RESUMO
In pathological or artificial conditions, memory can be formed as silenced engrams that are unavailable for retrieval by presenting conditioned stimuli but can be artificially switched into the latent state so that natural recall is allowed. However, it remains unclear whether such different states of engrams bear any physiological significance and can be switched through physiological mechanisms. Here, we show that an acute social reward experience switches the silent memory engram into the latent state. Conversely, an acute social stress causes transient forgetting via turning a latent memory engram into a silent state. Such emotion-driven bidirectional switching between latent and silent states of engrams is mediated through regulation of Rac1 activitydependent reversible forgetting in the hippocampus, as stress-activated Rac1 suppresses retrieval, while reward recovers silenced memory under amnesia by inhibiting Rac1. Thus, data presented reveal hippocampal Rac1 activity as the basis for emotion-mediated switching between latent and silent engrams to achieve emotion-driven behavioral flexibility.
Assuntos
Região CA1 Hipocampal , Rememoração Mental , Comportamento Social , Proteínas rac1 de Ligação ao GTP , Animais , Região CA1 Hipocampal/enzimologia , Sinais (Psicologia) , Rememoração Mental/fisiologia , Camundongos , Neurônios/enzimologia , Recompensa , Proteínas rac1 de Ligação ao GTP/metabolismoRESUMO
Despite women representing most of those affected by major depression, preclinical studies have focused almost exclusively on male subjects, partially due to a lack of ideal animal paradigms. As the persistent need regarding the sex balance of neuroscience research and female-specific pathology of mental disorders surges, the establishment of natural etiology-based and systematically validated animal paradigms for depression with female subjects becomes an urgent scientific problem. This study aims to establish, characterize, and validate a "Multiple Integrated Social Stress (MISS)" model of depression in female C57BL/6J mice by manipulating and integrating daily social stressors that females are experiencing. Female C57BL/6J mice randomly experienced social competition failure in tube test, modified vicarious social defeat stress, unescapable overcrowding stress followed by social isolation on each day, for ten consecutive days. Compared with their controls, female MISS mice exhibited a relatively decreased preference for social interaction and sucrose, along with increased immobility in the tail suspension test, which could last for at least one month. These MISS mice also exhibited increased levels of blood serum corticosterone, interleukin-6 L and 1ß. In the pharmacological experiment, MISS-induced dysfunctions in social interaction, sucrose preference, and tail suspension tests were amended by systematically administrating a single dose of sub-anesthetic ketamine, a rapid-onset antidepressant. Compared with controls, MISS females exhibited decreased c-Fos activation in their anterior cingulate cortex, prefrontal cortex, nucleus accumbens and some other depression-related brain regions. Furthermore, 24 h after the last exposure to the paradigm, MISS mice demonstrated a decreased center zone time in the open field test and decreased open arm time in the elevated plus-maze test, indicating anxiety-like behavioral phenotypes. Interestingly, MISS mice developed an excessive nesting ability, suggesting a likely behavioral phenotype of obsessive-compulsive disorder. These data showed that the MISS paradigm was sufficient to generate pathological profiles in female mice to mimic core symptoms, serum biochemistry and neural adaptations of depression in clinical patients. The present study offers a multiple integrated natural etiology-based animal model tool for studying female stress susceptibility.
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Transtorno Depressivo , Humanos , Masculino , Feminino , Animais , Camundongos , Camundongos Endogâmicos C57BL , Antidepressivos , Encéfalo , Sacarose/uso terapêutico , Estresse Psicológico/complicações , Depressão/etiologia , Modelos Animais de DoençasRESUMO
Phenotypic differences often stem from genetic/maternal differences and/or early-life adaptations to local environmental conditions. In colonial animals, little is known on how variation in the social environment is embedded into individual phenotypes, nor what the consequences are on individual fitness. We conducted an experimental cross-fostering study on king penguins (Aptenodytes patagonicus), exchanging eggs among 134 pairs breeding in high-density (67 pairs) or low-density (67 pairs) areas of the same breeding colony. We investigated differences in parent and chick phenotypes and survival in relation to the density of their origin and foster environment. Adults breeding in colony areas of high density exhibited decreased resting behaviour and increased aggression and vigilance, increased hypometabolism during incubation fasts, and more moderate corticosterone responses shaped by exposure to chronic stressors (e.g. constant aggression by neighbours). Chick phenotypes were more influenced by the environment in which they were raised than their genetic/maternal origin. Chicks raised in high-density colonial environments showed enhanced weight gain and survival rates regardless of the density of their genetic parents' breeding areas. Our study experimentally shows advantages to breeding in colonial areas of higher breeder densities in king penguins, and highlights the importance of social settings in shaping phenotype expression in colonial seabirds.
