Harnessing technology to improve sleep in frontline healthcare workers: A pilot study of electronic noise-masking earbuds on subjective and objective sleep measures.

Objective: This pilot study assessed the effects of electronic noise-masking earbuds on subjective sleep perception and objective sleep parameters among healthcare workers (HCWs) reporting sleep difficulties during the COVID-19 pandemic. Methods: Using a pre-post design, 77 HCWs underwent 3 nights of baseline assessment followed by a 7-night intervention period. Participants wore an at-home sleep monitoring headband to assess objective sleep measures and completed subjective self-report assessments. The difference in mean sleep measures from baseline to intervention was estimated in linear mixed models. Results: Compared to baseline assessments, HCWs reported significant improvements in sleep quality as measured by the Insomnia Severity Index (ISI) (Cohen's d = 1.74, p < 0.001) and a significant reduction in perceived sleep onset latency (SOL) during the intervention (M = 17.2 minutes, SD = 7.7) compared to baseline (M = 24.7 minutes, SD = 16.1), (Cohen's d = -0.42, p = 0.001). There were no significant changes in objective SOL (p = 0.703). However, there was a significant interaction between baseline objective SOL (<20 minutes vs >20 minutes) and condition (baseline vs intervention) (p = 0.002), such that individuals with objective SOL >20 minutes experienced a significant decrease in objective SOL during the intervention period compared to baseline (p = 0.015). Conclusions: HCWs experienced a significant improvement in perceived SOL and ISI scores after using the electronic noise-masking earbuds. Our data provide preliminary evidence for a nonpharmacological intervention to improve the sleep quality of HCWs which should be confirmed by future controlled studies.

Relationship between functional connectivity and weight-gain risk of antipsychotics in schizophrenia.

BACKGROUND: The mechanisms by which antipsychotic medications (APs) contribute to obesity in schizophrenia are not well understood. Because AP effects on functional brain connectivity may contribute to weight effects, the current study investigated how AP-associated weight-gain risk relates to functional connectivity in schizophrenia. METHODS: Fifty-five individuals with schizophrenia (final N = 54) were divided into groups based on previously reported AP weight-gain risk (no APs/low risk [N = 19]; moderate risk [N = 17]; high risk [N = 18]). Resting-state functional magnetic resonance imaging (fMRI) was completed after an overnight fast ("fasted") and post-meal ("fed"). Correlations between AP weight-gain risk and functional connectivity were assessed at the whole-brain level and in reward- and eating-related brain regions (anterior insula, caudate, nucleus accumbens). RESULTS: When fasted, greater AP weight-gain risk was associated with increased connectivity between thalamus and sensorimotor cortex (pFDR = 0.021). When fed, greater AP weight-gain risk was associated with increased connectivity between left caudate and left precentral/postcentral gyri (pFDR = 0.048) and between right caudate and multiple regions, including the left precentral/postcentral gyri (pFDR = 0.001), intracalcarine/precuneal/cuneal cortices (pFDR < 0.001), and fusiform gyrus (pFDR = 0.008). When fed, greater AP weight-gain risk was also associated with decreased connectivity between right anterior insula and ventromedial prefrontal cortex (pFDR = 0.002). CONCLUSIONS: APs with higher weight-gain risk were associated with greater connectivity between reward-related regions and sensorimotor regions when fasted, perhaps relating to motor anticipation for consumption. Higher weight-gain risk APs were also associated with increased connectivity between reward, salience, and visual regions when fed, potentially reflecting greater desire for consumption following satiety.

Mechanistically Guided Materials Chemistry: Synthesis of Ternary Nitrides, CaZrN2 and CaHfN2.

Recent computational studies have predicted many new ternary nitrides, revealing synthetic opportunities in this underexplored phase space. However, synthesizing new ternary nitrides is difficult, in part because intermediate and product phases often have high cohesive energies that inhibit diffusion. Here, we report the synthesis of two new phases, calcium zirconium nitride (CaZrN2) and calcium hafnium nitride (CaHfN2), by solid state metathesis reactions between Ca3N2 and MCl4 (M = Zr, Hf). Although the reaction nominally proceeds to the target phases in a 1:1 ratio of the precursors via Ca3N2 + MCl4 → CaMN2 + 2 CaCl2, reactions prepared this way result in Ca-poor materials (CaxM2-xN2, x < 1). A small excess of Ca3N2 (ca. 20 mol %) is needed to yield stoichiometric CaMN2, as confirmed by high-resolution synchrotron powder X-ray diffraction. In situ synchrotron X-ray diffraction studies reveal that nominally stoichiometric reactions produce Zr3+ intermediates early in the reaction pathway, and the excess Ca3N2 is needed to reoxidize Zr3+ intermediates back to the Zr4+ oxidation state of CaZrN2. Analysis of computationally derived chemical potential diagrams rationalizes this synthetic approach and its contrast from the synthesis of MgZrN2. These findings additionally highlight the utility of in situ diffraction studies and computational thermochemistry to provide mechanistic guidance for synthesis.

