Early life stress unravels epistatic genetic associations of cortisol pathway genes with depression.

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis represents one of the most consistent pathophysiological findings in depressive disorders. Cortisol signaling is affected by proteins that mediate its cellular responses or alters its availability to mineralocorticoid and glucocorticoid receptors. In our study, we evaluated candidate genes that may influence the risk for depression and suicide due to its involvement in cortisol signaling. The aim of the study was to assess whether the genotypes of these genes are associated with the risk for depression, severity of depressive symptoms, suicidal ideation, and suicide attempts. And whether there is interaction between genes and early-life stress. In this study, 100 healthy controls and 140 individuals with depression were included. The subjects were clinically assessed using the 21-item GRID-Hamilton questionnaires (GRID-HAMD-21), Beck Scale for Suicidal Ideation (BSI), and the Childhood Trauma Questionnaire (CTQ). A robust multifactorial dimensionality reduction analysis was used to characterize the interactions between the genes HSD11B1, NR3C1, NR3C2, and MDR1 and early-life stress. It was found a significant association of the heterozygous genotype of the MDR1 gene rs1128503 polymorphism with reduced risk of at least one suicide attempt (OR: 0.08, p = 0.003*) and a reduction in the number of suicide attempts (ß = -0.79, p = 0.006*). Furthermore, it was found that the MDR1 rs1228503 and NR3C2 rs2070951 genes interact with early-life stress resulting in a strong association with depression (p = 0.001). Our findings suggest that polymorphisms in the MDR1 and NR3C2 genes and their interaction with childhood trauma may be important biomarkers for depression and suicidal behaviors.

The Association of Biochemical and Genetic Biomarkers in VEGF Pathway with Depression.

VEGF is an important neurotrophic and vascular factor involved in mental disorders. The objective of this study was to verify the effect of genetic polymorphisms in the VEGF pathway on the risk for depression, symptom intensity, and suicide attempts. To examine the association between the VEGF pathway and depression, we genotyped polymorphisms and measured the plasma concentrations of VEGF, KDR, and FLT1 proteins. The participants were 160 patients with depression and 114 healthy controls. The questionnaires that assessed the clinical profile of the patients were the MINI-International Neuropsychiatric Interview, GRID-HAMD21, CTQ, BSI, and the number of suicide attempts. Genotyping of participants was performed using the real-time PCR and protein measurements were performed using the enzyme-linked immunosorbent assay (ELISA). VEGF and its inhibitors were reduced in depression. Individuals with depression and displaying the homozygous AA of the rs699947 polymorphism had higher plasma concentrations of VEGF (p-value = 0.006) and were associated with a greater number of suicide attempts (p-value = 0.041). Individuals with depression that were homozygous for the G allele of the FLT1 polymorphism rs7993418 were associated with lower symptom severity (p-value = 0.040). Our results suggest that VEGF pathway polymorphisms are associated with the number of suicide attempts and the severity of depressive symptoms.

Differential Diagnosis of Major Depressive Disorder and Bipolar Disorder: Genetic and Hormonal Assessment and the Influence of Early-Life Stress.

Few studies have assessed biomarkers for the differentiation of major depressive disorder (MDD) and bipolar disorder (BD). However, some elements of depression such as hormones and receptors of the renin-angiotensin-adrenal system (RAAS), the hypothalamus-pituitary-adrenal (HPA) axis, and history of early-life stress (ELS) could be considered for differential diagnosis. Therefore, this study aimed to assess aldosterone and cortisol levels, MR and GR gene polymorphisms, and ELS as potential biomarkers for differentiating MDD and BD. This study presents a case-control design. Groups comprised samples for genetic, cortisol, and aldosterone analysis: healthy control (HC; n = 113/97/103), MDD (n = 78/69/67) and BD (n = 82/68/65) subjects. Furthermore, all subjects were assessed for diagnostic screening, the severity of depression, and history of ELS by applying MINI-PLUS, GRID-HDRS, and CTQ, respectively. In addition, genotype and allelic frequencies of GR (N363S, R22/23K and BclI) and MR (MI180V and -2G/C) polymorphisms were evaluated via PCR. Our findings demonstrate that basal aldosterone levels may be a biomarker for differentiating BD and MDD. Furthermore, ELS affects the HPA axis in BD, cortisol may be considered a biomarker for distinguishing BD and MDD, but only in the absence of ELS, and, finally, history of ELS and MR-2G/C variant alleles are factors that contribute to the severity of depressive symptoms in MDD and BD.

Posttraumatic stress disorder (PTSD) and depression severity in sexually assaulted women: hypothalamic-pituitary-adrenal (HPA) axis alterations.

