The anxiolytic effect of cannabidiol depends on the nature of the trauma when patients with post-traumatic stress disorder recall their trigger event

Objectives: We assessed whether administering cannabidiol (CBD) before recalling the traumatic event that triggered their disorder attenuates anxiety in patients with post-traumatic stress disorder (PTSD). As an exploratory pilot analysis, we also investigated whether this effect depends on the nature of the event (sexual vs. nonsexual trauma). Methods: Thirty-three patients of both sexes with PTSD were recruited and randomized 1:1 into two groups. One group received oral CBD (300 mg), and the other received a placebo before listening to a digital audio playback of their previously recorded report of the trigger event. Subjective and physiological measurements were taken before and after recall. We analyzed the data in two subsamples: trigger events involving sexual and nonsexual trauma. Results: In the nonsexual trauma group, the differences between measurements before and after recall were significantly smaller with CBD than placebo; this held true for anxiety and cognitive impairment. However, in the sexual trauma group, the differences were non-significant for both measurements. Conclusion: A single dose of CBD (300mg) attenuated the increased anxiety and cognitive impairment induced by recalling a traumatic event in patients with PTSD when the event involved nonsexual trauma.

Cannabidiol induces autophagy via ERK1/2 activation in neural cells.

Autophagy is a lysosomal catabolic process essential to cell homeostasis and is related to the neuroprotection of the central nervous system. Cannabidiol (CBD) is a non-psychotropic phytocannabinoid present in Cannabis sativa. Many therapeutic actions have been linked to this compound, including autophagy activation. However, the precise underlying molecular mechanisms remain unclear, and the downstream functional significance of these actions has yet to be determined. Here, we investigated CBD-evoked effects on autophagy in human neuroblastoma SH-SY5Y and murine astrocyte cell lines. We found that CBD-induced autophagy was substantially reduced in the presence of CB1, CB2 and TRPV1 receptor antagonists, AM 251, AM 630 and capsazepine, respectively. This result strongly indicates that the activation of these receptors mediates the autophagic flux. Additionally, we demonstrated that CBD activates autophagy through ERK1/2 activation and AKT suppression. Interestingly, CBD-mediated autophagy activation is dependent on the autophagy initiator ULK1, but mTORC1 independent. Thus, it is plausible that a non-canonical pathway is involved. Our findings collectively provide evidence that CBD stimulates autophagy signal transduction via crosstalk between the ERK1/2 and AKT kinases, which represent putative regulators of cell proliferation and survival. Furthermore, our study sheds light on potential therapeutic cannabinoid targets that could be developed for treating neurodegenerative disorders.

Adverse childhood experiences and chronic lung diseases in adulthood: a systematic review and meta-analysis.

Background: Adverse childhood experiences (ACE) affect physical and mental health and may appear as risk factors for the development of different conditions in adult life. Objective: To perform a literature review and meta-analysis on risk indicators for the development of chronic lung diseases in adulthood associated with ACE. Method: We conducted a systematic literature review according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using the online databases PubMed, PsycINFO, and Web of Science. Quantitative studies involving male and female adults were included. Fixed- and random-effect models were used in the estimation of meta-analytical measures. The heterogeneity between studies was assessed using I2 statistics and Cochran's Q test. Results: A total of 19 studies were selected for the meta-analysis. The analyses showed statistically significant associations between ACE and lung diseases in general (OR = 1.41; CI 95%: 1.28-1.54), besides specific associations with asthma (OR = 1.32; CI 95%: 1.13-1.50) and COPD (OR = 1.44; CI 95%: 1.13-1.76). When the mediating effect of smoking was assessed separately we found a significant - although not quite expressive - association (OR = 1.06; CI 95%: 1.02 to 1.10), which weakens the hypothesis that a direct relationship exists between childhood trauma and the occurrence of lung diseases. Conclusions: ACE are an important risk factor for the development of lung diseases in adulthood, whether through direct or indirect contribution to this outcome, which highlights the relevance of increasing the awareness of health staff for the early detection and intervention in situations of vulnerability or risk in childhood as an important preventative measure.

