Exposure to prenatal stressors and infant autonomic nervous system regulation of stress.

OBJECTIVES: The purpose of this study was to determine the relationship between fetal exposure to maternal prenatal stressors and infant parasympathetic (PNS) and sympathetic (SNS) nervous function at 3 timepoints across the first year of life. BACKGROUND: Autonomic nervous system impairments may mediate associations between gestational exposure to stressors and later infant health problems. Heart rate variability (HRV) provides a sensitive index of PNS and SNS function. However, no studies have assessed longitudinal associations between prenatal stressors and infant HRV measures of both PNS and SNS over the first year of life. METHODS: During the third trimester of pregnancy, 233 women completed measures of life stressors and depression. At 1, 6 and 12 months of age, a stressor protocol was administered while infant electrocardiographic (ECG) data were collected from a baseline through a post-stressor period. HRV measures of PNS and SNS activity (HF, LF, LF/HF ratio) were generated from ECG data. We used multilevel regression to examine the aims, adjusting for maternal depression and neonatal morbidity. RESULTS: There were no associations between prenatal stressors and any baseline or reactivity HRV metric over the infant's first year of life. However, exposure to more stressors was associated with lower post-stressor LF HRV at both 6 (ß = -.44, p = .001) and 12 (ß = -.37, p = .005) months of age. CONCLUSIONS: Findings suggest potential alterations in development of the vagally mediated baroreflex function as a result of exposure to prenatal stressors, with implications for the infants' ability to generate a resilient recovery in response to stressors.

Prenatal exposure to social adversity and infant cortisol in the first year of life.

Exposure to social adversity has been associated with cortisol dysregulation during pregnancy and in later childhood; less is known about how prenatal exposure to social stressors affects postnatal cortisol of infants. In a secondary analysis of data from a longitudinal study, we tested whether a pregnant woman's reports of social adversity during the third trimester were associated with their infant's resting cortisol at 1, 6, and 12 months postnatal. Our hypothesis was that prenatal exposure to social adversity would be associated with elevation of infants' cortisol. Measures included prenatal survey reports of social stressors and economic hardship, and resting cortisol levels determined from infant saliva samples acquired at each postnatal timepoint. Data were analyzed using linear mixed effects models. The final sample included 189 women and their infants (46.56% assigned female sex at birth). Prenatal economic hardship was significantly associated with infant cortisol at 6 months postnatal; reports of social stressors were not significantly associated with cortisol at any time point. Factors associated with hardship, such as psychological distress or nutritional deficiencies, may alter fetal HPA axis development, resulting in elevated infant cortisol levels. Developmental changes unique to 6 months of age may explain effects at this timepoint. More work is needed to better comprehend the complex pre- and post-natal physiologic and behavioral factors that affect infant HPA axis development and function, and the modifying role of environmental exposures.

Postpartum symptoms of anxiety, depression and stress: differential relationships to women's cortisol profiles.

PURPOSE: Women are at high risk of stress, anxiety, and depression during the postpartum but the ways in which these different types of psychological distress are related to cortisol regulation is not clear. We examined the distinct association of each type of distress with women's average cortisol level, cortisol awakening response (CAR), cortisol decline across the day (diurnal slope), and overall amount of cortisol secretion across the day (AUCG). METHODS: At 6 months postpartum, a diverse group of 58 women completed measures of depression, anxiety, perceived stress, and life stressors. Each woman provided 4 salivary samples for cortisol assay from waking to bedtime on each of 2 consecutive days. Linear regressions were used to examine associations of stress, anxiety and depression to each of the 4 cortisol measures, controlling for number of stressful life events. RESULTS: Depressive symptoms were associated with less of a rise in the CAR (ß = -.46, p = 0.01), steeper diurnal slope (ß = .51, p = 0.006), and higher average cortisol level (ß = .42, p = .01). Women who met the clinical cutoff for an anxiety disorder had lower overall cortisol output (ß = -.29, p = 0.03). Stress was not related to any cortisol metric. CONCLUSIONS: Findings suggest that stress is less associated with cortisol alterations in the postpartum than are more severe types of psychological distress. Anxiety and depression may have distinct and opposite profiles of cortisol dysregulation. Results indicate that mental health assessment is critical even in the later postpartum so that interventions can be initiated to reduce emotional suffering and the risk of impaired cortisol regulation.

