Mood Disorders In Women Research Articles

Gut bacteriome and mood disorders in women with PCOS.

How does the gut bacteriome differ based on mood disorders (MDs) in women with polycystic ovary syndrome (PCOS), and how can the gut bacteriome contribute to the associations between these two conditions? Women with PCOS who also have MDs exhibited a distinct gut bacteriome with reduced alpha diversity and a significantly lower abundance of Butyricicoccus compared to women with PCOS but without MDs. Women with PCOS have a 4- to 5-fold higher risk of having MDs compared to women without PCOS. The gut bacteriome has been suggested to influence the pathophysiology of both PCOS and MDs. This population-based cohort study was derived from the Northern Finland Birth Cohort 1966 (NFBC1966), which includes all women born in Northern Finland in 1966. Women with PCOS who donated a stool sample at age 46years (n = 102) and two BMI-matched controls for each case (n = 205), who also responded properly to the MD criteria scales, were included. A total of 102 women with PCOS and 205 age- and BMI-matched women without PCOS were included. Based on the validated MD criteria, the subjects were categorized into MD or no-MD groups, resulting in the following subgroups: PCOS no-MD (n = 84), PCOS MD (n = 18), control no-MD (n = 180), and control MD (n = 25). Clinical characteristics were assessed at age 31years and age 46years, and stool samples were collected from the women at age 46years, followed by the gut bacteriome analysis using 16 s rRNA sequencing. Alpha diversity was assessed using observed features and Shannon's index, with a focus on genera, and beta diversity was characterized using principal components analysis (PCA) with Bray-Curtis Dissimilarity at the genus level. Associations between the gut bacteriome and PCOS-related clinical features were explored by Spearman's correlation coefficient. A P-value for multiple testing was adjusted with the Benjamini-Hochberg false discovery rate (FDR) method. We observed changes in the gut bacteriome associated with MDs, irrespective of whether the women also had PCOS. Similarly, PCOS MD cases showed a lower alpha diversity (Observed feature, PCOS no-MD, median 272; PCOS MD, median 208, FDR = 0.01; Shannon, PCOS no-MD, median 5.95; PCOS MD, median 5.57, FDR = 0.01) but also a lower abundance of Butyricicoccus (log-fold changeAnalysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC)=-0.90, FDRANCOM-BC=0.04) compared to PCOS no-MD cases. In contrast, in the controls, the gut bacteriome did not differ based on MDs. Furthermore, in the PCOS group, Sutterella showed positive correlations with PCOS-related clinical parameters linked to obesity (BMI, r2=0.31, FDR = 0.01; waist circumference, r2=0.29, FDR = 0.02), glucose metabolism (fasting glucose, r2=0.46, FDR < 0.001; fasting insulin, r2=0.24, FDR = 0.05), and gut barrier integrity (zonulin, r2=0.25, FDR = 0.03). Although this was the first study to assess the link between the gut bacteriome and MDs in PCOS and included the largest PCOS dataset for the gut microbiome analysis, the number of subjects stratified by the presence of MDs was limited when contrasted with previous studies that focused on MDs in a non-selected population. The main finding is that gut bacteriome is associated with MDs irrespective of the PCOS status, but PCOS may also modulate further the connection between the gut bacteriome and MDs. This research was funded by the European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie Grant Agreement (MATER, No. 813707), the Academy of Finland (project grants 315921, 321763, 336449), the Sigrid Jusélius Foundation, Novo Nordisk Foundation (NNF21OC0070372), grant numbers PID2021-12728OB-100 (Endo-Map) and CNS2022-135999 (ROSY) funded by MCIN/AEI/10.13039/501100011033 and ERFD A Way of Making Europe. The study was also supported by EU QLG1-CT-2000-01643 (EUROBLCS) (E51560), NorFA (731, 20056, 30167), USA/NIH 2000 G DF682 (50945), the Estonian Research Council (PRG1076, PRG1414), EMBO Installation (3573), and Horizon 2020 Innovation Grant (ERIN, No. EU952516). The funders did not participate in any process of the study. We have no conflicts of interest to declare. N/A.

Risk Factors for Peripartum Mood Disorders in Women with MS: A Prospective Study (P4-6.014)

Risk Factors for Peripartum Mood Disorders in Women with MS: A Prospective Study (P4-6.014)

Maternal Sleeping Problems Before and After Childbirth - A Systematic Review.