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Spheniscidae , Estresse Fisiológico , Animais , Spheniscidae/fisiologia , Feminino , Fenótipo , Masculino , Corticosterona , Comportamento Social , Agressão , Densidade DemográficaRESUMO
Elucidating mechanisms by which early-life adversity (ELA) contributes to increased disease risk is important for mitigating adverse health outcomes. Prior work has found differences in immune cell gene expression related to inflammation and mitochondrial activity. Using a within-person between-group experimental design, we investigated differences in gene expression clusters across acute psychosocial stress and no-stress conditions. Participants were young adults (N = 29, aged 18 - 25 years, 62 % female, 47 % with a history of ELA). Gene expression was assessed in peripheral blood mononuclear cells collected at 8 blood draws spanning two 5-hour sessions (stress vs. no-stress) separated by a week, 4 across each session (number of observations = 221). We applied two unsupervised gene clustering methods - latent profile analysis (LPA) and weighted gene co-expression analysis (WGCNA) - to cluster genes with similar expression patterns across participants. LPA identified 11 clusters, 7 of which were significantly associated with ELA-status. WGCNA identified 5 clusters, 3 of which were significantly associated with ELA-status. LPA- and WGCNA-identified clusters were correlated, and all clusters were highly preserved across sessions and time. There was no significant effect of acute stress on cluster gene expression, but there was a significant effect of time, and significant differences by ELA-status. ELA-associated clusters related to RNA splicing/processing, inflammation, leukocyte differentiation and division, and mitochondrial activity were differentially expressed across time: ELA-exposed individuals showed decreased expression of these clusters at 90-minutes while controls showed increased expression. Our findings replicate previous work in this area and highlight additional mechanisms by which ELA may contribute to disease risk.
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Experiências Adversas da Infância , Leucócitos Mononucleares , Estresse Psicológico , Humanos , Feminino , Estresse Psicológico/metabolismo , Estresse Psicológico/genética , Estresse Psicológico/imunologia , Masculino , Adulto , Adulto Jovem , Adolescente , Leucócitos Mononucleares/metabolismo , Análise por Conglomerados , Expressão Gênica/genética , Transcriptoma , Inflamação/genética , Inflamação/metabolismoRESUMO
Successful and efficient emotion regulation (ER) is a key mechanism for mental health. However, acute stress may impact the ability to cognitively regulate negative emotions due to its immediate effects on executive functioning. Based on previous studies, we expected that the time at which ER is tested after a stressor might have a decisive influence, with impairments in ER being more pronounced immediately after stress as compared to a later post-stress phase. To investigate such a time-dependent effect of stress on ER, we investigated 50 healthy adults (26 female) who were exposed to either the Trier Social Stress Test (n = 25) or a control condition (n = 25). Afterwards subjects conducted a cognitive ER task during which they were instructed to either regulate (cognitive reappraisal) or passively view neutral and negative visual stimuli. The ER task was divided into an early (0-20 minutes) and a late post-stress phase (20-40 minutes). Salivary cortisol and α-amylase were assessed as markers of the neuroendocrine stress response. Self-reported emotional state, the mean activity of the late positive potential measured via electroencephalogram (EEG), and corrugator electromyographic activity (EMG) were used as indices of ER. While the groups did not differ in the early post-stress phase, our results suggest a stress-related impairment in ER in the late post-stress phase. This effect was evident in all ER outcome variables (subjective rating, EEG, and EMG data). These results suggest a time-specific stress effect on cognitive reappraisal, which would have implications for reappraisal as a possible stress management technique.
