Clozapine Safety in Pregnancy: A Clinical Study.

BACKGROUND AND HYPOTHESIS: Pregnant women with persistent schizophrenia and related disorders may require ongoing antipsychotic treatment, including clozapine. However, the potential risks of using clozapine during pregnancy and the postnatal period remain uncertain. STUDY DESIGN: We conducted a nested case-control study using the National Register of Antipsychotic Medication in Pregnancy (NRAMP) database. Our study assessed pregnancy outcomes among Australian women diagnosed with schizophrenia spectrum disorder and treated with clozapine (n = 14) during the first trimester. These women were compared to 2 subgroups: those treated with quetiapine (n = 53) and those not taking any medication (n = 24) during pregnancy. STUDY RESULTS: We observed higher rates of miscarriage in the clozapine group compared to the quetiapine and drug-free groups. The clozapine group had a higher early pregnancy body mass index but lower overall pregnancy weight gain than the other groups. The prevalence of gestational diabetes was significantly higher in the clozapine group. The percentage of vaginal delivery was higher in the clozapine group than in the other 2 groups. Neonatal outcomes such as gestational age, and Apgar scores were similar across groups. The birth weight was lower in the clozapine group compared to the other 2 groups. CONCLUSIONS: This study suggests that pregnant women taking clozapine and their babies have greater adverse outcomes compared to other groups. Clozapine appears to be associated with a greater risk of miscarriages, maternal gestational diabetes, and lower birth weight. However, the gestational age, Apgar scores, and admission to NICU/SCN were comparable between all groups.

Menopause depression: Under recognised and poorly treated.

Menopause is a biological process experienced by all people assigned female at birth. A significant number of women experience mental ill health related to the major brain gonadal hormone shifts that occur in their midlife. There is poor understanding and management of the complex mental ill health issues, with the biological brain hormone changes receiving little formal attention. The current treatment advice is to manage this special type of mental ill health in the same way that all mental ill health is managed. This leads to poor outcomes for women and their families. Many women leave the workforce earlier than expected due to menopause-related depression and anxiety, with subsequent loss of salary and superannuation. Others describe being unable to adequately parent or maintain meaningful relationships - all ending in a poor quality of life. We are a large and diverse group of national and international clinicians, lived experience and social community advocates, all working together to innovate the current approaches available for women with menopausal mental ill health. Above all, true innovation is only possible when the woman with lived experience of menopause is front and centre of this debate.

(S)-S-adenosylmethionine in the treatment of pre-menstrual disorders in adult women: A protocol for an open-label pilot study.

Pre-menstrual disorders, including pre-menstrual syndrome and pre-menstrual dysphoric disorder, are highly prevalent disorders in women of reproductive age. Pre-menstrual disorders are associated with debilitating symptoms that onset in the days prior to menses. A complex interplay between hormonal fluctuations, cellular sensitivity, and psychosocial stressors likely underly the pathophysiology of pre-menstrual disorders. Current treatment options include selective serotonin reuptake inhibitors, hormonal therapies, and psychosocial support. There is growing evidence for oestrogen, progesterone, gonadotropin Releasing Hormone analogues and Complementary and Alternative Medicines in treating Pre-menstrual disorders. (S)-S-adenosylmethionine is a complementary and alternative medicine with postulated roles in the treatment of depression, with a rather rapid onset of action and minimal side effect profile. We propose a protocol for investigating the efficacy of (S)-S-adenosylmethionine in the treatment of pre-menstrual disorders. The proposed study is an open label pilot study, that will recruit thirty women between the ages of 18-45 who experience a pre-menstrual disorder. Daily and interval questionnaires will provide a quantification of symptoms across four menstrual cycles (16 weeks). During two consecutive menstrual cycles it is proposed that participants receive oral (S)-S-adenosylmethionine Complex 400 mg three times a day (total daily dose 1200 mg), during the pre-menstrual time-period (14 days prior to menses). Changes in pre-menstrual disorder symptoms between control and treatment cycles will assist in elucidating the clinical efficacy of (S)-S-adenosylmethionine. This study has the potential to support a larger double blinded, placebo controlled randomised control trial and aims to enrich the knowledge surrounding pre-menstrual disorders.

Estrogen and psychosis - a review and future directions.

