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Gastrointestinal (GI) symptoms such as bloating, constipation, and nausea are common in the days before menstruation, experienced by as many as 73 % of menstruating individuals. Mood may influence the link between menstrual cycle and GI symptoms, with prior studies indicating that even among healthy controls, GI symptoms worsen premenstrually and are associated with worsening mood. Associations between GI symptoms and mood are poorly understood among those with premenstrual syndrome (PMS), a cluster of mood and/or physical symptoms that occur in the week before menses affecting roughly 20 % of menstruators. Our primary aim was to examine associations between GI symptoms and mood symptoms across the menstrual cycle, in those who do and do not report PMS using a menstrual tracking app. We hypothesized that GI symptoms would be reported more frequently in the luteal phase than follicular phase, and that frequency of GI symptoms would be positively associated with mood symptoms in those with PMS. We analyzed data from 33,628 menstrual cycles across 32,241 participants, including n = 27,897 controls (29,137 menstrual cycles) and n = 4344 PMS participants (4491 menstrual cycles). GI symptoms were reported significantly more frequently in the luteal phase than the follicular phase in both control and PMS groups (p < 0.001). Mood symptoms were significantly positively associated with GI symptoms in both groups, in both follicular and luteal phases (p < 0.001). Results suggest that premenstrual GI symptoms are a common issue, and additional work is needed to explore associations between mood and GI symptoms in the context of the menstrual cycle.
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Premenstrual symptoms, including physical and mood symptoms, affect a large proportion of women worldwide. Data on premenstrual symptoms across nations and age groups is limited. In the present study, we leveraged a large international dataset to explore patterns in premenstrual symptom frequency with age. A survey was administered to users of the Flo mobile application (app), aged 18 to 55. The survey queried app users about a range of premenstrual symptoms. Respondents were asked whether they experienced each symptom every menstrual cycle, some cycles, or never. Age was also captured and categorized as 18-27, 28-37, 38-47, 48-55. Data was summarized and Pearson's chi square test for count data assessed differences in symptom frequency by age group. A sample of 238,114 app users from 140 countries responded to the survey. The most common symptoms reported were food cravings (85.28%), mood swings or anxiety (64.18%), and fatigue (57.3%). Absentmindedness, low libido, sleep changes, gastrointestinal symptoms, weight gain, headaches, sweating or hot flashes, fatigue, hair changes, rashes, and swelling were significantly more frequent with increasing age (p's < 0.001). Mood swings and anxiety did not vary by age group. Of the respondents, 28.61% reported that premenstrual symptoms interfered with their everyday life each menstrual cycle. In a large international sample, the majority of women reported premenstrual food cravings, mood changes, and fatigue every menstrual cycle. Mood symptoms did not vary by age group, suggesting that premenstrual mood changes are a persistent issue among women of reproductive age.
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Aplicativos Móveis , Síndrome Pré-Menstrual , Fadiga/epidemiologia , Feminino , Humanos , Longevidade , Ciclo Menstrual , Síndrome Pré-Menstrual/diagnóstico , Síndrome Pré-Menstrual/epidemiologiaRESUMO
Recent research has implicated allopregnanolone (ALLO), a neuroactive steroid and metabolite of progesterone, in perinatal mood and anxiety symptoms. We sought to add to the limited literature examining ALLO and mood and anxiety at multiple time points across the peripartum. We measured mood and anxiety symptoms and ALLO levels by ELISA at the second and third trimester (T2 and T3) and week 6 postpartum (W6) in N = 73 women with prior histories of mood and/or anxiety disorders and N = 38 healthy controls. Analytic methods included multivariate and logistic regressions with linear mixed effect models. Among all participants (N = 111), higher ALLO levels at W6 were associated with higher depression and anxiety scores: each one unit increase in log ALLO at W6 was associated with a 2.54 point increase on the Edinburgh Postnatal Depression Scale (EPDS) (95% CI: 0.73 to 4.33) and an 8.0 point increase on the Perinatal Anxiety Screening Scale (PASS) (95% CI: 3.82 to 12.6). In addition, the nature of the relationship between log ALLO level and psychological measures changed across time; from T2 to W6 for EPDS, ß = 3.73 (95% CI:1.16, 6.30), p = 0.0045; for PASS ß = 9.78 (95% CI:3.77, 15.79), p = 0.0014); from T3 to W6, for (EPDS, ß = 2.52 (95% CI:0.08, 4.96), p = 0.043; for PASS ß = 7.33 (95% CI:1.63, 13.02), p = 0.018). The relationship of log ALLO to mood and anxiety symptoms was the same among women with and without psychiatric histories. Our exploratory findings indicate that the relationship between ALLO and mood and anxiety symptoms may change across the peripartum.
