Evidence for Immune Activation and Resistance to Glucocorticoids Following Childhood Maltreatment in Adolescents Without Psychopathology.

Early-life stress (ELS) increases the risk for psychopathology. Immune and endocrine changes have been reported in adults and are associated with maladaptation of stress-responsive systems. Here we investigated the effects of ELS on endocrine and immune pathways in adolescents without psychopathology. Thirty adolescents with a history of childhood maltreatment and 27 adolescents without ELS history were recruited. Blood and hair samples were obtained from all participants. Lymphocytes were isolated and stimulated in vitro. Flow cytometry was used to evaluate lymphocyte subsets, Th1/Th2/Th17 cytokines, mitogen-activated protein kinase (MAPK), and nuclear factor kappa B (NF-κB) signaling pathways, as well as lymphocyte sensitivity to dexamethasone. Brain-derived neurotrophic factor (BDNF) and hair cortisol were assessed with enzyme-linked immunosorbent assays (ELISAs). Adolescents with a history of ELS had increased percentages of T-cell activation markers (CD3+CD4+CD25+ and CD3+CD69+) and senescent T cells (CD8+CD28- and CD4+CD28-), as well as decreased percentages of NK (CD3-CD56+) and NK T cells (CD3+CD56+). Following stimulation, lymphocytes of ELS+ adolescents produced significantly more IL-2, IL-4, IFN-γ, and IL-17 and engaged more MAPK ERK and NF-κB signaling. ELS was associated with increased hair cortisol levels in parallel with increased lymphocyte resistance to dexamethasone and low plasma BDNF levels. These data provide the first indication of the presence of immune activation and pro-inflammatory profiles in healthy adolescents exposed to ELS, which could contribute to increased vulnerability of trauma-related psychopathology later in life. The underlying mechanisms of this impairment may include the enhanced activation of both MAPK and NF-κB signaling in parallel to partial resistance to glucocorticoids.

Intimate partner violence is associated with increased maternal hair cortisol in mother-child dyads.

BACKGROUND: The chronic consequences of intimate partner violence (IPV) on HPA activation are a topic of debate. The current study investigated hair cortisol concentrations in female victims of IPV and their children. METHODS: A total of 52 mother-child dyads were divided into two groups depending on exposure to IPV: IPV group (n=27 dyads) and control group (n=25 dyads). Hair cortisol concentration was measured in 1-cm-long hair strands, representing 30days of exposure before assessment. PTSD and depression symptoms were assessed in the mother and child. RESULTS: Women reporting IPV presented with higher hair cortisol levels, depression and PTSD symptoms severity in comparison to control women. Children who witnessed IPV reported more severe PTSD symptoms, but depressive symptoms and hair cortisol were not statistically different than those in control children. Correlation analyses revealed a positive association between the number of injury events and the level of hair cortisol in children. No associations between the hair cortisol levels in mothers and those in their children were found. CONCLUSION: Higher hair cortisol levels detected in women exposed to IPV reflected long-lasting changes in HPA axis functioning associated with chronic stress exposure. Children whose parents recurrently engage in violent conflicts with intimate partners may often feel threatened and consequently reporting more PTSD-related symptoms. Given that experiencing and witnessing violence during childhood and adolescence are predictive of intimate partner violence in adulthood, the need of early interventions is crucial.

Hair cortisol in drug-naïve first-episode individuals with psychosis

Objectives: To compare hair cortisol concentrations (HCC) in drug-naïve first-episode psychosis (FEP) patients and healthy controls and to investigate the correlations between HCC and psychopathology. Methods: Twenty-four drug-naïve FEP patients and 27 gender- and age-matched healthy control subjects were recruited. The Structured Clinical Interview for DSM-IV (SCID-1) was used to confirm/rule out diagnoses, and the Positive and Negative Symptoms Scale (PANSS) was used to assess symptom severity. Hair samples (2-3 cm long) obtained from the posterior vertex region of the scalp were processed in 1-cm segments considering a hair growth rate of 1 cm per month. The 1-cm segments were classified according to their proximity to the scalp: segment A was the closest to the scalp and referred to the month prior to inclusion in the study. Segments B and C referred to the 2nd and 3rd months prior to the time of evaluation respectively. Hair steroid extraction was performed using a known protocol. Results: Two-way analysis of covariance (ANCOVA) with gender and age as covariates revealed a group effect (F1.106 = 4.899, p = 0.029) on HCC. Between-segment differences correlated with total PANSS score and with PANSS General Psychopathology subscale and total score. Conclusions: Our findings suggest that hypothalamic-pituitary-adrenal (HPA) axis, as assessed by long-term (3-month) cortisol concentration, is abnormal in the early stages of psychosis. The magnitude of changes in HCC over time prior to the FEP correlates to psychopathology. HPA axis abnormalities might begin prior to full-blown clinical presentation requiring hospital admission.

