L’infection par le cytomégalovirus (CMV) au cours de la grossesse est fréquente et représente la première cause de pathologie neurodéveloppementale. En dépit de cette importance médicale, il n’existe à ce jour aucun traitement préventif ou curatif satisfaisant, et les mécanismes physiopathologiques mis en jeu, en particulier au niveau du cerveau foetal, restent mal connus. Des découvertes récentes sur les modèles murins d’infection cérébrale par le CMV, principalement réalisées pendant la période néonatale, ont apporté des données convergentes sur la physiopathologie de ces infections cérébrales ; notamment, le rôle joué par les cellules immunitaires périphériques dans la résolution de l’infection, et l’implication du système immunitaire cérébral (SIC) au cours du processus infectieux. Afin de compléter et préciser les résultats précédemment obtenus dans différents modèles murins, et de comprendre le rôle joué par le SIC, le premier objectif de ma thèse a consisté à mettre au point et à caractériser un nouveau modèle d’infection cérébrale par le CMV au cours du développement in utero chez le rat. Dans l'ensemble, nos résultats confirment l'altération du SIC au cours de l'infection par le CMV du cerveau en développement, et suggèrent fortement, dans ce modèle, un rôle majeur joué par le système microglie/macrophage dans l'émergence de troubles neurologiques semblables à ceux observés dans la pathologie humaine correspondante. / Cytomegalovirus (CMV) infection during pregnancy is the leading cause of neurodevelopmental disorders (polymicrogyria, microcephaly) and may lead to severe sensorineural consequences (deafness, epilepsy, cerebral palsy and hearing loss). Despite this medical importance, no preventive or curative treatment is satisfactory to date, and the pathophysiological mechanisms, notably in the fetal brain, remain poorly understood. Recent findings in murine brain CMV infection, mostly in neonatal models, have brought converging insights into the pathogenesis of these infections; the possible role played by peripheral immune cells against infection and the involvement of the brain immune system (BIS) have been proposed. The actual roles of BIS during in utero infection, and more specifically that of microglial cells and macrophages, remain unclear. In order to expand and precise the data previously obtained in the murine models, and to clarify the role of BIS, the first objective of my thesis was to design and to characterize a novel model of CMV infection during the fetal development of the rat brain. Overall, our datas confirm the altered state of BIS as a consequence of CMV infection of the developing brain, and strongly suggest, in the rat model studied here, that the microglia/macrophages system plays critical role in the pathogenesis of neurological manifestations similar to those classically seen after human congenital CMV infection.

Purpose: This study aimed to investigate how neurodevelopmental disorders (NDs) are represented in the Swedish news media. The study can contribute to gaining more excellent knowledge about how Swedish news media such as Dagens Nyheter (DN) and Expressen represent disabilities such as NDs. Theory: To carry out the study, we must present theoretical starting points. The study was based on the power of journalism, representation, media representation, framing theory, and stereotypes. The power of journalism is used to explain how powerful the media is. Representation and media representation is used to describe how things make sense. Framing theory is used to describe the effect of the media on people because, according to the theory, people always try to create meaning. Finally, stereotypes are used to explain how NDs are perceived in society. Previous research: Previous research has been used to motivate studies that have previously been used on the subject and then linked to our study. The study used health communication and journalism, news media (daily- and evening newspapers), and gender as in previous research. Health communication and journalism explain how vital health-related information is to society. News media are used to create an in-depth understanding of NDs while discussing the difference between daily- and evening newspapers to understand them. Finally, studies on gender are used to explain gender differences and inequalities between the genders. Method: The study was carried out with the help of a quantitative content analysis, where the Swedish news sites DN and Expressen were analyzed by searching for news about various NDs; ADHD, ADD, ASD, Autism, Asperger's, and Tourettes. A total of 190 articles from both news sites were included—123 articles from Expressen and 67 from DN. A time frame has been set within one year, from 8 March 2021 to 8 March 2022. To obtain the survey results, the SPSS program has been used where it was prepared before the study with knowledge of statistical analysis—then prepared variables and variable values to be used in SPSS to make the study feasible. Results: The results were presented by comparing relevant variables in the SPSS software for