The perinatal and postpartum period is of great significance for women due to physiological changes, shifts in circadian rhythms, social setting, and psychological well-being, all of which affect the quality and quantity of their sleep. A mixed-studies systematic review was undertaken to enhance our understanding of sleep disturbances and mood disorders in women in late pregnancy and the postpartum period, their connection with breastfeeding, and the assessment of interventions for sleep disturbance. Three electronic databases (PUBMED, EMBASE and Google Scholar) were searched for qualitative, observational, and mixed-method studies from the year 2016 to June 2023. Twenty-nine articles were included in the analysis. The results were synthesized into four overarching themes: (і) the sleep quality of women in the perinatal period; (ii) the relationship between sleep and breastfeeding; (iii) the relationship between sleep quality and emotional disturbance in the perinatal period; (iv) sleep interventions in the researched group. The subjective nature of the perception of sleep disturbances, along with the absence of an objective measurement tool is clearly an inconvenience. It is advisable to include the assessment of maternal sleep hygiene and family sleep patterns during postpartum healthcare provider appointments to develop strategies not only for women's sleep quality but also for their mental well-being.

French Society for Biological Psychiatry and Neuropsychopharmacology and French-speaking Marcé Society guidelines for the management of mood disorders in women before, during, and after pregnancy.

The French Society for Biological Psychiatry and Neuropsychopharmacology and the French-speaking Marcé Society have joined forces to establish expert recommendations on the prescription of psychotropic drugs before, during, and after pregnancy in women with major depressive disorder (MDD) and bipolar disorder (BD). To elaborate recommendations, we used the RAND/UCLA Appropriateness Method, which combines scientific evidence and expert clinicians' opinions. A written survey was completed by 48 psychiatrists, who have expertise in the management of mood disorders and/or in perinatal psychiatry. Key recommendations are provided by the scientific committee based on data analysis and interpretation of the results of the survey. The recommendations address the following three areas that are deemed essential in women with mood disorders, with an emphasis on screening, treatment options, and monitoring: (i) management of mood disorders in women of childbearing age, (ii) management during pregnancy, (iii) management during the post-partum period. As first-line strategies, experts recommend treating mood symptoms during pregnancy and maintaining a pharmacological treatment, even in euthymic or stabilized patients. First-line options include only medications with no teratogenic risk, and during breastfeeding, only medications without evidence of adverse effects in nursing infants. The expert consensus guidelines will help facilitate treatment decisions for clinicians in the daily assessment and management of mood disorders in women of childbearing age, during pregnancy, and in the post-partum period.

Mood disorders in postpartum patients at the University Hospital in Zielona Góra according to the Edinburgh Postnatal Depression Scale (EPDS)

Introduction. Childbirth and its course have a significant impact on a woman’s mental functioning during the postpartum period and motherhood. The mother’s mental state affects not only her child’s life and health, but also the functioning of the entire family. The literature distinguishes several types of mental disorders that occur in the postpartum period, including postpartum depression. Aim. This study aims to determine the incidence of mood disorders in women up to 6 months postpartum. Material and methods. The research was carried out using a standardized questionnaire – the Edinburgh Postnatal Depression Scale (EPDS) – designed to determine the severity of mood disorders in the postpartum period in women at the University Hospital in Zielona Góra. The survey was conducted among 100 women aged from 17 to 43. Results. The results of the analysis showed that in women who noticed mood disorders during pregnancy (n=11, i.e. 11% of the total and n=10, i.e. 10% of the total), there is a possibility of postpartum depressive disorders (score ≥12 points on the ESDP scale) (p=0.0006). Respondents who answered “Definitely yes”, accounted for 42.31% of women who scored ≥12 points on the ESDP scale, and those who answered “Rather yes”, accounted for 38.46%. Conclusion. Respondents, whose pregnancy ended in a physiological delivery (forces of nature), feel more satisfied with childbirth than the other respondents (n=29 – definitely yes; n=24 – rather yes). In women whose pregnancy ended in caesarean section, the level of dissatisfaction with childbirth (n=9 – rather not) or less satisfaction (n=3 – definitely not) was higher than in the other women (p=0.0124). Keywords: depression, childbirth, depression scale