Childhood stress, gender, and cognitive control: Midline theta power.

The emergence of psychiatric symptoms is a common consequence of childhood stress exposure. However, there are a dearth of reliable clinical hallmarks or physiological biomarkers to predict post-trauma symptom emergence. The objective of this study was to examine if childhood stressors and stress-related symptoms are associated with altered midline theta power (MTP) during cognitive control demands, and how these associations interact with gender and early adversity. N = 53 children (ages 9-13 years old) from a longitudinal study of children maltreated during early childhood and non-maltreated children participated in this study. EEG recorded neural activity during a Zoo-Themed Go/No-Go task. Stress-related symptoms, recent stressful events, and other adversity experiences were identified. MTP was analyzed with clinical variables in a series of follow-up analyses. The number of stressors in the past six months was negatively correlated with MTP in those with low preschool adversity, but not in those with high preschool adversity. MTP was higher in girls than in boys, and the associations of MTP with stressors and symptoms were moderated by gender. MTP was negatively associated with stressors in the past six months in girls, while in boys, MTP was associated with stress-related symptoms. Childhood stressful events were associated with reduced MTP during cognitive control demands, and this was finding was moderated by gender and early life adversity. These preliminary findings suggest that boys and girls may process stressful experiences in distinct ways, and preschool adversity may potentially blunt the interaction between current stress and neural dynamics. However, ongoing investigation is needed.

The role of the hypothalamic-pituitary-adrenal axis in depression across the female reproductive lifecycle: current knowledge and future directions.

The aim of this narrative review is to consolidate knowledge on the role of the hypothalamic-pituitary-adrenal (HPA) axis in depression pathophysiology at different reproductive stages across the female lifespan. Despite growing evidence about the impact of gonadal hormones on mood disorders, no previous review has examined the interaction between such hormonal changes and the HPA axis within the context of depressive disorders in women. We will focus on HPA axis function in depressive disorders at different reproductive stages including the menstrual cycle (e.g., premenstrual dysphoric disorder [PMDD]), perinatally (e.g., postpartum depression), and in perimenopausal depression. Each of these reproductive stages is characterized by vast physiological changes and presents major neuroendocrine reorganization. The HPA axis is one of the main targets of such functional alterations, and with its key role in stress response, it is an etiological factor in vulnerable windows for depression across the female lifespan. We begin with an overview of the HPA axis and a brief summary of techniques for measuring HPA axis parameters. We then describe the hormonal milieu of each of these key reproductive stages, and integrate information about HPA axis function in depression across these reproductive stages, describing similarities and differences. The role of a history of stress and trauma exposure as a contributor to female depression in the context of HPA axis involvement across the reproductive stages is also presented. This review advances the pursuit of understanding common biological mechanisms across depressive disorders among women. Our overarching goal is to identify unmet needs in characterizing stress-related markers of depression in women in the context of hormonal changes across the lifespan, and to support future research in women's mental health as it pertains to pathophysiology, early diagnosis, and treatment targets.

Cognitive Problems in Perimenopause: A Review of Recent Evidence.

PURPOSE OF REVIEW: To review recent research regarding cognitive problems during perimenopause, including which menopause-related symptoms, demographic variables, stress exposures, and neural biomarkers are associated with cognitive problems and which interventions demonstrate efficacy at improving cognitive performance. RECENT FINDINGS: Cognitive problems are common during perimenopause and have a significant impact on a substantial proportion of women. Evidence continues to indicate that verbal learning and verbal memory are the cognitive functions that are most negatively affected during perimenopause, and new research suggests that perimenopause may also be associated with deficits in processing speed, attention, and working memory. Recent research suggests that the cognitive profiles of women transitioning through perimenopause are heterogenous - with some showing strengths and others demonstrating weaknesses in particular cognitive domains. Depression, sleep problems, and vasomotor symptoms in perimenopause may be associated with cognitive difficulties. Recent neuroimaging studies are identifying changes in activity patterns within brain regions that correlate with cognitive performance in perimenopause, but future causal studies are needed to understand the neural mechanisms of cognitive problems during this time. Although clinical treatment studies for cognitive concerns have historically focused on postmenopause, some small trials in perimenopausal samples have been conducted recently but are frequently underpowered. Current guidelines from the North American Menopause Society do not support the use of hormone therapy at any age for cognitive problems. Animal research demonstrates that estradiol and levonorgestrel combined may alleviate working memory problems. Much progress has been made in understanding how perimenopause impacts cognition, and more research is needed to better identify who is at highest risk and how to meaningfully prevent and alleviate cognitive problems during this reproductive stage. Larger-scale randomized intervention trials specifically during perimenopause are urgently needed to address cognitive concerns in this population of women. More consistent reproductive staging, inclusion of covariates, and analyses examining perimenopause specifically would improve study quality and the ability to draw clear conclusions from this research.