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Cognição , Estresse Psicológico , Adulto , Humanos , Feminino , Cognição/fisiologia , Emoções/fisiologia , Função Executiva , EletroencefalografiaRESUMO
BACKGROUND: Adolescents exposed to victimization are at an increased risk for a variety of adverse mental health outcomes, including depressive symptoms. Yet, the biological pathways underlying these associations remain poorly understood. Focusing on within-person processes, we examined whether low-grade systemic inflammation mediated the longitudinal associations between peer victimization and depressive symptoms in adolescence. METHODS: 207 adolescents (at baseline Mage = 12.69 years; SD = 0.49; 43.5% female) participated in a multi-wave longitudinal study, with assessments repeated every 6 months over 1.5 years. At each assessment wave, participants self-reported their peer victimization experiences and depressive symptoms. Dried blood spots were collected at each wave using a finger prick procedure to assay a key marker of low-grade systemic inflammation, interkeukin-6 (IL-6). Data were analyzed using random-intercept cross-lagged panel models. RESULTS: The cross-lagged paths from IL-6 to depressive symptoms were significant across all models and waves (ß12 = .13; ß23 = .12; ß34 = .08), indicating that when adolescents' levels of low-grade systemic inflammation were above their person-specific average, they reported increased levels of depressive symptoms in the subsequent months. However, no significant cross-lagged within-person associations emerged between peer victimization and either IL-6 or depressive symptoms. CONCLUSIONS: The findings provide no evidence for the hypothesized mediating role of inflammation in the within-person associations between peer victimization and depressive symptoms. Nevertheless, they extend prior research by indicating that elevated levels of low-grade systemic inflammation predict the development of depressive symptoms in adolescence.
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BACKGROUND: Perinatal psychological distress adversely impacts the well-being and social adjustment of parents and their children. Expectant parents who have migrated may be at higher risk for perinatal psychological distress due to various migration-specific stressors and healthcare service barriers. Limited studies have examined the perceived determinants of perinatal distress in immigrant parents, particularly men. This study explored first and second-generation immigrant parents' lived experiences of social stressors and facilitators of perinatal psychological well-being. METHODS: Participants were recruited by convenience and purposive sampling as part of a larger study. Semi-structured interviews were conducted virtually with first and second-generation immigrant women and men in Quebec, Canada. An inductive thematic analysis was performed. RESULTS: Sixteen women (age = 34.8 ± 3.7 years) and ten men (age = 35.1 ± 4.9 years) from various ethnic backgrounds participated in the study at 7.4 ± 0.73 and 7.5 ± 0.72 months postpartum, respectively. Three themes were identified: (1) cultural pressures (cultural differences in parenting, gender-related cultural pressures, health and baby-related practices), (2) health and social service access (social benefits and resources, and systemic barriers in health care), and (3) discrimination (physical appearance or parental-related discrimination, gender-related discrimination, ethnic-related discrimination). First-generation immigrant parents reported greater acculturative stress (i.e. mental health stigma, health care access) and ethnic discrimination concerns related to their distress. Among men, barriers include feeling as though the paternal role was devalued by society and not receiving consideration by health care. CONCLUSIONS: Our results highlight different social factors of perinatal well-being perceived by men and women from various ethnic and immigration backgrounds during the perinatal period. Perceived factors include macro-level factors, such as a country's social climate, health and social policies and services, and social aspects of acculturative stress. Our findings suggest the need for continued efforts to challenge and eliminate discriminatory practices. Interventions and resources directed at first-generation immigrant parents should be bolstered. Understanding what parents perceive to facilitate or hinder their psychological well-being can help inform the development of tailored evidence-based programs and policies to better meet the mental health needs of Canadians and reduce gender disparities in the treatment of perinatal distress.