Incidence of Mood Disorders in Women Treated With Linzagolix: 52-week Results From Two Phase 3 Trials [A106

INTRODUCTION: Safety data from two Phase 3 trials of linzagolix, a GnRH receptor antagonist, for the treatment of women with uterine fibroids (UFs) for 52 weeks were reviewed for treatment emergent adverse events (TEAEs) of depression and other mood disorders. We note that the incidence of TEAEs of depression and other mood disorders, previously reported up to 24 weeks, was low and revealed no consistent drug-related pattern. METHODS: PRIMROSE 1 and 2 are randomized, double-blind, placebo-controlled Phase 3 trials investigating the efficacy and safety of linzagolix 100 mg and 200 mg once daily, with and without hormonal add-back therapy (ABT) in women with UFs. After 24 weeks, the placebo group in PRIMROSE2 was switched to 200 mg+ABT. The incidence of depression and other mood disorder TEAEs from week 24 to week 52 was assessed using the Standardized MedDRA Query for Depression and suicide/self-injury and adding TEAEs of anxiety. RESULTS: Safety data from 336 and 421 patients, in PRIMROSE1 and PRIMROSE2, respectively, were collected from week 24 to week 52. Mood swings were reported for one (1.1%) subject in PRIMROSE2, and anxiety was reported in one (1.1%) subject in PRIMROSE1, both in the placebo/200 mg+ABT group. Depression was reported in one (1.1%) subject in PRIMROSE2 in the 200 mg/200 mg+ABT group. There were no reports of suicidal ideation, affect lability, or altered mood. CONCLUSION: The low incidence of depression and other mood disorder TEAEs was maintained up to 52 weeks of treatment with linzagolix. Linzagolix appears to be well tolerated in women with symptomatic UFs.

Depression, Estrogens, and Neuroinflammation: A Preclinical Review of Ketamine Treatment for Mood Disorders in Women.

Ketamine has been shown to acutely and rapidly ameliorate depression symptoms and suicidality. Given that women suffer from major depression at twice the rate of men, it is important to understand how ketamine works in the female brain. This review explores three themes. First, it examines our current understanding of the etiology of depression in women. Second, it examines preclinical research on ketamine's antidepressant effects at a neurobiological level as well as how ovarian hormones present a unique challenge in interpreting these findings. Lastly, the neuroinflammatory hypothesis of depression is highlighted to help better understand how ovarian hormones might interact with ketamine in the female brain.

Regulation of Serotonin 1A Receptor SUMOylation by SENP2 and PIASxα.

Serotonin 1A receptors (5-HT1ARs) are implicated in the control of mood, cognition, and memory and in various neuropsychiatric disorders such as depression and anxiety. As such, understanding the regulation of 5-HT1ARs will inform the development of better treatment approaches. We previously demonstrated 5-HT1ARs are SUMOylated by SUMO1 in the rat brain. Agonist stimulation increased SUMOylation and was further enhanced when combined with 17β-estradiol-3-benzoate (EB), which are treatments that cause the transient and prolonged desensitization of 5-HT1AR signaling, respectively. In the current study, we identified the protein inhibitor of activated STAT (PIAS)xα as the enzyme that facilitates SUMOylation, and SENP2 as the protein that catalyzes the deSUMOylation of 5-HT1ARs. We demonstrated that PIASxα significantly increased in the membrane fraction of rats co-treated with EB and an agonist, compared to either the EB-treated or vehicle-treated groups. The acute treatment with an agonist alone shifted the location of SENP2 from the membrane to the cytoplasmic fraction, but it has little effect on PIASxα. Hence, two separate mechanisms regulate SUMOylation and the activity of 5-HT1ARs by an agonist and EB. The effects of EB on 5-HT1AR SUMOylation and signaling may be related to the higher incidence of mood disorders in women during times with large fluctuations in estrogens. Targeting the SUMOylation of 5-HT1ARs could have important clinical relevance for the therapy for several neuropsychiatric disorders in which 5-HT1ARs are implicated.