Adverse childhood experiences and hormonal contraception: Interactive impact on sexual reward function.

The current literature suggests that some women are uniquely vulnerable to negative effects of hormonal contraception (HC) on affective processes. However, little data exists as to which factors contribute to such vulnerability. The present study evaluated the impact of prepubertal adverse childhood experiences (ACEs) on reward processing in women taking HC (N = 541) compared to naturally cycling women (N = 488). Participants completed an online survey assessing current and past HC use and exposure to 10 different adverse childhood experiences (ACEs) before puberty (ACE Questionnaire), with participants categorized into groups of low (0-1) versus high (≥2) prepubertal ACE exposure. Participants then completed a reward task rating their expected and experienced valence for images that were either erotic, pleasant (non-erotic), or neutral. Significant interactions emerged between prepubertal ACE exposure and HC use on expected (p = 0.028) and experienced (p = 0.025) valence ratings of erotic images but not pleasant or neutral images. Importantly, follow-up analyses considering whether women experienced HC-induced decreases in sexual desire informed the significant interaction for expected valence ratings of erotic images. For current HC users, prepubertal ACEs interacted with HC-induced decreased sexual desire (p = 0.008), such that high ACE women reporting decreased sexual desire on HC showed substantially decreased ratings for anticipated erotic images compared to both high prepubertal ACE women without decreased sexual desire (p < 0.001) and low prepubertal ACE women also reporting decreased sexual desire (p = 0.010). The interaction was not significant in naturally cycling women reporting previous HC use, suggesting that current HC use could be impacting anticipatory reward processing of sexual stimuli among certain women (e.g., high prepubertal ACE women reporting HC-induced decreases in sexual desire). The study provides rationale for future randomized, controlled trials to account for prepubertal ACE exposure to promote contraceptive selection informed by behavioral evidence.

Effect of progesterone administration in male and female smokers on nicotine withdrawal and neural response to smoking cues: role of progesterone conversion to allopregnanolone.

BACKGROUND: Progesterone administration has therapeutic effects in tobacco use disorder (TUD), with females benefiting more than males. Conversion of progesterone to the neurosteroid allopregnanolone is hypothesized to partly underlie the therapeutic effects of progesterone; however, this has not been investigated clinically. METHODS: Smokers (n = 18 males, n = 21 females) participated in a randomized, double-blind, placebo-controlled crossover study of 200 mg progesterone daily across 4 days of abstinence. The ratio of allopregnanolone:progesterone was analyzed in relationship to nicotine withdrawal, smoking urges, mood states, subjective nicotine effects, and neural response to smoking cues. RESULTS: Allopregnanolone:progesterone ratio interacted with sex to predict withdrawal symptoms (p = 0.047), such that females with higher allopregnanolone:progesterone ratios reported lower withdrawal severity (b = - 0.98 [- 1.95, - 0.01]; p = 0.048). In addition, allopregnanolone:progesterone ratio interacted with sex to predict confusion (p = 0.014) and fatigue (p = 0.034), such that females with higher allopregnanolone:progesterone ratios reported less confusion (b = - 0.45 [- 0.78, - 0.12]; p = 0.008) and marginally lower fatigue (b = - 0.50 [- 1.03, 0.02]; p = 0.062. Irrespective of sex, higher ratios of allopregnanolone:progesterone were associated with stronger "good effects" of nicotine (b = 8.39 [2.58, 14.20]); p = 0.005) and weaker "bad effects" of nicotine (b = - 7.13 [- 13.53, - 0.73]; p = 0.029). CONCLUSIONS: Conversion of progesterone to allopregnanolone correlated with smoking-related outcomes in both sex-dependent and sex-independent ways. Sex-dependent effects suggest that conversion of progesterone to allopregnanolone may contribute to greater therapeutic benefits in females but not males with TUD. Trial registration Clinicaltrials.gov registration, retrospectively registered: NCT01954966; https://clinicaltrials.gov/ct2/show/NCT01954966 \.