Assuntos
Emigrantes e Imigrantes , Pais , Pesquisa Qualitativa , Estresse Psicológico , Humanos , Feminino , Emigrantes e Imigrantes/psicologia , Quebeque , Adulto , Masculino , Gravidez , Pais/psicologia , Estresse Psicológico/etnologia , Estresse Psicológico/psicologia , Acessibilidade aos Serviços de Saúde , Angústia Psicológica , Período Pós-Parto/psicologia , Período Pós-Parto/etnologia , Poder Familiar/psicologia , Poder Familiar/etnologiaRESUMO
OBJECTIVES: The impacts of stress on inflammation, although hypothesized, have not been thoroughly examined, especially in relation to social and environmental factors and particularly within Black populations. This study aims to explore the biological mechanisms of embodiment linking stress and health to understand physiological changes in the body's response to psychological stress in a Nigerian population. Through a multidisciplinary approach, this study queries the relationship between stress, cortisol, and salivary C-reactive protein (sCRP), a biomarker of inflammation, while also validating the use of sCRP as a potential and accurate stress indicator in the field. METHODS: In this cross-sectional study, 138 passive drool saliva samples (nfemale = 89 nmale = 49) were collected and assessed for sCRP and cortisol levels in adults. Participants also completed a short demographic survey and, to measure psychological stress, the General Health Questionnaire 12 (GHQ-12). Relationships between sCRP and stress-related variables (i.e., cortisol, GHQ-12, and demographic data) were assessed using Spearman's correlations, simple regression, multivariable linear regression, and exploratory factor analysis. RESULTS: sCRP levels ranged from 20.57 to 6879.41 pg/mL across all samples, with significant differences between female and male participants. The GHQ-12 was not a significant predictor of sCRP variability. However, socio-demographic factors such as body mass index (BMI), age, self-reported sex, ethnic identity, and cortisol were significant predictors, collectively explaining 24%-27% of the variation in sCRP. CONCLUSION: Socio-demographic predictors like BMI, age, sex, and particularly ethnic group experience in Nigeria encapsulate aspects of embodied stress, that significantly affect sCRP variability.
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There are competing theoretical hypotheses regarding the consequences of early adversity, such as childhood maltreatment, for individuals' autonomic nervous system activity. Research examining potential implications of child maltreatment for sympathetic nervous system activity, specifically, is scarce. In this preregistered study, we examined whether childhood maltreatment history is associated with pregnant adults' sympathetic responses to different stressors. This population is particularly relevant, given potential intergenerational consequences of pregnant individuals' physiological responses to stress. Pregnant women's (N = 162) electrodermal levels were recorded while completing the Trier Social Stress Test (TSST), which elicits social-evaluative threat, and while watching a video of an unfamiliar infant crying, which was intended to activate the attachment system. Pregnant women's retrospective reports of childhood maltreatment were negatively associated with their electrodermal reactivity to the TSST and to the video of the infant crying. Follow-up analyses indicated that these associations were specific to reported experiences of childhood abuse and not childhood neglect. Altogether, these findings indicate that self-reported childhood maltreatment experiences, and childhood abuse in particular, may result in blunted activity of the sympathetic nervous system in response to multiple types of stressors.
Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis , Resposta Galvânica da Pele , Estresse Psicológico , Humanos , Feminino , Gravidez , Adulto , Estresse Psicológico/fisiopatologia , Resposta Galvânica da Pele/fisiologia , Sistema Nervoso Simpático/fisiopatologia , Sistema Nervoso Simpático/fisiologia , Adulto Jovem , Experiências Adversas da Infância , Maus-Tratos InfantisRESUMO
We experimentally demonstrated that chronic social stress during the development of a depression-like state enhances lung metastasis and modifies the expression of many carcinogenesis- and apoptosis-related genes in the hypothalamus of mice, including genes involved in lung cancer pathogenesis in humans. Analysis of the expression of genes encoding the major clinical markers of lung cancer in the hypothalamus of mice with depression-like behavior revealed increased expression of the Eno2 gene encoding neuron-specific enolase, a blood marker of lung cancer progression in humans. It was shown that the expression of this gene in the hypothalamus correlated with the expression of many carcinogenesis- and apoptosis-related genes. The discovered phenomenon may have a fundamental significance and requires further studies.