Venus and Mars: The Importance of Sex In Late-Life Neuropsychiatric Disorders

Sex has increasingly become recognized as an important biological variable in brain disorders. Differences in the risk for both cognitive and emotional disorders by sex and gender are an increasing area of investigation. While women are at higher risk for depression and Alzheimer's disease, the causes of these differences are poorly understood and the implications for therapy not exploited in a systematic way. Advances in clinical and translational neuroscience have begun to reveal potential reasons for these sex differences. Differences in how men and women process emotional information and react to psychological and psychosocial stress as well as the unique hormone environment of women versus men have identified potential causative factors in the preponderance of mood disorders in women. New advances in brain imaging and analysis have revealed novel sex-related differences in structural network connectivity that affects the spread of abnormal proteins, which may help to explain sex-related differences in neurodegenerative disease. Hormonal changes that occur at menopause and beyond may have significant implications for how neurotransmitter system activity changes with normal and pathologic aging and may help to explain why women may be at higher risk for developing Alzheimer's disease. This session will explore advances in our understanding of sex differences in late life neuropsychiatric disorders including depression and neurodegenerative disease. For example, research has identified specific circuits in the brain that are sensitive to sex hormones and are involved in the processing of negative emotional information and in modulating response to psychological stress. These circuits react differentially to the presence of sex hormones and change following menopause and aging. These results may help explain sex differences in mood disorders and changes in sex ratios with normal aging. New research has identified sex-related differences in the spread of tau protein in the brains of patients with normal aging, with women showing more advanced spread and greater structural network connectivity. Whether this sex difference extends to early syndromes such as subjective cognitive decline is under investigation. Women may differ from men in the earliest expression of self-perceived cognitive symptoms due to changes at menopause. The role of gonadal steroids and other individual difference factors like lifetime hormone exposure as well mood and lifetime stress have the potential to modulate these relationships. Discussion will center on how this research may point the way towards sex-specific treatments, prevention strategies, and specific therapies.

Polycystic Ovary Syndrome and Brain: An Update on Structural and Functional Studies.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of women in reproductive age and is associated with reproductive, endocrine, metabolic, cardiovascular, and psychological outcomes. All these disorders are thought to be affected by central mechanisms which could be a major contributor in pathogenesis of PCOS. This mini-review discusses the relevance of central nervous system imaging modalities in understanding the neuroendocrine origins of PCOS as well as their relevance to understanding its comorbidities. Current data suggest that central nervous system plays a key role in development of PCOS. Decreased global and regional brain volumes and altered white matter microstructure in women with PCOS is shown by structural imaging modalities. Functional studies show diminished reward response in corticolimbic areas, brain glucose hypometabolism, and greater opioid receptor availability in reward-related regions in insulin-resistant patients with PCOS. These structural and functional disturbances are associated with nonhomeostatic eating, diminished appetitive responses, as well as cognitive dysfunction and mood disorders in women with PCOS. Structural and functional brain imaging is an emerging modality in understanding pathophysiology of metabolic disorders such as diabetes and obesity as well as PCOS. Neuroimaging can help researchers and clinicians for better understanding the pathophysiology of PCOS and related comorbidities as well as better phenotyping PCOS.

Schizophrenia and Sex Hormones: What Is the Link?

The involvement of gonadal hormones in the pathogenesis of schizophrenia has long been suspected because the psychosis differs in women and men and the illness first makes its appearance shortly after puberty. Changes in sex hormones have been linked with increased vulnerability to mood disorders in women, while testosterone have been associated with increased sexual drive and aggressiveness in men as well as women. Some studies have found abnormal levels of estrogens and testosterone in schizophrenia patients, but the results have been inconsistent and sometimes attributed to the hyperprolactinemia effect of antipsychotics, which may interfere with sex hormones production. The purpose of this review is to present the current knowledge on the link between blood levels of sex-hormones in women during the various stages of the female reproductive life (i.e. puberty, menstrual cycle, pregnancy, contraception, and menopause) and the course of schizophrenia. We also attempt to optimize the clinical approach to women with schizophrenia at these different stages.

Added Sugar Consumption and the Relationship With Mood Disorders in Women

This cross-sectional study examined the association between added sugar consumption and levels of depression in adult women (N = 74). The 97-item online survey included Patient Health Questionnaire-9 depression scale, Block Fat/Sugar/Fruit/Vegetable Screener, added sugar knowledge questions, and a question regarding nutrition education referral during mental health treatment. A weak positive association between added sugar consumption and levels of depression was identified, r = .389, p &lt; .05. A majority of participants (67.5%) who sought mental health treatment were not referred to a nutrition professional. These findings underscore a need for nutrition educators and mental health professionals to work collaboratively for impactful patient well-being.

