Evolutionism and genetics of posttraumatic stress disorder

The authors discuss, from the evolutionary concept, how flight and fight responses and tonic immobility can lead to a new understanding of posttraumatic stress disorder. Through the analysis of symptom clusters (revivals, avoidance and hyperexcitation), neurobiological and evolutionary findings are correlated. The current discoveries on posttraumatic stress disorder genetics are summarized and analyzed in this evolutionary perspective, using concepts to understand the gene-environment interaction, such as epigenetic. The proposal is that the research of susceptibility factors in posttraumatic stress disorder must be investigated from the factorial point of view, where their interactions increase the risk of developing the disorder, preventing a unique search of the cause of this disorder. The research of candidate genes in posttraumatic stress disorder must take into consideration all the systems associated with processes of stress response, such as the hypothalamus-pituitary-adrenal and sympathetic axes, mechanisms of learning, formation and extinguishing of declarative memories, neurogenesis and apoptosis, which involve many systems of neurotransmitters, neuropeptides and neurohormones.Os autores discutem, a partir do conceito evolutivo, como a resposta de estresse, nas suas possibilidades de fuga e luta e de imobilidade tônica, pode levar a uma nova compreensão etiológica do transtorno de estresse pós-traumático. Através da análise dos agrupamentos de sintomas desse diagnóstico - revivência, evitação e hiperexcitação -, procuram correlacionar os achados neurobiológicos e evolutivos. As descobertas atuais sobre a genética do transtorno de estresse pós-traumático são resumidas e colocadas nessa perspectiva evolutiva, dentro de conceitos que possibilitam o entendimento da interação gene/ambiente, como a epigenética. Propõem que a pesquisa dos fatores de risco do transtorno de estresse pós-traumático deva ser investigada do ponto de vista fatorial, onde a somatória destes aumenta o risco de desenvolvimento do quadro, não sendo possível a procura da causa do transtorno de forma única. A pesquisa de genes candidatos no transtorno de estresse pós-traumático deve levar em consideração todos os sistemas associados aos processos de respostas ao estresse, sistemas dos eixos hipotálamo-hipofisário-adrenal e simpático, mecanismos de aprendizado, formação de memórias declarativas, de extinção e esquecimento, da neurogênese e da apoptose, que envolvem vários sistemas de neurotransmissores, neuropeptídeos e neuro-hormônios.Universidade Federal de São Paulo (UNIFESP)(UNIFESP)UNIFESP Departamento de PsiquiatriaUniversidade de São Paulo Faculdade de Medicin Hospital de ClínicasUNIFESP, Depto. de PsiquiatriaSciEL

Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

Multigenerational adversity impacts on human gut microbiome composition and socioemotional functioning in early childhood

10.1073/pnas.2213768120Proceedings of the National Academy of Sciences of the United States of America (PNAS)12030e221376812

The placental lipidome of maternal antenatal depression predicts socio-emotional problems in the offspring

While maternal mental health strongly influences neurodevelopment and health in the offspring, little is known about the determinants of inter-individual variation in the mental health of mothers. Likewise, the in utero biological pathways by which variation in maternal mental health affects offspring development remain to be defined. Previous studies implicate lipids, consistent with a known influence on cognitive and emotional function, but the relevance for maternal mental health and offspring neurodevelopment is unclear. This study characterizes the placental and circulatory lipids in antenatal depression, as well as socio-emotional outcomes in the offspring. Targeted liquid chromatography-mass spectrometry covering 470 lipid species was performed on placenta from 186 women with low (n = 70) or high (n = 116) levels of antenatal depressive symptoms assessed using the Edinburgh Postnatal Depression Scale at 26 weeks' gestation. Child socio-emotional outcomes were assessed from the Child Behavior Check List (CBCL) at 48 months. Seventeen placental lipid species showed an inverse association with antenatal EPDS scores. Specifically, lower levels of phospholipids containing LC-PUFAs: omega-3 docosapentaenoic acid (DPA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and omega-6 arachidonic acid (AA) were significantly associated with depressive symptoms. Additional measurement of LC-PUFA in antenatal plasma samples at mid-gestation confirmed the reduced circulation of these specific fatty acids in mothers. Reduced concentration of the placental phospholipids also predicted poorer socio-emotional outcomes in the offspring. This study provides new insights into the role of the materno-fetal lipid cross-talk as a mechanism linking maternal mental health to that of the offspring. These findings show the potential utility of nutritional approaches among pregnant women with depressive symptoms to reduce offspring risk for later socio-emotional problems