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Depressão Pós-Parto , Pregnanolona , Ansiedade/diagnóstico , Depressão/diagnóstico , Depressão/metabolismo , Depressão Pós-Parto/diagnóstico , Depressão Pós-Parto/epidemiologia , Feminino , Humanos , Período Periparto/psicologia , Gravidez , Escalas de Graduação PsiquiátricaRESUMO
PURPOSE OF REVIEW: To provide an overview of existing studies on alterations in gonadal and neuroactive steroids (NASs) and mood symptoms among women with polycystic ovary syndrome (PCOS). RECENT FINDINGS: Recent studies have demonstrated a previously underappreciated association between PCOS and comorbid depression and anxiety. However, most studies on affective symptoms among women with PCOS have been cross-sectional, limiting our knowledge about fluctuations in symptoms over the menstrual cycle and reproductive lifespan for women with PCOS, as well as the potential interplay between NAS alterations and mood symptoms. Changes in the NAS allopregnanolone (ALLO) have been implicated in several reproductive-related psychiatric disorders (e.g., premenstrual dysphoric disorder (PMDD) and postpartum depression (PPD)) as well as in normal reproductive functioning, warranting further investigation for its potential role in the psychiatric symptoms observed in women with PCOS. Prospective studies evaluating associations between psychiatric symptoms and NAS are needed to elucidate the biological causes of the increased rates of psychiatric symptoms among women with PCOS and inform clinical treatment. ALLO, with its role in normal reproductive function, menstrual dysregulation among women with PCOS, and reproductive-related psychiatric conditions, makes it a particularly intriguing candidate for future investigation.
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Neuroesteroides , Síndrome do Ovário Policístico , Sintomas Afetivos , Estudos Transversais , Feminino , Humanos , Síndrome do Ovário Policístico/epidemiologia , Pregnanolona , Estudos ProspectivosRESUMO
BACKGROUND: Adverse childhood experiences (ACEs), such as abuse or chronic stress, program an exaggerated adult inflammatory response to stress. Emerging rodent research suggests that the gut microbiome may be a key mediator in the association between early life stress and dysregulated glucocorticoid-immune response. However, ACE impact on inflammatory response to stress, or on the gut microbiome, have not been studied in human pregnancy, when inflammation increases risk of poor outcomes. The aim of this study was to assess the relationships among ACE, the gut microbiome, and cytokine response to stress in pregnant women. METHODS: Physically and psychiatrically healthy adult pregnant women completed the Adverse Childhood Experiences Questionnaire (ACE-Q) and gave a single stool sample between 20 and 26â¯weeks gestation. Stool DNA was isolated and 16S sequencing was performed. Three 24-hour food recalls were administered to assess dietary nutrient intake. A subset of women completed the Trier Social Stress Test (TSST) at 22-34â¯weeks gestation; plasma interleukin-6 (IL-6), interleukin-1ß (IL-1ß), high sensitivity C-reactive protein (hsCRP), tumor necrosis factor α (TNF-α), and cortisol were measured at four timepoints pre and post stressor, and area under the curve (AUC) was calculated. RESULTS: Forty-eight women completed the ACE-Q and provided stool; 19 women completed the TSST. Women reporting 2 or more ACEs (high ACE) had greater differential abundance of gut Prevotella than low ACE participants (qâ¯=â¯5.7â¯×â¯10^-13). Abundance of several gut taxa were significantly associated with cortisol, IL-6, TNF-α and CRP AUCs regardless of ACE status. IL-6 response to stress was buffered among high ACE women with high intake of docosahexaenoic acid (DHA) (pâ¯=â¯0.03) and eicosapentaenoic acid (EPA) (pâ¯=â¯0.05). DISCUSSION: Our findings suggest that multiple childhood adversities are associated with changes in gut microbiota composition during pregnancy, and such changes may contribute to altered inflammatory and glucocorticoid response to stress. While preliminary, this is the first study to demonstrate an association between gut microbiota and acute glucocorticoid-immune response to stress in a clinical sample. Finally, exploratory analyses suggested that high ACE women with high dietary intake of ω-3 polyunsaturated fatty acids (PUFAs) had a dampened inflammatory response to acute stress, suggesting potentially protective effects of ω-3s in this high-risk population. Given the adverse effects of inflammation on pregnancy and the developing fetus, mechanisms by which childhood adversity influence the gut-brain axis and potential protective factors such as diet should be further explored.
