The Nucleus Accumbens CRH-CRHR1 System Mediates Early-Life Stress-Induced Sleep Disturbance and Dendritic Atrophy in the Adult Mouse / 神经科学通报·英文版

Adverse experiences in early life have long-lasting negative impacts on behavior and the brain in adulthood, one of which is sleep disturbance. As the corticotropin-releasing hormone (CRH)-corticotropin-releasing hormone receptor 1 (CRHR1) system and nucleus accumbens (NAc) play important roles in both stress responses and sleep-wake regulation, in this study we investigated whether the NAc CRH-CRHR1 system mediates early-life stress-induced abnormalities in sleep-wake behavior in adult mice. Using the limited nesting and bedding material paradigm from postnatal days 2 to 9, we found that early-life stress disrupted sleep-wake behaviors during adulthood, including increased wakefulness and decreased non-rapid eye movement (NREM) sleep time during the dark period and increased rapid eye movement (REM) sleep time during the light period. The stress-induced sleep disturbances were accompanied by dendritic atrophy in the NAc and both were largely reversed by daily systemic administration of the CRHR1 antagonist antalarmin during stress exposure. Importantly, Crh overexpression in the NAc reproduced the effects of early-life stress on sleep-wake behavior and NAc morphology, whereas NAc Crhr1 knockdown reversed these effects (including increased wakefulness and reduced NREM sleep in the dark period and NAc dendritic atrophy). Together, our findings demonstrate the negative influence of early-life stress on sleep architecture and the structural plasticity of the NAc, and highlight the critical role of the NAc CRH-CRHR1 system in modulating these negative outcomes evoked by early-life stress.

Role of an enriched environment in ameliorating early life stress-induced changes in structure and functions of hippocampus and amygdala in rats

Objectives: This study aimed to understand whether an enriched environment (EE) in adulthood benefits in mitigating the early life stress-induced changes in the structure and functions of the hippocampus and amygdala. Materials and Methods: Male Wistar rats were exposed daily for 6 h to early maternal separation and isolation (MS) stress from postnatal days (PND) 4–14 and later at PND 60–70 days subjected to EE, while, the normal control (NC) rats were not subjected to stress but reared with the mother under standard housing conditions. The effects of MS and EE on adulthood behaviour were not subjected to stress but assessed by measuring the ambulatory, repetitive and anxiety-like behaviour. The study has also done the plasma corticosterone concentrations. The dendritic remodelling in the amygdala and hippocampus was assessed using the Golgi cox staining approach. Finally, the present study compared the reactive oxygen species-induced lipid peroxidation and total antioxidant capacity in MS rats as an indirect measure of oxidative stress to study the impact of MS stress on the limbic circuit and peripheral organs. Results: MS rats showed increased anxiety and lower plasma corticosterone levels. The pyramidal neurons’ dendritic plasticity displayed a different pattern, with shrinkage in the CA1 hippocampal neurons and hypertrophy in the amygdala’s primary neurons. Variations in antioxidant activity and peroxidation observed in NC to MS across tissues indicate the occurrence and management of oxidative stress in MS. The 10 days of EE in young adulthood helped to reduce MS stress-induced structural abnormalities in hippocampal and amygdala pyramidal neurons, as well as anxiety and plasma corticosterone levels. Conclusion: These findings together indicate that exposure to adverse experiences may cause harmful effects on brain plasticity and behaviour in young adulthood. Exposure to EE may be beneficial in reducing the early life stress-induced pathophysiology later in life.

Effect of early-life maternal deprivation on depressive-like behavior and neurogenesis in hippocampal granular layer of adolescent rat / 中华行为医学与脑科学杂志

Objective:To explore the effects of early-life maternal deprivation on depressive-like behavior and neurogenesis in the granular layer of hippocampus in adolescent rats (6-7 weeks old).Methods:Neonatal rats were randomly divided into maternal deprivation group and control group, with 3 litters in each group.Rats in the maternal deprivation group were given maternal deprivation from 1 to 14 days after birth and rats in the control group were caged with the mother rats and raised normally.The body weight of rats at 5-6 weeks old was recorded and the increased body weight was calculated.When the rats were 6 weeks old, the sucrose preference test was carried out.Then the rats were killed and immunofluorescence histochemistry was applied to compare the expression of Ki67 and Nestin positive cells in the dentate gyrus of hippocampus.SPSS 22.0 software was used for statistical analysis.The data of the two groups were tested to conform to the normal distribution, and then t-test was carried out. Results:There was significant difference in body weight growth between the two groups at the age of 5-6 weeks.Compared with the control group, rats in the maternal deprivation group had lower body weight growth ((20.57±2.19) g, (30.57±1.25) g, t=3.96, P<0.01)) and lower sucrose preference rate((58.38±53.14)%, (73.88±3.67)%, t=3.21, P<0.01). The results of immunofluorescence showed that the number of Ki67 positive cells in the granular layer of hippocampus in the maternal deprivation group was less than that in the control group ((5.13±0.31), (7.60±0.38), t=5.09, P<0.01), and the number of Nestin immunofluorescence positive cells was more than that in the control group ((16.65±0.79), (7.64±0.70), t=8.51, P<0.01). The Nestin immunofluorescence positive cells in the maternal deprivation group had more protrusions and branches, and the morphology was similar to astrocytes, while the immunofluorescence positive cells in the control group had fewer protrusions, and the cell body was oval. Conclusions:Early-life maternal deprivation leads to depressive-like behavior in adolescent rats, which may be associated with the decrease of neurogenesis and activation of astrocytes in the dentate gyrus of the hippocampus.

