Associação entre neurotrofinas, estresse oxidativo e marcadores inflamatórios e psicopatologia na infância

The first manifestations of mental disorders (MD) usually occur in childhood and adolescence. Recently, MD have been characterized as neurodevelopmental disorders. The course and clinical presentation of MD are influenced by risk and protective factors in different ways in specific developmental windows. Several biomarkers related to neurotrophism, oxidative stress and inflammation have been investigated among the factors that potentially influence underlying pathophysiological processes in psychiatric disorders. This dissertation will include a review of the literature contextualizing the study of neuroplasticity biomarkers for mental disorders in childhood and an original article exploring the relationship between neuroplasticity biomarkers and child psychopathology. Neuroplasticity is a broad term that encompasses a variety of structural and functional mechanisms involved in the brain?s perception and adaptation in the face of external and internal stimuli. Several molecules and proteins are involved in these processes, among them neurotrophins, and oxidative stress and inflammation mediators. Neurotrophins, of which the brainHderived neurotrophic factor (BDNF) is a major representative, are a class of proteins known as growth factors directly involved in the processes of differentiation, proliferation and survival of neurons. Oxidative stress is a process of imbalance between production of ROS, reactive oxygen species generated by cells oxygen metabolism, and their consumption by antioxidant molecules. Inflammation is a process by which a body reacts to aggression and it is mediated by various molecules including cytokines. Overall, there were no marked associations between the concentration of BDNF and child psychopathology. High levels of BDNF were found in women, particularly in children with a diagnosed psychiatric disorder. This result reinforces findings that the influence of BDNF in mental disorders may be mediated by gender and that BDNF changes can be found late in the development of mental disorders. High levels of oxidative stress markers were particularly associated with externalizing symptoms, especially aggression and defiant behavior in children with a psychiatric diagnosis and in the total sample. 101 In children with a psychiatric diagnosis, we found serum levels of ILH6 increased significantly only in internalizing symptoms such as anxiety and depression. However, there was an association between ILH6 and different groups of symptoms in CBCL in typical children, pointing to a possible involvement of this interleukin in other underlying aspects of psychopathology, even in the absence of depression. High levels of sTNFR2 were negatively associated with overall scores in CBCL as well as with various subgroups of symptoms, possibly featuring a neuroprotective action of this receptor, indicating a new target in studies of resiliency mechanisms. This is the first study to examine the relationship between a wide range of peripheral biomarkers of neuroplasticity and inflammatory activity and measures of general psychopathology in both clinical and nonHclinical populations. These results reinforce the findings that there is an association between biomarkers of neuroplasticity and general psychopathology in children even in the absence of specific MD. Additional research on the significance of these associations can provide new perspectives in this field. The followHup of this cohort will provide data on the potential predictive role of these biomarkers and can clarify some of the issues raised by the current findings.As primeiros manifestações dos transtornos mentais (TM) usualmente ocorrem na infância e na adolescência. Recentemente, os TM vem sendo caracterizados como transtornos do neurodesenvolvimento. O curso e a apresentação clínica dos TM são influenciados por fatores de risco e protetores de diferentes formas em janelas específicas do desenvolvimento. Diversos biomarcadores relacionados a neurotrofismo, estresse oxidativo e inflamação vem sendo investigados entre os fatores que potencialmente influenciam processos fisiopatológicos subjacentes em transtornos psiquiátricos. Essa dissertação compreenderá uma revisão da literatura contextualizando o estudo de marcadores de neuroplasticidade em transtornos mentais na infância e um artigo original explorando a relação entre marcadores de neuroplasticidade e psicopatologia infantil. Neuroplasticidade é um termo amplo que engloba uma variedade de mecanismos estruturais e funcionais envolvidos na percepção e adaptação cerebral, diante de estímulos externos e internos. Diversas moléculas e proteínas estão envolvidas nesses processos, entre elas neurotrofinas, mediadores de estresse oxidativo e de inflamação. Neurotrofinas, entre as quais destacaDse o fator neurotrófico derivado do cérebro (BDNF), são uma classe de proteínas denominadas fatores de crescimentos envolvidas diretamente nos processos de diferenciação, proliferação e sobrevivência dos neurônios. O estresse oxidativo representa um processo de desequilíbrio entre a produção ROS, espécies reativas de oxigênio geradas pelo metabolismo de oxigênio pelas células, e seu consumo por moléculas antioxidantes. Inflamação é o processo pelo qual um organismo reage a agressões e é mediada por diversas moléculas, entre as quais as citocinas. No geral, não foram encontradas associações marcantes entre a concentração de BNDF e psicopatologia infantil. Níveis elevados de BDNF foram encontrados no sexo feminino, particularmente em crianças com um distúrbio psiquiátrico diagnosticado. Esse resultado reforçam achados de que a influência de BDNF em transtornos mentais podem ser mediados pelo gênero e de que alterações de BDNF podem ser achados tardios na evolução dos transtornos mentais. Níveis elevados de marcadores de estresse oxidativo foram particularmente associados a sintomas externalizantes, especialmente agressividade e comportamento desafiador, em crianças com diagnóstico psiquiátrico e na amostra total. Em crianças com diagnóstico psiquiátrico, encontramos níveis séricos de ILD6 significativamente aumentados apenas relacionados com sintomas internalizantes, como ansiedade e depressão. Entretanto, houve uma associação entre IlD6 e diferentes grupos de sintomas na CBCL em crianças típicas, apontando para um possível envolvimento dessa interleucina em outros aspectos subjacentes da psicopatologia, mesmo na ausência de depressão. Níveis elevados de sTNFR2 foram negativamente associados com escores totais na CBCL, assim como de diversos subgrupos de sintomas, possivelmente caracterizando uma ação neuroprotetora desse receptor, indicando um novo alvo no estudos de mecanismos de resiliência. Esse é o primeiro estudo a analisar a relação entre uma ampla gama de biomarcadores periféricas da neuroplasticidade e atividade inflamatória e medidas psicopatologia geral em populações clínicas e nãoDclínicas. Nossos resultados reforçam achados de que existe uma associação entre biomarcadores de neuroplasticidade e psicopatologia geral em crianças mesmo na ausência de TM específicos. Investigações adicionais sobre o significado dessas associações podem fornecer novas perspectivas neste campo. O acompanhamento desta coorte fornecerá dados sobre o potencial papel preditivo desses biomarcadores e pode esclarecer algumas das questões levantadas pelos achados atuais.Dados abertos - Sucupira - Teses e dissertações (2013 a 2016

