day study of 200 ug adjunctive estradiol treatment in women with schizophrenia. Group-based trajectory models was used to account for potential heterogeneity (subgroups). Receiver operating characteristic (ROC) curves were evaluated to define the predictive value of endogenous estradiol levels as a treatment-response biomarker of estradiol treatment. The results generated two subgroups; a treatment-responder group who demonstrated decreasing PANSS scores across time, and a treatment non-responder group, demonstrating stable PANSS scores across time. The treatment-responder subgroup was significantly negatively predicted by estradiol blood level (b= -2.34, SE= 1.17, p = 0.047), while FSH blood level was positively associated with the treatment non-responders (b= 7.14, SE= 2.54, p = 0.008). ROC for day 28, 56 time points yielded area under the curve of 0.52 and 0.55, respectively. Harrell's C-statistic = 0.59. This is the first study to identify endocrine markers in blood serum predicting response to estradiol treatment in female schizophrenia patients, highlighting the existence of heterogeneity of response, indicative of molecular subtypes. Characterising the differential underlying biology of the subgroups may lead to better targeted, specific treatments in the future.(ClinicalTrials.gov Identifier: NCT00357006). https://www.clinicaltrials.gov/ct2/show/NCT00357006.

Family Violence: An Insight Into Perspectives and Practices of Australian Health Practitioners.

Family violence is threatening behavior carried out by a person to coerce or control another member of the family or causes the family member to be fearful. Health practitioners are well placed to play a pivotal role in identifying and responding to family violence; however, their perceived capacity to respond to patients experiencing family violence is not well understood. We aim to explore Australian health practitioners' current perspectives, practices, and perceived barriers in working with family violence, including perceived confidence in responding effectively to cases of family violence encountered during their work with patients. A total of 1,707 health practitioners primarily practicing in the wider Melbourne region were identified, and 114 health practitioners participated in the study between March 2016 and August 2016 by completing an investigator-developed questionnaire. Descriptive, qualitative, and thematic analyses were performed. The majority of participants recognized family violence to be a health issue and that family violence would impact the mental health of afflicted persons. Despite this, only a fifth of participants felt they were very confident in screening, supporting, and referring patients with family violence experiences. Perceived barriers to inquire about family violence included time constraints and greater importance placed on screening for other health issues. Health practitioners reported that additional training on screening, supporting, and referring patients would be beneficial. Australian health practitioners need to be upskilled. Recently, in Australia, state-relevant toolkits have been developed to provide succinct information about responding to initial patient presentations of family violence, how to inquire about family violence, and how to handle disclosures (and nondisclosures) by patients. Further resources could be developed to aid health practitioners in providing assistance to their patients as indicated. These initiatives would be a step toward addressing the concerns with regard to the lack of training and could possibly optimize outcomes for patients experiencing family violence.

Systematic review and meta-analysis of basal cortisol levels in Borderline Personality Disorder compared to non-psychiatric controls.

OBJECTIVE: Borderline personality disorder (BPD) is a prevalent, complex, and serious mental disorder involving multiple symptoms and maladaptive behaviour. The underlying psychobiological mechanisms involved are not yet fully understood, but increasing evidence indicates that changes in hypothalamic-pituitary-adrenal stress axis (HPA) activity may contribute to BPD. Whilst various studies have demonstrated elevated levels of cortisol (the end-product of the HPA axis) in BPD sufferers, others have presented opposite findings. Inconsistent findings may be attributable to comorbidities, collection and measurement methods, gender, and sample size. Considering these discrepancies, the aim of this systematic review and meta-analysis was to assess available studies in the scientific literature examining basal/ baseline cortisol levels in patients diagnosed with borderline personality disorder compared to non-psychiatric controls. METHODS: A systematic literature review was conducted with descriptions of primary studies in addition to a meta-analysis of studies with a control group. Meta-analysis was performed using Comprehensive Meta-analysis software (CMA version 2). The effect size (Hedges' g) was calculated with random-effect model. RESULTS: A systematic literature search identified 16 studies that met the eligibility criteria from a total of 1076 unique records initially examined. Twelve studies (N = 546; 278 borderline personality disorder and 268 non-psychiatric controls) fulfilled the inclusion criteria for meta-analysis. The standardised mean difference (Hedges' g) of basal cortisol level between BPD and control groups was -0.32 (pooled data from 12 studies; 95% confidence interval -0.56 to -0.06, p = 0.01), indicating significantly lower mean cortisol level for the BPD group. CONCLUSION: Cortisol as a biomarker of the HPA axis is an important and helpful measure in the study of stress disorders such as BPD. However, considerations of potential confounding factors must be considered.