Relationship between early factors life stress and college students’ risk-taking behaviors: gender difference and situational influence / 中华行为医学与脑科学杂志

Objective:To explore the differences in risk-taking behaviors of individuals with early life stress between different genders under the control of social situation.Methods:A total of 160 college students including 78 males and 82 females were selected by the child psychological abuse and neglect scale.Then the subjects were divided into the early life stress group ( n=80) and the non-early life stress group ( n=80) according to the scores of the above scales.According to the presence or absence of peers, the subjects in the two groups were randomly assigned to peer presence group ( n=80) or no peer presence group ( n=80). The study adopted an experimental design of 2 (early life stress, non-early life stress) ×2 (peer presence, no peer presence) ×2 (male, female) among the subjects.All subjects performed the task of simulating risky behavior, and the number of times they chose "forward" and did not crash in the task was used as the measurement index of risky behavior.Three-factor ANOVA and Bonferroni simple effect test were carried out using SPSS 22.0 software under various conditions. Results:There were significant differences in the main effects of early life stress ( F(1, 152)=162.06, P<0.01, η2=0.52). In the simulated risk behavior task, the risk behavior of the early life stressed individuals was higher than that of the non-early life stressed individuals (no peer presence: (59.11±11.48) vs (34.91±7.42), P<0.01); peer presence: (59.24±8.59) vs (55.08±10.32), P<0.01). The interaction between early life stress and the presence of peers was statistically significant ( F(1, 152)=65.35, P<0.01, η2=0.30), for non-early life stressed individuals, the risk-taking behaviors in the peer presence group was significantly higher than that in the no peer presence group ((55.08±10.32) vs (34.91±7.42), P<0.01, but the difference was not significant for early life stressed individuals ((59.24±8.59) vs (59.11±11.48), P>0.05). The interaction of early life stress, peer presence and gender was statistically significant ( F(1, 152) =5.92, P=0.016, η2=0.04). In the presence of companions, female early-life stressed individuals exhibited higher risk behaviors than non-early life stressed individuals ((53.91±5.12) vs (46.30±4.57), P<0.01), while the difference between male early life stressed individuals and non-early life stressed individuals was not statistically significant ((65.75±7.42) vs (62.27±7.78), P>0.05). Conclusion:The influence of early life stress on individual risk-taking behavior is related with presence and gender.

Early childhood abuse: adult impulsivity and risky behavior / Abuso na infância: impulsividade no adulto e comportamentos de risco

We review the role of childhood abuse (CA) in the practice of impulsive, risk-taking behaviors during adulthood. CA deregulates the adult response to stress, which in turn disrupts the prefrontal-striatal systems that provide executive control over reward-related behavior. The result is impulsivity and risk-taking, including self-medication with drugs and alcohol and the practice of unsafe sex. These behaviors decrease quality of life and impair the attainment of long-term goals. Risky sexual behavior, in particular, increases the chance of HIV infection and perpetuates the epidemic.

Revisamos o papel do abuso na infância na prática de comportamentos impulsivos e de risco durante a vida adulta. O abuso na infância desregula a resposta do adulto ao estresse, o que, por sua vez, impede os circuitos frontoestriatais de fornecerem o adequado controle executivo sobre comportamentos associados à recompensa. O resultado é a impulsividade e escolhas de risco, incluindo automedicação com drogas e álcool e a prática de sexo inseguro, reduzindo a qualidade de vida e prejudicando o alcance de metas de longo prazo. O comportamento sexual de risco, em particular, aumenta a chance de infecção pelo Vírus de Imunodeficiência Humana e perpetua a sua epidemia.

