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1.
Mol Psychiatry ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38816586

RESUMO

The serotonin deficit hypothesis explanation for major depressive disorder (MDD) has persisted among clinicians and the general public alike despite insufficient supporting evidence. To combat rising mental health crises and eroding public trust in science and medicine, researchers and clinicians must be able to communicate to patients and the public an updated framework of MDD: one that is (1) accessible to a general audience, (2) accurately integrates current evidence about the efficacy of conventional serotonergic antidepressants with broader and deeper understandings of pathophysiology and treatment, and (3) capable of accommodating new evidence. In this article, we summarize a framework for the pathophysiology and treatment of MDD that is informed by clinical and preclinical research in psychiatry and neuroscience. First, we discuss how MDD can be understood as inflexibility in cognitive and emotional brain circuits that involves a persistent negativity bias. Second, we discuss how effective treatments for MDD enhance mechanisms of neuroplasticity-including via serotonergic interventions-to restore synaptic, network, and behavioral function in ways that facilitate adaptive cognitive and emotional processing. These treatments include typical monoaminergic antidepressants, novel antidepressants like ketamine and psychedelics, and psychotherapy and neuromodulation techniques. At the end of the article, we discuss this framework from the perspective of effective science communication and provide useful language and metaphors for researchers, clinicians, and other professionals discussing MDD with a general or patient audience.

2.
Curr Psychiatry Rep ; 25(10): 501-511, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37755656

RESUMO

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.


Assuntos
Menopausa , Perimenopausa , Feminino , Humanos , Perimenopausa/psicologia , Pós-Menopausa/psicologia , Estradiol , Cognição
3.
Nicotine Tob Res ; 24(12): 1898-1905, 2022 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-35713950

RESUMO

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.


Assuntos
Abandono do Hábito de Fumar , Síndrome de Abstinência a Substâncias , Tabagismo , Masculino , Feminino , Humanos , Nicotina , Fumantes , Progesterona/uso terapêutico , Abandono do Hábito de Fumar/psicologia , Estudos Cross-Over , Síndrome de Abstinência a Substâncias/psicologia , Tabagismo/psicologia , Ansiedade
4.
Curr Psychiatry Rep ; 24(11): 687-695, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36181572

RESUMO

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.


Assuntos
Complicações na Gravidez , Efeitos Tardios da Exposição Pré-Natal , Criança , Feminino , Humanos , Recém-Nascido , Gravidez , Feto , Mães , Complicações na Gravidez/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos
5.
Curr Psychiatry Rep ; 24(9): 419-429, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35870062

RESUMO

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.


Assuntos
Terapia Cognitivo-Comportamental , Saúde Mental , Transtornos de Ansiedade/psicologia , Transtornos de Ansiedade/terapia , Feminino , Humanos , Transtornos do Humor , Gravidez , Tecnologia
6.
Eur J Contracept Reprod Health Care ; 27(3): 212-220, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35133231

RESUMO

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.


Assuntos
Experiências Adversas da Infância , Contracepção Hormonal , Adolescente , Adulto , Anticoncepção/efeitos adversos , Anticoncepcionais , Feminino , Humanos , Libido , Adulto Jovem
7.
Front Neuroendocrinol ; 59: 100869, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32822707

RESUMO

Epidemiological, clinical, and basic research over the past thirty years have described the benefits of estrogen on cognition, mood, and brain health. Less is known about tamoxifen, a selective estrogen receptor modifier (SERM) commonly used in breast cancer which is able to cross the blood-brain barrier. In this article, we review the basic pharmacology of tamoxifenas well as its effects on cognition and mood. The literature reveals an overall impairing effect of tamoxifen on cognition in breast cancer patients, hinting at central antiestrogen activity. On the other hand, tamoxifen demonstrates promising effects in psychiatric disorders, like bipolar disorder, where its therapeutic action may be independent of interaction with estrogen receptors. Understanding the neuropsychiatric properties of SERMs like tamoxifen can guide future research to ameliorate unwanted side-effects and provide novel options for difficult to treat disorders.