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Microbioma Gastrointestinal/fisiologia , Estresse Psicológico/microbiologia , Adulto , Experiências Adversas da Infância , Proteína C-Reativa/análise , Citocinas/análise , Citocinas/metabolismo , Dieta , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Insaturados/sangue , Fezes/microbiologia , Feminino , Humanos , Hidrocortisona/análise , Hidrocortisona/sangue , Inflamação/metabolismo , Interleucina-1beta/análise , Interleucina-1beta/sangue , Interleucina-6/análise , Interleucina-6/sangue , Gravidez , RNA Ribossômico 16S/genética , Estresse Psicológico/metabolismo , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/sangueRESUMO
Despite high risk for serious non-AIDS events (SNAEs) and accelerated age-related increases in inflammatory markers relative to HIV+ men, HIV+ women have been understudied, particularly in terms of stress impacts on immune parameters. The purpose of this study was to examine sex differences in glucocorticoid-immune stress response in mid-life HIV+ individuals, as poor glucocorticoid control of stress-induced inflammation may contribute to health risk in HIV+ women. Male and female participants completed a threat of shock laboratory stressor. Serum cortisol and cytokines [interleukin (IL)-6, IL-8, IL-10, IL-1ß, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interferon (IFN)-γ] were assessed at six timepoints prior to and in response to the stressor. Participants included 8 HIV- controls (n = 5 female) and 9 HIV+ (n = 5 female) who were virally suppressed. Repeated measures mixed models revealed a significant sex by HIV status by time interaction for IL-10, IL-1ß, TNF-α, and cortisol. IL-10 response, an anti-inflammatory cytokine, was larger in males than females, regardless of HIV status. TNF-α response was blunted in HIV+ individuals compared with HIV-, and specifically in HIV+ women, IL-1ß and cortisol response were blunted. Individuals living with HIV may have impaired coordination between the immune system and hypothalamic pituitary adrenal (HPA) axis. HIV+ women in particular exhibited dysregulated IL-1ß and cortisol response to acute stress. Future work should focus on relationships among proinflammatory cytokines, stress, and SNAEs in HIV, with attention to sex as a biological variable.
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Citocinas/sangue , Infecções por HIV/fisiopatologia , Hidrocortisona/sangue , Estresse Fisiológico/fisiologia , Estresse Psicológico/fisiopatologia , Adulto , Feminino , Infecções por HIV/sangue , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/fisiopatologia , Caracteres Sexuais , Estresse Psicológico/sangueRESUMO
PURPOSE OF REVIEW: This review highlights the neurobiological aspects of sex differences in posttraumatic stress disorder (PTSD), specifically focusing on the physiological responses to trauma and presents evidence supporting hormone and neurosteroid/peptide differences from both preclinical and clinical research. RECENT FINDINGS: While others have suggested that trauma type or acute emotional reaction are responsible for women's disproportionate risk to PTSD, neither of these explanations fully accounts for the sex differences in PTSD. Sex differences in brain neurocircuitry, anatomy, and neurobiological processes, such as those involved in learning and memory, are discussed as they have been implicated in risk and resilience for the development of PTSD. Gonadal and stress hormones have been found to modulate sex differences in the neurocircuitry and neurochemistry underlying fear learning and extinction. Preclinical research has not consistently controlled for hormonal and reproductive status of rodents nor have clinical studies consistently examined these factors as potential moderators of risk for PTSD. Sex as a biological variable (SABV) should be considered, in addition to the endocrine and reproductive status of participants, in all stress physiology and PTSD research.
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Hormônios Esteroides Gonadais/metabolismo , Transtornos de Estresse Pós-Traumáticos , Medo/fisiologia , Feminino , Humanos , Masculino , Neurobiologia/métodos , Caracteres Sexuais , Fatores Sexuais , Transtornos de Estresse Pós-Traumáticos/metabolismo , Transtornos de Estresse Pós-Traumáticos/psicologiaRESUMO
PURPOSE OF REVIEW: Neuroactive steroid hormones, such as estradiol and progesterone, likely play a role in the pathophysiology of female-specific psychiatric disorders such as premenstrual dysphoric disorder (PMDD) and postpartum depression and may contribute to the marked sex differences observed in the incidence and presentation of affective disorders. However, few tools are available to study the precise contributions of these neuroactive steroids (NSs). In this review, we propose that the acoustic startle response (ASR), an objective measure of an organism's response to an emotional context or stressor, is sensitive to NSs. As such, the ASR represents a unique translational tool that may help to elucidate the contribution of NSs to sex differences in psychiatric disorders. RECENT FINDINGS: Findings suggest that anxiety-potentiated startle (APS) and prepulse inhibition of startle (PPI) are the most robust ASR paradigms for assessing contribution of NSs to affective disorders, while affective startle response modulation (ASRM) appears less diagnostic of sex or menstrual cycle (MC) effects. However, few studies have appropriately used ASR to test a priori hypotheses about sex or MC differences. We recommend that ASR studies account for sex as a biological variable (SABV) and hormonal status to further knowledge of NS contribution to affective disorders.