BACKGROUND: Sexual assault is implicated in several adverse psychological and physical health outcomes, including posttraumatic stress disorder (PTSD) and depression. Neurobiological research has shown variations related to the hypothalamic-pituitary-adrenal (HPA) axis, immune alterations, metabolic function, and brain circuitry. Although these mechanisms have been extensively studied, the results have demonstrated different outcomes in PTSD. METHODS: We compared the plasma adrenocorticotropin (ACTH) and salivary cortisol levels of fifty-eight women with PTSD developed after sexual assault to those of forty-four female controls with no history of trauma. We also evaluated the psychiatric diagnosis and symptom severity of PTSD and depression. The participants' clinical conditions were associated with their hormonal levels to assess whether symptom severity was related to hormonal imbalance. RESULTS: A large percentage of sexually assaulted women had PTSD and comorbid depression. The ACTH levels were higher in the PTSD group than the control group and increased as PTSD severity increased, considering depressive symptoms, measured by the Beck Depression Inventory (BDI) (p < 0.0001), as well as PTSD symptoms, measured by subscale D of the Clinician-Administered PTSD Scale (CAPS-5) (p = 0.045) and the CAPS-5 total scale (p = 0.026). Cortisol levels measured at 10 pm were higher for the PTSD group than the control group (p = 0.045, p = 0.037, respectively), and the cortisol awakening response showed elevated cortisol levels for the PTSD group. CONCLUSIONS: These results show a correlation between symptom severity and HPA axis imbalance in patients with PTSD. Elevated ACTH and an elevated cortisol response in patients with comorbid depressive symptoms were the opposite of the expected response for patients with PTSD only. This association leads to the hypothesis that the neurobiological alterations of PTSD are related to the type of symptoms presented and their severity. These manifestations likely influence the disease course, prognosis and response to treatment. These outcomes highlight the need to discuss particular neurobiological alterations in patients with PTSD developed after sexual assault, mainly those with severe depressive symptoms.

Confirmatory factorial analysis of the Maslach Burnout Inventory - Human Services Survey in health professionals in emergency services.

OBJECTIVE: to confirm the factorial validity of the Maslach Burnout Inventory - Human Services Survey version in a sample of health professionals from the emergency services. METHOD: a quantitative, exploratory, descriptive and analytical study. Two hundred and eighty-two health professionals participated in the study. For data collection, a sociodemographic questionnaire and the Maslach Burnout Inventory were used. The psychometric sensitivity for the MBI-HSS items was estimated by measures of central tendency, variability and the distribution shape. Internal consistency was estimated using Cronbach's alpha coefficient and the adequacy of the sample was verified using the Kaiser-Meyer-Olkin (KMO) index. As indexes for assessing the quality of fit of the model, the chi-square ratio by the degrees of freedom (χ2/DoF), the comparative fit index (CFI), the goodness of fit index (GFI), the Tucker Lewis index (TLI) and the root mean square error of approximation (RMSEA) were considered. To test data fit, the maximum likelihood method was used. RESULTS: the three-factor structure of the Maslach Burnout Inventory was confirmed. Items 9, 12, 15 and 16 had a factorial weight below what was considered appropriate and were removed from the model. The second order hierarchical model with the aforementioned modifications presented an adequate adjustment to the data and can be considered the best and most parsimonious model tested according to the information theory indexes. The internal consistency of the instrument's factors was recalculated considering the exclusion of the items and the three factors were considered adequate. CONCLUSION: the results obtained show that the Maslach Burnout Inventory is a reliable and factorially valid instrument for measuring the burnout syndrome in emergency service professionals in Brazil.

Evaluation of the HPA Axis' Response to Pharmacological Challenges in Experimental and Clinical Early-Life Stress-Associated Depression.

Early-life stress (ELS) is associated with a higher risk of psychopathologies in adulthood, such as depression, which may be related to persistent changes in the hypothalamic-pituitary-adrenal (HPA) axis. This study aimed to evaluate the effects of ELS on the functioning of the HPA axis in clinical and experimental situations. Clinically, patients with current depressive episodes, with and without ELS, and healthy controls, composed the sample. Subjects took a capsule containing placebo, fludrocortisone, prednisolone, dexamethasone or spironolactone followed by an assessment of plasma cortisol the morning after. Experimentally, male Wistar rats were submitted to ELS protocol based on variable, unpredictable stressors from postnatal day (PND)1 to PND21. On PND65 animals were behaviorally evaluated through the forced-swimming test (FST). At PND68, pharmacological challenges started, using mifepristone, dexamethasone, spironolactone, or fludrocortisone, and corticosterone levels were determined 3 h after injections. Cortisol response of the patients did not differ significantly from healthy subjects, regardless of their ELS history, and it was lower after fludrocortisone, prednisolone, and dexamethasone compared with placebo, indicating the suppression of plasma cortisol by all these treatments. Animals exposed to ELS presented altered phenotype as indicated by an increased immobility time in the FST when compared with control, but no significant long-lasting effects of ELS were observed on the HPA axis response. Limitations on the way the volunteers were sampled may have contributed to the lack of ELS effects on the HPA axis, pointing out the need for further research to understand these complex phenomena.

Confirmatory factorial analysis of the Maslach Burnout Inventory - Human Services Survey in health professionals in emergency services / Análise fatorial confirmatória do Maslach Burnout Inventory - Human Services Survey em profissionais de saúde dos serviços de emergência / Análisis factorial confirmatorio del Maslach Burnout Inventory - Human Services Survey en profesionales de la salud de los servicios de emergencia

Objective: to confirm the factorial validity of the Maslach Burnout Inventory - Human Services Survey version in a sample of health professionals from the emergency services. Method: a quantitative, exploratory, descriptive and analytical study. Two hundred and eighty-two health professionals participated in the study. For data collection, a sociodemographic questionnaire and the Maslach Burnout Inventory were used. The psychometric sensitivity for the MBI-HSS items was estimated by measures of central tendency, variability and the distribution shape. Internal consistency was estimated using Cronbach's alpha coefficient and the adequacy of the sample was verified using the Kaiser-Meyer-Olkin (KMO) index. As indexes for assessing the quality of fit of the model, the chi-square ratio by the degrees of freedom (χ2/DoF), the comparative fit index (CFI), the goodness of fit index (GFI), the Tucker Lewis index (TLI) and the root mean square error of approximation (RMSEA) were considered. To test data fit, the maximum likelihood method was used. Results: the three-factor structure of the Maslach Burnout Inventory was confirmed. Items 9, 12, 15 and 16 had a factorial weight below what was considered appropriate and were removed from the model. The second order hierarchical model with the aforementioned modifications presented an adequate adjustment to the data and can be considered the best and most parsimonious model tested according to the information theory indexes. The internal consistency of the instrument's factors was recalculated considering the exclusion of the items and the three factors were considered adequate. Conclusion: the results obtained show that the Maslach Burnout Inventory is a reliable and factorially valid instrument for measuring the burnout syndrome in emergency service professionals in Brazil.