later analysis. Variables such as "NDs diagnoses," "NDs main or secondary subject," "emotional or non-emotional," and "newspaper." Detailed analysis and discussion were performed of the results of the variables examined. The analysis was based on relevant previous research and theories related to news media, representation, and NDs. Conclusion: Journalists significantly influence how the reader perceives, interprets, and forms opinions. Therefore, the representation of NDs by both the news sites, DN and Expressen, can lead the reader to create stereotypical images about NDs. Individuals with NDs may be discriminated against because of the stereotypes that have been created about them. They can also be exposed to misunderstandings of the environment because they do not behave the same way society expects. The two news pages examined represent NDs differently in that DN is classified as a daily newspaper and Expressen is classified as an evening newspaper. The different diagnoses within NDs are represented differently in the articles. Finally, female journalists try to counter stereotypes about women with NDs. Many articles written by female journalists are about publishing their stories and encouraging others to seek help. In contrast, articles written by male journalists are often about men with NDs, whereas articles are often about crime and sports, which they are also often associated with. / Syfte: Syftet med denna studie var att undersöka hur neuropsykiatriska funktionsnedsättningar (NPF) representeras i svensk nyhetsmedia. Studien kan bidra till att få större kunskap om hur svenska nyhetsmedier som Dagens Nyheter (DN) och Expressen representerar funktionsnedsättningar som NPF. Teori: För att genomföra studien har vi behövt redovisa teoretiska utgångspunkter. Studien bygger på: journalistens makt, representation, media representation, gestaltningsteori och stereotyper. Journalistens makt används för att förklara hur mäktigt media är. Representation och mediarepresentation används för att förklara hur saker och ting får mening. Gestaltningsteorin används för att förklara mediernas effekt på människor eftersom enligt teorin människor alltid försöker skapa mening. Till sist används stereotyper för att förklara hur NPF uppfattas i samhället. Tidigare forskning: Tidigare forskning använts för att motivera studier som tidigare använts på ämnet, för att sedan koppla det till vår studie. I studien användes hälsokommunikation och journalistik, nyhetsmedia (dags- och kvällspress), och genus som tidigare forskning. Hälsokommunikation och journalistik används för att förklara hur viktig hälsorelaterad information är för samhället. Nyhetsmedia används för att skapa fördjupad förstående om neuropsykiatriska funktionsnedsättning, samtidigt diskuteras skillnaden mellan dags- och kvällspress för att förstå skillnaden mellan de. Till sist används genus för att förklara könsskillnader och ojämlikheter mellan könen. Metod: Studien genomfördes med hjälp av en kvantitativ innehållsanalys, där svenska nyhetssidorna DN och Expressen analyserades genom att söka efter nyheter om olika NPF; ADHD, ADD, ASD, Autism, Asperger's och Tourettes. Totalt inkluderades 190 artiklar från både nyhetssidorna. 123 artiklar från Expressen och 67 artiklar från DN. En tidsram har ställts in inom ett år, från datumen, 8 mars 2021 till 8 mars 2022. För att få fram undersökningens resultat har programmet SPSS använts där det förbereddes innan studien med kunskap om statistisk analys. Därefter förberett variabler och variabelvärden för att användas i SPSS för att göra studien genomförbar. Resultat: Resultaten presenterades genom att relevanta variabler har ställts mot varandra i programvaran SPSS för att senare analysera de. Variabler såsom “NPF diagnoser”, “NPF huvud- eller biämne”, “känslomässig eller icke känslomässig” samt “tidning”. En utförlig analys och diskussion genomfördes av resultaten av de undersökta variablerna. Analysen byggdes på relevanta tidigare forskning och teorier som är relaterade till nyhetsmedier, representation och NPF. Slutsats: Journalister har stor påverkan på hur läsaren uppfattar, tolkar och bildar åsikter. Därför representationen av NPF av både nyhetssidorna, DN och Expressen, kan leda till att läsaren skapar stereotypa bilder om NPF. Individer med NPF kan utsättas för diskriminering på grund av de stereotyperna som har skapats om de. De kan också utsättas för missuppfattning av omgivningen på grund av att de inte beter sig på samma sätt som samhället förväntar sig. De två undersökta nyhetssidorna representerar NPF annorlunda i och med att DN klassas som dagstidning och Expressen klassas som kvällstidning. De olika diagnoserna inom NPF representeras på olika sätt i artiklarna. Slutligen kvinnliga journalister försöker att motverka stereotyper om kvinnor med NPF. Många artiklar skrivna av kvinnliga journalister handlar om att ge ut deras berättelser och uppmana andra till att söka hjälp. Medan artiklar skrivna av manliga journalister handlar ofta om män med NPF, där artiklar ofta handlar om brott och sport, vilket de också ofta är associerade med.