The link between sex hormones and schizophrenia has been suspected for over a century; however, scientific evidence supporting the pharmacotherapeutic effects of exogenous estrogen has only started to emerge during the past three decades. Accumulating evidence from epidemiological and basic research suggests that estrogen has a protective effect in women vulnerable to schizophrenia. Such evidence has led multiple researchers to investigate the role of estrogen in schizophrenia and its use in treatment. This narrative review provides an overview of the effects of estrogen as well as summarizes the recent work regarding estrogen as a treatment for schizophrenia, particularly the use of new-generation selective estrogen receptor modulators.

Adjunctive agents to antipsychotics in schizophrenia: a systematic umbrella review and recommendations for amino acids, hormonal therapies and anti-inflammatory drugs.

QUESTION: This umbrella review and guidelines aimed to provide evidence to support the rational choice of selected adjunctive therapies for schizophrenia. STUDY SELECTION AND ANALYSIS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and World Federation of Societies of Biological Psychiatry (WFSBP)-grading recommendations, 63 randomised control trials (RCTs) (of which 4219 unique participants have completed the RCTs) and 29 meta-analyses were analysed. FINDINGS: Provisional recommendations (WFSBP-grade 1) could be made for two molecules in augmentation to antipsychotics: (1) N-acetyl-cysteine (NAC, 1200-3600 mg/day, for >12 consecutive weeks) in improving negative symptoms, general psychopathology (positive and negative syndrome scale for schizophrenia (PANSS) general psychopathology factor (G)-G subscale), with the RCTs with the longer duration showing the most robust findings; (2) polyunsaturated fatty acids (3000 mg/day of eicosapentaenoic acid, for >12 weeks) in improving general psychopathology. Weaker recommendations (ie, WFSBP-grade 2) could be drawn for sarcosine (2 g/day) and minocycline (200-300 mg/day) for improving negative symptoms in chronic schizophrenia (not early schizophrenia), and NAC for improving positive symptoms and cognition. Weak recommendations are not ready for clinical practice. There is provisional evidence that oestrogens and raloxifene are effective in some patients, but further research is needed to determine their benefit/risk ratio. CONCLUSIONS: The results of this umbrella review should be interpreted with caution as the number of RCTs included in the meta-analyses was generally small and the effect sizes were weak or medium. For NAC, two RCTs with low risk of bias have provided conflicting results and the WFSBP-grade recommendation included also the results of meta-analyses. These drugs could be provisionally prescribed for patients for whom no other treatments have been effective, but they should be discontinued if they prove ineffective.

Perceived Discrimination in Australia During the COVID-19 Pandemic: a Longitudinal Study.

OBJECTIVES: There have been global reports of increased discrimination during the COVID-19 pandemic relative to the pre-pandemic era, though this has not been well explored within Australia. The aim of the study was to characterise discriminatory behaviour experienced by groups previously identified as most at risk of experiencing discrimination (i.e. those of Asian descent or healthcare workers) both from pre-pandemic to pandemic and during the pandemic era in Australia. METHODS: From April 2020 to September 2021, 1479 Australian adults completed the everyday discrimination scale (EDS). Initially, participants were asked to retrospectively consider discrimination experienced pre-COVID-19 pandemic and then to consider experiences in the past month during the pandemic. Participants were invited to repeat the latter every 2 months. RESULTS: Collectively, there was a reduction in EDS scores from pre-pandemic to pandemic. Within the pandemic era, mean trajectory graphs across time revealed that changes in EDS scores in the 'non-Asian healthcare workers' and 'Asian healthcare workers' subgroups tended to mirror onto fluctuations in Australian COVID-19 case numbers. CONCLUSION: Our findings suggest social solidarity amongst the general Australian population during the pandemic, but still highlight a need to dedicate resources towards groups with heightened risk of experiencing discrimination during future public health threats.

Correction: A Prospective Cohort Study of Antipsychotic Medications in Pregnancy: The First 147 Pregnancies and 100 One Year Old Babies.

[This corrects the article DOI: 10.1371/journal.pone.0094788.].

A Study of Cardiac Outcomes After Droperidol Administration in an Inpatient Psychiatric Cohort.