Assuntos
Afeto/efeitos dos fármacos , Antineoplásicos Hormonais/farmacologia , Cognição/efeitos dos fármacos , Antagonistas de Estrogênios/farmacologia , Tamoxifeno/farmacologia , Animais , Humanos
8.
Dev Psychopathol ; 29(5): 1619-1626, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29162169

RESUMO

Serotonin signaling pathways play a key role in brain development, stress reactivity, and mental health. Epigenetic alterations in the serotonin system may underlie the effect of early life stress on psychopathology. The current study examined methylation of the serotonin receptor 2A (HTR2A) gene in a sample of 228 children including 119 with child welfare documentation of moderate to severe maltreatment within the last 6 months. Child protection records, semistructured interviews in the home, and parent reports were used to assess child stress exposure, psychiatric symptoms, and behavior. The HTR2A genotype and methylation of HTR2A were measured at two CpG sites (-1420 and -1224) from saliva DNA. HTR2A genotype was associated with HTR2A methylation at both CpG sites. HTR2A genotype also moderated associations of contextual stress exposure and HTR2A methylation at site -1420. Contextual stress was positively associated with -1420 methylation among A homozygotes, but negatively associated with -1420 methylation among G homozygotes. Posttraumatic stress disorder and major depressive disorder symptoms were negatively associated with methylation at -1420, but positively associated with methylation at -1224. Results support the view that the serotonin system is sensitive to stress exposure and psychopathology, and HTR2A methylation may be a mechanism by which early adversity is biologically encoded.


Assuntos
Maus-Tratos Infantis/psicologia , Metilação de DNA , Transtorno Depressivo Maior/genética , Receptor 5-HT2A de Serotonina/genética , Transtornos de Estresse Pós-Traumáticos/genética , Pré-Escolar , Transtorno Depressivo Maior/psicologia , Feminino , Interação Gene-Ambiente , Genótipo , Humanos , Masculino , Regiões Promotoras Genéticas , Transdução de Sinais/genética , Transtornos de Estresse Pós-Traumáticos/psicologia , Estresse Psicológico/genética , Estresse Psicológico/psicologia
9.
Schizophr Res ; 267: 173-181, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38552340

RESUMO

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.


Assuntos
Antipsicóticos , Imageamento por Ressonância Magnética , Esquizofrenia , Aumento de Peso , Humanos , Esquizofrenia/tratamento farmacológico , Esquizofrenia/fisiopatologia , Esquizofrenia/diagnóstico por imagem , Masculino , Feminino , Adulto , Antipsicóticos/efeitos adversos , Antipsicóticos/farmacologia , Aumento de Peso/efeitos dos fármacos , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Adulto Jovem , Pessoa de Meia-Idade , Recompensa , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Vias Neurais/efeitos dos fármacos , Risco , Conectoma , Obesidade/fisiopatologia , Obesidade/induzido quimicamente
10.
Sci Prog ; 107(2): 368504241242276, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38614463

RESUMO

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.


Assuntos
Pandemias , Sono , Humanos , Projetos Piloto , Tecnologia , Eletrônica , Pessoal de Saúde
11.
J Psychiatr Res ; 169: 298-306, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38070470

RESUMO

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.


Assuntos
Depressão , Estresse Psicológico , Masculino , Criança , Feminino , Humanos , Pré-Escolar , Adolescente , Estudos Longitudinais , Estresse Psicológico/psicologia , Depressão/psicologia , Escolaridade , Cognição
12.
Behav Brain Funct ; 9: 39, 2013 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-24134918

RESUMO

BACKGROUND: Adolescent social stress is associated with increased incidence of mental illnesses in adulthood that are characterized by deficits in cognitive focus and flexibility. Such enhanced vulnerability may be due to psychosocial stress-induced disruption of the developing mesocortical dopamine system, which plays a fundamental role in facilitating complex cognitive processes such as spatial working memory. Adolescent rats exposed to repeated social defeat as a model of social stress develop dopaminergic hypofunction in the medial prefrontal cortex as adults. To evaluate a direct link between adolescent social stress and later deficits in cognitive function, the present study tested the effects of adolescent social defeat on two separate tests of spatial working memory performance. METHODS: Adult rats exposed to adolescent social defeat and their controls were trained on either the delayed win-shift task or the delayed alternating T-Maze task and then challenged with various delay periods. To evaluate potential differences in motivation for the food reward used in memory tasks, consumption and conditioned place preference for sweetened condensed milk were tested in a separate cohort of previously defeated rats and controls. RESULTS: Compared to controls, adult rats defeated in adolescence showed a delay-dependent deficit in spatial working memory performance, committing more errors at a 90 s and 5 min delay period on the T-maze and win-shift tasks, respectively. Observed memory deficits were likely independent of differences in reward motivation, as conditioned place preference for the palatable food used on both tasks was similar between the adolescent social defeat group and control. CONCLUSIONS: The results demonstrate that severe social stressors during adolescence can produce long term deficits in aspects of cognitive function. Given the dependence of spatial working memory on prefrontal dopamine, pharmacologically reversing dopaminergic deficiencies caused by adolescent social stress has the potential to treat such cognitive deficits.