Hair cortisol in drug-naïve first-episode individuals with psychosis.

OBJECTIVES: To compare hair cortisol concentrations (HCC) in drug-naïve first-episode psychosis (FEP) patients and healthy controls and to investigate the correlations between HCC and psychopathology. METHODS: Twenty-four drug-naïve FEP patients and 27 gender- and age-matched healthy control subjects were recruited. The Structured Clinical Interview for DSM-IV (SCID-1) was used to confirm/rule out diagnoses, and the Positive and Negative Symptoms Scale (PANSS) was used to assess symptom severity. Hair samples (2-3 cm long) obtained from the posterior vertex region of the scalp were processed in 1-cm segments considering a hair growth rate of 1 cm per month. The 1-cm segments were classified according to their proximity to the scalp: segment A was the closest to the scalp and referred to the month prior to inclusion in the study. Segments B and C referred to the 2nd and 3rd months prior to the time of evaluation respectively. Hair steroid extraction was performed using a known protocol. RESULTS: Two-way analysis of covariance (ANCOVA) with gender and age as covariates revealed a group effect (F1.106 = 4.899, p = 0.029) on HCC. Between-segment differences correlated with total PANSS score and with PANSS General Psychopathology subscale and total score. CONCLUSIONS: Our findings suggest that hypothalamic-pituitary-adrenal (HPA) axis, as assessed by long-term (3-month) cortisol concentration, is abnormal in the early stages of psychosis. The magnitude of changes in HCC over time prior to the FEP correlates to psychopathology. HPA axis abnormalities might begin prior to full-blown clinical presentation requiring hospital admission.

Influence of personality traits in coping skills in individuals with bipolar disorder / A influência dos traços de personalidade nas habilidades de coping de indivíduos com transtorno de humor bipolar

Background: Bipolar disorder is marked by alterations in coping skills which in turn impacts the disease course. Personality traits are associated with coping skills and for this reason it has been suggested that personality traits of patients with BD may have influence over their coping skills. Objective: To investigate possible associations between coping skills and personality in individuals with bipolar disorder (BD). Methods: Thirty-five euthymic subjects with BD were compared with 40 healthy controls. Coping skills were evaluated using Ways of Coping Checklist Revised and Brief-COPE. Personality traits were assessed by Neo Personality Inventory. MANCOVA was used for between groups comparison. Results: Regarding coping, individuals with BD reported more frequent use of emotion-focused strategies than problem-focused strategies, and high levels of neuroticism and low levels of extroversion and conscientiousness on personality measures. Neuroticism influenced negatively the use of problem-focused strategies, and positively emotion-focused coping. Conscientiousness influenced the use of problem-focused strategies in both groups. There was a significant difference between emotion focused coping and personality traits between BD and control groups. Discussion: Personality traits seem to modulate coping skills and strategies in BD which may be took into account for further interventions...

Contexto: O transtorno de humor bipolar (THB) é marcado por estratégias de enfrentamento, ou coping, que determinam comportamentos que podem influenciar negativamente o curso da doença. Traços de personalidade são altamente associados com estratégias de coping, portanto se faz a hipótese de que traços de personalidade influenciem as estratégias de coping de portadores de THB. Objetivo: Este estudo buscou investigar associações entre traços de personalidade e estratégias de coping em pacientes com THB. Métodos: Trinta e cinco participantes eutímicos diagnosticados com THB e 40 controles saudáveis participaram deste estudo. Estratégias de coping foram avaliadas com a Ways of Coping Checklist Revised and Brief – COPE – e traços de personalidade foram avaliados com o Neo Personality Inventory. Resultados: Participantes com THB possuíram padrão de estratégias de coping significativamente mais baseados na emoção. Em termos de traços de personalidade, participantes com THB tiveram significativamente mais características de neuroticismo e reduzidas características de extroversão e consciência. Foram encontradas associações positivas entre índices de neuroticismo e estratégias de coping baseadas em emoções e associações negativas com estratégias baseadas no problema. Conclusão: Traços de personalidade são fundamentais para as estratégias de coping de pacientes com THB, portanto traços de personalidade devem ser considerados alvos terapêuticos para a psicopatologia...