Early maladaptive schemas and harm avoidance as mediating factors between early life stress and psychiatric symptoms in adults

Objective: This study investigated how factors of temperament and early maladaptive schemas predict psychiatric symptoms, as well as how they mediate the relation between early life stress and psychiatric symptoms in adults. Methods: A cross-sectional study was conducted with a sample of 200 university students. Data was collected through a sociodemographic questionnaire, the Adult Self-Report Inventory, the Childhood Trauma Questionnaire, the Young Schema Questionnaire, and the Temperament and Character Inventory-Revised. Results: A model including early maladaptive schemas, harm avoidance (temperament factor), and early life stress explained 69% of the variation of the psychiatric symptoms; among the predictors, early maladaptive schemas explained 31% of psychiatric symptoms, while harm avoidance explained 25%. Most of the predictive power associated with early life stress can be better explained by early maladaptive schemas and, to a lesser extent, harm avoidance. Conclusion: By managing these processes therapeutically, deleterious effects associated with early life stress can be minimized.

Early-life stress alters sleep structure and the excitatory-inhibitory balance in the nucleus accumbens in aged mice / 中华医学杂志(英文版)

Background@#Exposure to adverse experiences in early life may profoundly reshape the neurodevelopmental trajectories of the brain and lead to long-lasting behavioral and neural alterations. One deleterious effect of early-life stress that manifests in later life is sleep disturbance, but this has not been examined in aged mice and the underlying neural mechanisms remain unknown. Considering the important role of the nucleus accumbens (NAc) in the sleep-wake regulation, this study aimed to assess the effects of early-life stress on the sleep behaviors in aged mice and the potential involvement of the NAc in stress-induced sleep abnormalities.@*Methods@#Twenty aged male C57BL/6 mice (>16 months, n = 10 per group) were used in this study. During post-natal days 2 to 9, dams were provided with either sufficient (control) or a limited nesting and bedding materials (stressed). When the mice were 16 to 17 months old, their sleep-wake behaviors were recorded over 24 h using electroencephalogram and electromyelogram. The amount of each sleep-wake stage, mean duration, and stage transition was analyzed. Then, five animals were randomly chosen from each group and were used to measure the expression levels of vesicular glutamate transporter-1 (VGluT1) and vesicular transporters of γ-aminobutyric acid (VGAT) in the NAc using immunohistochemistry. Group comparisons were carried out using Student t test or analysis of variances when appropriate.@*Results@#Compared with the control mice, the early-life stressed aged mice spent less time awake over 24 h (697.97 ± 77.47 min vs. 631.33 ± 34.73 min, t17 = 2.376, P = 0.030), accordingly, non-rapid eye movement sleep time was increased (667.37 ± 62.07 min vs. 723.54 ± 39.21 min, t17 = 2.326, P = 0.033) and mean duration of rapid eye movement sleep was prolonged (73.00 ± 8.98 min vs. 89.39 ± 12.69 min, t17 = 3.277, P = 0.004). Meanwhile, we observed decreased VGluT1/VGAT ratios in the NAc in the stressed group (F(1, 16) = 81.04, P < 0.001).@*Conclusion@#Early adverse experiences disrupt sleep behaviors in aged mice, which might be associated with the excitatory-inhibitory imbalance in the NAc.

Early-Life Stress in D2 Heterozygous Mice Promotes Autistic-like Behaviors through the Downregulation of the BDNF-TrkB Pathway in the Dorsal Striatum

A number of specific genetic variants including gene mutations and single nucleotide variations have been identified in genomewide association studies of autism spectrum disorder (ASD). ASD phenotypes in individuals carrying specific genetic variations are manifest mostly in a heterozygous state. Furthermore, individuals with most genetic variants show incomplete penetrance and phenotypic variability, suggesting that non-genetic factors are also involved in developing ASD. However, the mechanisms of how genetic and environmental factors interactively promote ASD are not clearly understood. In the present study, we investigated whether early-life stress (ELS) in D2 dopamine receptor heterozygous knockout (D2(+/−)) mice induces ASD-like symptoms. To address that, we exposed D2 heterozygous pups to maternal separation stress for 3 h daily for 13 days beginning on postnatal day 2. D2(+/−) adult mice that had experienced ELS exhibited impaired sociability in the three-chamber test and home-cage social interaction test and increased grooming behavior, whereas wildtype littermates exposed to ELS did not show those phenotypes. ELS-exposed D2(+/−) mice had decreased levels of BDNF, TrkB, phospho-ERK1/2 and phospho-CREB in the dorsal striatum. Administration of the TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) to ELS-exposed D2(+/−) mice rescued the sociability deficits and repetitive behavior. In contrast, behavioral rescue by 7,8-DHF in ELS-exposed D2(+/−) mice was blocked when TrkB expression in the dorsal striatum was locally inhibited by the injection of TrkB-siRNA. Together, our results suggest that the interaction between ELS and defective D2 gene function promotes autistic-like behaviors by downregulating the BDNF-TrkB pathway in the dorsal striatum.