Adolescents with neurodevelopmental disabilities (NDD) tend to face great challenges in school which can affect their school wellbeing. This paper investigates the relations between school wellbeing and NDD. The purpose of the study was to examine if NDD, class climate, bullying, mental health, and mental health problems predicted school wellbeing and if there were differences between upper secondary students with and without self-rated NDD. The data of this study was retrieved from wave four of the longitudinal multidisciplinary research programme LoRDIA. Study participants were 288 adolescents in year two of upper secondary school, where 61 had self-related NDD and 227 did not. First a Mann-Whitney U-test tested the differences between the groups. Then a multiple regression analysis was conducted to test the predictors’ influence on school wellbeing. Lastly, a correlation test was conducted to see if any predictor was masked by the difference in group size. The results showed that NDD, class climate and bullying are predictors to school wellbeing, where NDD is the strongest predictor. There was also a difference between the groups concerning psychiatric problems where the group with NDD reported more problems, although this still not being a predictor to school wellbeing for this group. In conclusion, class climate and bullying are predictors to school wellbeing for both students with and without self-related NDD which suggests that schools should work for a positive social climate in school. Secondly, the group of students with NDD experience lower levels of school wellbeing but this could not be explained by any of the variables used in this study which calls for further investigations as to what the causes are.

In vitro models are often used both to characterize and test therapeutics for neurodevelopmental disorders (‘NDDs’). While in vitro models have extraordinary potential to develop therapies for patients, they have historically been confounded by absence of robust phenotypes and/or in vitro phenotypes that fail to translate from laboratory bench to bedside. Within this thesis work, we attempt to address three areas in which in vitro models may be improved – gene selection, model validation and identification of disease-relevant functional assays suited for therapeutic testing. Publicly available databases aggregating identified and annotated disease-causing variants for Mendelian diseases have rapidly expanded over the past two decades. Elucidating mechanisms of disease and developing therapies using in vivo model systems often is both time and cost intensive. Thus, determining which subsets of genes are more likely to generate addressable signals in a dish may lead to more effective drug development. In chapter 1, we identify a set of genes ideally suited for therapeutic inhibition. Specifically, we leverage the aforementioned large genetic databases to identify a set of genes likely to act through a gain-of-function mechanism that are both tolerant to loss-of-function mutations and in the druggable genome. In chapter 2, we aim to characterize the degree of conservation of transcriptomic dysregulation between a human in vitro cortical organoid (‘hCOs’) model, and two mouse models of a severe neurodevelopmental disorder resulting from HNRNPU deficiency. Human model systems may improve upon animal models when human pathogenesis and patient phenotypes are divergent from animal models due to species-specific etiology. However, human model systems often lack the heterogeneity and cell-type specificity and maturity seen in primary fetal samples. Importantly, some mouse models of HNRNPU deficiency have muted phenotypes compared with human patients. We hypothesized that while there are distinctions between humans and mice with HNRNPU deficiency, there will be overlap in transcriptomic dysregulation between human and mouse models. In fact, we find 45-day-old HNRNPU+/- hCOs have consistent transcriptomic dysregulation to embryonic mouse models, but not to perinatal mice. Our findings suggest hCOs are a viable model for characterizing HNRNPU deficiency; however, such models may only be appropriate for elucidating a transcriptomic disease state at a specific developmental time period. Functional assays for neurodevelopmental disorders can aid in understanding whether transcriptomic dysregulation is relevant to patient symptoms, as genomic findings may not always correlate to disease-relevant phenotypes. Further, relevant functional phenotypes can then be utilized for testing potential therapeutics. Importantly, seizures are commonly present in a significant subset of neurodevelopmental disorders and seizure phenotypes have been described as driven by aberrant synchrony in neuronal networks. Using a multielectrode array platform, investigators can use a variety of computational methods to quantify aspects of synchrony in vitro. In chapter 3a, we introduce topological approaches capable of identifying novel synchrony phenotypes in primary neuronal networks from mouse models of neurodevelopmental disorders. Certain mouse models will be confounded by species-specific pathogenesis and/or vastly different developmental timelines and fail to generalize to human patients, motivating the need for functionally active and physiologically relevant human in vitro models. In chapter 3b, we attempt to generate human networks with balanced levels of excitation and inhibition and find confounding lack of functional maturation of inhibitory neuronal subtypes in 90-day-old stem cell-derived neuronal networks. Future work generating in vitro human neuronal networks with functionally mature inhibitory neurons would complement the findings in chapters 1 and 2 and allow for more efficient therapeutic development strategies that may lead to improved patient outcomes.