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Estimulação Acústica/métodos , Emoções/fisiologia , Transtornos do Humor , Reflexo de Sobressalto/fisiologia , Feminino , Humanos , Masculino , Transtornos do Humor/metabolismo , Transtornos do Humor/psicologia , Neurotransmissores/metabolismo , Psicofisiologia/métodos , Caracteres Sexuais , Fatores Sexuais , Esteroides/metabolismoRESUMO
PURPOSE OF REVIEW: With increasing numbers of transgender and gender non-binary individuals presenting for care, knowing how to elucidate the mental health and cognitive outcomes of gender-affirming hormone therapy (GAHT) is necessary. This article reviews the present literature covering GAHT effects on mood, behavioral health, and cognition in these individuals and offers research priorities to address knowledge gaps. RECENT FINDINGS: Although there are some conflicting data, GAHT overwhelmingly seems to have positive psychological effects in both adolescents and adults. Research tends to support that GAHT reduces symptoms of anxiety and depression, lowers perceived and social distress, and improves quality of life and self-esteem in both male-to-female and female-to-male transgender individuals. Clinically, prescribing GAHT can help with gender dysphoria-related mental distress. Thus, timely hormonal intervention represents a crucial tool for improving behavioral wellness in transgender individuals, though effects on cognitive processes fundamental for daily living are unknown. Future research should prioritize better understanding of how GAHT may affect executive functioning.
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Cognição/efeitos dos fármacos , Identidade de Gênero , Hormônios Esteroides Gonadais/farmacologia , Hormônios Esteroides Gonadais/uso terapêutico , Saúde Mental , Qualidade de Vida , Pessoas Transgênero/psicologia , Depressão/tratamento farmacológico , Depressão/etiologia , Depressão/psicologia , Disforia de Gênero/complicações , Disforia de Gênero/psicologia , Disforia de Gênero/terapia , Hormônios Esteroides Gonadais/administração & dosagem , Humanos , Autoimagem , Transexualidade/complicações , Transexualidade/psicologia , Transexualidade/terapiaRESUMO
INTRODUCTION AND HYPOTHESIS: The aim of this study was to measure physiologic and psychologic stress reactivity in women with overactive bladder (OAB). There is growing evidence in preclinical models that central nervous system dysregulation, particularly in response to psychological stress, may contribute to lower urinary tract symptoms in women with OAB. METHODS: Postmenopausal women with OAB and healthy controls underwent Structured Clinical Interview for DSM-IV Axis I disorders (SCID) to identify those without identifiable psychiatric disease. Eligible participants underwent physiologic measures including basal (cortisol-awakening response; CAR) and stress-activated salivary cortisol levels, heart rate (HR), urinary metanephrines and neurotrophins, as well as validated symptom assessment for stress, anxiety, depression, and bladder dysfunction at baseline and during, and following an acute laboratory stressor, the Trier Social Stress Test (TSST). RESULTS: Baseline measures of cortisol reactivity measured by CAR showed blunted response among women with OAB (p = 0.015), while cortisol response to the TSST was greater in the OAB group (p = 0.019). Among OAB patients, bladder urgency as measured by visual analog scale (VAS) increased from pre- to post-TSST (p = 0.04). There was a main effect of TSST on HR (p < 0.001), but no group interaction. CONCLUSIONS: Preliminary findings suggest that women with OAB have greater physiologic and psychologic stress reactivity than healthy controls. Importantly for women with OAB, acute stress appears to exacerbate bladder urgency. Evaluation of the markers of stress response may suggest targets for potential diagnostic and therapeutic interventions.
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Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Pós-Menopausa/psicologia , Estresse Psicológico/fisiopatologia , Bexiga Urinária Hiperativa/fisiopatologia , Adaptação Psicológica/fisiologia , Idoso , Ansiedade/fisiopatologia , Estudos de Casos e Controles , Depressão/fisiopatologia , Feminino , Frequência Cardíaca , Humanos , Hidrocortisona/análise , Pessoa de Meia-Idade , Pós-Menopausa/fisiologia , Bexiga Urinária Hiperativa/psicologiaRESUMO
Recently designated as a disorder in the DSM-5, premenstrual dysphoric disorder (PMDD) presents an array of avenues for further research. PMDD's profile, characterized by cognitive-affective symptoms during the premenstruum, is unique from that of other affective disorders in its symptoms and cyclicity. Neurosteroids may be a key contributor to PMDD's clinical presentation and etiology, and represent a potential avenue for drug development. This review will present recent literature on potential contributors to PMDD's pathophysiology, including neurosteroids and stress, and explore potential treatment targets.