Antecedentes: Experiencias infantiles adversas (ACE) afectan la salud física y mental y pueden aparecer como factores de riesgo para el desarrollo de diferentes afecciones en la vida adulta.Objetivo: realizar una revisión de la literatura y un metanálisis sobre indicadores de riesgo para el desarrollo de enfermedades pulmonares crónicas en la edad adulta asociadas con ACE.Método: Realizamos una revisión sistemática de la literatura de acuerdo con las pautas PRISMA (Elementos de Referencia para Revisiones Sistemáticas y Metaanálisis) utilizando las bases de datos en línea PubMed, PsycINFO y Web of Science. Se incluyeron estudios cuantitativos con hombres y mujeres adultos. Se utilizaron modelos de efectos fijos y aleatorios en la estimación de medidas meta-analíticas. La heterogeneidad entre los estudios se evaluó mediante estadísticas I 2 y la prueba Q de Cochran.Resultados: Se seleccionaron un total de 19 estudios para el metanálisis. Los análisis mostraron asociaciones estadísticamente significativas entre el ACE y las enfermedades pulmonares en general (OR = 1.41; IC 95%: 1.28­1.54), además de asociaciones específicas con el asma (OR = 1.32; IC 95%: 1.13 ­ 1.50) y EPOC (OR = 1,44; IC 95%: 1,13­1,76). Cuando el efecto mediador del tabaquismo se evaluó por separado, encontramos una asociación significativa (aunque no del todo clara) (OR = 1.06; IC 95%: 1.02 a 1.10), lo que debilita la hipótesis de que existe una relación directa entre el trauma infantil y la ocurrencia de enfermedades pulmonares.Conclusiónes: las experiencias ACE son un factor de riesgo importante para el desarrollo de enfermedades pulmonares en la edad adulta, ya sea a través de una contribución directa o indirecta, lo que resalta la relevancia de aumentar la conciencia del personal de salud para la detección temprana y la intervención en situaciones de vulnerabilidad o riesgo en la infancia como una medida preventiva importante.

Personality Inventory for DSM-5 (PID-5): cross-cultural adaptation and content validity in the Brazilian context / Inventário de Personalidade para o DSM-5 (PID-5): adaptação transcultural e validade de conteúdo para o contexto brasileiro

Abstract Objective To describe the process of cross-cultural adaptation of the Personality Inventory for DSM-5 (PID-5) to the Brazilian context. Methods Cross-cultural adaptation involved the steps of independent translation of the instrument, synthesis version, and back-translation. Analysis of content validity was conducted by a multidisciplinary expert committee and consisted of quantitative assessment of agreement indicators. The test was then applied to a target population. Results All the steps required for a cross-cultural adaptation were followed and satisfactory agreement values (≥ 4.75) were reached for most of the structures assessed. Most of the changes suggested by the experts were followed; these changes consisted primarily of adjustments to verb tense and agreement and the inclusion of letters and words to allow gender inflection. In the pre-test, no suggestions were made and the instrument was considered comprehensible. Conclusion The Brazilian version of the PID-5 was found to be adequate to the Brazilian context from semantic, idiomatic, cultural, and conceptual perspectives. The Brazilian version assessed here can be freely used, was approved by the publishers who hold the copyright on the instrument, and is considered the official version of the instrument. New studies are underway to determine the validity and reliability of the PID-5.

Resumo Objetivo Apresentar o processo de adaptação transcultural do Personality Inventory for DSM-5 (PID-5) para o contexto brasileiro. Métodos A adaptação transcultural envolveu as etapas de tradução independente, versão síntese e retrotradução. A validade de conteúdo foi realizada por um comitê multidisciplinar de especialistas, com avaliação quantitativa dos índices de concordância. Por fim, o pré-teste foi conduzido com a população-alvo. Resultados Todos os estágios da adaptação transcultural foram seguidos, e na maioria das estruturas avaliadas, os valores de concordância foram satisfatórios (≥ 4.75). Grande parte das sugestões de modificações feitas pelos especialistas foram acatadas, sendo as principais relacionadas a ajustes no tempo e concordância verbal e a inclusão de letras e palavras para permitir a flexão de gênero. No pré-teste nenhuma sugestão foi apresentada e o instrumento foi considerado compreensível. Conclusão A versão brasileira do PID-5 mostrou-se adequada ao contexto brasileiro sob as perspectivas semântica, idiomática, cultural e conceitual. A versão brasileira avaliada é de uso livre, foi aprovada pelas editoras responsáveis pelos direitos autorais do instrumento e é considerada oficial. Novos estudos estão sendo conduzidos para aprimorar a busca por evidencias de validade e confiabilidade.

Antiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron overload.

Iron accumulation in the brain has been recognized as a common feature of both normal aging and neurodegenerative diseases. Cognitive dysfunction has been associated to iron excess in brain regions in humans. We have previously described that iron overload leads to severe memory deficits, including spatial, recognition, and emotional memory impairments in adult rats. In the present study we investigated the effects of neonatal iron overload on proteins involved in apoptotic pathways, such as Caspase 8, Caspase 9, Caspase 3, Cytochrome c, APAF1, and PARP in the hippocampus of adult rats, in an attempt to establish a causative role of iron excess on cell death in the nervous system, leading to memory dysfunction. Cannabidiol (CBD), the main non-psychotropic component of Cannabis sativa, was examined as a potential drug to reverse iron-induced effects on the parameters analyzed. Male rats received vehicle or iron carbonyl (30 mg/kg) from the 12th to the 14th postnatal days and were treated with vehicle or CBD (10 mg/kg) for 14 days in adulthood. Iron increased Caspase 9, Cytochrome c, APAF1, Caspase 3 and cleaved PARP, without affecting cleaved Caspase 8 levels. CBD reversed iron-induced effects, recovering apoptotic proteins Caspase 9, APAF1, Caspase 3 and cleaved PARP to the levels found in controls. These results suggest that iron can trigger cell death pathways by inducing intrinsic apoptotic proteins. The reversal of iron-induced effects by CBD indicates that it has neuroprotective potential through its anti-apoptotic action.

Novel insights into mitochondrial molecular targets of iron-induced neurodegeneration: Reversal by cannabidiol.

Evidence has demonstrated iron accumulation in specific brain regions of patients suffering from neurodegenerative disorders, and this metal has been recognized as a contributing factor for neurodegeneration. Using an experimental model of brain iron accumulation, we have shown that iron induces severe memory deficits that are accompanied by oxidative stress, increased apoptotic markers, and decreased synaptophysin in the hippocampus of rats. The present study aims to characterize iron loading effects as well as to determine the molecular targets of cannabidiol (CBD), the main non-psychomimetic compound of Cannabis sativa, on mitochondria. Rats received iron in the neonatal period and CBD for 14 days in adulthood. Iron induced mitochondrial DNA (mtDNA) deletions, decreased epigenetic modulation of mtDNA, mitochondrial ferritin levels, and succinate dehydrogenase activity. CBD rescued mitochondrial ferritin and epigenetic modulation of mtDNA, and restored succinate dehydrogenase activity in iron-treated rats. These findings provide new insights into molecular targets of iron neurotoxicity and give support for the use of CBD as a disease modifying agent in the treatment of neurodegenerative diseases.

Ayahuasca: what mental health professionals need to know

Abstract Background Ayahuasca is a psychoactive ethnobotanical concoction that has been used for decades by indigenous groups of the Northwestern Amazon and by syncretic religious organizations for ritual and therapeutic purposes. In the last two decades, it is being used worldwide in evolving practices. Ayahuasca seem to therapeutic effects, but controlled studies are lacking. Moreover, its safety and toxicity are not completely understood. Objectives To present an overview of the effects of ayahuasca based on the most recent human studies. Methods Narrative review. Results Ayahuasca administration in controlled settings appears to be safe from a subjective and physiological perspective, with few adverse reactions being reported. More frequent adverse reactions occur in non-controlled settings. Prolonged psychotic reactions are rare and seem to occur especially in susceptible individuals. Ayahuasca showed antidepressive, anxiolytic, and antiaddictive effects in animal models, observational studies, and in open-label and controlled studies. Discussion Ayahuasca administration in controlled settings appear to be safe. Moreover, ayahuasca seem to have therapeutic effects for treatment-resistant psychiatric disorders that should be further investigated in randomized controlled clinical trials. However, medical complications and cases of prolonged psychotic reactions have been reported, and people with personal or family history of psychotic disorders should avoid ayahuasca intake.