Seguridad de los antipsicóticos atípicos en el embarazo / Safety of atypical antipsychotic drugs during pregnancy

Introducción. Desde la introducción de los antipsicóticos de segunda generación (ASG), su prescripción ha incrementado notablemente en mujeres con enfermedad mental, y cada vez son más las mujeres embarazadas expuestas. Sin embargo, la información disponible con respecto a la seguridad de estos fármacos en gestantes es todavía limitada. Objetivos. Aclarar el impacto de los ASG durante el embarazo a partir de la literatura disponible para ofrecer una herramienta clínica de apoyo. Metodología. Se ha llevado a cabo una revisión exhaustiva de la literatura disponible. Siguiendo los criterios PRISMA para la búsqueda, se ha identificado literatura publicada desde mayo de 1995 hasta octubre de 2015 en: PUBMED (Medline), SCOPUS, LILACS y MEDES. Resultados. La búsqueda arrojó un total de 192 estudios tras descartarse duplicados, y 47 artículos fueron incluidos en la revisión de acuerdo con los criterios de inclusión establecidos. Conclusiones. Aunque se necesitan más estudios, no parece existir un daño consistente congénito en el feto con el uso de ASG. Según la literatura disponible, la exposición intrauterina a ASG se ha asociado con algunas complicaciones neonatales y obstétricas. Hay alguna evidencia que relaciona olanzapina y clozapina con un mayor riesgo de diabetes gestacional y macrosomía en el neonato, pero es evidente que el tratamiento de la enfermedad mental durante el embarazo es vital y promueve mejores resultados para la madre y el infante. Actualmente, olanzapina y quetiapina son los ASG más frecuentemente usados durante el embarazo y, a pesar de algunos riesgos observados, parecen seguros en general (AU)

Introduction. Since the introduction of second generation antipsychotics (SGAs), prescribing has increased considerably in women with a range of mental illnesses, and now increasingly used by women during pregnancy. However, information regarding the safety of SGAs during pregnancy is limited. Objectives. To clarify the impact of SGAs during pregnancy from the available literature, and to provide a clinical support tool. Methodology. An exhaustive review of the available literature was conducted. Following the PRISMA criteria, literature published from May 1995 to October 2015 was identified from PubMed (Medline), SCOPUS, LILACS and MEDES databases. Results. The search yielded a total of 192 studies after duplicates were excluded, and 47 articles were included in the review in accordance with the inclusion criteria. Conclusions. While more research is needed, SGAs do not appear to cause marked congenital foetal harm. According to the available literature, in utero exposure to SGAs is associated with some neonatal and obstetric complications. While olanzapine, and clozapine in particular, is associated with increased risk of gestational diabetes and large for gestational age newborns, from this review of the literature it is clear that treating mental illness during pregnancy is vital and promotes better outcomes for both mother and infant. Currently olanzapine and quetiapine are the most frequently used SGAs during pregnancy, and despite some risks observed, overall safety is reported (AU)

Antipsychotic use in pregnancy.

INTRODUCTION: Antipsychotic medications are being prescribed for a growing number of women with mental illnesses. However, evidence regarding their safety in pregnancy is still insufficient to provide adequate support for clinical practice, creating increasing concern among pregnant women and clinicians. AREAS COVERED: The aim of this article is to review published data regarding the safety of antipsychotic medications in pregnancy with a focus on the most commonly used atypical antipsychotics. EXPERT OPINION: Given the potential harm of not treating severe psychiatric illnesses during pregnancy, careful administration of antipsychotics is recommended for pregnant women who suffer from severe mental disorders. The most frequently used antipsychotics in pregnancy are olanzapine, risperidone and quetiapine, and do not appear to cause consistent, congenital harm to the fetus. No specific patterns of fetal limb or organ malformation related to these drugs have been reported. There is some evidence suggesting an association between antipsychotic use in pregnancy and the development of gestational diabetes. Also there appears to be an association between antipsychotic medication use in pregnancy and increased neonatal respiratory distress and withdrawal symptoms. Further studies are needed for clinicians to balance good maternal mental health, healthy pregnancies and good infant health outcomes.