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Transtornos do Humor/diagnóstico , Transtorno Disfórico Pré-Menstrual , Síndrome Pré-Menstrual/diagnóstico , Ácido gama-Aminobutírico/metabolismo , Diagnóstico Diferencial , Manual Diagnóstico e Estatístico de Transtornos Mentais , Gerenciamento Clínico , Feminino , Humanos , Transtorno Disfórico Pré-Menstrual/diagnóstico , Transtorno Disfórico Pré-Menstrual/metabolismo , Transtorno Disfórico Pré-Menstrual/psicologia , Transtorno Disfórico Pré-Menstrual/terapiaRESUMO
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age. Individuals with PCOS report reduced quality of life compared with those without PCOS, with possible contributing factors including infertility, hirsutism, irregular menses, and weight gain. Recent literature also supports increased associations between PCOS and co-occurring psychiatric conditions, particularly depression, anxiety, bipolar disorder, and eating disorders. It is concerning that a higher prevalence of suicidal ideation has been observed in individuals with PCOS. Given the high rates of psychiatric burden among those with PCOS, psychiatric care providers are well suited to be on the front lines of screening for psychiatric symptoms as well as initiating treatment. Current interventions include lifestyle changes (improving exercise and nutrition), pharmacological treatments (e.g., insulin-sensitizing agents, oral contraceptives, and psychotropic drugs), and psychotherapeutic interventions (e.g., cognitive-behavioral therapy and mindfulness-based therapy). This review provides an overview of recent research on the prevalence of comorbid psychiatric conditions, a foundation in PCOS-specific symptom screening and diagnosis, and an overview of treatments for psychiatric symptoms among individuals with PCOS.
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RATIONALE: Premenstrual dysphoric disorder (PMDD) affects approximately 5% of menstruating individuals, with significant negative mood symptoms in the luteal phase of the menstrual cycle. PMDD's pathophysiology and treatment mechanisms are poorly characterized, but may involve altered neuroactive steroid function in the brain. Selective serotonin reuptake inhibitors (SSRIs), a first-line PMDD treatment, reportedly alter gamma-aminobutyric acid (GABA)ergic neuroactive steroid levels in PMDD. AIMS: The aims of this study were to determine whether the SSRI sertraline increased serum levels of neuroactive steroids that modulate the effect of GABA at GABA-A receptors (GABAAR) and if so, whether an increase was associated with improvement in PMDD symptoms. METHODS: Participants included controls and individuals with PMDD. Serum levels of 9 neuroactive steroids were measured (3α,5α-THP; 3α5ß-THP; pregnenolone; 3α,5α-androsterone; 3α,5ß-androsterone; 3α,5α-A-diol; 3α5ß-A-diol; 3α,5α-THDOC; 3α5ß-THDOC) in the follicular and luteal phases. In the subsequent luteal phase, neuroactive steroids were measured during sertraline treatment (50â¯mg sertraline from approximate ovulation to menses onset) in the PMDD group. Mixed models assessed associations among diagnostic group, menstrual cycle phase, and sertraline treatment. RESULTS: Participants included 38 controls and 32 women with PMDD. There were no significant differences in neuroactive steroid levels between controls and participants with PMDD in the luteal phase (pâ¯>â¯0.05). Within the PMDD group, sertraline treatment significantly increased serum pregnanolone levels and the pregnanolone:progesterone ratio, and decreased 3α,5α-androsterone. CONCLUSIONS: This was the first study to assess the impact of SSRI treatment on peripheral levels of GABAergic neuroactive steroids in PMDD. Within the PMDD group, sertraline treatment was associated with a significant increase in luteal phase serum pregnanolone levels and a significantly increased pregnanolone:progesterone ratio, a novel finding. Future research should examine alterations in the metabolic pathways among GABAergic neuroactive steroids in individuals with PMDD, in a placebo-controlled design.