Objetivo: confirmar a validade fatorial do Maslach Bunout Inventory - versão Human Services Survey numa amostra de profissionais da saúde dos serviços de emergência. Método: estudo de abordagem quantitativa, exploratório, descritivo e analítico. Participaram do estudo 282 profissionais de saúde. Utilizou-se para a coleta de dados, um questionário sociodemográfico e o Maslach Burnout Inventory. A sensibilidade psicométrica dos itens do Maslach Bunout Inventory - versão Human Services Survey foi estimada pelas medidas de tendência central, variabilidade e forma da distribuição. A consistência interna foi estimada por meio do Coeficiente alfa de Cronbach e a adequação da amostra verificada por meio do índice de Kaiser-Meyer-Olkin (KMO). Como índices para a avaliação da qualidade de ajustamento do modelo foram considerados a razão de qui-quadrado pelos graus de liberdade (χ2 /gl), comparative fit index (CFI), goodness of fit index (GFI), índice de Tucker Lewis (TLI) e root mean square error of aproximation (RMSEA). Para testar o ajustamento dos dados utilizou-se o método de máxima verossimilhança. Resultados: confirmou-se a estrutura trifatorial do Maslach Burnout Inventory. Os itens 9, 12, 15 e 16 apresentaram peso fatorial abaixo do considerado adequado e foram removidos do modelo. O modelo hierárquico de segunda ordem, com as modificações mencionadas, apresentou ajustamento adequado aos dados e pôde ser considerado o melhor e mais parcimonioso modelo testado de acordo com os índices da teoria da informação. A consistência interna dos fatores do instrumento foi recalculada considerando-se a exclusão dos itens e foi considerada adequada nos três os fatores. Conclusão: os resultados obtidos mostram que o Maslach Burnout Inventory é um instrumento confiável e fatorialmente válido para medir a síndrome de o burnout em profissionais dos serviços de emergência no Brasil.

Objetivo: confirmar la validez factorial del Maslach Bunout Inventory - versión Human Services Survey en una muestra de profesionales de la salud de los servicios de emergencia. Método: estudio cuantitativo, exploratorio, descriptivo y analítico. Participaron en el estudio 282 profesionales de la salud. Para la recopilación de datos, se utilizó un cuestionario sociodemográfico y el Maslach Burnout Inventory . La sensibilidad psicométrica de los ítems del Maslach Bunout Inventory - versión Human Services Survey se estimó mediante medidas de tendencia central, variabilidad y forma de distribución. La consistencia interna se estimó usando el Coeficiente alfa de Cronbach y la adecuación de la muestra se verificó usando el índice de Kaiser-Meyer-Olkin (KMO). Como índices para evaluar la calidad de ajuste del modelo fueron considerados la razón chi-cuadrado para los grados de libertad (χ 2 /gl), comparative fit index (CFI), goodness of fit index (GFI), índice de Tucker Lewis (TLI) y root mean square error of aproximation (RMSEA). Para probar el ajuste de los datos, se utilizó el método de máxima verosimilitud. Resultados: se confirmó la estructura de tres factores del Maslach Burnout Inventory . Los ítems 9, 12, 15 y 16 presentaron un peso factorial por debajo de lo que se consideraba adecuado y se eliminaron del modelo. El modelo jerárquico de segundo orden, con las modificaciones antes mencionadas, presentó un ajuste adecuado a los datos y puede considerarse el mejor y más parsimonioso modelo probado de acuerdo con los índices de teoría de la información. La consistencia interna de los factores del instrumento se recalculó ponderando la exclusión de los ítems y se consideró adecuada en los tres factores. Conclusión: los resultados obtenidos muestran que el Maslach Burnout Inventory es un instrumento confiable y factorialmente válido para medir el síndrome de burnout en los profesionales de los servicios de emergencia en Brasil.

Intervening variables of Burnout in health professionals of emergency services / Variables de intervención del Burnout en los profesionales sanitarios de los servicios de emergencia / Variáveis interventoras do Burnout em profissionais de saúde dos serviços emergenciais

ABSTRACT Objective: to analyze the association between Burnout, stress, mental suffering and other personal and work factors associated with this syndrome. Method: cross-sectional, descriptive and correlational study with 282 health professionals from the emergency services of the city of Ribeirão Preto, Brazil, collected from October 2015 to March 2016. The instruments used were: sociodemographic questionnaire, Maslach Burnout Inventory, Childhood Trauma Questionnaire, Stress Symptom Inventory, Perceived Stress Scale, Psychiatric Screening Questionnaire, Fantastic Lifestyle Checklist, Hospital Anxiety and Depression Scale and Holmes-Rahe Social Readjustment Rating Scale. Descriptive writing of the data. Pearson's Chi-Square or Fisher's Exact Tests to check the association between variables and later regression analysis, in which ORs were calculated, with 95% CI and 5% significance level. Results: there was statistical evidence of an association between Burnout and education, early stress, stress, common mental disorders, lifestyle, anxiety and depression. The regression analysis shows that the variables that influence Burnout are: type of service (p=0.032; OR=0.187), education (p=0.029; OR=2.313), perception of stress (p=0.037; OR=1.67) and social readjustment (p=0.031; OR=1.279). Conclusion: this study points to a profile for the development of Burnout, consisting of health professionals with higher education, who suffered early stress, who have symptoms and perception of stress, who do not have a healthy lifestyle and show symptoms of mental suffering. Such results can assist in the development and implementation of strategies aimed at reducing both work stress and the prevalence of Burnout syndrome.