Identifying Autism with a Brief and Low-Cost Screening Instrument-OERA: Construct Validity, Invariance Testing, and Agreement Between Judges

Simple and low-cost observational-tools to detect symptoms of Autism Spectrum Disorder (ASD) are still necessary. The OERA is a new assessment tool to screen children eliciting observable behaviors with no substantial knowledge on ASD required. The sample was 99 children aged 3-10: 76 with ASD and 23 without ASD (11/23 had intellectual disability). The 13 remained items exhibited high interrater agreement and high reliability loaded onto a single latent trait. Such model showed excellent fit indices evaluated via confirmatory factor analysis and no item showed differential function in terms of age/sex/IQ. A cutoff of five points or higher resulted in the highest sensitivity (92.75) and specificity (90.91) percentages. OERA is a brief, stable, low-cost standardized observational-screening to identify ASD children.State of Sao Paulo Funding Agency-FAPESP under Maria Cecilia Souto Vidigal FoundationNational Research Council-CNPqUniv Prebiteriana Mackenzie, Dev Disorders Program, Rua Consolacao 930,Edificio 28, BR-01302907 Sao Paulo, SP, BrazilFed Univ Sao Paulo UNIFESP, Dept Psychiat, Sao Paulo, SP, BrazilFed Univ Sao Paulo UNIFESP, Dept Genet, Sao Paulo, SP, BrazilUniv Fed Rio Grande do Sul, Dept Psychol, Porto Alegre, RS, BrazilFed Univ Sao Paulo UNIFESP, Dept Psychiat, Sao Paulo, SP, BrazilFed Univ Sao Paulo UNIFESP, Dept Genet, Sao Paulo, SP, BrazilFAPESP: 2012/51584-0CNPq: 401468/2010-0Web of Scienc

Exploring the Acquisition of Social Communication Skills in Children with Autism: Preliminary Findings from Applied Behavior Analysis (ABA), Parent Training, and Video Modeling

Social communication skills, especially eye contact and joint attention, are frequently impaired in autism spectrum disorder (ASD) and predict functional outcomes. Applied behavior analysis is one of the most common evidence-based treatments for ASD, but it is not accessible to most families in low- and middle-income countries (LMICs) as it is an expensive and intensive treatment and needs to be delivered by highly specialized professionals. Parental training has emerged as an effective alternative. This is an exploratory study to assess a parental intervention group via video modeling to acquire eye contact and joint attention. Four graded measures of eye contact and joint attention (full physical prompt, partial physical prompt, gestural prompt, and independent) were assessed in 34 children with ASD and intellectual disability (ID). There was a progressive reduction in the level of prompting required over time to acquire eye contact and joint attention, as well as a positive correlation between the time of exposure to the intervention and the acquisition of abilities. This kind of parent training using video modeling to teach eye contact and joint attention skills to children with ASD and ID is a low-cost intervention that can be applied in low-resource settings