Establishing female-only areas in psychiatry wards to improve safety and quality of care for women.

OBJECTIVE: Our aim was to assess the impact of creating a female-only area within a mixed-gender inpatient psychiatry service, on female patient safety and experience of care. METHOD: The Alfred hospital reconfigured one of its two psychiatry wards to include a female-only area. Documented incidents compromising the safety of women on each ward in the 6 months following the refurbishment were compared. Further, a questionnaire assessing perceived safety and experience of care was administered to female inpatients on both wards, and staff feedback was also obtained. RESULTS: The occurrence of documented incidents compromising females' safety was found to be significantly lower on the ward containing a female-only area. Women staying on this ward rated their perceived safety and experience of care significantly more positively than women staying where no such gender segregation was available. Further, the female-only area was identified by the majority of surveyed staff to provide a safer environment for female patients. CONCLUSIONS: Establishing female-only areas in psychiatry wards is an effective way to improve the safety and experience of care for female patients.

The role of estrogen in the treatment of men with schizophrenia.

Schizophrenia is a debilitating and pervasive mental illness with devastating effects on many aspects of psychological, cognitive and social wellbeing. Epidemiological and life-cycle data point to significant differences in the incidence and course of schizophrenia between men and women, suggesting that estrogen plays a "protective" role . Adjunctive estrogen therapy has been shown to be effective in enhancing the treatment of schizophrenia in women. In men, consideration of estrogen therapy has been impacted by concerns of feminisation, however, clinical trials using estrogen to treat prostate cancer, bone density loss and even aggression in men with dementia or traumatic brain injury, show estrogen to be a safe and effective therapy. Findings do, however, suggest that further exploration of a therapeutic role for adjunctive estradiol treatment in men with schizophrenia is warranted. The development of the new estrogen compounds - Selective Estrogen Receptor Modulators (SERMs) which do not cause feminisation - opens up the possibility of using a different type of estrogen for a longer period of time at higher doses. Estrogen could therefore prove to be an important component in the treatment of psychotic symptoms in men with schizophrenia. This review explains the scientific rationale behind the estrogen hypothesis and how it can be clinically utilised to address concerns unique to the care of men with schizophrenia.

Special biological issues in the management of women with schizophrenia.

Schizophrenia is a debilitating and pervasive mental illness with devastating effects on psychological, cognitive and social wellbeing, and for which current treatment options are far from ideal. Gender differences and the influence of the female reproductive life cycle on the onset, course and symptoms of schizophrenia and the discovery of estrogen's remarkable psychoprotective properties in animal models led to the proposal of the 'estrogen protection hypothesis' of schizophrenia. This has fueled the recent successful investigation of estradiol as a potential adjuvant therapeutic agent in the management of schizophrenia in women. This review explains the scientific rationale behind the estrogen hypothesis and how it can be clinically utilized to address concerns unique to the care of women with schizophrenia.

Role of estrogen treatment in the management of schizophrenia.

Increasing evidence from epidemiological, preclinical and clinical studies suggests that estrogens may exert psychoprotective effects in schizophrenia. Observations of gender differences in the onset and course of schizophrenia have prompted exploration of the effects of estrogen on the CNS. The aim of this paper is to provide an overview of different applications of adjunctive estrogen as a possible treatment for symptoms of schizophrenia in both men and women. Recent trials have suggested that estrogen augmentation therapy may be able to enhance the management of schizophrenia; however, the clinical application of estrogen as a treatment has been limited by potential side effects, the most worrying being breast and uterine cancer in women, and feminization in men. Selective estrogen receptor modulators (SERMs), however, may offer therapeutic benefits for both men and women with schizophrenia without posing threat to breast and uterine tissue and without feminizing effects. The use of estrogen opens up new possibilities for both men and women in the treatment of severe mental illnesses such as schizophrenia. With further preclinical and clinical research, it is hoped that this promising field of hormone modulation can continue to evolve and eventually be translated into real therapeutic potential.