Modelo teórico sobre os significados do estresse precoce e a vida adulta com depressão / Theoretical model of the meanings of early life stress and adulthood with depression

O desenvolvimento humano, presente desde a formação primária do indivíduo é constituído pelo conjunto das experiências vividas durante infância, incluindo as experiências de estresse precoce. Tais vivências repercutem nas ações do sujeito, podendo ser importante no aparecimento da depressão. Objetivos: explorar e analisar o significado do Estresse Precoce para portadores de depressão e construir um modelo teórico sobre o fenômeno estudado; caracterizar a amostra quanto às características sociodemográficas e de saúde; explorar e analisar, à luz do Interacionismo Simbólico, o significado do estresse precoce entre adultos portadores de depressão. Método: Estudo qualitativo que teve como referencial teórico norteador o Interacionismo Simbólico e como referencial metodológico a Teoria Fundamentada nos Dados. Os participantes desse estudo foram portadores de depressão que vivenciaram Estresse Precoce, recrutados no Centro de Atenção Psicossocial - CAPS III do interior paulista. Instrumentos utilizados: Childhood Trauma Questionnaire -CTQ, questionário sociodemográfico e entrevista em profundidade. O número de participantes foi se configurando conforme a análise da teoria emergente (amostragem teórica), totalizando 12 participantes. Resultados: a análise dos dados permitiu identificar o modelo teórico "Caminhando entre a infância traumática e a vida adulta com depressão". Sete categorias estruturaram a experiência relatada pelos participantes do estudo: "Vivenciando o Estresse Precoce"; "Sentindo diferenciação de tratamento dentro no núcleo familiar"; "Percebendo a distribuição de papeis dentro do núcleo familiar"; "Construindo a si próprio"; "Aliando-se à passividade frente a incapacidade de decisões"; "Percebendo comportamentos nos pais e em si próprio" e "Vivenciando a depressão". Conclusões: o estudo permitiu identificar um modelo teórico que simbolizou a forma como as vivências foram compreendidas pelos próprios sujeitos e como o significado de cada experiência foi se entrelaçando na composição do ser, moldando seu conjunto de símbolos, sendo expresso em sentimentos, percepções e comportamentos. O modelo teórico contribuiu para a compreensão dos significados construídos e as condições que afetam o indivíduo desde a infância traumática até a depressão na idade adulta

Human development, present since the primary formation of the individual, consists of all the lived experiences during childhood, including the early life stress experiences. Such experiences have repercussions on the subject actions, and may be important in the depression onset. Objectives: To explore and to analyze the meaning of early life stress in adulthood with depression and to construct a theoretical model about the phenomenon; To characterize the sample regarding sociodemographic and health characteristics; to explore and to analyze, in the according to Symbolic Interactionism, the meaning of early life stress among adults with depression. Method: Qualitative study that had as a guiding theoretical referential the Symbolic Interactionism and Grounded Theory as a methodological referential. The study participants were depressive individuals who experienced early life stress, recruited at the Center for Psychosocial Care - CAPS III in inner city of São Paulo, Brazil. Instruments: Childhood Trauma Questionnaire - CTQ, sociodemographic questionnaire and in-depth interview. The participants number was configured according to the analysis of the emerging theory (theoretical sampling), totaling 12 participants. Results: Data analysis allowed the identification of the theoretical model "Walking between traumatic childhood and adulthood with depression". Seven categories structures the experience: "Experiencing early life stress"; "Feeling treatment differentiation within the family nucleus"; "Perceiving the distribution of characters within the family"; "Building Yourself"; "Allying to passivity in the face of inability to make decisions"; "Perceiving behaviors in parents and in yorurself" and "Experiencing depression". Conclusions: the study allowed to identify a theoretical model that symbolized the way as the experiences were understood by the individuals and how the meaning of each experience was interlaced in the composition of being, shaping its set of symbols, being expressed in feelings, perceptions and behaviors. The theoretical model contributed to the understanding of the raised meanings and the conditions that affect the individual from traumatic childhood to depression in adulthood

Maternal Separation Does Not Produce a Significant Behavioral Change in Mice

Early life adversities together with genetic predispositions have been associated with elevated risks of neuropsychiatric disorders during later life. In order to investigate the underlying mechanisms, many chronic, early-life stress paradigms in multiple animal models have been developed. Previously, studies reported that maternal separation (MS) in the early postnatal stages triggers depression-and/or anxiety-like behaviors in rats. However, similar studies using mice have reported inconsistent behavioral outcomes. In this study, we sought to assess behavioral outcomes from two different early-life stress paradigms; a conventional 3-hour MS and a maternal separation with early weaning (MSEW) paradigm using C57BL/6J male mice with independent cohorts. Our data demonstrated that both MS and MSEW paradigms did not produce reported behavioral anomalies. Therefore, MS paradigms in mice require further validation and modification.