Childhood maltreatment and coping in bipolar disorder

A personal history of childhood maltreatment has been associated with unfavorable outcomes in bipolar disorder (BD). The impact of early life stressors on the course of BD may be influenced by individual differences in coping skills. The coping construct relies on neurocognitive mechanisms that are usually influenced by childhood maltreatment. The objective of the present study was to verify the association between childhood maltreatment and coping skills in individuals with BD Type 1. Thirty female euthymic outpatients with BD Type 1 were evaluated using the Childhood Trauma Questionnaire and two additional instruments to measure their coping preferences: Ways of Coping Questionnaire (coping strategies) and Brief COPE (coping styles). Reports of physical abuse (B = .64, p < .01) and emotional abuse (B = .44, p = .01) were associated with the use of maladaptive strategies that focused on emotional control. Adaptive strategies and styles of coping, such as focusing on the problem, were chosen less frequently by women who had experienced emotional neglect (B = .53, p < .01) and physical abuse (B = -.48, p < .01) in childhood. The small sample size in the present study prevented subgroup analyses. The sample did not include male BD participants. Our results indicate that early traumatic events may have a long-lasting deleterious influence on coping abilities in female BD patients. Future prospective studies may investigate whether the negative impact of childhood maltreatment over the course of BD is mediated by individual differences in coping abilities...

Bipolar disorder and metabolic syndrome: a systematic review.

OBJECTIVE: Summarize data on metabolic syndrome (MS) in bipolar disorder (BD). METHODS: A systematic review of the literature was conducted using the Medline, Embase and PsycInfo databases, using the keywords "metabolic syndrome", "insulin resistance" and "metabolic X syndrome" and cross-referencing them with "bipolar disorder" or "mania". The following types of publications were candidates for review: (i) clinical trials, (ii) studies involving patients diagnosed with bipolar disorder or (iii) data about metabolic syndrome. A 5-point quality scale was used to assess the methodological weight of the studies. RESULTS: Thirty-nine articles were selected. None of studies reached the maximum quality score of 5 points. The prevalence of MS was significantly higher in BD individuals when compared to a control group. The analysis of MS subcomponents showed that abdominal obesity was heterogeneous. Individuals with BD had significantly higher rates of hypertriglyceridemia than healthy controls. When compared to the general population, there were no significant differences in the prevalence of low HDL-c in individuals with BD. Data on hypertension were also inconclusive. Rates of hyperglycemia were significantly greater in patients with BD compared to the general population. CONCLUSIONS: The overall results point to the presence of an association between BD and MS, as well as between their subcomponents.

Bipolar disorder and metabolic syndrome: a systematic review

OBJECTIVE: Summarize data on metabolic syndrome (MS) in bipolar disorder (BD). METHODS: A systematic review of the literature was conducted using the Medline, Embase and PsycInfo databases, using the keywords "metabolic syndrome", "insulin resistance" and "metabolic X syndrome" and cross-referencing them with "bipolar disorder" or "mania". The following types of publications were candidates for review: (i) clinical trials, (ii) studies involving patients diagnosed with bipolar disorder or (iii) data about metabolic syndrome. A 5-point quality scale was used to assess the methodological weight of the studies. RESULTS: Thirty-nine articles were selected. None of studies reached the maximum quality score of 5 points. The prevalence of MS was significantly higher in BD individuals when compared to a control group. The analysis of MS subcomponents showed that abdominal obesity was heterogeneous. Individuals with BD had significantly higher rates of hypertriglyceridemia than healthy controls. When compared to the general population, there were no significant differences in the prevalence of low HDL-c in individuals with BD. Data on hypertension were also inconclusive. Rates of hyperglycemia were significantly greater in patients with BD compared to the general population. CONCLUSIONS: The overall results point to the presence of an association between BD and MS, as well as between their subcomponents.