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Neuroesteroides , Transtorno Disfórico Pré-Menstrual , Síndrome Pré-Menstrual , Humanos , Feminino , Transtorno Disfórico Pré-Menstrual/tratamento farmacológico , Sertralina/farmacologia , Sertralina/uso terapêutico , Progesterona , Pregnanolona , Androsterona , Ácido gama-Aminobutírico , Síndrome Pré-Menstrual/tratamento farmacológicoRESUMO
RATIONALE: Premenstrual dysphoric disorder (PMDD) is characterized by severe affective symptoms during the luteal phase of the menstrual cycle. There is some evidence of altered interactions between the hypothalamic pituitary gonadal (HPG) and hypothalamic pituitary adrenal (HPA) axes in PMDD. There is also evidence that similar affective disorders such as major depression and perinatal depression are associated with dysregulation in immune factors, but this has not been characterized in PMDD. AIMS: The goals of this exploratory study were to identify 1) whether HPA-HPG axis interactions and immune markers differ between PMDD patients and controls across the menstrual cycle; 2) how luteal phase sertraline treatment impacts stress and inflammatory markers. METHODS: Participants were females age 18-50 with regular menstrual cycles, not using psychotropic or hormonal medications, and were assigned to a control group or PMDD group based on prospective daily symptom ratings and clinical interview. Blood was drawn in the follicular and luteal phases, during laboratory sessions involving a mildly stressful task. In a second luteal phase, PMDD participants received open-label sertraline (50â¯mg/d) from ovulation to menses. Serum cortisol and ACTH were measured via ELISA and operationalized as area under the curve with respect to ground (AUCg), and peak level following laboratory task. Serum TNF-α, IL-6, CXCL-8, and IL-1ß were measured using multiplex kits. Serum allopregnanolone (ALLO) was measured by gas chromatography/mass spectroscopy. To characterize HPA-HPG axis interactions across the menstrual cycle in PMDD participants and controls, multilevel linear models predicted cortisol and ACTH from the interaction of cycle phase (controlling for sertraline treatment), ALLO, and group. To determine the effects of sertraline treatment on inflammatory markers and how groups might differ in cyclical change on each marker, multilevel linear models predicted inflammatory markers from cycle phase (controlling for sertraline treatment) and group. A final set of exploratory models tested whether inflammatory markers predict premenstrual symptom score severity. RESULTS: The sample included n=77 participants (41 controls, 36 PMDD); 28 participants with PMDD completed sertraline treatment. Group x phase x ALLO interactions showed that higher ALLO levels predicted lower cortisol peak in the treated luteal phase (interaction between phase and ALLO, p=0.042), and there was a higher cortisol peak in the treated luteal phase than the untreated luteal phase (p=0.038). CXCL-8 was significantly associated with premenstrual symptom severity after controlling for group and cycle phase (p=0.011). There were no main effects of group, phase, or ALLO on cortisol AUCg, ACTH AUCg, IL-6, CXCL-8, IL-1ß, nor TNF-α (p's>0.05). CONCLUSION: Serum markers of HPA axis and immune function did not vary by menstrual cycle phase nor PMDD status. However, sertraline treatment in the luteal phase was associated with higher ALLO levels predicting lower cortisol peak in response to mild laboratory stress, suggesting that sertraline treatment may normalize HPG-HPA axis interactions among individuals with PMDD. Greater premenstrual symptomatology was associated with higher levels of the inflammatory marker CXCL-8, but further research is needed into the potential role of inflammation in PMDD.
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Sistema Hipotálamo-Hipofisário , Inflamação , Fase Luteal , Sistema Hipófise-Suprarrenal , Transtorno Disfórico Pré-Menstrual , Sertralina , Humanos , Feminino , Adulto , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sertralina/uso terapêutico , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Transtorno Disfórico Pré-Menstrual/metabolismo , Transtorno Disfórico Pré-Menstrual/tratamento farmacológico , Adulto Jovem , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Pessoa de Meia-Idade , Adolescente , Biomarcadores/sangue , Hidrocortisona/sangue , Hidrocortisona/metabolismoRESUMO
Background: Premenstrual Syndrome (PMS) and Premenstrual Dysphoric Disorder (PMDD), collectively known as Premenstrual Disorders (PMDs), cause significant distress and functional impairment, and premenstrual exacerbation (PME) affects a large proportion of women with psychiatric diagnoses. Childhood trauma is one factor that may contribute to PMD/PME risk. This study examines the relationship between childhood trauma and PMDs, PME, and non-PMD psychiatric illness. Methods: This study is a secondary analysis of data from a prospective cohort. Participants completed self-assessments on childhood trauma using the Childhood Traumatic Event Scale (CTE-S) and on premenstrual symptoms using the Premenstrual Symptoms Screening Tool (PSST). Psychiatric diagnoses were assessed through structured clinical interviews. Participants were divided into four groups based on their PSST scores and psychiatric illness status: (1) Premenstrual Disorders (PMDs; moderate to severe PMS and PMDD), (2) PME, (3) psychiatric controls (PC; individuals with psychiatric illness but no significant premenstrual symptoms), and (4) healthy controls (HC; individuals with no psychiatric illness and no significant premenstrual symptoms). Statistical analyses, including ANOVA, Tukey's HSD test, Fisher's exact test, and logistic regression, were conducted to examine differences among the groups. Results: Data from 391 participants were analyzed. Participants with PME and PC reported a higher quantity and severity of childhood traumatic events compared to HCs (p <.05). There was a weak but significant correlation between childhood trauma and premenstrual symptom burden across all groups (R = .18, p <.001). Within-group analysis revealed moderate correlations between childhood trauma and premenstrual symptoms driven by the PMD group (R = .42, p = .01). Conclusions: The findings underscore the impact of childhood traumatic events on mental health and premenstrual symptoms and highlight the need for additional research to explore the underlying mechanisms linking childhood trauma to the continuum of premenstrual disorders, to improve the efficacy of trauma-focused interventions for affected individuals.