The 15q13.3 microdeletion is a common genetic disorder associated with multiple neurodevelopmental disorders including autism spectrum disorder, epilepsy, and schizophrenia. Patients have diverse clinical presentations, often prompting genetic assays that identify the CNV in the clinic. This late-stage screening leaves a considerable gap in our understanding of the prenatal and prediagnostic developmental impairments in these individuals, providing a barrier to understanding the disease pathobiology. We provide the first investigation into embryonic brain development of individuals with the 15q13.3 microdeletion by generating multiple 3D neural organoid models from the largest clinical cohort in reported literature. We incorporated unguided and guided forebrain organoid models into our multi-transcriptomic phenotyping pipeline to uncover changes in cell type emergence and disruptions to circuit development, all of which had underlying changes to cell adhesion pathways. Specifically, we identified accelerated growth trajectories in 15q13.3del unguided neural organoids and used single cell RNA sequencing to identify changes in radial glia dynamics that affect neurogenesis. We measured changes in the pseudotemporal trajectory of matured unguided neural organoids, and later identified disruptions in synaptic signaling modules amongst the primary constituents to neural circuitry, excitatory and inhibitory neurons. We leveraged dorsal and ventral forebrain organoid models to better assess circuit dynamics, as they faithfully produce the excitatory and inhibitory neurons in the pallium and subpallium, respectively. We then used the entire 15q13.3del cohort and performed bulk RNA sequencing on each tissue type at two timepoints and discovered convergence on transcriptional dysregulation and disruptions to human-specific zinc finger proteins localized to chromosome 19. We also identified cell type-specific vulnerabilities to DNA damage and cell migration amongst the dorsal and ventral organoids, respectively, which was consistent with the excitatory and inhibitory neural subpopulations amongst the unguided neural organoids scRNA Seq, respectively. We then examined neuron migration in a 3D assembloid model by sparsely labeling dorsal-ventral forebrain organoids from multiple genotype-lineage combinations. Light sheet microscopy identified deficits in inhibitory neuron migration and morphology, but not migration distance, suggesting a complex disruption to cortical circuitry. This novel combination of cell type characterization, pathway identification, and circuitry phenotyping provides a novel perspective of how the 15q13.3 deletions impair prenatal development and can be applied to other NDD models to leverage understanding of early disease pathogenesis. / Dissertation / Doctor of Science (PhD) / The development of the human brain is a highly complex and tightly regulated process that requires the participation of multiple cell types throughout development. Disturbances to the emergence, differentiation, or placement of these cell types can cause disruptions and local miswiring of neural circuits, which is often associated with neurodevelopmental disorders (NDDs). The 15q13.3 microdeletion syndrome is a highly complex condition associated with multiple NDDs and has seldom been studied in a human context. To address this, we used stem cells derived from a 15q13.3 microdeletion syndrome cohort and their typically developing familial controls to generate unguided (“whole brain”) and region-specific organoids to investigate early fetal development across time. We used the largest 15q13.3 microdeletion cohort in reported literature to identify shared disruptions in early developmental milestones such as neurogenesis, neural migration, and neural patterning. We identified expansion of specific cell populations, including progenitors that later give rise to mature neurons. Abnormalities persisted in more mature cell populations, including the inhibitory neurons responsible for establishing critical microcircuitry in the human cortex. By generating guided organoids that enrich for excitatory and inhibitory neural populations, we were able to merge the models to form assembloids, where we captured early migratory and morphological deficits in inhibitory neuron populations, which is supported by the multi-transcriptomics experiments performed in both organoid models. This study provides a framework for examining fetal development in a neurodevelopmental disorder context. By using the 15q13.3 microdeletion background, we found novel disruptions in cell type emergence and circuit formation previously unreported in mouse or 2D neuron models, highlighting the utility of the phenotyping platform for disease modeling.