Serum copeptin in children exposed to maltreatment

AimChildhood maltreatment (CM) has been related to a persistent reprograming of stress-response. Copeptin is a marker of hypothalamic-pituitary-adrenal axis activationhowever, few studies have examined copeptin levels in children exposed to CM. The aim of this study was to compare serum copeptin levels in children reporting child abuse and/or neglect and children with no history of CM. MethodsThis study included 65 children with a positive history of moderate to severe CM, as reported by themselves and their parent(s) during a clinical interview, and 71 children with no history of CM as a comparison group. CM was considered moderate to severe based on the child-reported frequency of being exposed to events related to sexual abuse, physical abuse, emotional abuse, emotional neglect, and/or physical neglect. Child psychopathology symptoms were assessed using the Child Behavior Checklist (CBCL). We measured serum copeptin concentration using enzyme-linked immunosorbent assay. ResultsChildren exposed to CM exhibited higher levels of serum copeptin compared to children without CM when controlling for sex, age, and psychiatric morbidity. The CBCL total score, including internalizing and externalizing symptoms, was higher in children with CM. We found no correlation between copeptin and CBCL scores for internalizing symptoms and externalizing symptoms. Conclusion CM is associated with copeptin serum levels independently of age, sex, and symptom severity. Copeptin is a promising new biomarker for children with a history of abuse and/or neglect.National Institute of Developmental Psychiatry for Children and Adolescents, a science and technology instituteConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Pontifical Catholic Univ Rio Grande Sul PUCRS, DCNL, Ave Ipiranga 6681,Predio 11,Sala 928 Partenon, BR-90619900 Porto Alegre, RS, BrazilUniv Fed Rio Grande do Sul, Dept Psychiat, Porto Alegre, RS, BrazilCNPq, Natl Inst Dev Psychiat Children & Adolescents, Sao Paulo, BrazilFed Univ Sao Paulo UNIFESP, Dept Psychiat, Sao Paulo, BrazilUniv Fed Sao Paulo, Interdisciplinary Lab Clin Neurosci LINC, Sao Paulo, BrazilUniv Sao Paulo, Inst Psychiat IPq, Sao Paulo, BrazilUniv Toronto, Univ Hlth Network, MDPU, Toronto, ON, CanadaDepartment of Psychiatry, Universidade Federal de São Paulo (UNIFESP), Sao Paulo, BrazilInterdisciplinary Laboratory of Clinical Neurosciences (LINC), Universidade Federal de São Paulo (UNIFESP), Sao Paulo, BrazilCNPq: 573974/2008-0CNPq: 305141/2011-2CNPq: 476468/ 2012-4FAPESP: 2008/57896-8Web of Scienc

An International Clinical Study of Ability and Disability in Autism Spectrum Disorder Using the WHO-ICF Framework

© 2018 The Author(s) This is the fourth international preparatory study designed to develop International Classification of Functioning, Disability and Health (ICF, and Children and Youth version, ICF-CY) Core Sets for Autism Spectrum Disorder (ASD). Examine functioning of individuals diagnosed with ASD as documented by the ICF-CY in a variety of clinical settings. A cross-sectional study was conducted, involving 11 units from 10 countries. Clinical investigators assessed functioning of 122 individuals with ASD using the ICF-CY checklist. In total, 139 ICF-CY categories were identified: 64 activities and participation, 40 body functions and 35 environmental factors. The study results reinforce the heterogeneity of ASD, as evidenced by the many functional and contextual domains impacting on ASD from a clinical perspective

Towards Precision Medicine in Psychosis: Benefits and Challenges of Multimodal Multicenter Studies-PSYSCAN: Translating Neuroimaging Findings From Research into Clinical Practice

In the last 2 decades, several neuroimaging studies investigated brain abnormalities associated with the early stages of psychosis in the hope that these could aid the prediction of onset and clinical outcome. Despite advancements in the field, neuroimaging has yet to deliver. This is in part explained by the use of univariate analytical techniques, small samples and lack of statistical power, lack of external validation of potential biomarkers, and lack of integration of nonimaging measures (eg, genetic, clinical, cognitive data). PSYSCAN is an international, longitudinal, multicenter study on the early stages of psychosis which uses machine learning techniques to analyze imaging, clinical, cognitive, and biological data with the aim of facilitating the prediction of psychosis onset and outcome. In this article, we provide an overview of the PSYSCAN protocol and we discuss benefits and methodological challenges of large multicenter studies that employ neuroimaging measures