Measuring child maltreatment using multi-informant survey data: a higher-order confirmatory factor analysis / Dados de levantamento com múltiplos informantes para a mensuração de maus-tratos na infância: uma análise fatorial confirmatória de segunda ordem

Objective To investigate the validity and reliability of a multi-informant approach to measuring child maltreatment (CM) comprising seven questions assessing CM administered to children and their parents in a large community sample. Methods Our sample comprised 2,512 children aged 6 to 12 years and their parents. Child maltreatment (CM) was assessed with three questions answered by the children and four answered by their parents, covering physical abuse, physical neglect, emotional abuse and sexual abuse. Confirmatory factor analysis was used to compare the fit indices of different models. Convergent and divergent validity were tested using parent-report and teacher-report scores on the Strengths and Difficulties Questionnaire. Discriminant validity was investigated using the Development and Well-Being Assessment to divide subjects into five diagnostic groups: typically developing controls (n = 1,880), fear disorders (n = 108), distress disorders (n = 76), attention deficit hyperactivity disorder (n = 143) and oppositional defiant disorder/conduct disorder (n = 56). Results A higher-order model with one higher-order factor (child maltreatment) encompassing two lower-order factors (child report and parent report) exhibited the best fit to the data and this model's reliability results were acceptable. As expected, child maltreatment was positively associated with measures of psychopathology and negatively associated with prosocial measures. All diagnostic category groups had higher levels of overall child maltreatment than typically developing children. Conclusions We found evidence for the validity and reliability of this brief measure of child maltreatment using data from a large survey combining information from parents and their children.

Objetivo Investigar a validade e confiabilidade de uma abordagem de múltiplos informantes para a mensuração de maus-tratos na infância, composta por sete questões avaliando maus-tratos na infância respondidas pelas crianças e seus pais em uma ampla amostra comunitária. Métodos A amostra foi composta por 2.512 crianças com idades entre 6 e 12 anos e seus pais. Maus-tratos na infância foram avaliados com três questões respondidas pelas crianças e quatro respondidas pelos seus pais, investigando violência física, negligência física, violência emocional e violência sexual. Análises fatoriais confirmatórias foram utilizadas para comparar os índices de ajuste de diferentes modelos. Validade convergente e divergente foi testada utilizando escores de relato parental e de relato dos professores no Strengths and Difficulties Questionnaire. Validade discriminante foi investigada utilizando a entrevista Development and Well-Being Assessment para dividir os participantes em cinco grupos diagnósticos: controles com desenvolvimento típico (n = 1.880), transtornos do medo (n = 108), transtornos do estresse (n = 76), transtorno de déficit de atenção-hiperatividade (n = 143) e transtorno opositivo-desafiador/conduta (n = 56). Resultados Um modelo de segunda ordem com um fator de segunda ordem (maus-tratos na infância) englobando dois fatores de primeira ordem (relato da criança e relato parental) demonstrou o melhor ajuste aos dados, e os resultados de confiabilidade desse modelo foram aceitáveis. Como esperado, maus-tratos na infância estiveram positivamente associados a medidas de psicopatologia e negativamente associados a medidas pró-sociais. Todos os grupos de categorias diagnósticas tiveram níveis mais altos de maus-tratos na infância do que as crianças com desenvolvimento típico. Conclusões Foram encontradas evidências de validade e confiabilidade dessa medida breve de maus-tratos na infância utilizando dados de um grande levantamento combinando o relato de pais e seus filhos.

Cross-cultural adaptation of the Maltreatment and Abuse Chronology of Exposure (MACE) scale to Brazilian Portuguese / Adaptação transcultural da escala Maltreatment and Abuse Chronology of Exposure (MACE) para o português brasileiro

Introduction : There is strong evidence to indicate that childhood maltreatment can negatively affect both physical and mental health and there is increasing interest in understanding the occurrence and consequences of such experiences. While several tools have been developed to retrospectively investigate childhood maltreatment experiences, most of them do not investigate the experience of witnessing family violence during childhood or bullying exposure. Moreover, the majority of scales do not identify when these experiences may have occurred, who was involved or the feelings evoked, such as helplessness or terror. The Maltreatment and Abuse Chronology of Exposure (MACE) scale was developed to overcome these limitations. Objective : In view of the improvements over previous self-report instruments that this new tool offers and of the small number of self-report questionnaires for childhood maltreatment assessment available in Brazil, this study was conducted to conduct cross-cultural adaptation of the MACE scale for Brazilian Portuguese. Method : The following steps were performed: translation, back-translation, committee review for semantic and conceptual evaluation, and acceptability trial for equivalence. Results : Semantic and structural changes were made to the interview to adapt it for the Brazilian culture and all 75 of the items that comprise the longer version of MACE were translated. The results of the acceptability trial suggest that the items are comprehensible. Conclusion : The MACE scales may be useful tools for investigation of childhood maltreatment and make a valuable contribution to research in Brazil. Future studies should consider testing the availability and reliability of the three versions of the instrument translated into Brazilian Portuguese.