Infant emotion regulation in the context of stress: Effects of heart rate variability and temperament.

Stressful events are inherently emotional. As a result, the ability to regulate emotions is critical in responding effectively to stressors. Differential abilities in the management of stress appear very early in life, compelling a need to better understand factors that may shape the capacity for emotion regulation (ER). Variations in both biologic and behavioural characteristics are thought to influence individual differences in ER development. We sought to determine the differential contributions of temperament and heart rate variability (HRV; an indicator of autonomic nervous system function) to infant resting state emotionality and emotional reactivity in response to a stressor at 6 months of age. Participants included 108 mother-infant dyads. Mothers completed a measure of infant temperament at 6 months postnatal. Mother and infant also participated in a standardized stressor (the Repeated Still Face Paradigm) at that time. Electrocardiographic data were acquired from the infant during a baseline resting state and throughout the stressor. Fast Fourier Transformation was used to analyse the high frequency (HF) domain of HRV, a measure of parasympathetic nervous system activity. Infant ER was measured via standardized coding of emotional distress behaviours from video-records at baseline and throughout the stressor. Severity of mothers' depressive symptoms was included as a covariate in analyses. Results of linear regression indicate that neither temperament nor HRV were associated significantly with an infant's emotional resting state, although a small effect size was found for the relationship between infant negative affectivity and greater emotional distress (ß = 0.23, p = 0.08) prior to the stressor. Higher HF-HRV (suggesting parasympathetic dominance) was related to greater emotional distress in response to the stressor (ß = 0.34, p = 0.009). This greater emotional reactivity may reflect a more robust capacity to mount an emotional response to the stressor when infants encounter it from a bedrock of parasympathetic activation. Findings may inform eventual markers for assessment of ER in infancy and areas for intervention to enhance infant management of emotions, especially during stressful events.

Relationships Among Number of Stressors, Perceived Stress, and Salivary Cortisol Levels During the Third Trimester of Pregnancy.

OBJECTIVE: To examine relationships among the number of stressors, perceived stress, and salivary cortisol levels during the third trimester of pregnancy. DESIGN: Secondary analysis of cross-sectional data. SETTING: Participants' homes. PARTICIPANTS: Women during the third trimester of pregnancy (N = 73). METHODS: Participants provided saliva samples at four time points over 2 days for cortisol assay and completed questionnaires to assess stressors and perceived stress. We computed multiple linear regression models to examine the relationships among the number of stressors and perceived stress to cortisol awakening response, diurnal slope, and overall cortisol secretion. We also computed a multiple linear regression model to examine the relationship between perceived stress and the number of stressors. RESULTS: Greater perceived stress was associated with reduced overall cortisol secretion across the day (ß = -0.41, p = .01). The number of stressors was associated with perceived stress (ß = 0.48, p = .002) but not salivary cortisol measures. CONCLUSION: Elevated perceived stress and the related cortisol alterations that we identified could represent salient targets for enhancing hypothalamic-pituitary-adrenal axis function during the third trimester. Perceived stress may shape the relationship between exposure to stressors and cortisol response during pregnancy. Future research is warranted to confirm study results and to understand the implications for parturition and fetal development.

WITHDRAWN: Exposure to Ambient Particulate Matter during Pregnancy: Implications for Infant Telomere Length.

This manuscript has been withdrawn by the authors as it was submitted and made public without the full consent of all the authors. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author. The authors have an approved version for citation that is peer reviewed. Ahlers, N.E.; Lin, J.; Weiss, S.J. Exposure to Ambient Particulate Matter during Pregnancy: Implications for Infant Telomere Length. Air 2024, 2, 24-37. https://doi.org/10.3390/air2010002.

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.

Unique Characteristics of Women and Infants Moderate the Association between Depression and Mother-Infant Interaction.