RESUMEN Objetivo: analizar la asociación entre Burnout, estrés, sufrimiento mental y otros factores personales y laborales asociados a este síndrome. Método: estudio transversal, descriptivo y correlacional entre 282 profesionales sanitarios de los servicios de emergencia de la ciudad de Ribeirão Preto, Brasil, recolectados de octubre de 2015 a marzo de 2016. Utilizados os instrumentos: Los instrumentos utilizados fueron: cuestionario sociodemográfico, Inventario de Burnout de Maslach, Cuestionario de Trauma Infantil, Inventario de Síntomas de Estrés, Escala de Estrés Percibido, Cuestionario de Exploración Psiquiátrica, Cuestionario de Estilo de Vida Fantástico, Escala de Ansiedad y Depresión Hospitalaria y Escala de Reajuste Social de Holmes-Rahe. Redacción descriptiva de los datos. Prueba Chi-Cuadrado de Pearson o Prueba exacta de Fisher para comprobar la asociación entre variables y posterior análisis de regresión, en el que se calcularon OR, con IC del 95% y nivel de significancia del 5%. Resultados: hubo evidencia estadística de asociación entre Burnout y educación, estrés temprano, estrés, trastornos mentales comunes, estilo de vida, ansiedad y depresión. El análisis de regresión muestra que las variables que influyen en el Burnout son: tipo de servicio (p=0.032; OR=0.187), educación (p=0.029; OR=2.313), percepción de estrés (p=0.037; OR=1.67) y reajuste social (p=0.031; OR=1.279). Conclusión: Este estudio apunta a un perfil para el desarrollo del Burnout, conformado por profesionales sanitarios con educación superior, que sufrieron estrés temprano, que presentan síntomas y percepción de estrés, que no tienen un estilo de vida saludable y presentan síntomas de sufrimiento mental. Dichos resultados pueden ayudar en el desarrollo e implementación de estrategias destinadas a reducir tanto el estrés laboral como la prevalencia del síndrome de Burnout.

RESUMO Objetivo: analisar a associação entre Burnout, estresse, sofrimento mental e demais fatores pessoais e laborais associados a esta síndrome. Método: estudo transversal, descritivo e correlacional entre 282 profissionais de saúde dos serviços de emergências da cidade de Ribeirão Preto, Brasil, coletado de outubro de 2015 a março de 2016. Utilizados os instrumentos: questionário sociodemográfico, Maslach Burnout Inventory, Childhood Trauma Questionnaire, Inventário de Sintomas de Stress, Escala de Estresse Percebido, Psychiatric Screeming Questionnaire, Questionário de Estilo de Vida Fantástico, Escala Hospitalar de Ansiedade e Depressão e Escala de Reajustamento Social de Homes-Rahe. Redação descritiva dos dados. Testes Qui-Quadrado de Pearson ou Exato de Fisher para verificar a associação entre as variáveis e posteriormente análise de regressão, na qual foram calculados OR, com IC de 95% e o nível de significância de 5%. Resultados: houve evidência estatística de associação entre Burnout e escolaridade, estresse precoce, estresse, transtornos mentais comuns, estilo de vida, ansiedade e depressão. A análise de regressão evidencia que as variáveis que influenciam no Burnout são: tipo de serviço (p=0,032; OR=0,187), escolaridade (p=0,029; OR=2,313), percepção de estresse (p=0,037; OR=1,67) e reajustamento social (p=0,031; OR=1,279). Conclusão: este estudo aponta um perfil para o desenvolvimento de Burnout, constituído por profissionais de saúde com maior escolaridade, que sofreram estresse precoce, que apresentam sintomas e percepção de estresse, que não possuem um estilo de vida saudável e apresentam sintomas de sofrimento mental. Tais resultados podem auxiliar no desenvolvimento e implementação de estratégias visando reduzir tanto o estresse laboral como a prevalência da síndrome de Burnout.

The pharmacological interaction of compounds in ayahuasca: a systematic review

Ayahuasca is a South American psychoactive plant brew used as traditional medicine in spiritual and in cultural rituals. This is a review of the current understanding about the pharmacological mechanisms that may be interacting in ayahuasca. Searches were performed using PubMed, PsycINFO, and Web of Science databases and 16 papers were selected. As hypothesized, the primary narrative in existing research revolved around prevention of deamination of N,N-dimethyltryptamine (N,N-DMT, also referred to as DMT) by monoamine oxidase inhibitors (MAOIs) in ayahuasca. Two of the constituents, DMT and harmine, have been studied more than the secondary harmala alkaloids. At present, it is unclear whether the pharmacological interactions in ayahuasca act synergistically or additively to produce psychoactive drug effects. The included studies suggest that our current understanding of the preparation's synergistic mechanisms is limited and that more complex processes may be involved; there is not yet enough data to determine any potential synergistic interaction between the known compounds in ayahuasca. Our pharmacological understanding of its compounds must be increased to avoid the potential risks of ayahuasca use.