Introdução : Há evidências robustas na literatura indicando que os maus-tratos na infância podem afetar negativamente a saúde física e mental. Além disso, há um crescente interesse em compreender a ocorrência e as consequências dessas experiências. Vários instrumentos vêm sendo desenvolvidos para investigar retrospectivamente experiências de maus-tratos na infância, mas a maioria deles não investiga a experiência de testemunhar violência familiar durante a infância ou a ocorrência de bullying . Além disso, a maioria não identifica quando as experiências ocorreram, quem estava envolvido ou os sentimentos que evocaram, como desespero ou terror. A escala Maltreatment and Abuse Chronology of Exposure (MACE) foi desenvolvida para superar essas limitações. Objetivos : Considerando as vantagens dessa nova escala em relação aos instrumentos de autorrelato existentes e o reduzido número de questionários de autorrelato disponíveis no Brasil para avaliar maus-tratos na infância, este estudo teve como objetivo conduzir a adaptação transcultural da escala MACE para o português brasileiro. Método : Foram realizadas as etapas de tradução, retrotradução, análise de equivalência semântica e correspondência conceitual por um comitê avaliador e teste de aceitabilidade. Resultados : Adaptações semânticas e estruturais foram realizadas na entrevista para a realidade cultural brasileira, e todos os 75 itens incluídos na versão estendida da MACE foram traduzidos. Os resultados do teste de aceitabilidade sugerem que os itens foram adequadamente compreendidos. Conclusões : A escala MACE é uma ferramenta útil para a investigação de maus-tratos na infância, contribuindo para a pesquisa no Brasil. Futuros estudos devem considerar testar a validade e fidedignidade das três versões do instrumento traduzidas para o português do Brasil.

Effects of Early-Life Stress on the Structural and Functional Development of Central Nervous System : A Review of the Studies Focusing on Animal Models / 신경정신의학

Early-life stress (ELS), a complex traumatic stress including abuse, neglect and bullying during childhood or adolescence, is closely related to the development of psychiatric disorders. Conduct of a prospective study on the effect of ELS in human subjects is difficult due to ethical issues and limitations, and animal model study can be a reasonable alternative. Articles regarding structural and functional changes in the animal brain associated with ELS have been reviewed in this study. An up-to-date literature search on the effect of ELS on animal brain was performed ; keywords included ELS, central nervous system (CNS), and animal study using PubMed. A total of 623 articles were found and important articles were reviewed. First, we summarized the neurobiological changes in CNS associated with ELS, and then the effects of ELS on emotional and cognitive function and behavioral characteristics were recapped. ELS can induce overreactivity of the hypothalamus-pituitary-adrenal axis and cortical-subcortical structural changes including prefrontal cortex, hippocampus, and amygdala. These changes may be associated with neuroendocrine, cognitive, and emotional dysfunctions and related behavioral changes. Although most animal model studies used a single mode of stress, ELS tends to be experienced with complex types in human-life. Design of a new animal model examining the effects of complex trauma during early-life is important. Studies on the association between complex trauma and brain development can provide important insights regarding the pathogenetic mechanism of complex psychiatric disorders such as personality disorder and treatment-resistant depression.

O traumático na psicanálise e psiquiatria: implicações ético-políticas / The traumatic in psychoanalysis and psychiatry: ethical and political implications

O objetivo do artigo consiste em articular o discurso psicanalítico e psiquiátrico sobre o trauma, extraindo as implicações ético-políticas desta articulação, além de promover um resgate da subjetividade pela psiquiatria. A justificativa é ético-pragmática. A metodologia consiste na revisão não sistemática da literatura, mediante a seleção de textos que enfocam o traumático na psicanálise - a partir das categorias freudianas "neurose traumática", "compulsão à repetição", "pulsão de morte" e "passagem ao ato", além de textos de autores pós-freudianos e da literatura acerca dos testemunhos de catástrofes históricas, que situam o traumático na ordem do irrepresentável - bem como a seleção de textos na área da psiquiatria, que tratam das categorias "estressores precoces" e "estresse pós-traumático", enfatizando a relação entre os estressores precoces e o desenvolvimento posterior de quadros psicopatológicos. Enfatiza-se também a susceptibilidade individual a determinados eventos traumáticos, bem como as bases neurobiológicas do TEPT. São extraídas importantes implicações ético-políticas a partir da articulação proposta, que impactam no âmbito da clínica, levando a uma prática mais efetiva, e no âmbito político-social, com relação à elaboração de políticas públicas de saúde mental, que visam à prevenção de eventos traumatogênicos, bem como a oferta de serviços qualificados aos pacientes submetidos a vivências traumáticas.