Childhood maltreatment and coping in bipolar disorder

A personal history of childhood maltreatment has been associated with unfavorable outcomes in bipolar disorder (BD). The impact of early life stressors on the course of BD may be influenced by individual differences in coping skills. The coping construct relies on neurocognitive mechanisms that are usually influenced by childhood maltreatment. The objective of the present study was to verify the association between childhood maltreatment and coping skills in individuals with BD Type 1. Thirty female euthymic outpatients with BD Type 1 were evaluated using the Childhood Trauma Questionnaire and two additional instruments to measure their coping preferences: Ways of Coping Questionnaire (coping strategies) and Brief COPE (coping styles). Reports of physical abuse (B = .64, p < .01) and emotional abuse (B = .44, p = .01) were associated with the use of maladaptive strategies that focused on emotional control. Adaptive strategies and styles of coping, such as focusing on the problem, were chosen less frequently by women who had experienced emotional neglect (B = .53, p < .01) and physical abuse (B = -.48, p < .01) in childhood. The small sample size in the present study prevented subgroup analyses. The sample did not include male BD participants. Our results indicate that early traumatic events may have a long-lasting deleterious influence on coping abilities in female BD patients. Future prospective studies may investigate whether the negative impact of childhood maltreatment over the course of BD is mediated by individual differences in coping abilities.(AU)

Hair cortisol and stressful life events retrospective assessment in crack cocaine users.

BACKGROUND: Some evidence suggests that altered hypothalamic-pituitary-adrenal (HPA) axis functioning in cocaine users might play a role in the pathophysiology of substance abuse. This study aimed to investigate the relationship between exposure to negative life events and cortisol hair concentrations in crack cocaine users during the 3 months prior to admission to a detoxification program. METHODS: A total of 23 treatment-seeking, crack cocaine-dependent women were selected for this study 1 week after admission to an inpatient treatment at a locked treatment facility. The Paykel Life Events Scale measured the occurrence of stressful life events 3 months before admission. Hair cortisol concentration was measured during these three previous months. RESULTS: The partial correlations, using severity of dependence as control variable, revealed that there is a positive association between hair cortisol concentration and the number of negative life events exposure 90 days (r = .56; p = .007) and 30 days (r = .42; p = .048) prior to admission at the hospital. One-way ANOVA suggests that hair cortisol levels and stress load significantly increase over 3 months prior to hospitalization. CONCLUSIONS: The results of this study indicate that there is a positive association between measures of long-term cumulative cortisol secretion and the number of stressful events reported by women receiving inpatient treatment for crack cocaine dependence. Therefore, this study suggests that stress load can be objectively quantified and noninvasively assessed. SCIENTIFIC SIGNIFICANCE: This study is the first to investigate HPA axis functioning using hair cortisol concentrations among crack cocaine-dependent users. It is a promising strategy to assess stress load in substance abusers.

New perspectives on coping in bipolar disorder

Bipolar disorder (BD) is a prevalent and highly disabling psychiatric condition. Despite the widely acknowledged importance of psychosocial interventions that involve a complex cognitive, behavioral, and biological process to help patients cope better with their illness, few studies have systematically evaluated coping in BD. Therefore, our objective was to examine recent developments in current research on coping in BD. Several studies have documented a strong association between BD and numerous neuroanatomical and neuropsychological abnormalities, particularly multiple episodes and longer durations of the disorder. The most marked effects of BD encompass brain areas involved in executive function, which may affect the mechanisms underlying an adequate selection of coping strategies. Thus, the ability of individuals to reduce their own stress burden is impaired, increasing vulnerability to stressful life events and negatively affecting the course of BD. Psychosocial interventions that focus on BD should be evaluated for their ability to improve coping abilities, and research on BD should consider neuropsychological impairment and cognitive-behavioral strategies for coping with stress

New perspectives on coping in bipolar disorder

Bipolar disorder (BD) is a prevalent and highly disabling psychiatric condition. Despite the widely acknowledged importance of psychosocial interventions that involve a complex cognitive, behavioral, and biological process to help patients cope better with their illness, few studies have systematically evaluated coping in BD. Therefore, our objective was to examine recent developments in current research on coping in BD. Several studies have documented a strong association between BD and numerous neuroanatomical and neuropsychological abnormalities, particularly multiple episodes and longer durations of the disorder. The most marked effects of BD encompass brain areas involved in executive function, which may affect the mechanisms underlying an adequate selection of coping strategies. Thus, the ability of individuals to reduce their own stress burden is impaired, increasing vulnerability to stressful life events and negatively affecting the course of BD. Psychosocial interventions that focus on BD should be evaluated for their ability to improve coping abilities, and research on BD should consider neuropsychological impairment and cognitive-behavioral strategies for coping with stress.(AU)