Selective Serotonin Reuptake Inhibitors (SSRIs) in Pregnancy: An Updated Review on Risks to Mother, Fetus, and Child.

PURPOSE OF REVIEW: To provide an updated summary and appraisal of work from 2019 to 2022 examining risks of selective serotonin reuptake inhibitor (SSRI) use in pregnancy. RECENT FINDINGS: Perinatal SSRI exposure does not increase risk of major malformations or gestational diabetes after accounting for underlying maternal illness. SSRIs are associated with small increase in risk of pre-eclampsia, postpartum hemorrhage, preterm delivery, persistent pulmonary hypertension of the newborn, and neonatal intensive care unit admissions, though absolute risk of these outcomes is low. While data suggests no increased risk of neurodevelopmental disorders in offspring, mixed evidence indicates increased risk of adverse cognitive outcomes and affective disorders. Recent evidence suggest low absolute risk of clinically relevant negative outcomes with perinatal SSRI exposure when compared to untreated perinatal depression. However, study design and ability to control for confounding remains an ongoing research challenge, highlighting need for ongoing rigorous study design and analysis.

Technology-Based Approaches for Supporting Perinatal Mental Health.

PURPOSE OF REVIEW: This review explores advances in the utilization of technology to address perinatal mood and anxiety disorders (PMADs). Specifically, we sought to assess the range of technologies available, their application to PMADs, and evidence supporting use. RECENT FINDINGS: We identified a variety of technologies with promising capacity for direct intervention, prevention, and augmentation of clinical care for PMADs. These included wearable technology, electronic consultation, virtual and augmented reality, internet-based cognitive behavioral therapy, and predictive analytics using machine learning. Available evidence for these technologies in PMADs was almost uniformly positive. However, evidence for use in PMADs was limited compared to that in general mental health populations. Proper attention to PMADs has been severely limited by issues of accessibility, affordability, and patient acceptance. Increased use of technology has the potential to address all three of these barriers by facilitating modes of communication, data collection, and patient experience.

Progesterone Increases Nicotine Withdrawal and Anxiety in Male but Not Female Smokers During Brief Abstinence.

INTRODUCTION: Although exogenous progesterone may hold promise as a treatment for nicotine use disorders, it is unclear whether it is similarly effective in males and females. This study examined the effects of progesterone on nicotine use disorder comprehensively using behavioral, psychological, and neural measures in male and female smokers exposed to brief abstinence. AIMS AND METHODS: Thirty-three male and 33 female non-treatment-seeking smokers participated in a double-blind, randomized, placebo-controlled crossover study of 200 mg of progesterone or placebo daily over a four-day abstinence period. Smoking behavior and subjective effects of nicotine were assessed at baseline and after final drug administration. Nicotine withdrawal, smoking urges, mood states, and neural response to smoking cues were measured at baseline, after the first drug administration, and after the final drug administration. RESULTS: No main effect of drug (progesterone vs. placebo) emerged for any outcome. Significant sex by drug interactions emerged for nicotine withdrawal (p = .020), perceived strength of nicotine (p = .040), and perceived bad effects of nicotine (p = .029). Males receiving progesterone reported worse nicotine withdrawal (p = .046) and a trend towards decreased bad effects of nicotine (p = .070). Males on progesterone also reported greater tension and anxiety relative to placebo (p = .021). Females on progesterone perceived nicotine's effects as being stronger relative to placebo (p = .046). CONCLUSIONS: Progesterone causes sex-dependent effects on smoking-related outcomes during brief abstinence. Specifically, progesterone in males may increase rather than decrease nicotine withdrawal and negative affect during abstinence, potentially hindering efforts to quit smoking. IMPLICATIONS: In male and female smokers undergoing a brief period of abstinence, we examined the effects of progesterone on smoking outcomes. While progesterone had limited effects in female smokers, in males, it worsened nicotine withdrawal and negative affect. Our findings emphasize the importance of analyzing sex differences in future studies examining progesterone as a potential treatment and suggest that progesterone in males could potentially exacerbate aspects of nicotine dependence. CLINICALTRIALS.GOV REGISTRATION: NCT01954966. https://clinicaltrials.gov/ct2/show/NCT01954966.

Discontinuation of hormonal contraception due to changes in mood and decreases in sexual desire: the role of adverse childhood experiences.