This paper aims to articulate the psychoanalytic and psychiatric discourse on trauma, extracting the ethical and political implications of this link, and promote a rescue of subjectivity by psychiatry. The justification is ethical and pragmatic. The methodology consists of the non-systematic review of the literature, by selecting texts that focus on the traumatic in psychoanalysis - from the Freudian categories "traumatic neurosis", "repetition compulsion", "death drive" and "passage to the act," as well as texts of post-Freudian authors and literature about the testimonies of historical catastrophes, which are located on the order of the traumatic unrepresentative - as well as the selection of texts in the field of psychiatry, which deal with "early stressors" and "post-traumatic stress", emphasizing the relationship between early stressors and the subsequent development of psychopathology. It also emphasizes the individual susceptibility to certain traumatic events, as well as the neurobiological bases of PTSD. Important ethical and policy implications from the joint proposal, that impact within the clinic are extracted, leading to a more effective practice, and socio-political context, with the formulation of public policies on mental health, aimed at preventing trauma generator events as well as the supply of qualified services to patients undergoing traumatic experiences.

The Protective Role of Resilience in Attenuating Emotional Distress and Aggression Associated with Early-life Stress in Young Enlisted Military Service Candidates

Early life stress (ELS) may induce long-lasting psychological complications in adulthood. The protective role of resilience against the development of psychopathology is also important. The purpose of this study was to investigate the relationships among ELS, resilience, depression, anxiety, and aggression in young adults. Four hundred sixty-one army inductees gave written informed consent and participated in this study. We assessed psychopathology using the Korea Military Personality Test, ELS using the Childhood Abuse Experience Scale, and resilience with the resilience scale. Analyses of variance, correlation analyses, and hierarchical multiple linear regression analyses were conducted for statistical analyses. The regression model explained 35.8%, 41.0%, and 23.3% of the total variance in the depression, anxiety, and aggression indices, respectively. We can find that even though ELS experience is positively associated with depression, anxiety, and aggression, resilience may have significant attenuating effect against the ELS effect on severity of these psychopathologies. Emotion regulation showed the most beneficial effect among resilience factors on reducing severity of psychopathologies. To improve mental health for young adults, ELS assessment and resilience enhancement program should be considered.

Highly Palatable Food during Adolescence Improves Anxiety-Like Behaviors and Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Rats that Experienced Neonatal Maternal Separation

BACKGROUND: This study was conducted to examine the effects of ad libitum consumption of highly palatable food (HPF) during adolescence on the adverse behavioral outcome of neonatal maternal separation. METHODS: Male Sprague-Dawley pups were separated from dam for 3 hours daily during the first 2 weeks of birth (maternal separation, MS) or left undisturbed (nonhandled, NH). Half of MS pups received free access to chocolate cookies in addition to ad libitum chow from postnatal day 28 (MS+HPF). Pups were subjected to behavioral tests during young adulthood. The plasma corticosterone response to stress challenge was analyzed by radioimmunoassay. RESULTS: Daily caloric intake and body weight gain did not differ among the experimental groups. Ambulatory activities were decreased defecation activity and rostral grooming were increased in MS controls (fed with chow only) compared with NH rats. MS controls spent less time in open arms, and more time in closed arms during the elevated plus maze test, than NH rats. Immobility duration during the forced swim test was increased in MS controls compared with NH rats. Cookie access normalized the behavioral scores of ambulatory and defecation activities and grooming, but not the scores during the elevated plus maze and swim tests in MS rats. Stress-induced corticosterone increase was blunted in MS rats fed with chow only, and cookie access normalized it. CONCLUSION: Prolonged access to HPF during adolescence and youth partly improves anxiety-related, but not depressive, symptoms in rats that experienced neonatal maternal separation, possibly in relation with improved function of the hypothalamic-pituitary-adrenal (HPA) axis.

Epigenetic Mechanisms of Early Adverse Experience in the Development of Depression / 대한정신약물학회지

Depression is a common mental illness with a high lifetime prevalence rate in the general population. However, the pathophysiology of depression is still poorly understood. Recent studies showed that environmental factors can affect gene expression by modifying epigenetic factors. Early life stress (ELS) is likely a risk factor of lifetime vulnerability to stress and development of depression. ELS or stressful lifetime can induce changes in gene expression through epigenetic mechanism, such as DNA methylation or histone modification. In this article, recent researches on the epigenetic mechanisms of depression will be discussed.