Avaliação do papel do sistema canabidiol em um modelo de lesão renal por isquemia/reperfusão em animais / Evaluation of the role of the cannabidiol system in an animal model of ischemia/reperfusion kidney injury

RESUMO Objetivo: Investigar os efeitos da administração de canabidiol em um modelo de isquemia/reperfusão renal em animais. Métodos: Foi induzida uma lesão renal, por meio de 45 minutos de isquemia renal seguida por reperfusão. Administrou-se canabidiol (5mg/kg) imediatamente após a reperfusão. Resultados: A isquemia/reperfusão aumentou os níveis de interleucina 1 e fator de necrose tumoral, o que foi atenuado pelo tratamento com canabidiol. Além disso, o canabidiol foi capaz de diminuir o dano oxidativo de lipídios e proteínas, mas não os níveis de nitrito/nitrato. A lesão renal após isquemia/reperfusão pareceu ser independente da expressão dos receptores canabidiol-1 e canabidiol-2, já que não houve aumento significante desses receptores após a reperfusão. Conclusão: O tratamento com canabidiol teve um efeito protetor contra a inflamação e o dano oxidativo em um modelo de isquemia/reperfusão renal. Esses efeitos parecem não ocorrer via ativação dos receptores canabidiol-1/canabidiol-2.

ABSTRACT Objective: This work aimed to investigate the effects of the administration of cannabidiol in a kidney ischemia/reperfusion animal model. Methods: Kidney injury was induced by 45 minutes of renal ischemia followed by reperfusion. Cannabidiol (5mg/kg) was administered immediately after reperfusion. Results: Ischemia/reperfusion increased the IL-1 and TNF levels, and these levels were attenuated by cannabidiol treatment. Additionally, cannabidiol was able to decrease lipid and protein oxidative damage, but not the nitrite/nitrate levels. Kidney injury after ischemia/reperfusion seemed to be independent of the cannabidiol receptor 1 and cannabidiol receptor 2 (CB1 and CB2) expression levels, as there was no significant increase in these receptors after reperfusion. Conclusion: The cannabidiol treatment had a protective effect against inflammation and oxidative damage in the kidney ischemia/reperfusion model. These effects seemed to be independent of CB1/CB2 receptor activation.

Reprint of "Caffeine protects against memory loss induced by high and non-anxiolytic dose of cannabidiol in adult zebrafish (Danio rerio)".

Cannabidiol (CBD) has been investigated in a wide spectrum of clinical approaches due to its psychopharmacological properties. CBD has low affinity for cannabinoid neuroreceptors and agonistic properties to 5-HT receptors. An interaction between cannabinoid and purinergic receptor systems has been proposed. The purpose of this study is to evaluate CBD properties on memory behavioral and locomotor parameters and the effects of pre-treatment of adenosine receptor blockers on CBD impacts on memory using adult zebrafish. CBD (0.1, 0.5, 5, and 10mg/kg) was tested in the avoidance inhibitory paradigm and anxiety task. We analyzed the effect of a long-term caffeine pre-treatment (~20mg/L - four months). Also, acute block of adenosine receptors was performed in co-administration with CBD exposure in the memory assessment. CBD promoted an inverted U-shaped dose-response curve in the anxiety task; in the memory assessment, CBD in the dose of 5mg/Kg promoted the strongest effects without interfering with social and aggressive behavior. Caffeine treatment was able to prevent CBD (5mg/kg) effects on memory when CBD was given after the training session. CBD effects on memory were partially prevented by co-treatment with a specific A2A adenosine receptor antagonist when given prior to or after the training session, while CBD effects after the training session were fully prevented by adenosine A1 receptor antagonist. These results indicated that zebrafish have responses to CBD anxiolytic properties that are comparable to other animal models, and high doses changed memory retention in a way dependent on adenosine.