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Biomarcadores Tumorais , Depressão , Hipotálamo , Neoplasias Pulmonares , Fosfopiruvato Hidratase , Animais , Masculino , Camundongos , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinogênese , Depressão/genética , Depressão/metabolismo , Depressão/patologia , Regulação Neoplásica da Expressão Gênica , Hipotálamo/metabolismo , Hipotálamo/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Fosfopiruvato Hidratase/análise , Fosfopiruvato Hidratase/genética , Estresse Psicológico/genética , Estresse Psicológico/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismoRESUMO
Individuals with a Religious or Spiritual Problem (RSP), as defined in the DSM-5, experience distress associated with faith-related moral dilemmas, existential meaning, and transpersonal attitudes toward other people. It is unclear whether a RSP reflects a generally heightened stress reactivity or whether the stress response is confined to religious and spiritual contexts. To elucidate this issue, we measured behavioral and physiological responses during social-evaluative stress (public speaking-Trier Social Stress Test) and in religious/spiritual contexts (Bible reading and listening to sacred music) in 35 individuals with RSP and 35 matched participants. We found no stress reduction in the religious/spiritual context in RSP, as indicated by increased heart rate, saliva cortisol, and relatively higher left than right frontal activity. Religious stimuli evoked physiological stress responses in RSP. Contrary to the physiological parameters, participants with RSP reported less anxiety in the religious/spiritual context. Religious individuals with and without RSP showed similar stress responses during public speaking. Religious individuals without RSP displayed reduced stress responses in the religious/spiritual context. These results indicate that specific physiological distress in religious/spiritual contexts should be considered in the psychological care of RSP.
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Ansiedade , Espiritualidade , Humanos , Hungria , Ansiedade/psicologia , Transtornos de Ansiedade , Estresse Psicológico/psicologia , Adaptação PsicológicaRESUMO
STUDY QUESTION: Does the exposure to job loss during pregnancy increase the risk of miscarriage or stillbirth? SUMMARY ANSWER: The experience of own or partner's job loss during the pregnancy is associated with an increased risk of miscarriageand stillbirth. WHAT IS KNOWN ALREADY: Prior research on the psycho-social aspect of pregnancy loss has investigated the contextual and the individual-level stressors. At the contextual level, natural disasters, air pollution, and economic downturns are associated with higher risk of pregnancy loss. At the individual level, intense working schedules and financial strain are linked with increased risk of pregnancy loss both at early and later stages of the gestation. STUDY DESIGN, SIZE, DURATION: This work draws on high-quality individual data of 'Understanding Society', a longitudinal survey that has interviewed a representative sample of households living in the UK annually since 2009. Approximately 40 000 households were recruited. The analyses use all the available survey waves (1-12, 2009-2022). PARTICIPANTS/MATERIALS, SETTING, METHODS: The final sample consisted of 8142 pregnancy episodes that contain complete informationon pregnancy outcome and date of conception. Ongoing pregnancies at the time of the interview were excluded from the final sample. The outcome variable indicated whether a pregnancy resulted in a live birth or a pregnancy loss whereas the exposure variable identified the women's or their partner's job loss because of redundancy or a dismissal. Logistic regression models were employed to estimate the relation between job loss during pregnancy and pregnancy loss. The models were adjusted for an array of socio-demographic and economic characteristics following a stepwise approach. Several sensitivity analyses complemented the main findings. MAIN RESULTS AND THE ROLE OF CHANCE: Baseline models controlling for women's demographic background and prior experience of miscarriage estimated an increased risk of pregnancy loss when women were exposed to their own or their partner's job loss during their pregnancy (odds ratio (OR) = 1.99, 95% CI: 1.32, 2.99). When the models were adjusted for all socio-economic and partnership-related covariates the association remained robust (OR = 1.81, 95% CI: 1.20, 2.73). LIMITATIONS, REASONS FOR CAUTION: First, the pregnancy outcome and the date of conception were self-reported and may besubjected to recall and social desirability bias. Second, although we adjusted for an array socio-demographic characteristics and self-reported health, other contextual factors might be correlated with both job loss and pregnancy loss. Third, owing to the limited sample size, we could not assess if the main finding holds across different socio-economic strata. WIDER IMPLICATIONS OF THE FINDINGS: By showing that exposure to a job loss during pregnancy increases the risk of miscarriage and stillbirth, we underline the relevance of pregnancy loss as a preventable public health matter. This result also calls for policy designthat enhances labour market protection and social security buffers for pregnant women and their partners. STUDY FUNDING/COMPETING INTERESTS: The authors received the following financial support for the research, authorship, and/or publication of this article: H2020 Excellent Science, H2020 European Research Council, Grant/Award Number: 694262 (project DisCont-Discontinuities in Household and Family Formation) and the Economic and Social Research Centre on Micro-Social Change (MiSoC). There are no conflicts of interest to declare.