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BACKGROUND: Reproductive health literacy and menstrual health awareness play a crucial role in ensuring the health and well-being of women and people who menstruate. Further, awareness of one's own menstrual cycle patterns and associated symptoms can help individuals identify and manage conditions of the menstrual cycle such as premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). Digital health products, and specifically menstrual health apps, have the potential to effect positive change due to their scalability and ease of access. OBJECTIVE: The primary aim of this study was to measure the efficacy of a menstrual and reproductive health app, Flo, in improving health literacy and health and well-being outcomes in menstruating individuals with and without PMS and PMDD. Further, we explored the possibility that the use of the Flo app could positively influence feelings around reproductive health management and communication about health, menstrual cycle stigma, unplanned pregnancies, quality of life, work productivity, absenteeism, and body image. METHODS: We conducted 2 pilot, 3-month, unblinded, 2-armed, remote randomized controlled trials on the effects of using the Flo app in a sample of US-based (1) individuals who track their cycles (n=321) or (2) individuals who track their cycles and are affected by PMS or PMDD (n=117). RESULTS: The findings revealed significant improvements at the end of the study period compared to baseline for our primary outcomes of health literacy (cycle tracking: DÌ=1.11; t311=5.73, P<.001; PMS or PMDD: DÌ=1.20; t115=3.76, P<.001) and menstrual health awareness (DÌ=3.97; t311=7.71, P<.001), health and well-being (DÌ=3.44; t311=5.94, P<.001), and PMS or PMDD symptoms burden (DÌ=-7.08; t115=-5.44, P<.001). Improvements were also observed for our secondary outcomes of feelings of control and management over health (DÌ=1.01; t311=5.08, P<.001), communication about health (DÌ=0.93; t311=2.41, P=.002), menstrual cycle stigma (DÌ=-0.61; t311=-2.73, P=.007), and fear of unplanned pregnancies (DÌ=-0.22; t311=-2.11, P=.04) for those who track their cycles, as well as absenteeism from work and education due to PMS or PMDD (DÌ=-1.67; t144=-2.49, P=.01). CONCLUSIONS: These pilot randomized controlled trials demonstrate that the use of the Flo app improves menstrual health literacy and awareness, general health and well-being, and PMS or PMDD symptom burden. Considering the widespread use and affordability of the Flo app, these findings show promise for filling important gaps in current health care provisioning such as improving menstrual knowledge and health. TRIAL REGISTRATION: OSF Registries osf.io/pcgw7; https://osf.io/pcgw7 ; OSF Registries osf.io/ry8vq; https://osf.io/ry8vq.
Assuntos
Letramento em Saúde , Aplicativos Móveis , Humanos , Feminino , Letramento em Saúde/estatística & dados numéricos , Letramento em Saúde/normas , Letramento em Saúde/métodos , Adulto , Projetos Piloto , Aplicativos Móveis/normas , Aplicativos Móveis/estatística & dados numéricos , Pessoa de Meia-Idade , Qualidade de Vida/psicologia , Síndrome Pré-Menstrual/psicologia , Síndrome Pré-Menstrual/terapia , Inquéritos e Questionários , Transtorno Disfórico Pré-Menstrual/psicologia , Transtorno Disfórico Pré-Menstrual/terapiaRESUMO
Premenstrual dysphoric disorder (PMDD) is a severe mood disorder, with affective symptoms that rise and fall in concert with the hormonal fluctuations of the menstrual cycle. PMDD's pathophysiology is poorly understood. This review describes recent research on potential biological contributors to PMDD, with a focus on neuroactive steroids, genetics, neuroimaging and cellular studies. Studies suggest that a key contributor is abnormal central nervous system (CNS) response to fluctuations in neuroactive steroid hormones. Imaging studies are limited but support alterations in serotonergic and GABA transmission. Genetic studies suggest heritability, yet specific genetic contributors have not been characterized. Finally, recent cutting-edge cellular studies indicate an underlying vulnerability to the effect of sex hormones at a cellular level. Overall the findings across studies do not yet fit together into a complete description of the underlying biology of PMDD. It is possible that PMDD consists of biological subtypes, and future research may benefit from a subtyping approach.