Research has shown mixed results regarding the association between women's postpartum depression and mother-infant interactions, suggesting that a woman's unique experience and context may moderate how depression shapes these interactions. We examined the extent to which a woman's comorbid anxiety, her exposure to adversity, and infant characteristics moderate the relationship between depressive symptoms of women and interactions with their infants at 6 (n = 647) and 12 months (n = 346) postpartum. The methods included standardized coding of mother-infant interactions and structural regression modeling. The results at 6 months of infant age indicated that infant male sex and infant negative affectivity were risk factors for mothers' depression being associated with less optimal interactions. At 12 months of infant age, two moderators appeared to buffer the influence of depression: a woman's history of trauma and infant preterm birth (≤37 weeks gestation). The results reinforce the salience of infant characteristics in the relationship between maternal depression and mother-infant interactions. The findings also suggest that experiences of trauma may offer opportunities for psychological growth that foster constructive management of depression's potential effect on mother-infant interactions. Further research is needed to clarify the underlying processes and mechanisms that explain the influence of these moderators. The ultimate goals are to reduce the risk of suboptimal interactions and reinforce healthy dyadic relations.

Factors associated with mobile medical clinic use: a retrospective cohort study.

BACKGROUND: Mobile medical clinics have been used for decades to provide primary and preventive care to underserved populations. While several studies have examined their return on investment and impact on chronic disease management outcomes in the Mid-Atlantic and East Coast regions of the United States, little is known about the characteristics and clinical outcomes of adults who receive care aboard mobile clinics on the West Coast region. Guided by the Anderson Behavioral Model, this study describes the predisposing, enabling, and need factors associated with mobile medical clinic use among mobile medical clinic patients in Southern California and examines the relationship between mobile clinic utilization and presence and control of diabetes and hypertension. METHODS: We conducted a retrospective cohort study of 411 adults who received care in four mobile clinic locations in Southern California from January 1, 2018, to December 31, 2019. Data were collected from patient charts on predisposing (e.g., sex, race, age), enabling (e.g., insurance and housing status), and need (e.g., chronic illness) factors based on Andersen's Behavioral Model. Zero-truncated negative binomial regression was used to examine the association of chronic illness (hypertension and diabetes) with number of clinic visits, accounting for potential confounding factors. RESULTS: Over the course of the 2-year study period, 411 patients made 1790 visits to the mobile medical clinic. The majority of patients were female (68%), Hispanic (78%), married (47%), with a mean age of 50 (SD = 11). Forty-four percent had hypertension and 29% had diabetes. Frequency of mobile clinic utilization was significantly associated with chronic illness. Patients with hypertension and diabetes had 1.22 and 1.61 times the rate of mobile medical clinic visit than those without those conditions, respectively (IRR = 1.61, 95% CI, 1.36-1.92; 1.22, 95% CI, 1.02-1.45). CONCLUSIONS: Mobile clinics serve as an important system of health care delivery, especially for adults with uncontrolled diabetes and hypertension.

Societal stigma and mistreatment in healthcare among gender minority people: a cross-sectional study.

BACKGROUND: Gender minority (GM; individuals whose gender is not aligned with that traditionally associated with the sex that was assigned to them at birth) people have widely reported mistreatment in healthcare settings. Mistreatment is enacted by individuals within society who hold stigmatizing beliefs. However, the relationship between healthcare mistreatment and societal stigma (i.e., the degree to which society disapproves of GM people) is unclear and not measured consistently. METHODS: We analyzed data from 2,031 GM participants in The Population Research in Identity and Disparities for Equality (PRIDE) Study's 2019 Annual Questionnaire to determine whether societal stigma was associated with participants' past-year reports of mistreatment (defined as denial of healthcare services and/or lower quality care) in medical or mental healthcare settings. We created a proxy measure of societal stigma by incorporating variables validated in existing literature. Participants reported whether they had experienced mistreatment in medical and mental health settings independently. RESULTS: Healthcare denial and/or lower quality care during the past year was reported by 18.8% of our sample for medical settings and 12.5% for mental health settings. We found no associations between the societal stigma variables and past-year reports of healthcare denial and/or lower quality care in medical or mental healthcare settings. CONCLUSIONS: Although a high proportion of GM people reported past-year healthcare mistreatment in both medical and mental health settings, mistreatment had no relationship with societal stigma. Factors other than societal stigma may be more important predictors of healthcare mistreatment, such as healthcare workers' knowledge of and attitudes toward GM people. However, other measures of societal stigma, or different types of mistreatment, may show stronger associations. Identifying key factors that contribute to mistreatment can serve as targets for intervention in communities and healthcare settings.