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Aborto Induzido , Aborto Espontâneo , Gravidez , Feminino , Humanos , Natimorto , Resultado da Gravidez , Nascido VivoRESUMO
BACKGROUND: Psychosocial stressors characterized by social threat, such as interpersonal loss and social rejection, are associated with depression in adolescents. Few studies, however, have examined whether social threat affects fronto-cingulate-limbic systems implicated in adolescent depression. METHODS: We assessed lifetime stressor severity across several domains using the Stress and Adversity Inventory (STRAIN) in 57 depressed adolescents (16.15 ± 1.32 years, 34 females), and examined whether the severity of social threat and non-social threat stressors was associated with gray matter volumes (GMVs) in the anterior cingulate cortex (ACC), amygdala, hippocampus, and nucleus accumbens (NAcc). We also examined how lifetime social threat severity and GMVs in these regions related to depressive symptoms at baseline and over 9 months. RESULTS: General stressor severity was related to greater depression severity at baseline and over 9 months. Moreover, greater severity of social threat (but not non-social threat) stressors was associated with smaller bilateral amygdala and NAcc GMVs, and smaller bilateral surface areas of caudal and rostral ACC (all pFDR ⩽ 0.048). However, neither social threat nor non-social threat stressor severity was related to hippocampal GMVs (all pFDR ⩾ 0.318). All fronto-cingulate-limbic structures that were associated with the severity of social threat were negatively associated with greater depression severity over 9 months (all pFDR ⩽ 0.014). Post-hoc analyses suggested that gray matter morphometry of bilateral amygdala, NAcc, and rostral and caudal ACC mediated the association between social threat and depression severity in adolescents over 9 months (all pFDR < 0.048). CONCLUSIONS: Social threat specifically affects fronto-cingulate-limbic pathways that contribute to the maintenance of depression in adolescents.
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Córtex Cerebral , Sistema Límbico , Feminino , Humanos , Adolescente , Sistema Límbico/diagnóstico por imagem , Giro do Cíngulo/diagnóstico por imagem , Tonsila do Cerebelo/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: Alcohol binge drinking may compromise the functioning of the nucleus accumbens (NAc), i.e. the neural hub for processing reward and aversive responses. METHODS: As socially stressful events pose particular challenges at developmental stages, this research applied the resident-intruder paradigm as a model of social stress, to highlight behavioural neuroendocrine and molecular maladaptive plasticity in rats at withdrawal from binge-like alcohol exposure in adolescence. In search of a rescue agent, cannabidiol (CBD) was selected due to its favourable effects on alcohol- and stress-related harms. RESULTS: Binge-like alcohol exposed intruder rats displayed a compromised defensive behaviour against the resident and a blunted response of the stress system, in addition to indexes of abnormal dopamine (DA)/glutamate plasticity and dysfunctional spine dynamics in the NAc. CBD administration (60 mg/kg) was able to: (1) increase social exploration in the binge-like alcohol exposed intruder rats, at the expenses of freezing time, and in control rats, which received less aggressive attacks from the resident; (2) reduce corticosterone levels independently on alcohol previous exposure; (3) restore DA transmission and (4) facilitate excitatory postsynaptic strength and remodelling. CONCLUSIONS: Overall, the maladaptive behavioural and synaptic plasticity promoted by the intersection between binge-like alcohol withdrawal and exposure to adverse social stress can be rescued by a CBD détente effect that results in a successful defensive strategy, supported by a functional endocrine and synaptic plasticity. The current data highlight CBD's relevant therapeutic potential in alcohol- and stress-related harms, and prompt further investigation on its molecular targets.