PURPOSE/BACKGROUND: Droperidol is an antipsychotic medication used in psychiatric emergencies to manage acute behavioral disturbance. Droperidol use carries a risk of prolonged QT interval on the electrocardiogram and associated cardiac arrhythmias including torsades de pointes and ventricular fibrillation. This study aimed to evaluate the safety of droperidol in adults admitted to the psychiatric inpatient unit of a large Australian hospital. METHODS/PROCEDURES: In this retrospective cohort study, psychiatric inpatients admitted between October 22, 2018, and March 1, 2021, who received at least 1 dose of intramuscular droperidol were consecutively included. Outcomes of interest were death, cardiac arrhythmias, and QT prolongation. QT prolongation was identified using the QT-interval nomogram. FINDINGS/RESULTS: This study included 263 patients without exclusion. No deaths or cases of cardiac arrhythmia were recorded within 24 hours of droperidol administration. Electrocardiogram data were available for 41.1% of patients (n = 108) within 7 days of droperidol administration. Two cases of QT prolongation were identified using the QT-interval nomogram, but these patients were also prescribed other medications that may have contributed to QT prolongation. IMPLICATIONS/CONCLUSIONS: This study contributes the first known large retrospective study of safety outcomes including QT prolongation after droperidol administration in a psychiatric inpatient setting. Our findings corroborate mounting evidence supporting the clinical safety of droperidol use in psychiatric settings. Nonetheless, we note that significant barriers remain with regard to timely electrocardiogram monitoring after droperidol use.

The use of first and second-generation antipsychotic drugs and the potential to develop gestational diabetes mellitus among perinatal patients with psychosis.

There is limited knowledge about the effects of antipsychotic exposure on the development of gestational diabetes mellitus (GDM) in women with mental illness. Studies have demonstrated an association between antipsychotic medications and metabolic problems such as weight gain and diabetes mellitus in non-pregnant patients with psychiatric disorders. GDM increases the risk of adverse maternal outcomes, including pregnancy-induced hypertension, antepartum and postpartum haemorrhage, and caesarean delivery. The National Register of Antipsychotic Medication in Pregnancy (NRAMP) is a prospective Australian cohort study that observed women who took antipsychotics during pregnancy. Data from 205 women were extracted for the final analysis and included women who took first or second-generation antipsychotics (FGA,SGA) during the first trimester of pregnancy (at minimum) and had a diagnosis of a psychotic disorder (n = 180). The comparison (non-exposed) group (n = 25) were women with psychosis who chose not to take any antipsychotic during the first trimester (at minimum). The comparison groups were not matched, although groups were homogenous in terms of sex, age range, diagnosis and perinatal status. The results of logistic regression analysis revealed that women who were exposed to FGAs, SGAs were seven and five times, respectively, more likely to develop GDM compared to non-exposed groups. When adjusted for confounding variables such as BMI and family history of diabetes, the potential of developing GDM decreased for women taking SGAs. In conclusion, the risk of developing GDM is lower in women taking SGAs compared with women taking FDAs. In addition, family history of diabetes and BMI adds to the risk.

The 26-Item Eating Attitudes Test (EAT-26): Psychometric Properties and Factor Structure in Vegetarians and Vegans.

The eating disorder screener, Eating Attitudes Test (EAT), has been used widely; however, its usability in specific dietary groups such as vegetarians and vegans remain unknown. Considering the rising popularity of vegetarianism and veganism, the current study aimed to assess the psychometric properties and theoretical assumptions of the 26-item EAT in separate groups of vegetarians (n = 278), vegans (n = 580), and omnivores (n = 413). Confirmatory factor analysis of four models from previous literature revealed inadequate fit of the data, with the exception of a 16-item four-factor model in vegetarians and vegans. Further assessment of the original three-factor model and 16-item four-factor model demonstrated poor psychometric properties. The primarily inadequate test-retest reliability discovered in this study, independent of whether a shortened version was used, raises concerns around the utility and stability of the EAT-26 in vegetarians and vegans. Future research should potentially investigate novel ways of measuring eating disorder pathology in these groups.

Estrogen - A key neurosteroid in the understanding and treatment of mental illness in women.