Maternal stress during the third trimester of pregnancy and the neonatal microbiome.

OBJECTIVES: Preliminary research suggests that maternal prenatal stress may alter the development of the fetal microbiome and resulting microbial composition after birth. However, the findings of existing studies are mixed and inconclusive. The purpose of this exploratory study was to assess whether maternal stress during pregnancy is associated with the overall number and diversity of various microbial species in the infant gut microbiome or the abundance of specific bacterial taxa. METHODS: Fifty-one women were recruited during their third trimester of pregnancy. The women completed a demographic questionnaire and Cohen's Perceived Stress Scale at recruitment. A stool sample was collected from their neonate at one month of age. Data on potential confounders, such as gestational age and mode of delivery, were extracted from medical records to control for their effects. 16s rRNA gene sequencing was used to identify the diversity and abundance of microbial species, along with multiple linear regression models to examine the effects of prenatal stress on microbial diversity. We employed negative binomial generalized linear models to test for differential expression of various microbial taxa among infants exposed to prenatal stress and those not exposed to prenatal stress. RESULTS: More severe symptoms of prenatal stress were associated with a greater diversity of microbial species in the gut microbiome of neonates (ß = .30, p = .025). Certain microbial taxa, such as Lactobacillus and Bifidobacterium, were enriched among infants exposed to greater maternal stress in utero, while others, such as Bacteroides and Enterobacteriaceae, were depleted in contrast to infants exposed to less stress. CONCLUSIONS: Findings suggest that mild to moderate stress exposure in utero could be associated with a microbial environment in early life that is more optimally prepared to thrive in a stressful postnatal environment. Adaptation of gut microbiota under conditions of stress may involve upregulation of bacterial species, including certain protective microorganisms (e.g. Bifidobacterium), as well as downregulation of potential pathogens (e.g. Bacteroides) via epigenetic or other processes within the fetal/neonatal gut-brain axis. However, further research is needed to understand the trajectory of microbial diversity and composition as infant development proceeds and the ways in which both the structure and function of the neonatal microbiome may mediate the relationship between prenatal stress and health outcomes over time. These studies may eventually yield microbial markers and gene pathways that are biosignatures of risk or resilience and inform targets for probiotics or other therapies in utero or during the postnatal period.

Stressors in health care and their association to symptoms experienced by gender diverse people.

OBJECTIVES: Many individuals whose gender does not align with the sex they were assigned at birth (gender diverse [GD] people) report stressful health care encounters. We examined the relationship of these stressors to symptoms of emotional distress and impaired physical functioning among GD people. STUDY DESIGN: This study was conducted using a cross-sectional design with data from the 2015 United States Transgender Survey. METHODS: Composite metrics of health care stressors and physical impairments were developed, and the Kessler Psychological Distress Scale (K-6) provided a measure of emotional distress. Linear and logistic regression were used to analyze the aims. RESULTS: A total of 22,705 participants from diverse gender identity subgroups were included. Participants who experienced at least one stressor in health care during the past 12 months had more symptoms of emotional distress (ß = 0.14, P < .001) and 85% greater odds of having a physical impairment (odds ratio = 1.85, P < .001). Transgender men exposed to stressors were more likely than transgender women to experience emotional distress and have a physical impairment, with other gender identity subgroups reporting less distress. Black participants exposed to stressful encounters reported more symptoms of emotional distress than White participants. CONCLUSIONS: The results suggest that stressful encounters in health care are associated with symptoms of emotional distress and greater odds of physical impairment for GD people, with transgender men and Black individuals being at greatest risk of emotional distress. The findings indicate the need for assessment of factors that contribute to discriminatory or biased health care for GD people, education of health care workers, and support for GD people to reduce their risk of stressor-related symptoms.