Posttraumatic Stress Disorder and Neuroprogression in Women Following Sexual Assault: Protocol for a Randomized Clinical Trial Evaluating Allostatic Load and Aging Process Acceleration.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a prevalent, chronic, and severe disorder related to traumatic events. Women are disproportionately affected by PTSD than men and are more at risk in the occurrence of sexual assault victimization. Estimates suggest that 50% of women develop PTSD following sexual assault and successful clinical management can be challenging. Growing evidence has implicated neural, immune, and endocrine alterations underpinning PTSD, but only few studies have assessed the evolution of acute PTSD in women. OBJECTIVE: This study aims to measure whether the onset of PTSD is associated with accelerated aging in women following sexual assault. We hypothesize that the increase of allostatic load caused by PTSD leads to neuroprogression. We will implement a randomized clinical trial to compare responses to treatment with either interpersonal psychotherapy adapted for PTSD (IPT-PTSD) or the selective serotonin reuptake inhibitor sertraline. METHODS: We will include women between 18 and 45 years of age, who experienced sexual assault from 1 to 6 months before the initial evaluation, and present with a Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) diagnosis of PTSD. Baseline evaluation will comprise clinical and psychometric assessments, structural and functional magnetic resonance imaging, neuropsychological testing, polysomnography, evaluation of immune and endocrine parameters, and genetic analyses. Age-matched female healthy controls will be included and subjected to the same evaluation. Patients will be randomized for treatment in 1 of the 2 arms of the study for 14 weeks; follow-up will continue until 1 year after inclusion via treatment as usual. The researchers will collect clinical and laboratory data during periodic clinical assessments up to 1-year follow-up. RESULTS: Data collection started in early 2016 and will be completed by the end of the first semester of 2020. Analyses will be performed soon afterward, followed by the elaboration of several articles. Articles will be submitted in early 2021. This research project has obtained a grant from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2014/12559-5). CONCLUSIONS: We expect to provide insight into the consequences of recent sexual assault exposure in women by investigating the degree of neuroprogression developing from an early stage of PTSD. We also expect to provide important evidence on the efficacy of a non-exposure psychotherapy (IPT-PTSD) to mitigate PTSD symptoms in recently sexually assaulted women. Further, we aim to obtain evidence on how treatment outcomes are associated with neuroprogression measures. TRIAL REGISTRATION: Brazilian Clinical Trials Registry RBR-3z474z; http://www.ensaiosclinicos.gov.br/rg/RBR-3z474z/. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/19162.

The pharmacological interaction of compounds in ayahuasca: a systematic review.

Ayahuasca is a South American psychoactive plant brew used as traditional medicine in spiritual and in cultural rituals. This is a review of the current understanding about the pharmacological mechanisms that may be interacting in ayahuasca. Searches were performed using PubMed, PsycINFO, and Web of Science databases and 16 papers were selected. As hypothesized, the primary narrative in existing research revolved around prevention of deamination of N,N-dimethyltryptamine (N,N-DMT, also referred to as DMT) by monoamine oxidase inhibitors (MAOIs) in ayahuasca. Two of the constituents, DMT and harmine, have been studied more than the secondary harmala alkaloids. At present, it is unclear whether the pharmacological interactions in ayahuasca act synergistically or additively to produce psychoactive drug effects. The included studies suggest that our current understanding of the preparation's synergistic mechanisms is limited and that more complex processes may be involved; there is not yet enough data to determine any potential synergistic interaction between the known compounds in ayahuasca. Our pharmacological understanding of its compounds must be increased to avoid the potential risks of ayahuasca use.

Association of 11ß-hydroxysteroid dehydrogenase type1 (HSD11b1) gene polymorphisms with outcome of antidepressant therapy and suicide attempts.

The hypothalamic-pituitary-adrenal axis has been implicated in the pathophysiology of depressive disorders. HSD11B1 encodes 11ß-hydroxysteroid dehydrogenase type1 enzyme, responsible for converting cortisone to cortisol. Genetic polymorphisms in HSD11B1 may impact in depression outcome and risk of suicide. This study aimed to assess whether HSD11B1 genotypes and haplotypes are associated with depression risk, severity of symptoms and suicidal attempts, considering early-life stress as an environmental factor. Here, 142 depressive patients and 103 healthy controls were included. Patients were enrolled from the Affective Disorders ambulatory and day hospital units, both within the University General Hospital of Ribeirao Preto. All subjects were clinically assessed applying the Mini-PLUS International Neuropsychiatric Interview, followed by the 21-item GRID-Hamilton Depression Scale, Childhood Trauma Questionnaire and Beck Scale for Suicidal Ideation (BSI). All subjects underwent antecubital vein puncture to obtain blood for DNA extraction. Genotyping of rs11119328 and rs11811440 were performed using allele-specific oligonucleotide polymerase chain reaction. We found a significant association of rs11119328 variant genotypes with increased risk for at least one suicide attempt (OR: 7.10, p = 0.049) and an association of variant genotypes of rs11811440 with euthymic mood under optimized pharmacological treatment (OR: 0.05, P = 0.014). These tests included correction for confounding factors. The association of genetic markers with depression risk, GRID-HAM-D21 and BSI scores and the number of suicidal attempts were nonsignificant. Haplotypes combining both markers were not associated with the studied phenotypes. We conclude that HSD11B1 polymorphisms may be relevant biomarkers for detecting subjects genetically vulnerable to poorer antidepressant response and higher risk of suicide attempts.