SAT-717 Region-Specific Effects of the Exposome on Brain Monoamine Levels in Female Rats

Prenatal programming with endocrine disrupting chemicals (EDCs), in particular the ubiquitous plasticizers bisphenol A (BPA) and di(2-ethylhexyl) phthalate (DEHP), can induce long-lasting behavioral changes in rats. Additionally, changes in estrogen are correlated with the development of mood disorders in women; however, the underlying neurobiological mechanisms are unclear. This study was conducted to determine the cumulative effects of prenatal exposure to EDCs followed by chronic estradiol treatment in adult female rats on monoamine levels in the prefrontal cortex (PFC) and hippocampus (HC). Dams were orally administered saline (control; 10 µL/kg), BPA (B; 5 µg/kg), DEHP (D; 7.5 mg/kg) or a combination of BPA+DEHP (B+D) during days 6 through 21 of pregnancy. Adult female offspring were sham-implanted or implanted with pellets that release 17β-estradiol (E2) for 90 days (20 ng/day; Innovative Research America). The offspring then underwent a battery of behavioral tests at the end of treatment. Brains collected from the offspring were sectioned and the PFC and HC were microdissected and analyzed for levels of norepinephrine (NE), dopamine (DA) and serotonin (5-HT), using High-Performance Liquid Chromatography (HPLC). Significant reductions in monoamine levels were observed in the PFC while NE and 5-HT levels were markedly reduced in the HC after prenatal exposure to D or BD. BPA’s effects on monoamines were comparatively modest. E2 exposure increased DA but decreased 5-HT levels in the PFC of control animals. Prenatal exposure to EDCs made the offspring non-responsive to E2. The marked reduction in monoamine levels could have implications for learning and memory.

VENUS AND MARS: THE IMPORTANCE OF SEX IN LATE-LIFE NEUROPSYCHIATRIC DISORDERS

Sex has increasingly become recognized as an important biological variable in brain disorders. Differences in the risk for both cognitive and emotional disorders by sex and gender are an increasing area of investigation. While women are at higher risk for depression and Alzheimer's disease, the causes of these differences are poorly understood and the implications for therapy not exploited in a systematic way. Advances in clinical and translational neuroscience have begun to reveal potential reasons for these sex differences. Differences in how men and women process emotional information and react to psychological and psychosocial stress as well as the unique hormone environment of women versus men have identified potential causative factors in the preponderance of mood disorders in women. New advances in brain imaging and analysis have revealed novel sex-related differences in structural network connectivity that affects the spread of abnormal proteins, which may help to explain sex-related differences in neurodegenerative disease. Hormonal changes that occur at menopause and beyond may have significant implications for how neurotransmitter system activity changes with normal and pathologic aging and may help to explain why women may be at higher risk for developing Alzheimer's disease. This session will explore advances in our understanding of sex differences in late life neuropsychiatric disorders including depression and neurodegenerative disease. For example, research has identified specific circuits in the brain that are sensitive to sex hormones and are involved in the processing of negative emotional information and in modulating response to psychological stress. These circuits react differentially to the presence of sex hormones and change following menopause and aging. These results may help explain sex differences in mood disorders and changes in sex ratios with normal aging. New research has identified sex-related differences in the spread of tau protein in the brains of patients with normal aging, with women showing more advanced spread and greater structural network connectivity. Whether this sex difference extends to early syndromes such as subjective cognitive decline is under investigation. Women may differ from men in the earliest expression of self-perceived cognitive symptoms due to changes at menopause. The role of gonadal steroids and other individual difference factors like lifetime hormone exposure as well mood and lifetime stress have the potential to modulate these relationships. Discussion will center on how this research may point the way towards sex-specific treatments, prevention strategies, and specific therapies.

Longitudinal assessment of symptoms of postpartum mood disorder in women with and without a history of depression.