Hormones and schizophrenia.

PURPOSE OF REVIEW: It is a well established fact that many serious mental illnesses, in particular psychoses such as schizophrenia, may have a significant hormonal aetiological component. This study aims to discuss the oestrogen protection hypothesis of schizophrenia in particular, with an emphasis on findings from the recent literature in support of this theory. RECENT FINDINGS: Epidemiological and life-cycle data point to significant differences in the incidence and course of schizophrenia between men and women, suggesting a protective role of oestrogen. In-vitro and in-vivo preclinical research has confirmed oestradiol's interactions with central neurotransmitter systems implicated in the pathogenesis of schizophrenia, whereas results from randomized controlled trials investigating the antipsychotic potential of oestrogen have been promising. Research into other neuroactive hormones with possible effects on mental state is a field still in its infancy but is evolving rapidly. SUMMARY: Schizophrenia and related psychoses are pervasive and debilitating conditions, for which currently available treatments are often only partially effective and entail a high risk of serious side effects. Thus, new therapeutic strategies are needed, and the literature reviewed here suggests that hormones such as oestrogen could be a viable option. It is hoped that, with further research and larger trials, the oestrogen hypothesis can be translated into effective clinical practice.

Piloting the effective therapeutic dose of adjunctive selective estrogen receptor modulator treatment in postmenopausal women with schizophrenia.

Estrogen treatment may enhance the recovery of schizophrenia in women. However, adverse effects on uterine and breast tissue and other physical side effects may limit the long-term therapeutic use of estrogen. Raloxifene hydrochloride is a selective estrogen receptor modulator that acts as an estrogen antagonist in breast tissue and may have agonistic actions in the brain, potentially offering mental health benefits with few estrogenic side effects. To provide an indication of the potential therapeutic dose for raloxifene hydrochloride in postmenopausal women with schizophrenia, this study pools data from an ongoing randomized controlled trial of adjunctive 120 mg/day oral raloxifene hydrochloride (n=13) versus oral placebo (n=13), with data from a previous pilot study administering 60 mg/day raloxifene hydrochloride (n=9). Analysis of variance found significant interaction effects for total (p=.01) and general (p=.02) Positive and Negative Syndrome Scale (PANSS) symptomatology. Participants randomized to receive 120 mg/day raloxifene hydrochloride experienced a significantly more rapid recovery of total and general psychotic symptoms compared to both 60 mg/day raloxifene hydrochloride and placebo. The demonstrated benefit of adjunctive treatment with 120 mg/day raloxifene hydrochloride offers support for the potential role of this selective estrogen receptor modulator in treating postmenopausal women with schizophrenia.

Hormone modulation: a novel therapeutic approach for women with severe mental illness.

OBJECTIVES: Accumulating evidence describes the effects of oestrogen and other gonadal hormones on the central nervous system and, in particular, on the mental state of women. Evidence supporting the psychotherapeutic effects of exogenous oestrogen has started to emerge only over the past two decades. The purpose of the present paper was to provide an overview of different applications of adjunctive hormones, as treatments for symptoms of severe mental illness in women. METHODS: Three case reports are presented: in each case the woman selected had participated in large, double-blind, randomized controlled trials exploring hormone modulation. Case study 1 presents a premenopausal woman with schizophrenia, who received an 8 week trial of daily adjunctive 200 microg transdermal oestradiol. Case study 2 presents a postmenopausal woman with schizophrenia on a 12 week trial of adjunctive raloxifene hydrochloride 120 mg per day. Case study 3 presents a woman with schizoaffective disorder, in the manic phase, who received tamoxifen 40 mg per day for 28 days. RESULTS: Adjunctive oestradiol was associated with an improvement in symptoms of psychosis in a premenopausal woman with schizophrenia; adjunctive raloxifene was associated with an improvement in cognitive functioning in a postmenopausal woman with schizophrenia; and adjunctive tamoxifen was associated with an improvement in symptoms of mania in a woman with schizoaffective disorder. CONCLUSIONS: These findings are consistent with preliminary research trials suggesting that adjunctive hormone modulation is a promising area of gender-specific treatment for serious mental illness.