Caffeine protects against memory loss induced by high and non-anxiolytic dose of cannabidiol in adult zebrafish (Danio rerio).

Cannabidiol (CBD) has been investigated in a wide spectrum of clinical approaches due to its psychopharmacological properties. CBD has low affinity for cannabinoid neuroreceptors and agonistic properties to 5-HT receptors. An interaction between cannabinoid and purinergic receptor systems has been proposed. The purpose of this study is to evaluate CBD properties on memory behavioral and locomotor parameters and the effects of pre-treatment of adenosine receptor blockers on CBD impacts on memory using adult zebrafish. CBD (0.1, 0.5, 5, and 10mg/kg) was tested in the avoidance inhibitory paradigm and anxiety task. We analyzed the effect of a long-term caffeine pre-treatment (~20mg/L - four months). Also, acute block of adenosine receptors was performed in co-administration with CBD exposure in the memory assessment. CBD promoted an inverted U-shaped dose-response curve in the anxiety task; in the memory assessment, CBD in the dose of 5mg/Kg promoted the strongest effects without interfering with social and aggressive behavior. Caffeine treatment was able to prevent CBD (5mg/kg) effects on memory when CBD was given after the training session. CBD effects on memory were partially prevented by co-treatment with a specific A2A adenosine receptor antagonist when given prior to or after the training session, while CBD effects after the training session were fully prevented by adenosine A1 receptor antagonist. These results indicated that zebrafish have responses to CBD anxiolytic properties that are comparable to other animal models, and high doses changed memory retention in a way dependent on adenosine.

Mesial temporal lobe epilepsy with psychiatric comorbidities: a place for differential neuroinflammatory interplay.

BACKGROUND: Despite the strong association between epilepsy and psychiatric comorbidities, few biological substrates are currently described. We have previously reported neuropathological alterations in mesial temporal lobe epilepsy (MTLE) patients with major depression and psychosis that suggest a morphological and neurochemical basis for psychopathological symptoms. Neuroinflammatory-related structures and molecules might be part of the altered neurochemical milieu underlying the association between epilepsy and psychiatric comorbidities, and such features have not been previously investigated in humans. METHODS: MTLE hippocampi of subjects without psychiatric history (MTLEW), MTLE + major depression (MTLE + D), and MTLE + interictal psychosis (MTLE + P) derived from epilepsy surgery and control necropsies were investigated for reactive astrocytes (glial fibrillary acidic protein (GFAP)), activated microglia (human leukocyte antigen, MHC class II (HLA-DR)), glial metallothionein-I/II (MT-I/II), and aquaporin 4 (AQP4) immunohistochemistry. RESULTS: We found an increased GFAP immunoreactive area in the molecular layers, granule cell layer, and cornus ammonis region 2 (CA2) and cornus ammonis region 1 (CA1) of MTLEW and MTLE + P, respectively, compared to MTLE + D. HLA-DR immunoreactive area was higher in cornus ammonis region 3 (CA3) of MTLE + P, compared to MTLE + D and MTLEW, and in the hilus, when compared to MTLEW. MTLEW cases showed increased MT-I/II area in the granule cell layer and CA1, compared to MTLE + P, and in the parasubiculum, when compared to MTLE + D and MTLE + P. Differences between MTLE and control, such as astrogliosis, microgliosis, increased MT-I/II, and decreased perivascular AQP4 in the epileptogenic hippocampus, were in agreement to what is currently described in the literature. CONCLUSIONS: Neuroinflammatory-related molecules in MTLE hippocampus show a distinct pattern of expression when patients present with a comorbid psychiatric diagnosis, similar to what is found in the pure forms of schizophrenia and major depression. Future studies focusing on inflammatory characteristics of MTLE with psychiatric comorbidities might help in the design of better therapeutic strategies.