PURPOSE: To evaluate if adverse childhood experiences are associated with hormonal contraception discontinuation due to mood and sexual side effects. MATERIALS AND METHODS: Women, ages 18-40 (N = 826), with current and/or previous hormonal contraceptive use completed surveys on demographics, contraceptive history, and the Adverse Childhood Experiences Questionnaire. We characterised women into high (≥2 adverse experiences) and low (0 or 1) adverse childhood experience groups. We calculated risk ratios for associations between adverse childhood experiences and outcomes of interest using log binomial generalised linear models, and adjusted for relevant demographic variables. RESULTS: Women in the high adverse childhood experiences group (n = 355) were more likely to report having discontinued hormonal contraception due to decreases in sexual desire (adjusted risk ratio 1.44, 1.03-2.00, p = .030). Covariates included age, current hormonal contraception use, and various demographic variables associated with discontinuation. Adverse childhood experiences were not associated with mood or sexual side effects among current (n = 541) hormonal contraceptive users. CONCLUSIONS: Self-reported adverse childhood experiences were associated with greater likelihood of discontinuing hormonal contraception due to behavioural side effects, particularly decreases in sexual desire. Identification of risk factors for behavioural side effects can assist patients and clinicians in making informed choices on contraception that minimise risk of early discontinuation.

Adverse childhood experiences interact with inflammation and menopause transition stage to predict verbal memory in women.

OBJECTIVE: Women with more adverse childhood experiences (ACEs) may face a triple threat of risk factors for cognitive concerns during the menopause transition: reduced estradiol, increased inflammation, and early life stress sequelae. Our objective was to determine the extent to which ACEs and peripheral basal inflammatory markers associate with verbal memory across the menopause transition. METHODS: Penn Ovarian Aging cohort participants (n â€‹= â€‹167) were assessed for ACEs (low (0-1) or high (≥2)) and had remaining stored blood samples at study end assayed for interleukin (IL)-6, IL-1-beta (IL-1ß), C-reactive protein (CRP), and tumor necrosis factor alpha (TNF-α). Annual assessment included a verbal memory test (the Buschke Selective Reminding Test) and menopause stage determination. To estimate the effects of menopause stage, ACEs, and cytokines on verbal memory, repeated cognitive outcome measures were modeled in generalized estimating equations. Covariates included body mass index, smoking, race, education, age at baseline, and baseline verbal memory performance. Cytokine levels were log-transformed. RESULTS: Advancing menopause stage was associated with worse performance on immediate verbal recall and delayed verbal recall (ps â€‹< â€‹0.001). During perimenopause, higher ACE exposure was associated with worse immediate verbal recall at higher levels of TNF-α (slope difference p â€‹= â€‹0.041). CONCLUSIONS: Inflammation may mechanistically link ACEs and verbal memory for high ACE women during perimenopause. Reducing inflammation for these individuals may have positive impact on verbal memory across the menopause transition.

Adapting psychiatric research in the age of COVID-19: role of online studies.

Virtual platforms can provide a socially distanced mechanism by which to promote ongoing research progress in the coronavirus disease 2019 (COVID-19) era and may change our approach to online research in the future. Understanding how to best utilise online research represents an important task for our field.

Hypoactive Sexual Desire Disorder in Women: Physiology, Assessment, Diagnosis, and Treatment.

Nearly half of women in the United States report problems with sexual function. Many health care providers do not ask about sexual concerns during routine clinical encounters because of personal discomfort, lack of familiarity with treatment, or the belief that they lack adequate time to address this complex issue. This may be especially true for hypoactive sexual desire disorder (HSDD), the most commonly identified sexual problem among women. HSDD is characterized by a deficiency of sexual thoughts, feelings, or receptiveness to sexual stimulation that has been present for at least 6 months, causes personal distress, and is not due to another medical condition. This is an up-to-date overview of HSDD for clinicians, discussing its physiology, assessment, diagnosis, and treatment strategies. Although a definitive physiology of HSDD is still unknown, multiple hormones and neurotransmitters likely participate in a dual-control model to balance excitation and inhibition of sexual desire. For assessment and diagnosis, validated screening tools are discussed, and the importance of a biopsychosocial assessment is emphasized, with guidance on how this can be implemented in clinical encounters. The 2 recently approved medications for HSDD, flibanserin and bremelanotide, are reviewed as well as off-label treatments. Overall, HSDD represents a common yet likely underrecognized disorder that midwives and other health care providers who care for women across the life span are in a unique position to address.