Relationship Between Depression and Subtypes of Early Life Stress in Adult Psychiatric Patients.

Numerous studies have researched the aggravating and maintainer effect of Early Life Stress in patients adults with psychiatric disorders. This study examined the relationship between depression and subtypes of early life stress among 81 psychiatric patients treated at the inpatient Day Hospital Unit of a University General Hospital. Psychiatric diagnosis was confirmed according to the MINI International Neuropsychiatric Interview (MINI). The Childhood Trauma Questionnaire (CTQ) was used for evaluating as retrospective assessment of the presence of ELS on these patients, and we also evaluated the severity of hopelessness with the Beck Hopelessness Scale (BHS). Our results suggested that the occurrence of depression in adulthood is related to situations of emotional abuse, sexual, and physical neglect during childhood. The analysis between depression and childhood emotional abuse was significant after a multiple logistic regression analysis OR (IC 95%): 4.4 (1.7-11.2), even accounting for gender adjusted OR [AOR] 4.0; (IC 1.5-10.5); psychiatry family history AOR 3.8 (1.4-10.5); previous suicide attempted AOR 3.7; (1.4-10.5) and Hopelessness AOR 3.2 (1.11-9.4). Thus, these findings demonstrate emotional abuse as a significant risk factor to be part of the mechanism involved in the pathogenesis of depression related to early life stress.

Bipolar affective disorder and borderline personality disorder: Differentiation based on the history of early life stress and psychoneuroendocrine measures.

INTRODUCTION: Borderline Personality Disorder (BPD) and Bipolar Affective Disorder (BD) have clinical characteristics in common which often make their differential diagnosis difficult. The history of early life stress (ELS) may be a differentiating factor between BPD and BD, as well as its association with clinical manifestations and specific neuroendocrine responses in each of these diagnoses. OBJECTIVE: Assessing and comparing patients with BD and BPD for factors related to symptomatology, etiopathogenesis and neuroendocrine markers. METHODOLOGY: The study sample consisted of 51 women, divided into 3 groups: patients with a clinical diagnosis of BPD (n = 20) and BD (n = 16) and healthy controls (HC, n = 15). Standardized instruments were used for the clinical evaluation, while the history of ELS was quantified with the Childhood Trauma Questionnaire (CTQ), and classified according to the subtypes: emotional abuse, physical abuse, sexual abuse, emotional neglect and physical neglect. The functioning of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by measuring a single plasma cortisol sample. RESULTS: Patients with BPD presented with more severe psychiatric symptoms of: anxiety, impulsivity, depression, hopelessness and suicidal ideation than those with BD. The history of ELS was identified as significantly more prevalent and more severe in patients (BPD and BP) than in HC. Emotional abuse, emotional neglect and physical neglect also showed differences and were higher in BPD than BD patients. BPD patients had greater severity of ELS overall and in the subtypes of emotional abuse, emotional neglect and physical neglect than BD patients. The presence of ELS in patients with BPD and BP showed significant difference with lower cortisol levels when compared to HC. The endocrine evaluation showed no significant differences between the diagnoses of BPD and BD. Cortisol measured in patients with BPD was significantly lower compared to HC in the presence of emotional neglect and physical neglect. A significant negative correlation between the severity of hopelessness vs cortisol; and physical neglect vs cortisol were found in BPD with ELS. The single cortisol sample showed a significant and opposite correlations in the sexual abuse diagnosis-related groups, being a negative correlation in BD and positive in BPD. DISCUSSION: Considering the need for a multi-factorial analysis, the differential diagnosis between BPD and BD can be facilitated by the study of psychiatric symptoms, which are more severe in the BPD patients with a history of early life stress. The function of the HPA axis assessed by this cortisol measure suggests differences between BPD and BP with ELS history. CONCLUSION: The integrated analysis of psychopathology, ELS and neuroendocrine function may provide useful indicators to differentiate BPD and BD diagnoses. These preliminary data need to be replicated in a more significant sample with improved and multiple assessments of HPA axis activity.

Genetic biomarkers for differential diagnosis of major depressive disorder and bipolar disorder: A systematic and critical review.

Depressive symptoms are present in the depressive mood state of bipolar disorder (BPD) and major depression disorder (MDD). Often, in clinical practice, BPD patients are misdiagnosed with MDD. Therefore, genetic biomarkers could contribute to the improvement of differential diagnosis between BPD and MDD. This systematic and critical review aimed to find in literature reliable genetic biomarkers that may show differences between BPD and MDD. This systematic review followed the PRISMA-P method. The terms used to search PubMed, Scopus, PsycINFO, and Web of Science were depress*, bipolar, diagnos*, genetic*, biomark*. After applying the selection criteria, N = 27 studies were selected, being n = 9 about biomarkers for BPD; n = 15, about MDD; and n = 3 for distinguishing MDD from BPD. A total of N = 3086 subjects were assessed in the selected studies (n = 486 in BPD group; n = 1212 in MDD group; and n = 1388, healthy control group). The articles were dated up to June 2017. Of the N = 27 studies, n = 16 assessed gene, n = 1 miRNA, n = 2 lcnRNA and n = 3 protein expressions, n = 4 methylation, and n = 4 polymorphisms. Some studies applied more than one of these genetic analyses. To find reliable genetic biomarkers we have taken into account the methodological care during the studies development and their validity. The genetic biomarkers selected are related to genes that play a fundamental role in synaptic plasticity, neurogenesis, mood control, brain ageing, immune-inflammatory processes and mitochondrial respiratory chain. BDNF gene expression was one of the genetic biomarkers that highlighted because of its capacity of distinguishing BPD and MDD groups, and being adequately reproduced by more than one selected study.