Assuntos
Dominação-Subordinação , Memória de Curto Prazo/fisiologia , Comportamento Social , Percepção Espacial/fisiologia , Estresse Psicológico/fisiopatologia , Fatores Etários , Animais , Condicionamento Psicológico/fisiologia , Modelos Animais de Doenças , Dopamina/fisiologia , Aprendizagem em Labirinto/fisiologia , Mesencéfalo/crescimento & desenvolvimento , Mesencéfalo/fisiologia , Córtex Pré-Frontal/crescimento & desenvolvimento , Córtex Pré-Frontal/fisiologia , Ratos , Ratos Sprague-Dawley , Recompensa , Maturidade Sexual
13.
PLoS One ; 18(1): e0279764, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36649369

RESUMO

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.


Assuntos
Experiências Adversas da Infância , Contracepção Hormonal , Humanos , Feminino , Comportamento Sexual , Libido , Recompensa
14.
Front Endocrinol (Lausanne) ; 14: 1295261, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38149098

RESUMO

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.


Assuntos
Depressão , Transtorno Disfórico Pré-Menstrual , Animais , Feminino , Humanos , Depressão/etiologia , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Ciclo Menstrual/fisiologia , Estágios do Ciclo de Vida
15.
Brain Behav Immun Health ; 20: 100411, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35079709

RESUMO

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.

16.
Biol Sex Differ ; 13(1): 60, 2022 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-36274158

RESUMO

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 \.


Assuntos
Neuroesteroides , Síndrome de Abstinência a Substâncias , Feminino , Humanos , Nicotina/farmacologia , Progesterona , Pregnanolona/farmacologia , Pregnanolona/uso terapêutico , Fumantes , Sinais (Psicologia) , Estudos Cross-Over , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Fumar , Fadiga
17.
J Midwifery Womens Health ; 66(6): 740-748, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34510696

RESUMO

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.


Assuntos
Tocologia , Disfunções Sexuais Psicogênicas , Feminino , Humanos , Gravidez , Disfunções Sexuais Psicogênicas/diagnóstico , Disfunções Sexuais Psicogênicas/terapia
18.
BJPsych Open ; 7(5): e177, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34635873

RESUMO

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.

19.
BJPsych Adv ; 26(6): 327-330, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36570879

RESUMO

Patients with psychiatric illness present a unique challenge to clinicians: in contrast to the traditional medical model, in which patients are conceptualized as being stricken by a disease, patients with certain psychiatric illnesses may seem complicit with the illness. Questions of free will, choice, and the role of the physician can cause clinicians to feel helpless, disinterested, or even resentful. These tensions are a lasting legacy of centuries of mind-body dualism. Over the past several decades, modern tools have finally allowed us to break down this false dichotomy. Integrating a modern neuroscience perspective into practice allows clinicians to conceptualize individuals with psychiatric illness in a way that promotes empathy and enhances patient care. Specifically, a strong grasp of neuroscience prevents clinicians from falling into the trap in which behavioral aspects of a patient's presentation are perceived as being somehow separate from the disease process. We demonstrate the value of incorporating neuroscience into a biopsychosocial formulation through the example of a "difficult patient."

20.
Focus (Am Psychiatr Publ) ; 18(2): 106-119, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33162848

RESUMO

Whether a major depressive episode occurring in the postpartum period (i.e., postpartum depression [PPD]) is sufficiently distinct from major depressive episodes occurring at other times (i.e., major depressive disorder) to warrant a separate diagnosis is a point of debate with substantial clinical significance. The evidence for and against diagnostic distinction for PPD is reviewed with respect to epidemiology, etiology, and treatment. Overall, evidence that PPD is distinct from major depressive disorder is mixed and is largely affected by how the postpartum period is defined. For depression occurring in the early postpartum period (variably defined, but typically with onset in the first 8 weeks), symptom severity, heritability, and epigenetic data suggest that PPD may be distinct, whereas depression occurring in the later postpartum period may be more similar to major depressive disorder occurring outside of the perinatal period. The clinical significance of this debate is considerable given that PPD, the most common complication of childbirth, is associated with immediate and enduring adverse effects on maternal and offspring morbidity and mortality. Future research investigating the distinctiveness of PPD from major depressive disorder in general should focus on the early postpartum period when the rapid decline in hormones contributes to a withdrawal state, requiring profound adjustments in central nervous system function.

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