Associations between chronic pelvic pain and psychiatric disorders and symptoms

Background Chronic pelvic pain (CPP) is a complex condition wich is associated with emotional factors, specially depression and anxiety. Objectives To make a systematic review to provide a detailed summary of relevant literature on the association between CPP and different psychiatric disorders/symptoms. Methods A systematic review of articles in the international literature published between 2003 and 2014 was performed in the electronic databases PubMed, PsycINFO, LILACS, and SciELO using the terms (chronic pelvic pain) AND (psychiatry OR psychiatric OR depression OR anxiety OR posttraumatic stress OR somatoform). The searches returned a total of 529 matches that were filtered according to predefined inclusion and exclusion criteria. A total of 18 articles were selected. Results The investigations focused mainly on the assessment of depression and anxiety disorders/symptoms, with rather high rates (17-38.6%). Depression and anxiety symptoms were more prevalent among women with CPP compared to healthy groups. Comparisons between groups with CPP and with specific pathologies that also have pain as a symptom showed that depression indicators are more frequent in CPP. Depressive symptoms tend to be more common in CPP and have no particular association with pain itself, the core feature of CPP. Discussion Other aspects of CPP seem to play a specific role in this association. Anxiety and other psychiatric disorders require further investigation so that their impact on CPP can be better understood.

Evaluation of the role of the cannabidiol system in an animal model of ischemia/reperfusion kidney injury.

OBJECTIVE: This work aimed to investigate the effects of the administration of cannabidiol in a kidney ischemia/reperfusion animal model. METHODS: Kidney injury was induced by 45 minutes of renal ischemia followed by reperfusion. Cannabidiol (5mg/kg) was administered immediately after reperfusion. RESULTS: Ischemia/reperfusion increased the IL-1 and TNF levels, and these levels were attenuated by cannabidiol treatment. Additionally, cannabidiol was able to decrease lipid and protein oxidative damage, but not the nitrite/nitrate levels. Kidney injury after ischemia/reperfusion seemed to be independent of the cannabidiol receptor 1 and cannabidiol receptor 2 (CB1 and CB2) expression levels, as there was no significant increase in these receptors after reperfusion. CONCLUSION: The cannabidiol treatment had a protective effect against inflammation and oxidative damage in the kidney ischemia/reperfusion model. These effects seemed to be independent of CB1/CB2 receptor activation.

Modelos animais em psiquiatria: avanços e desafios / Animal models in psychiatry: advances and challenges / Les modèles animaux en psychiatrie: progrès et défis / Los modelos animales en psiquiatría: avances y desafios

Objetivos: Discutir os avanços e limitações do uso dos modelos animais nos transtornos psiquiátricos. Método: Uma revisão narrativa de artigos. Resultados: Diferentes modelos animais atualmente demonstram validade adequada para características específicas de determinados transtornos mentais. Conclusão: Resguardadas as devidas limitações que impossibilitam mimetizar sintomas psicopatológicos complexos em modelos animais, estes seguem como úteis ferramentas de estudo na psiquiatria.

Objectives: To discuss the advances and limitations of animal models in psychiatric disorders. Method: A narrative review of articles. Results: Different animal models currently demonstrate adequate validity for specific characteristics of certain mental disorders. Conclusion: Recognizing limitations that stay away from any mimicking of complex psychopathological symptoms in animal models, such models nonetheless represent useful tools in the study of psychiatry.

Objectifs: Examiner les progrès et les limites des modèles animaux pour l'étude des troubles psychiatriques. Méthode: Révision narrative d'articles. Résultats: De différents modèles animaux possèdent actuellement une validité suffisante par rapport aux caractéristiques spécifiques de certains troubles mentaux. Conclusion: Malgré le fait des limites qui ne permettent pas de reproduire les symptômes psychopathologiques complexes dans les modèles animaux, ceux-ci restent néanmoins des outils utiles d'étude en psychiatrie.