Childhood Sexual Abuse and Indicators of Immune Activity: A Systematic Review.

Background: Childhood sexual abuse (CSA) is a prevalent subtype of early life stress associated with changes in immunological and neuroendocrine systems leading to inflammatory responses of the organism and increasing several inflammatory and immune markers. We aimed to conduct a systematic review concerning the association between CSA and indicators of immune activity. Methods: We conducted a search for articles in PubMed, Scopus, PsycINFO, and Web of Science, using the key words: ("Child sexual abuse" OR "childhood maltreatment" OR "sexual violence" OR "posttraumatic stress disorder" OR "rape") AND ("cytokines" OR "inflammatory markers" OR "interleukin" OR "tumor necrosis factor" OR "C-reactive protein"). PRISMA guidelines were used in order to improve the quality of this research, and MeSH terms were used in PubMed. Results: A total of 3,583 studies were found and, after application of the exclusion criteria, 17 studies were included in this review. Most studies reported an increase of inflammatory activity associated with the presence of early abuse. IL-6, TNF- α, and C-reactive protein were the most frequently analyzed markers and some studies showed higher levels in individuals that suffered CSA compared with controls, although the results were heterogeneous, as was the assessment of CSA, repeated trauma, and time of occurrence. It was not possible to perform a meta-analysis because the results were diversified. Conclusion: CSA is associated with changes in inflammatory markers levels. Improving the assessment of subtypes of trauma is important to further understand the complex correlations of CSA and its biological consequences such as psychiatric and physical illness in later life.

Contribuições de um hospital-dia para as redes de apoio social a pessoas com transtornos mentais / Contribuciones de un hospital día para redes de apoyo social para personas con trastornos mentales / A day hospital's contributions for social support networks for people with mental disorders

Resumo: Objetivo: Identificar as práticas terapêuticas de um Hospital-Dia em Saúde Mental dirigidas ao suporte às redes de apoio social a pessoas com transtornos mentais. Metodologia: Estudo qualitativo, exploratório, descritivo associado às técnicas de observação participante, entrevistas e revisão documental realizadas no período de 31 de março a 17 de abril de 2014, no Hospital-Dia do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo - HD/HCFMRP/USP. Resultados: O Grupo Comunitário de Saúde mental do HD/HCFMRP/USP se constitui em uma das abordagens terapêuticas do plano terapêutico para os pacientes em tratamento sob o regime de semi-internação, ao mesmo tempo em que se consolidou como uma estrutura para além do Hospital-Dia. É uma atividade aberta à comunidade e objetiva ser um espaço para o exercício dialogado de apropriação e comunicação de vivências cotidianas. Discussão: A Terapia Comunitária Integrativa vem se consolidando como uma nova tecnologia de intervenção psicossocial caracterizado por acolher, escutar e cuidar dos sujeitos e de seus sofrimentos. É um espaço de promoção de encontros interpessoais e intercomunitários, de compartilhamento de experiências e acumulações de vida de forma a valorizar cada uma das histórias de vida dos participantes, resgatando a auto-estima, a confiança em si, na perspectiva de ampliação da percepção dos problemas e do consequente vislumbrar de possibilidades de suas resoluções a partir das competências locais.

Resumen: Objetivo: Identificar las prácticas terapéuticas del Hospital de Día dirigidas a las redes de apoyo social de personas con trastornos mentales. Metodología: Estudio cualitativo, exploratorio descriptivo asociado a técnicas de observación participante, entrevistas y revisión documental realizados del 31 de marzo al 17 de abril de 2014 en el Hospital de Día del Hospital de Clínicas de la Facultad de Medicina de Ribeirão Preto Universidad de San Pablo. Resultados: El Grupo Comunitario de Salud Mental del HD/HCFMRP/USP se constituye en uno de los enfoques terapéuticos del plan terapéutico para los pacientes en tratamiento bajo el régimen de semi-internación, al tiempo que se consolidó como una estructura más allá del Hospital de Día. Es una actividad abierta a la comunidad y tiene como objetivo ser un espacio para el ejercicio dialogado de apropiación y comunicación de vivencias cotidianas. Discusión: La Terapia Comunitaria Integrativa se viene consolidando como una nueva tecnología de intervención psicosocial caracterizada por acoger, escuchar y cuidar de los sujetos y de sus sufrimientos. Es un espacio de promoción de encuentros interpersonales e intercomunitarios, para compartir experiencias de vida, para valorar cada una de las historias de vida de los participantes, promoviendo la autoestima y la confianza en sí, a modo de ampliar la percepción de los problemas y encontrar posibilidades de resolución a partir de las competencias locales.