Life Chart retrospectivo: instrumento para assinalar graficamente a presença e a evolução do impacto funcional de episódios afetivos maníacos e depressivos

CONTEXTO: Entre os instrumentos utilizados, em pesquisa e na prática clínica, para representar e detalhar o curso longitudinal do transtorno bipolar, o Life Chart tem sido o mais utilizado. Além de ser comprovadamente de fácil aplicação, possui fidedignidade em relatar o histórico clínico do paciente. OBJETIVO: Apresentar o Life Chart Retrospectivo em sua versão em português. MÉTODOS: Foram realizadas tradução e retradução, revisão e avaliação de equivalência semântica, idiomática, experimental ou cultural e conceitual. RESULTADOS: Estão apresentados em forma de gráfico. CONCLUSÃO: A partir do desenvolvimento dessa versão do Life Chart para o português, os estudos realizados no Brasil podem fazer uso dos mesmos parâmetros de registro que os estudos internacionais.

BACKGROUND: A life chart is a widely used instrument both in research and clinical practice to document the longitudinal course of bipolar disorder, being easy to apply and accuratly reports the clinical history. OBJECTIVE: The goal of this paper is to present the Brazilian Portuguese version of the Retrospective Life Chart. METHODS: Translation and retrotranslation, review, and semantic, language, cultural and conceptual equivalence were done. RESULTS: Results are presented in graphic format. DISCUSSION: The Portuguese version of Life Chart will allow that studies conducted in Brazil to use the same parameters that are used in international research.

Coping como função executiva / Coping as executive function / Coping como función ejecutiva

As respostas de adaptação (coping) referem-se às estratégias utilizadas para adaptar o indivíduo ao estresse. Este artigo teórico revisa a estrutura do coping em quatro níveis, com o nível inferior correspondendo às “instâncias” de coping e o nível superior correspondendo às “estratégias de adaptação”. Assim é introduzida a hipótese de que o coping se aproximaria das funções executivas e provavelmente dependeria de estruturas corticais frontais. Propõe-se que o coping ocorreria através de um controle primário, ou ação direta na fonte de estresse/emoções, de um controle secundário ou adaptação à fonte de estresse, e do desligamento ou escape da fonte de estresse/emoções desagradáveis. Também se argumenta que o coping envolveria a avaliação, planejamento, análise e antecipação dos resultados, processos tipicamente vinculados às funções executivas.(AU)

Coping is the term to describe the strategies used to adapt individuals to stress. This theoretical paper reviews the four levels model of coping, with low order processes corresponding to coping instances and the high order processes corresponding to a global adaptation strategies. The article reviews characteristics of coping that approach it to executive functions, primarily dependent of frontal cortical structures. Coping would perform trough primary controlor direct action in source of stress or negative emotion, through secondary control or adaptation to source of stress, and through disengage or escape stressors or negative emotions. Besides that, this paper argument that coping involves evaluation, planning, analysis and results anticipation, and that it is typically related to executive functions.(AU)

Social anxiety disorder in 300 patients hospitalized for alcoholism in Brazil: high prevalence and undertreatment.

BACKGROUND: Although the frequency of social phobia is high among alcoholic patients, this anxiety disorder is often neglected because treatment tends to be focused exclusively on alcohol dependence. METHODS: A total of 300 hospitalized alcoholic patients were interviewed using Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition and Liebowitz Social Anxiety Scale as well a questionnaire to check the use of medication for social phobia among alcoholics and the relationship between social phobia and alcohol use. RESULTS: A prevalence of 30.6% was found for specific phobia, 24.7% for social phobia, 22.2% for anxiety disorder induced by alcohol, 19.3% for generalized anxiety disorder, 5% for obsessive-compulsive disorder, 4.6% for posttraumatic stress disorder, and 2% for panic disorder with agoraphobia. Social phobia preceded alcohol dependence in 90.2% of the patients. The frequency of the use of medication for social phobia among social phobic alcoholics was 20.3%. CONCLUSIONS: The study confirms the high prevalence of anxiety disorders among alcoholics, particularly of social phobia. It also suggests that social phobia precedes alcohol dependence but shows that the use of medication for social phobia is still infrequent. Further studies are required to check if the failure to identify this comorbidity can make the recovery of alcoholics even more difficult.