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Alcoolismo , Canabidiol , Síndrome de Abstinência a Substâncias , Ratos , Humanos , Animais , Canabidiol/farmacologia , Dopamina , Núcleo Accumbens , Etanol/farmacologiaRESUMO
BACKGROUND: The authors sought to clarify the impact of spousal psychiatric disorders of differing severity [major depression or anxiety disorders (DAD) v. bipolar disorder or nonaffective psychosis (BPN)] on proband risk for alcohol use disorder (AUD) during marriage. METHODS: In a Swedish cohort (N = 744 628), associations between spousal DAD and BPN and proband AUD were estimated with Cox proportional hazards; associations between parental AUD, proband premarital AUD, and spousal lifetime DAD and BPN were estimated with logistic regression; and whether spousal DAD or BPN causally increased risk for AUD was evaluated with frailty models. RESULTS: Spousal premarital DAD, spousal marital-onset DAD, and spousal BPN (premarital or marital-onset) were associated with proband AUD during marriage [hazard ratios (HR) range 1.44-3.72]. Those with a parental or premarital history of AUD (v. without) were more likely to marry a spouse with DAD or BPN (odds ratios 1.22-2.77). Moving from an unaffected first spouse to a DAD-affected second spouse increased AUD risk in males (HR 2.90). Moving from an unaffected first spouse to a BPN-affected second spouse increased AUD risk (HRmales 3.96; HRfemales 5.64). Moving to an unaffected second spouse from a DAD-affected first spouse decreased AUD risk, with stronger evidence in females compared to males (HRmales 0.59; HRfemales 0.28). CONCLUSIONS: Associations between spousal DAD or BPN and proband AUD reflect both selection and causal effects. Marriage to a BPN-affected spouse has a particularly strong effect on AUD risk, with more modest effects for spousal DAD.
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Alcoolismo , Transtornos Mentais , Masculino , Feminino , Humanos , Alcoolismo/epidemiologia , Alcoolismo/psicologia , Cônjuges/psicologia , Casamento/psicologia , PaisRESUMO
BACKGROUND: This study investigates the impact of childhood maltreatment (CM) on hypothalamic-pituitary-adrenal (HPA)-axis functioning and on anxiety perception. Moreover, the influence of CM severity and frequency was also explored. METHODS: In total, 187 participants aged 7-17 were assessed for CM history using validated questionnaires and ad hoc interviews to be classified according to the criteria of the Tool for Assessing the Severity of Situations in which Children are Vulnerable (TASSCV). Psychopathology was ascertained using the K-SADS-PL5. To assess HPA-axis functioning, salivary cortisol samples were collected throughout a normal day and during an acute psychosocial stressor, the Trier Social Stress Test for children (TSST-C). Subjective anxiety was evaluated using STAI/-C. RESULTS: Youth with a CM history had higher overall diurnal cortisol levels (p = 0.001), blunted cortisol response to acute psychosocial stress (p = 0.002) and greater perceived anxiety (p = 0.003), than those without CM. Specifically, participants exposed to moderate/severe or often/frequent CM showed the greater diurnal cortisol output (pseverity = 0.002; pfrequency = 0.003), and blunted cortisol response during the TSST-C (pseverity = 0.006; pfrequency = 0.008). Meanwhile, youth with low CM severity/frequency exhibited a similar cortisol response to those without CM. However, perceived anxiety was higher in those exposed to CM (p < 0.001), regardless of its severity/frequency. CONCLUSIONS: Disturbances in HPA-axis functioning are already evident early after CM exposure, while psychological and physiological responses to an acute stressor are dissociated in youth exposed to CM. The dose-response relationship described in this paper highlights the need to comprehensively evaluate CM so that vulnerable children can be identified and assigned to proper interventions.
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Maus-Tratos Infantis , Hidrocortisona , Humanos , Adolescente , Criança , Estresse Psicológico/psicologia , Saliva , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-SuprarrenalRESUMO
BACKGROUND: Women are at increased risk for psychosocial stress-related anxiety disorders, yet mechanisms regulating this risk are unknown. Psychosocial stressors activate microglia, and the resulting neuroimmune responses that females exhibit heightened sensitivity to may serve as an etiological factor in their elevated risk. However, studies examining the role of microglia during stress in females are lacking. METHODS: Microglia were manipulated in the stress-sensitive locus coeruleus (LC) of female rats in the context of social stress in two ways. First, intra-LC lipopolysaccharide (LPS; 0 or 3 µg/side, n = 5-6/group), a potent TLR4 agonist and microglial activator, was administered. One hour later, rats were exposed to control or an aggressive social defeat encounter between two males (WS, 15-min). In a separate study, females were treated with intra-LC or intra-central amygdala mannosylated liposomes containing clodronate (m-CLD; 0 or 25 µg/side, n = 13-14/group), a compound toxic to microglia. WS-evoked burying, cardiovascular responses, and sucrose preference were measured. Brain and plasma cytokines were quantified, and cardiovascular telemetry assessed autonomic balance. RESULTS: Intra-LC LPS augmented the WS-induced burying response and increased plasma corticosterone and interleukin-1ß (IL-1ß). Further, the efficacy and selectivity of microinjected m-CLD was fully characterized. In the context of WS, intra-LC m-CLD attenuated the hypervigilant burying response during WS as well as the accumulation of intra-LC IL-1ß. Intra-central amygdala m-CLD had no effect on WS-evoked behavior. CONCLUSIONS: These studies highlight an innovative method for depleting microglia in a brain region specific manner and indicate that microglia in the LC differentially regulate hypervigilant WS-evoked behavioral and autonomic responses.