The commentary is an invited brief about my contribution to Psychiatry Research. My work has built on the "estrogen hypothesis", as stated by Hafner, Riecher-Rossler and Seeman in the 1990's. This hypothesis was that estrogen provides 'protection' against the early onset of severe schizophrenia in women, and with decreasing brain estrogens at the menopause, mental ill health worsens in women. In this paper, results from clinical trials conducted over many decades, that involved administering exogenous estrogen in different types and doses, show an overall positive impact - with improved symptoms of schizophrenia in women. This led to the conduct of further successful clinical trials of gonadal hormone treatment in women with PMDD and menopausal depression, plus understanding more about depression caused by hormone contraceptives. The role of estrogens in stress vulnerability is reflected in the sex-dependent reaction to childhood trauma, which has led to our new work in the neurobiological effects of early life trauma in women.

Oral contraceptives and cognition: A systematic review.

Oral contraceptives (OCs) are widely used. While the physical impacts of OCs have been well researched, there is increasing interest on potential impacts of OCs on brain, behaviour and cognition. We systematically reviewed the literature to determine the influence of OCs on cognition, including neurocognition, social cognition and emotional processing. Inclusionary criteria were: (a) premenopausal females taking OCs; (b) a control group of naturally cycling women or OCs users in their inactive (i.e. 'sugar pill') phase; and (c) at least one measure of performance on a neurocognitive or social cognitive task. The systematic review found that OC use was associated with some differences in performance on all cognitive domains examined (with the exception of basic auditory attention and psychomotor performance). Several factors were identified that are likely to modulate the way OCs influence cognition, including task related factors, OC type and control group characteristics. Directions for future research are highlighted.

The relationship between cognitive clusters and telomere length in bipolar-schizophrenia spectrum disorders.

BACKGROUND: Schizophrenia and bipolar disorder are complex mental illnesses that are associated with cognitive deficits. There is considerable cognitive heterogeneity that exists within both disorders. Studies that cluster schizophrenia and bipolar patients into subgroups based on their cognitive profile increasingly demonstrate that, relative to healthy controls, there is a severely compromised subgroup and a relatively intact subgroup. There is emerging evidence that telomere shortening, a marker of cellular senescence, may be associated with cognitive impairments. The aim of this study was to explore the relationship between cognitive subgroups in bipolar-schizophrenia spectrum disorders and telomere length against a healthy control sample. METHODS: Participants included a transdiagnostic group diagnosed with bipolar, schizophrenia or schizoaffective disorder (n = 73) and healthy controls (n = 113). Cognitive clusters within the transdiagnostic patient group, were determined using K-means cluster analysis based on current cognitive functioning (MATRICS Consensus Cognitive Battery scores). Telomere length was determined using quantitative PCRs genomic DNA extracted from whole blood. Emergent clusters were then compared to the healthy control group on telomere length. RESULTS: Two clusters emerged within the patient group that were deemed to reflect a relatively intact cognitive group and a cognitively impaired subgroup. Telomere length was significantly shorter in the severely impaired cognitive subgroup compared to the healthy control group. CONCLUSIONS: This study replicates previous findings of transdiagnostic cognitive subgroups and associates shorter telomere length with the severely impaired cognitive subgroup. These findings support emerging literature associating cognitive impairments in psychiatric disorders to accelerated cellular aging as indexed by telomere length.

Psychometric properties and factor structure of the Eating Disorder Examination-Questionnaire in omnivores, vegetarians, and vegans.

The psychometric properties of the Eating Disorder Examination-Questionnaire (EDE-Q) have been widely reported, but there remains considerable uncertainty regarding the factor structure of the tool, with vegetarians and vegans remaining no exception. Due to the utility of the EDE-Q as a screening and outcome measure, we assessed the theoretical assumptions and psychometric properties of the EDE-Q in vegetarians (n = 278), vegans (n = 580), and omnivores (n = 413) separately, owing to the expectation of different structures within each dietary population given their varying degrees of restraint. We undertook confirmatory factor analysis of five models previously described demonstrating inadequate fit. Exploratory factor analysis supported unique three-factor models across dietary groups incorporating Weight and Shape Concern subscales, potentially suggesting that community samples of varying of dietary restraint consistently interpret weight/shape to be related to general body image concerns. These novel findings also suggest a shorter version of the EDE-Q may be more suitable in community samples to reduce the time burden of the tool. The predominately poor test-retest reliability raises doubt around the overall utility and stability of the EDE-Q in all dietary populations, regardless of whether a shortened version is employed. Future research is needed to validate of other eating disorder tools across dietary populations.