Objetivos: Discutir los avances y las limitaciones de los modelos animales en los trastornos psiquiátricos. Método: Una revisión narrativa de artículos. Resultados: Los diferentes modelos animales actualmente demuestran validez adecuada para las características específicas de determinados trastornos mentales. Conclusión: Guardadas las debidas limitaciones que imposibilitan mimetizar los síntomas psicopatológicos complejos en modelos animales, estes siguen siendo herramientas útiles en el estudio de la psiquiatría.

Neurotrophin receptors expression in mesial temporal lobe epilepsy with and without psychiatric comorbidities and their relation with seizure type and surgical outcome.

Epilepsy and psychiatric comorbidities are frequently associated, but their common biological substrate is unknown. We have previously reported altered structural elements and neurotrophins (NTs) expression in mesial temporal lobe epilepsy (MTLE) patients with psychiatric comorbidities. NTs receptors can regulate neurotransmission and promote neuroplasticity, being important candidates in the regulation and manifestation of psychopatological states and seizure-related events. MTLE hippocampi of subjects without psychiatric history, MTLE + major depression, MTLE + interictal psychosis derived from epilepsy surgery, and control necropsies were investigated for p75(NTR), TrkB, TrkA, and TrkC immunohistochemistry. Increased expression of p75(NTR), decreased TrkA, unaltered TrkC, and complex alterations involving TrkB expression were seen in MTLE groups. Increased TrkB expression in patients without complete seizure remission and in those with secondarily generalized seizures was seen. Decreased p75(NTR) expression associated with interictal psychosis, and increased TrkB in those with psychosis or major depression was also reported, although their p75(NTR)/TrkB ratios were lower than in MTLE without psychiatric comorbidities. Our results provide evidence of alterations in expression of NTs receptors in the epileptogenic hippocampus that are differentially modulated in presence of psychiatric comorbidities. As already explored in animal models, even in chronic human MTLE increased TrkB expression, among other NT receptors alterations, may play a major role in seizure type, frequency and surgery outcome.

A influência dos papéis sociais na qualidade de vida de portadores de esquizofrenia / The influence of social roles in the quality of life of patients with schizophrenia

Considering the damage caused by schizophrenia and the world tendency to treat and include its patients in the community, it is essential to review the scientific literature concerning the influential factors associated with quality of life in this population. Method: A literature review was carried out aiming to describe which social roles influence the quality of life and which variables have been investigated. Results: We selected 17 studies, mostly from European countries, conducted after 2000. Almost all studies were of the cross-sectional type and assessed outpatient samples. In general, most studies reported a better quality of life associated with a greater number of social roles. The social roles appeared linked to the areas of quality of life and none of the studies used a specific instrument for social roles. Conclusions: The review reveals the necessity for more studies regarding quality of life and social roles in schizophrenia.

Introdução: Considerando o prejuízo causado pela esquizofrenia e a tendência mundial de inserir e tratar seus portadores na comunidade, torna-se imprescindível rever a literatura científica referente aos fatores influentes associados à qualidade de vida dessa população. Método: Uma revisão bibliográfica foi realizada com o objetivo de descrever quais papéis sociais influenciam na qualidade de vida e quais variáveis foram investigadas. Resultados: Foram selecionados 17 estudos, a maior parte de países europeus. A maioria foi realizada após o ano 2000. Quase todos os estudos eram seccionais e a maior parte avaliou amostras ambulatoriais. De um modo geral, a maioria dos estudos relatou uma melhor qualidade de vida associada com maior número de papéis sociais. Os papéis sociais apareceram atrelados aos domínios da qualidade de vida e nenhum dos estudos utilizou um instrumento específico para papéis sociais. Conclusões: A necessidade de maior número de estudos com aprofundamento sobre os aspectos centrais do tema se fez notar, devido à importância percebida sobre a influência dos papéis sociais na qualidade de vida.

Cannabidiol normalizes caspase 3, synaptophysin, and mitochondrial fission protein DNM1L expression levels in rats with brain iron overload: implications for neuroprotection.