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Locus Cerúleo , Microglia , Masculino , Ratos , Animais , Feminino , Locus Cerúleo/fisiologia , Ratos Sprague-Dawley , Lipopolissacarídeos/farmacologia , Estresse PsicológicoRESUMO
Acute stress can impair human working memory. Little is known, however, about the effects of acute stress on working memory strategies. The goal of this research was to investigate the effects of acute stress on use of a systematic spatial working memory search strategy. Participants (28 females and 20 males per group) completed the Trier Social Stress Test (TSST) or control tasks. Use of a systematic spatial working memory search strategy was measured through performance on the spatial working memory subtest of the Cambridge Neuropsychological Test Automated Battery (CANTAB). The TSST was effective at producing subjective and cortisol stress responses, but there was no significant stress effect on use of a systematic search strategy or working memory search errors. There were also no significant relationships between subjective and cortisol stress responses and use of a systematic search strategy or working memory search errors within the stress group. These results suggest that acute stress does not impair the self-generation or execution of a systematic spatial working memory search strategy.
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Hidrocortisona , Memória de Curto Prazo , Masculino , Feminino , Humanos , Memória de Curto Prazo/fisiologia , Estresse Psicológico , Testes NeuropsicológicosRESUMO
The sense of agency (SoA) refers to the feeling of being in control of one's actions and the subsequent consequence of these actions. Emotional context seems to alter the strength of sense of agency. The present study explored the influence of acute psychosocial stress on the SoA by means of the Trier Social Stress Test (TSST). Self-assessment manikin (SAM) and objective physiological indicators (e.g. heart rate, electrodermal activity, and salivary cortisol levels) were utilized to evaluate the effect of the TSST. We also employed the temporal binding effect as an implicit assessment of the participant's SoA. The results indicated that the stress level of the experimental group after TSST was significantly higher than the control group, whilst the temporal binding scores of the experimental group decreased after TSST manipulation. In short, acute psychosocial stress with intense emotional arousal weakened the sense of agency.
Assuntos
Hidrocortisona , Estresse Psicológico , Humanos , Adulto , Hidrocortisona/metabolismo , Emoções , Testes Psicológicos , Nível de Alerta , Saliva/metabolismoRESUMO
BACKGROUND: Depression risk increases during adolescent development, and individual differences in neural sensitivity to peer feedback (rejection vs. acceptance) may be a key diathesis in understanding stress-related depression risk. METHODS: At baseline, adolescents (12-14 years old; N = 124) completed clinical interviews and self-report symptom measures, and the Chatroom Task while MRI data were acquired. The majority of participants provided usable MRI data (N = 90; 76% female), which included adolescents with no maternal depression history (low risk n = 64) and those with a maternal depression history (high risk n = 26). Whole-brain regression models probed group differences in neural sensitivity following peer feedback, and whole-brain linear mixed-effects models examined neural sensitivity to peer feedback by peer stress interactions relating to depression symptoms at up to nine longitudinal assessments over 2 years. RESULTS: Whole-brain cluster-corrected results indicated brain activation moderating the strong positive association between peer interpersonal stress and depression over time. This included activation in the anterior insula, cingulate, amygdala, and striatum during anticipation and receipt of feedback (i.e., rejection vs. acceptance). Moderation effects were stronger when examining peer interpersonal (vs. non-interpersonal) stress and in relation to depression (vs. social anxiety) symptoms. CONCLUSIONS: Neural responses to peer feedback in key social and incentive processing brain regions may reflect core dispositional risk factors that interact with peer interpersonal stressors to predict adolescent depression symptom severity over time.