Abstract: Objective: To identify the therapeutic practices of a Day Hospital Mental Health directed support to social support networks for people with mental disorders. Methodology: Qualitative, exploratory, descriptive study associated with participant observation techniques, interviews and documentary review carried out from March 31 to April 17, 2014, in Day Hospital, Hospital Clinical, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo - HD/HCFMRP/USP. Results: The Community Health Group of the HD/HCFMRP/USP constitutes one of the therapeutic approaches of the therapeutic plan for the patients under treatment under the semi-hospitalization regime, at the same time that it has consolidated as a structure beyond the Day Hospital. It is an activity open to the community and aims to be a space for the dialogical exercise of appropriation and communication of everyday experiences. Discussion: Integrative Community Therapy has been consolidating as a new technology of psychosocial intervention characterized by welcoming, listening and caring for the subjects and their sufferings. It is a space for the promotion of interpersonal and intercommunal meetings, sharing of experiences and accumulations of life in order to value each one of the life stories of the participants, rescuing the self-esteem, the confidence in itself, in the perspective of amplifying the perception of the problems and the consequent glimpsing of possibilities of their resolutions based on local competences.

Transtornos da personalidade / Personality disorders

RESUMO Os Transtornos da personalidade são padrões psicológicos de difícil diagnóstico que exigem uma avaliação criteriosa por parte do profissional da saúde mental. A relação médico-paciente também se configura como fator de extrema importância para o manejo destes quadros. Dentro deste contexto, é imprescindível orientar os alunos das áreas de graduação em saúde sobre a existência de tal categoria de transtornos. O presente artigo consiste em uma revisão descritiva, que busca elucidar a definição de transtornos da personalidade; além de discorrer sobre aspectos históricos, nosológicos e epidemiológicos. Nesta publicação ainda serão revisadas as particularidades referentes ao diagnóstico, as comorbidades, ao curso e tratamento destes transtornos. O enfoque maior será no manejo de indivíduos com transtorno da personalidade borderline, dada a maior procura destes por unidades de atendimento psiquiátrico.(AU)

Personality disorders are psychological patterns of difficult diagnosis that require careful evaluations from mental health professionals. The physician-patient relationship is a crucial condition for the management of these disorders. On this view it must be important guide undergraduate students from health care areas through the existence of such a category of disorders. This article consists of a descriptive review aiming at clarifying the definition of personality disorders; furthermore discuss historical, physiological and epidemiological aspects. On this publication will be reviewed some particularities from diagnostic comorbidity, course and treatment of these disorders. The management of individuals with borderline personality disorder will be emphasized in this publication due to increased seek from this public for mental health care units. (AU)

Transtorno bipolar: uma revisão dos aspectos conceituais e clínicos / Bipolar disorder: a review of conceptual and clinical aspects

Esta revisão tem o objetivo de introduzir aspectos históricos, epidemiológicos e etiológicos do transtorno bipolar, além de apresentar a caracterização e curso da doença e algumas questões relativas ao diagnóstico, tratamento e prognóstico. O Transtorno Bipolar (TB) é caracterizado por graves alterações de humor, que envolvem períodos de humor elevado e de depressão intercalados por períodos de remissão. O transtorno se diferencia em dois tipos principais: o Tipo I, em que ocorrem episódios de mania, e o Tipo II, em que a elevação do humor é mais branda e breve, caracterizando episódios de hipomania. O conceito de espectro bipolar amplia a classificação do TB, incluindo padrões clínicos e genéticos. O TB é uma doença comum, que atinge cerca de 30 milhões de pessoas no mundo, afetando homens e mulheres de modo diferente. As causas do TB incluem uma interação de fatores genéticos e ambientais, distinguindo-o como um transtorno complexo e multideterminado. O diagnóstico segundo os critérios do DSM-5 envolve a identificação de sintomas de mania ou hipomania e da avaliação do curso longitudinal da doença. A depressão é geralmente o quadro mais comum e persistente entre os pacientes bipolares. Embora não existam sintomas específicos que distinguem a depressão unipolar da depressão bipolar, foram encontradas características clínicas típicas de cada manifestação (e.g., perfil dos sintomas, história familiar, e curso da doença). O diagnóstico precoce e o tratamento dos episódios agudos de humor melhoram significativamente o prognóstico. O tratamento de primeira escolha é com medicamentos estabilizadores de humor, anticonvulsivantes e antipsicóticos atípicos. A combinação de medicamentos com intervenções psicossociais tem se mostrado efetiva. Não obstante, o uso de antidepressivos em monoterapia não é recomendado. (AU)

This review aims to introduce historical, epidemiological and etiological aspects of bipolar disorder, also to present the characterization and course of the disease, as well as some issues related to the diagnosis, treatment and prognosis. Bipolar disorder (BD) is characterized by severe mood disturbances, involving periods of elevated mood and depression intercalated with periods of remission. The disorder is distinguished into two main types: Type I, in which episodes of mania occur; and Type II, in which mood elevation is milder and briefer, characterizing episodes of hypomania. The concept of bipolar spectrum extends the classification of BD, including clinical and genetic patterns. BD is a common disease that strikes about 30 million people worldwide, affecting men and women differently. The causes of BD include the interaction of genetic and environmental factors, distinguishing it as a complex and multidimensional disorder. The diagnosis according to DSM-5 involves the identification of mania or hypomania symptoms and the longitudinal evaluation of the disease course. Depression is usually the most common and persistent condition among bipolar patients. Although there are no specific symptoms that distinguish unipolar depression from bipolar depression, typical clinical features of each manifestation were found (e.g., symptom profile, family history, and disease course). Early diagnosis and the treatment of acute mood episodes significantly improve the prognosis. The first choice treatment involves mood stabilizers, anticonvulsants and atypical antipsychotics. The combination of medication with psychosocial interventions has been proved effective. However, the use of antidepressant monotherapy is not recommended. (AU)