The Relationship Between Pharmacist Resilience, Burnout, and Job Performance.

BACKGROUND: Resilience aids healthcare professionals in navigating through and bouncing back from stressful situations in the workplace. Resilience can increase job satisfaction, work motivation, and professional commitment while decreasing burnout, and ultimately job turnover. More resilient employees experience lower instances of burnout and greater life satisfaction. OBJECTIVE: The primary study objective is to determine the relationship that pharmacist resilience has on burnout and job performance. METHODS: Licensed pharmacists in Florida were sent a Qualtrics survey (Qualtrics, Provo, UT) via email, which included demographics data, and valid and reliable assessment tools for resilience, burnout, and job performance. Linear regressions were used to test if resilience significantly predicted each of the output variables: burnout and job performance. RESULTS: Survey responses were received from 942 pharmacists. The regressions showed that resilience significantly predicted both burnout (ß1 = -.701, P < .001) and job performance (ß1 = .35, P < .001). As resilience increased, the levels of burnout decreased, and job performance increased. Resilience explained 29% of the variance in burnout, and 11% of the variance in job performance. CONCLUSION: The results of this study suggest that resilience significantly predicts both pharmacist work-related burnout and job performance. The more resilient the pharmacist, the lower the chances of work-related burnout and the higher the likelihood of better job performance. Organizations should pursue opportunities to educate healthcare workers on methods to increase resilience and to bring attention to the importance of this topic.

Exposure to antenatal corticosteroids and infant cortisol regulation.

Administration of antenatal corticosteroids (AC) is the standard of care during pregnancy for women who are at risk of early delivery. Evidence indicates that AC improve survival and reduce morbidity for preterm infants. However, research suggests that infants whose mothers receive AC have an altered hypothalamic-pituitary-axis (HPA) response to stressors in early life. Results are mixed regarding the nature of these effects, with studies showing both suppressed and augmented HPA activity. In addition, research is very limited beyond the 4th month of life. The purpose of this study was to determine if AC exposure was associated with infant cortisol levels in a resting state or in response to a stressor at 1, 6 and 12 months postnatal. We also evaluated the moderating role of preterm birth in this association. 181 women and their infants participated in the study. Women were recruited during the 3rd trimester of pregnancy; at this time, they completed the Perceived Stress Scale and provided 8 salivary samples over a 2-day period for cortisol assay. They provided these data again at 6 and 12 months postnatal. At 1, 6, and 12 months postnatal, salivary samples were collected from infants to examine their cortisol levels before and after participation in a 'stressor protocol'. Data were extracted from the medical record on AC exposure, gestational age, maternal obstetric risk, and neonatal morbidity. Mixed effects multilevel regression modeling was used to examine the aims. Infants whose mothers received AC had significantly lower resting state (B = -2.47, CI: -3.691, -0.0484) and post-stressor (B = -2.51, CI: -4.283, -0.4276) cortisol levels across the first year of life than infants whose mothers did not receive AC. There was no moderating effect of preterm birth on the relationship between AC exposure and cortisol. Results indicate a state of dampened HPA activation and cortisol hypo-arousal that persists across the first year of life among infants who were exposed to corticosteroids in utero. Further research is needed to examine mechanisms responsible for any alterations that occur during development of the fetal HPA axis, including epigenetic and biochemical factors that control hormonal secretion, negative feedback, and glucocorticoid receptor function throughout the HPA axis. Findings warrant careful consideration by obstetric clinicians of the benefits and risks of prescribing AC.

Cortisol Regulation among Women Who Experience Suicidal Ideation during Pregnancy.