We have recently shown that chronic treatment with cannabidiol (CBD) was able to recover memory deficits induced by brain iron loading in a dose-dependent manner in rats. Brain iron accumulation is implicated in the pathogenesis of neurodegenerative diseases, including Parkinson's and Alzheimer's, and has been related to cognitive deficits in animals and human subjects. Deficits in synaptic energy supply have been linked to neurodegenerative diseases, evidencing the key role played by mitochondria in maintaining viable neural cells and functional circuits. It has also been shown that brains of patients suffering from neurodegenerative diseases have increased expression of apoptosisrelated proteins and specific DNA fragmentation. Here, we have analyzed the expression level of brain proteins involved with mitochondrial fusion and fission mechanisms (DNM1L and OPA1), the main integral transmembrane protein of synaptic vesicles (synaptophysin), and caspase 3, an apoptosis-related protein, to gain a better understanding of the potential of CBD in restoring the damage caused by iron loading in rats. We found that CBD rescued iron-induced effects, bringing hippocampal DNM1L, caspase 3, and synaptophysin levels back to values comparable to the control group. Our results suggest that iron affects mitochondrial dynamics, possibly trigging synaptic loss and apoptotic cell death and indicate that CBD should be considered as a potential molecule with memory-rescuing and neuroprotective properties to be used in the treatment of cognitive deficits observed in neurodegenerative disorders.

Microtubule-associated proteins in mesial temporal lobe epilepsy with and without psychiatric comorbidities and their relation with granular cell layer dispersion.

BACKGROUND: Despite strong association between epilepsy and psychiatric comorbidities, biological substrates are unknown. We have previously reported decreased mossy fiber sprouting in mesial temporal lobe epilepsy (MTLE) patients with psychosis and increased in those with major depression. Microtubule associated proteins (MAPs) are essentially involved in dendritic and synaptic sprouting. METHODS: MTLE hippocampi of subjects without psychiatric history, MTLE + major depression, and MTLE + interictal psychosis derived from epilepsy surgery and control necropsies were investigated for neuronal density, granular layer dispersion, and MAP2 and tau immunohistochemistry. RESULTS: Altered MAP2 and tau expression in MTLE and decreased tau expression in MTLE with psychosis were found. Granular layer dispersion correlated inversely with verbal memory scores, and with MAP2 and tau expression in the entorhinal cortex. Patients taking fluoxetine showed increased neuronal density in the granular layer and those taking haloperidol decreased neuronal density in CA3 and subiculum. CONCLUSIONS: Our results indicate relations between MAPs, granular layer dispersion, and memory that have not been previously investigated. Differential MAPs expression in human MTLE hippocampi with and without psychiatric comorbidities suggests that psychopathological states in MTLE rely on differential morphological and possibly neurochemical backgrounds. This clinical study was approved by our institution's Research Ethics Board (HC-FMRP no. 1270/2008) and is registered under the Brazilian National System of Information on Ethics in Human Research (SISNEP) no. 0423.0.004.000-07.

Human experimental anxiety: actual public speaking induces more intense physiological responses than simulated public speaking

Objectives: a) To perform a systematic and meta-analytic review to verify whether the Simulated Public Speaking Task (SPST) leads to a greater increase in self-rated anxiety than in physiological correlates of anxiety; and b) to compare the results obtained with the SPST with an actual public speaking task involving healthy volunteers. Methods: a) The PubMed and ISI Web of Knowledge databases were searched for studies involving the SPST prior to 2012. Eleven publications were eligible and provided data from 143 healthy volunteers for meta-analysis; b) 48 university students without somatic or psychiatric disorders were divided into three experimental groups of 16 subjects to undergo one of the following: SPST, real-world public speaking task (real-world), and control situation (control). Results: The meta-analysis showed that the SPST induced a significant increase in the Visual Analogue Mood Scale (VAMS) anxiety factor, but no significant increases in systolic blood pressure or heart rate. The empirical study showed that the real-world public speaking task increased heart rate, systolic blood pressure and diastolic blood pressure significantly more than the control and SPST conditions. Conclusions: These results suggest that real public speaking might be better than SPST in inducing experimental anxiety. .