The main objective of the present study was to report the incidence, recurrence, prevalence, and course of depressive symptoms during the transition from late pregnancy to the postpartum period in healthy women with and without a history of depression. The study also aimed to examine the predictive value of a history of premenstrual syndrome (PMS)/premenstrual dysphoric disorder (PMDD) for peripartum depressive symptoms. A sample of 687 healthy women with (n = 192) and without (n = 495) a history of depression were included in the present analyses. Maternal depressive symptoms were assessed during late pregnancy, 1-2weeks postpartum, and 4-6weeks postpartum using the German version of the Edinburgh Postnatal Depression Scale. PMS/PMDD was assessed retrospectively using the German version of the Premenstrual Symptoms Screening Tool. Women with a history of depression were twice more likely to show peripartum depressive symptoms than women without a history of depression. A history of symptoms of PMS/PMDD prior to the current pregnancy was associated with increased odds of peripartum depressive symptoms (p values < .05). Peripartum depressive symptoms are highly prevalent, especially in women with a history of depression and co-existing symptoms of PMS/PMDD. Screening for depression in the antenatal period is highly recommended, particularly for individuals with previous PMS/PMDD or a history of depression.

Lithium and valproate serum level fluctuations within the menstrual cycle: a systematic review.

Some women affected by mood disorders experience mood instability during the premenstrual phase. Assuming that fluctuations in drug serum levels may contribute to the worsening of mood symptoms, we carried out a systematic review of available studies that investigated changes in lithium and valproate levels in relation to menstrual phases. We selected five studies; four of which assessed menstrual fluctuations in lithium serum levels and one in valproate levels. Study samples included women in their fertile age affected by bipolar disorder, epilepsy as well as healthy ones. Preliminary results showed a close relationship between cyclic premenstrual exacerbation of affective symptoms and a significant decrease in lithium levels during the luteal phase, despite stable oral doses, in bipolar women. In healthy women, lithium levels were influenced by neither menstrual cycle phases nor oral contraceptives use. Valproate serum levels in epileptic women showed a small, nonsignificant decline during the mid-luteal phase. Pharmacokinetic sex differences in adsorption, volume distribution, hepatic metabolism, and renal excretion of mood stabilizers have been supposed to partly explain such menstrual serum level fluctuations. A better understanding in this field could help to counteract the distress related to premenstrual phase, improving therapeutic management of mood disorders in women.

Neuroticism modulates mood responses to pharmacological sex hormone manipulation in healthy women

BackgroundWomen show increased risk of depressive symptoms during hormonal transition phases. The risk mechanisms may include changes in mood in response to fluctuating ovarian hormones moderated by predisposing risk factors for mood disorders, such as personality trait Neuroticism. MethodsA pooled sample of 92 mentally healthy women (28.3 ± 7.1, mean age ± SD) from two independent cohorts run in our lab, using gonadotropin-releasing hormone agonist (GnRHa) experimentally (n = 28) compared to placebo (n = 27) and as part in vitro fertilization (n = 37), were extracted from the Center for Integrated Molecular Brain Imaging database. All women filled in questionnaires of trait Neuroticism from the NEO personality Inventory-Revised (NEO PI-R) at baseline and self-reported levels of mood disturbances with the Profile of Mood States (POMS) daily during 14 days of GnRHa intervention or placebo. Effects of intervention by trait Neuroticism on serial daily reports of mood disturbances were examined using mixed model analyses. ResultsPersonality trait Neuroticism significantly modulated daily mood responses to GnRHa, but not placebo. Women with high and low scores on trait Neuroticism at baseline experienced more pronounced changes in mood when exposed to GnRHa, whereas women with medium trait Neuroticism scores remained relatively stable. ConclusionsThe susceptibility to hormone-triggered mood changes appears to depend upon women’s general tendency to experience distress and destabilization of mood, as captured by personality trait Neuroticism. This could aid clinicians evaluate hormone-related vulnerability for mood disorders in women and may guide targeted prevention in reproductive care.

Mood disorders in women with premature ovarian insufficiency.

Premature ovarian insufficiency (POI) and related oestrogen deficiency is a cause of many psychological symptoms, including: depression, psychological tension, anxiety, mood lability, loss of libido, feelings of loss of femininity and attractiveness, and decreased self- and sexual esteem. Distress related to POI diagnosis may be even more confusing when POI is diagnosed in relation to serious health complications such as cancer, due to surgery or chemotherapy. Every case of POI requires coordinated medical advice with special attendance of a gynaecological endocrinologist, psychotherapist, and sometimes even a psychiatrist.