Background: Suicidal thoughts occur in up to one third of pregnant women. Suicidal ideation (SI) has been linked to hypothalamic-pituitary-adrenal (HPA) axis dysregulation in other populations and could underlie SI during pregnancy when the HPA axis undergoes gestational transformation. However, no studies have evaluated the HPA axis in prenatal suicide risk, including regulation of cortisol. We examined whether SI is associated with distinct features of cortisol regulation among women during the 3rd trimester of pregnancy. Methods: Sixty-four women completed measures of SI and provided 8 saliva samples across 2 consecutive days for cortisol assay. Three cortisol metrics were assessed in separate linear regression models (awakening response, diurnal slope, and area under the curve), along with selected covariates. Results: Women with SI (n=10) had a dampened diurnal cortisol slope in contrast to other women (ß = -.32, p =.005; ηp2 =.094). Cortisol levels decreased from waking to 45 minutes after waking (.33ug/dL to .27ug/dL) rather than increasing as found for women without SI (.38ug/dL to .51ug/dL). Their cortisol also rose from 4pm to sleep (.09ug/dL to .31ug/dL) in contrast to a decrease among women without SI (.12ug/dL to .09ug/dL; F = 6.26 (4,59), p=.015). Limitations: The small number of women with SI may have reduced the power to detect significant effects. Conclusions: Findings for women with SI differ from the expected pattern of cortisol secretion across the day and indicate circadian rhythm dysfunction. Further research can build on these results to clarify mechanisms underlying perinatal suicidality, with improved assessment and intervention targets as the goal.

Molecular Mechanism of Sirtuin 1 Modulation by the AROS Protein.

The protein lysine deacylases of the NAD+-dependent Sirtuin family contribute to metabolic regulation, stress responses, and aging processes, and the human Sirtuin isoforms, Sirt1-7, are considered drug targets for aging-related diseases. The nuclear isoform Sirt1 deacetylates histones and transcription factors to regulate, e.g., metabolic adaptations and circadian mechanisms, and it is used as a therapeutic target for Huntington's disease and psoriasis. Sirt1 is regulated through a multitude of mechanisms, including the interaction with regulatory proteins such as the inhibitors Tat and Dbc1 or the activator AROS. Here, we describe a molecular characterization of AROS and how it regulates Sirt1. We find that AROS is a partly intrinsically disordered protein (IDP) that inhibits rather than activates Sirt1. A biochemical characterization of the interaction including binding and stability assays, NMR spectroscopy, mass spectrometry, and a crystal structure of Sirtuin/AROS peptide complex reveal that AROS acts as a competitive inhibitor, through binding to the Sirt1 substrate peptide site. Our results provide molecular insights in the physiological regulation of Sirt1 by a regulator protein and suggest the peptide site as an opportunity for Sirt1-targeted drug development.

Clinical correlates of women endorsing premenstrual suicidal ideation: a cross-sectional study.

BACKGROUND: Prevalence of premenstrual syndrome (PMS) may be as high as 13-18%, but it remains under-recognized and is associated with increased suicidal ideation (SI), plans, and attempts in epidemiological studies. The present study reports on women endorsing premenstrual SI (PMSI) and characterizes this at-risk group and its clinical correlates. METHODS: A cross-sectional study assessed demographics, anxiety and depression severity, psychiatric diagnoses, menstrual symptoms, SI, and trauma in adult women at a major medical center over 11 months. RESULTS: Three hundred two women were assessed. Of 153 participants endorsing premenstrual symptoms, 41 (27%) reported new or worsening concurrent premenstrual passive or active SI. Women who reported PMSI were significantly more likely to be single, unemployed, and childless as well as significantly more likely to report interference from premenstrual symptoms, histories of psychiatric hospitalization, adverse childhood events, suicide attempts, and current and past depression and anxiety compared to women without PMSI. The final regression model indicated the most significant predictors of PMSI were history of a depression diagnosis, severity of current depressive symptoms, and having experienced 3 or more childhood adverse events. CONCLUSION: Nearly one-third of women reporting premenstrual symptoms endorsed concurrent SI, a clinically valuable demonstration of the importance of this predictable cyclic risk factor.

Potential paths to suicidal ideation and suicide attempts among high-risk women.