A standardized method to determine the concentration of extracellular vesicles using tunable resistive pulse sensing

BACKGROUND: Understanding the pathogenic role of extracellular vesicles (EVs) in disease and their potential diagnostic and therapeutic utility is extremely reliant on in-depth quantification, measurement and identification of EV sub-populations. Quantification of EVs has presented several challenges, predominantly due to the small size of vesicles such as exosomes and the availability of various technologies to measure nanosized particles, each technology having its own limitations. MATERIALS AND METHODS: A standardized methodology to measure the concentration of extracellular vesicles (EVs) has been developed and tested. The method is based on measuring the EV concentration as a function of a defined size range. Blood plasma EVs are isolated and purified using size exclusion columns (qEV) and consecutively measured with tunable resistive pulse sensing (TRPS). Six independent research groups measured liposome and EV samples with the aim to evaluate the developed methodology. Each group measured identical samples using up to 5 nanopores with 3 repeat measurements per pore. Descriptive statistics and unsupervised multivariate data analysis with principal component analysis (PCA) were used to evaluate reproducibility across the groups and to explore and visualise possible patterns and outliers in EV and liposome data sets. RESULTS: PCA revealed good reproducibility within and between laboratories, with few minor outlying samples. Measured mean liposome (not filtered with qEV) and EV (filtered with qEV) concentrations had coefficients of variance of 23.9% and 52.5%, respectively. The increased variance of the EV concentration measurements could be attributed to the use of qEVs and the polydisperse nature of EVs. CONCLUSION: The results of this study demonstrate the feasibility of this standardized methodology to facilitate comparable and reproducible EV concentration measurements

Diagnosis and management of shellfish allergy: current approach and future needs

Purpose of review: Shellfish allergy is an increasing health concern worldwide with over 2% of the population affected and higher rates in countries with high consumption. Shellfish includes both crustaceans and mollusks and constitutes one of the major food groups triggering allergic reactions. Recent findings: Shrimp is the best-studied crustacean, in which the major shellfish allergen, tropomyosin, was initially characterized. Nevertheless, several other allergens have been identified and should be considered despite prevalence of sensitization being lower than tropomyosin (e.g., arginine kinase, myosin light chain, and sarcoplasmic calcium-binding protein). Summary: Diagnosis is not always straightforward; due to the conserved nature of most allergens, there is extensive cross-reactivity between different species which hampers proper diagnosis and management. Clinical symptoms can range from mild local ones to life-threatening anaphylaxis, sometimes with cofactor involvement. Currently, there is no available curative treatment besides diet avoidance and treatment of symptoms in case of accidental exposure

Catechol-O-methyltransferase (COMT) val158met Polymorphism as a Risk Factor for PTSD After Urban Violence

PTSD is a psychiatric disorder that requires a traumatic event as diagnostic criteria. Brazil has high rates of violence, and it is expected that urban victims of violence would be at risk to the development of PTSD. Studies have associated the COMT val158met polymorphism with diminished stress resilience, reduced ability to extinguish conditioned fear, and the development of PTSD after multiple traumatic experiences. the aim of this study was to identify, in a case-control study, whether the val158met polymorphism (rs4860) is associated with the development of PTSD in a group of victims of urban violence. To our knowledge, this is the first study that examines the association between PTSD and urban violence. the polymorphism of COMT in PTSD patients (n = 65) as well as in victims of violence without PTSD (n = 34) and in a community control group (n = 335) were genotyped. We found a significant relationship between the met allele (p < 0.02) and PTSD among cases (PTSD+)and victims of violence without PTSD (PTSD-; OR 2.57) and between cases and community control group (p < 0.003) Further analysis with larger samples and another ethnic group should be necessary to confirm our findings.Fundacao de Amparo a Pesquisa Estado de São PauloCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Dept Psiquiatria, Fac Med, BR-04023061 São Paulo, SP, BrazilKings Coll London, Inst Psychiat, Hlth Serv & Populat Res Dept, London WC2R 2LS, EnglandUniversidade Federal de São Paulo, Dept Psiquiatria, Fac Med, BR-04023061 São Paulo, SP, BrazilFundacao de Amparo a Pesquisa Estado de São Paulo: 2004/15039-0Web of Scienc