Brexanolone (SAGE-547 injection) in post-partum depression: a randomised controlled trial

Post-partum depression is a serious mood disorder in women that might be triggered by peripartum fluctuations in reproductive hormones. This phase 2 study investigated brexanolone (USAN; formerly SAGE-547 injection), an intravenous formulation of allopregnanolone, a positive allosteric modulator of γ-aminobutyric acid (GABAA) receptors, for the treatment of post-partum depression. For this double-blind, randomised, placebo-controlled trial, we enrolled self-referred or physician-referred female inpatients (≤6 months post partum) with severe post-partum depression (Hamilton Rating Scale for Depression [HAM-D] total score ≥26) in four hospitals in the USA. Eligible women were randomly assigned (1:1), via a computer-generated randomisation program, to receive either a single, continuous intravenous dose of brexanolone or placebo for 60 h. Patients and investigators were masked to treatment assignments. The primary efficacy endpoint was the change from baseline in the 17-item HAM-D total score at 60 h, assessed in all randomised patients who started infusion of study drug or placebo and who had a completed baseline HAM-D assessment and at least one post-baseline HAM-D assessment. Patients were followed up until day 30. This trial is registered with ClinicalTrials.gov, number NCT02614547. This trial was done between Dec 15, 2015 (first enrolment), and May 19, 2016 (final visit of the last enrolled patient). 21 women were randomly assigned to the brexanolone (n=10) and placebo (n=11) groups. At 60 h, mean reduction in HAM-D total score from baseline was 21·0 points (SE 2·9) in the brexanolone group compared with 8·8 points (SE 2·8) in the placebo group (difference -12·2, 95% CI -20·77 to -3·67; p=0·0075; effect size 1·2). No deaths, serious adverse events, or discontinuations because of adverse events were reported in either group. Four of ten patients in the brexanolone group had adverse events compared with eight of 11 in the placebo group. The most frequently reported adverse events in the brexanolone group were dizziness (two patients in the brexanolone group vs three patients in the placebo group) and somnolence (two vs none). Moderate treatment-emergent adverse events were reported in two patients in the brexanolone group (sinus tachycardia, n=1; somnolence, n=1) and in two patients in the placebo group (infusion site pain, n=1; tension headache, n=1); one patient in the placebo group had a severe treatment-emergent adverse event (insomnia). In women with severe post-partum depression, infusion of brexanolone resulted in a significant and clinically meaningful reduction in HAM-D total score, compared with placebo. Our results support the rationale for targeting synaptic and extrasynaptic GABAA receptors in the development of therapies for patients with post-partum depression. A pivotal clinical programme for the investigation of brexanolone in patients with post-partum depression is in progress. Sage Therapeutics, Inc.

Psychiatric outcomes after hysterectomy in women with uterine myoma: a population-based retrospective cohort study.

Controversy regarding psychological or psychiatric outcomes following hysterectomy still exists. The purpose of this study was to investigate the risk of postoperative psychiatric disorders in women with hysterectomy compared to that in women with uterus-conserving surgery for myomas by using population-based data from South Korea. This study was designed as a retrospective cohort study. We analyzed the National Health Insurance Service National Sample Cohort data including all administrative medical claims from 2002 to 2013. The study population, consisting of 9581 women, was defined as those diagnosed with uterine myoma who underwent medical procedures. The association between psychiatric and mood disorders and hysterectomy was assessed using Cox proportional hazard regression. During the study period, 1381 (14.4%) women experienced psychiatric disorders and 374 (3.9%) experienced mood disorders. The hazard ratio (HR) for psychiatric disorder was higher in women after hysterectomy than in women after uterus-conserving procedures (adjusted HR=1.44; 95% CI=1.27-1.64, p<0.0001). In addition, the HR for mood disorders in women after hysterectomy was significantly higher than in women after uterus-conserving procedures (adjusted HR=1.62; 95% CI=1.26-2.08, p=0.0002). Our study suggests that hysterectomy increased the risk of psychiatric disorders compared to uterus-conserving procedures in women with uterine myoma. Considering these findings, more focus on psychological responses in women following hysterectomy is needed, and appropriate psychosocial support or provisioning of information before or after procedures could reduce psychological distress.