Although men are more likely to die by suicide, women experience a greater and more rapidly increasing rate of suicidal ideation (SI) and are 3 times more likely to attempt suicide than men. Despite this increased risk, little is known about factors that contribute to SI or suicide attempts (SA) among women. We examined factors associated with SI and SA among women and identified mood-related symptoms that differentiate women who reported attempting suicide from those who did not. Women at elevated risk for depression from across the U.S. (N = 3372; age 18 to 90) completed a survey regarding depression, anxiety, sociodemographic and reproductive status, behavioral/mental health history, and exposure to adversity. Structural equation modeling and logistic regression were used to analyze the data. Variables with the most significant relationships to SI were severity of depression (OR = 5.2, p = 0.000) and perceived stress (OR = 1.18, p = 0.000) while frequency of suicidal thoughts (OR = 3.3, p = 0.000), family history of a depression diagnosis (OR = 1.6, p = 0.000) and exposure to violence (OR = 1.9, p = 0.000) had the strongest association with SA. Childhood abuse/trauma was associated with SA (OR = 1.13, p = 0.000) but not SI. 'Feeling bad about themselves, a failure, or having let themselves or their family down' was the symptom that most clearly differentiated women who attempted suicide from women who reported suicidal ideation but no SA. The salience of childhood abuse and domestic/community violence to women's risk for a suicide attempt reinforces previous findings that these adversities may differentiate suicide risk for women versus men. Continued research is essential to understand varied paths that may lead to suicidal behavior among women, some which appear unrelated to the frequency or intensity of their suicidal thoughts.

Potent and Specific Activators for Mitochondrial Sirtuins Sirt3 and Sirt5.

Sirtuins are NAD+-dependent protein deacylases involved in metabolic regulation and aging-related diseases. Specific activators for seven human Sirtuin isoforms would be important chemical tools and potential therapeutic drugs. Activators have been described for Sirt1 and act via a unique N-terminal domain of this isoform. For most other Sirtuin isoforms, including mitochondrial Sirt3-5, no potent and specific activators have yet been identified. We here describe the identification and characterization of 1,4-dihydropyridine-based compounds that either act as pan Sirtuin activators or specifically stimulate Sirt3 or Sirt5. The activators bind to the Sirtuin catalytic cores independent of NAD+ and acylated peptides and stimulate turnover of peptide and protein substrates. The compounds also activate Sirt3 or Sirt5 in cellular systems regulating, e.g., apoptosis and electron transport chain. Our results provide a scaffold for potent Sirtuin activation and derivatives specific for Sirt3 and Sirt5 as an excellent basis for further drug development.

Obstetric risk in pregnancy interacts with hair cortisone levels to reduce gestational length.

Background: Maternal psychological stress has been linked to preterm birth. However, the differential contribution of psychological stress versus stress hormones is not clear. Studies focus primarily on perceived stress and cortisol, with few assessing its inter-convertible hormone cortisone. Furthermore, little is known about the potential moderating roles of obstetric risk and fetal sex in the relationship between maternal stress and gestational length. This gap in knowledge is particularly evident for rural women who typically experience chronic multiple stressors during pregnancy. We explored the relationship of hormonal and psychological stress to gestational length and the effects of obstetric risks and fetal sex on this relationship among Kenyan pregnant women. Methods: The sample included 130 women recruited between 22 to 28 weeks gestation. They completed a clinical and sociodemographic questionnaire together with the Perceived Stress Scale and provided a hair sample for cortisol and cortisone assay. Women underwent an ultrasound to assess weeks of gestation. At delivery, their pregnancy-related health problems were identified using information extracted from medical records to compile each woman's number of pregnancy risks on the Obstetric Medical Risk Index (OMRI). Results: Perceived stress and hair cortisol were not significant predictors of gestational length. However, a greater number of obstetric risks on the OMRI was associated with shorter gestational length. This effect was further explained by the interaction between obstetric risk and hair cortisone (B = 0.709, p = 0.02). Hair cortisone levels of mothers who had a shorter gestation were significantly higher in mothers with 2 or more risks on the OMRI but not among mothers with only one or no risks (t = 2.39, p = 0.02). Fetal sex had no relationship to gestational length and also had no moderating effect on the relationship between any stress-related metric and gestational length. Conclusion: Cortisone levels may increase in anticipation of shorter gestation as a compensatory response to increased obstetric risk. Elevated cortisone may be a more sensitive marker of risk for early delivery than cortisol or psychological stress, with salience for both the male and female fetus.