Assuntos
Transtorno Disfórico Pré-Menstrual , Síndrome Pré-Menstrual , Feminino , Humanos , Transtorno Disfórico Pré-Menstrual/genética , Síndrome Pré-Menstrual/genética , Ciclo Menstrual/genética , Ácido gama-Aminobutírico , BiologiaRESUMO
BACKGROUND: Women with a history of adverse childhood experiences (ACEs) enter pregnancy and the postpartum with a physiologic system programmed by early life stress, potentially reflected in psychophysiologic reactivity. METHODS: We enrolled pregnant, psychiatrically healthy women ≥18 years old. Using the ACE Questionnaire, women were categorized as high (≥2 ACEs; n = 77) or low ACE (<2 ACEs; n = 72). Participants completed an affective modulation of acoustic startle response (ASR) task during pregnancy and postpartum, in which ASR magnitude was measured while participants viewed pleasant, unpleasant, and neutral pictures. Two types of control trials were included (habituation trials presented at baseline and intertrial interval trials presented when no picture was present). RESULTS: Among high ACE women, ASR was significantly higher postpartum compared with pregnancy in the unpleasant (p = 0.002, ß = 0.46, 95% CI [0.18, 0.74], χ2 = 10.12, z = 3.18) and intertrial interval trials (p = 0.002, ß = 0.44, 95% CI [0.16, 0.73], χ2 = 9.25, z = 3.04), accounting for multiple comparisons using a Bonferroni correction at p < 0.005. Among low ACE women, ASR was similar in pregnancy and postpartum. CONCLUSIONS: Physiological reactivity increased in high ACE women from pregnancy to postpartum, but no change was observed in low ACE women.
Assuntos
Experiências Adversas da Infância , Reflexo de Sobressalto , Gravidez , Humanos , Feminino , Adolescente , Período Pós-Parto , Emoções , AcústicaRESUMO
BACKGROUND: The mechanisms by which parental early life stress can be transmitted to the next generation, in some cases in a sex-specific manner, are unclear. Maternal preconception stress may increase susceptibility to suboptimal health outcomes via in utero programming of the fetal hypothalamic-pituitary-adrenal (HPA) axis. METHODS: We recruited healthy pregnant women (N = 147), dichotomized into low (0 or 1) and high (2+) adverse childhood experience (ACE) groups based on the ACE Questionnaire, to test the hypothesis that maternal ACE history influences fetal adrenal development in a sex-specific manner. At a mean (standard deviation) of 21.5 (1.4) and 29.5 (1.4) weeks gestation, participants underwent three-dimensional ultrasounds to measure fetal adrenal volume, adjusting for fetal body weight (waFAV). RESULTS: At ultrasound 1, waFAV was smaller in high versus low ACE males (b = - 0.17; z = - 3.75; p < .001), but females did not differ significantly by maternal ACE group (b = 0.09; z = 1.72; p = .086). Compared to low ACE males, waFAV was smaller for low (b = - 0.20; z = - 4.10; p < .001) and high ACE females (b = - 0.11; z = 2.16; p = .031); however, high ACE males did not differ from low (b = 0.03; z = .57; p = .570) or high ACE females (b = - 0.06; z = - 1.29; p = .196). At ultrasound 2, waFAV did not differ significantly between any maternal ACE/offspring sex subgroups (ps ≥ .055). Perceived stress did not differ between maternal ACE groups at baseline, ultrasound 1, or ultrasound 2 (ps ≥ .148). CONCLUSIONS: We observed a significant impact of high maternal ACE history on waFAV, a proxy for fetal adrenal development, but only in males. Our observation that the waFAV in males of mothers with a high ACE history did not differ from the waFAV of females extends preclinical research demonstrating a dysmasculinizing effect of gestational stress on a range of offspring outcomes. Future studies investigating intergenerational transmission of stress should consider the influence of maternal preconception stress on offspring outcomes.
Assuntos
Experiências Adversas da Infância , Masculino , Humanos , Feminino , Gravidez , Feto/diagnóstico por imagem , Sistema Hipotálamo-Hipofisário , Idade GestacionalRESUMO
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.