Relationship of Suicide Risk with Early Life Stress and Resilience in Patients with Major Depressive Disorder / 신경정신의학

OBJECTIVES: The aim of this study is to investigate the relationship of suicide risk with early-life stress (ELS) and resilience in patients with major depressive disorder (MDD). METHODS: The participants were 60 patients with MDD and 29 healthy volunteers. Each subject was assessed concerning ELS, resilience factors, suicide ideation, and depressive symptom severity using self-report questionnaires. Mann-Whitney test and stepwise multiple linear regression analyses were performed. RESULTS: Emotional abuse, physical abuse, neglect, and exposure to inter-parental violence were higher in the patient group than in the control group. Resilience factors were significantly lower in the patient group. In multiple regression analyses, final regression model including physical abuse, neglect, and self-regulation factor was significant explaining 45.6% variance of suicide ideation score. CONCLUSION: We found that ELS experiences, particularly exposure to inter-parental violence, might be a significant risk factor for development of depression. In particular, experiences of physical abuse and neglect might increase the risk of suicide in depression but resilience may play a protective role in development of depression and prevention of suicide in depressive patients.

Early life stress and schizophrenia:a retrospective case-control study / 中华全科医师杂志

A total of 105 patients with first-episode schizophrenia (male =51,female =54) and 99 normal controls (male =51,female =48) were included into this retrospective case-control study.Childhood trauma questionnaire-28 item short form (CTQ-SF) was used to assess the experience of childhood abuse.The result of binary logistic regression showed that emotional abuse (β =0.630,P ＜ 0.05) and emotional neglect(β =0.270,P ＜ 0.05) were included into the final model of predicting schizophrenia.It indicates that patients with first-episode schizophrenia experienced more early life stress than controls.Particularly emotional abuse and emotional neglect may play important roles in the onset of schizophrenia.

Brazilian version of the Structured Interview for Disorders of Extreme Stress - Revised (SIDES-R): adaptation and validation process / Versão brasileira da Structured Interview for Disorders of Extreme Stress - Revised (SIDES-R): processo de adaptação e validação

BACKGROUND: Posttraumatic stress disorder (PTSD) contemplates the impact of acute traumatic events, but the literature indicates that this is not true for chronic exposure to stress. In this sense, the category disorders of extreme stress not otherwise specified (DESNOS) has been proposed to characterize the behavior and cognitive alterations derived from exposure to continuous early life stress. The Structured Interview for Disorders of Extreme Stress - Revised (SIDES-R) was developed to investigate and measure DESNOS. Considering the lack of instruments designed to assess DESNOS, especially in Brazil, the aim of this study was to translate, adapt, and validate the contents of SIDES-R to Brazilian Portuguese (SIDES-R-BR). METHOD: The original interview was subjected to translation, back-translation, semantic equivalence and conceptual correspondence analyses by naive and specialized judges, respectively, an acceptability trial, and inter-rater validity analysis. RESULTS: The interview underwent semantic and structural adaptations considering the Brazilian culture. The final version, SIDES-R-BR, showed a mean understanding score of 4.98 on a 5-point verbal rating scale, in addition to a kappa coefficient of 0.853. CONCLUSION: SIDES-R-BR may be a useful tool in the investigation of DESNOS and contributes a valuable input to clinical research in Brazil. The availability of the instrument allows to test symptoms with adequate reliability, as verified by the kappa coefficient and translation steps (AU)

INTRODUÇÃO: O transtorno do estresse pós-traumático (posttraumatic stress disorder, PTSD) contempla o impacto de eventos traumáticos agudos, mas a literatura indica que o mesmo não se aplica a exposição crônica ao estresse. Nesse sentido, foi proposta a categoria transtornos de estresse extremo não especificados (disorders of extreme stress not otherwise specified, DESNOS). Com o objetivo de investigar e medir as alterações comportamentais e cognitivas relacionadas ao diagnóstico de DESNOS, foi desenvolvida a Structured Interview for Disorders of Extreme Stress - Revised (SIDES-R). Considerando a falta de instrumentos construídos para avaliar DESNOS, especialmente no Brasil, o objetivo deste estudo foi traduzir, adaptar e validar os conteúdos da SIDES-R para português brasileiro (SIDES-R-BR). MÉTODO: A entrevista original foi submetida a tradução, retrotradução, análise de equivalência semântica e correspondência conceitual por avaliadores leigos e especializados, respectivamente. Foi realizado teste de aceitabilidade e análise de validade interavaliadores. RESULTADOS: A entrevista passou por adaptações semânticas e estruturais considerando a cultura brasileira. A versão final, SIDES-R-BR, demonstrou um escore médio de compreensão de 4,98 em uma escala de avaliação verbal de 5 pontos, além de um coeficiente de kappa de 0,853. CONCLUSÃO: O SIDES-R-BR pode ser uma ferramenta útil na investigação de DESNOS e contribui com um input valioso para a pesquisa clínica no Brasil. A disponibilidade do instrumento permite testar sintomas com confiabilidade adequada, conforme verificado por meio do coeficiente de kappa e etapas de tradução (AU)