It is estimated that 15 percent of the world’s population live with some form of disability where neurodevelopmental disabilities [NDD] could be one. In Sweden it is estimated that five to seven percent of all children are diagnosed with NDD and attached to these children are parents who are in need of support due to unique stress problems. Support of other parents has been shown to be appreciated, but also support by interest organizations. The aim of this study was to explore how representatives from an interest organization experience their preconditions to support the health of parents of neurodivergent children. This was explored through qualitative semi-structured interviews with representatives from the interest organization Attention. The transcribed interviews were analyzed with a manifest content analysis and the result showed that time for the representatives to volunteer as well as time for the parents to participate affect the preconditions to support parents. Individual experiences of being a parent of a child with NDD, as well as finances and support from the main organization were seen as resources. Shared knowledge and networking between the organization Attention and authorities were experienced as preconditions to offer support. This study concludes that appropriate resources and cooperation would be beneficial for the representatives’ preconditions to support the health of these parents.

The aim of this study was to explore temperament, psychopathology and quality of life (QOL) in adolescents born at extremely low birth weight (ELBW), i.e., < 1000g. ELBW adolescents (N = 15) completed the Revised Cheek and Buss Scale and Mini International Neuropsychiatric Interview 5.0.0 (M.I.N.I.), while their legal guardians completed a biographical questionnaire and the Short Form 12 version 2. The median age of the sample was 13 SD = 2.526 years (60% male) and all participants spoke English. ELBW adolescents with social phobia (n = 6) were more shy (p = .041) and had poorer mental health-related QOL (p = .041) than those without such symptoms. The results suggest that ELBW could be a predisposing factor for increased shyness and psychological disorders including social phobia. Planning of interventions for ELBW individuals should therefore include strategies to prevent or mitigate the effects of these factors in adolescence / Psychology / M.A. (Clinical Psychology)

Schizophrenia is a complex disorder affecting 1% of the population and is highly heritable, but the majority of contributing genetic factors has remained elusive. Current risk estimates for clinical practice are primarily determined by family history and associated empirical risk. Copy number variants (CNVs) may hold the key to explaining the missing heritability in schizophrenia research; schizophrenia risk estimates as high as 30% have been found for the most-studied CNV associated with schizophrenia, 22q11. Currently, there are methods to identify CNVs though previously collected data from SNP microarrays that would facilitate these types of studies. To determine if algorithms that call CNVs from microarray data are robust four genomic regions with putative CNVs called by the Wellcome Trust Consortium using Birdseye in Birdsuite with Affymetrix 6.0 array raw SNP intensities, primarily affecting genes CHD1L, COX5B, PAK7, ZFYVE20, were validated using Taqman real-time qPCR assays in 29 samples by research groups at VCU and Dublin. CNVs called from the algorithm were 100% validated at VCU though there were false negatives from the algorithm that were validated. Two samples at loci with putative duplications were not called by the Dublin group, which may be because of differing sensitivities of the Taqman assays to be able to detect a 50% difference in copy number between duplications and diploid controls, or because of another technical or analytical difference between the two sites. Deletion frequency of one common CNV found in the gene ERBB4, was assessed by qPCR in both Irish singleton (ICCSS) and Irish family (IHDSF) samples and compared with Irish control (Trinity Biobank) and North American control populations. The ERBB4 deletion frequency was not significantly different when comparing the Irish controls to the Irish singleton or the Irish family samples though the family samples were different when compared against the North American control population, which suggests population stratification, rather than a true association between ERBB4 and increased schizophrenia risk. Current clinical practice has been improved by knowledge and evaluation of CNV-related disorders that include risk for psychosis and additional phenotypes. Genotyping of individuals with known psychosis has led to improved patient care for non-psychosis-related phenotypes associated with CNVs. Individuals with suspected genomic disorders that are found to have CNVs can be counseled on potential psychosis risk and potential risk to their offspring. Recurrent CNVs may hold promise in future clinical practice in order to individualize risk estimates in the general patient population, and increase the number of individuals able to receive anticipatory treatment to minimize disease severity.

Os transtornos psiquiátricos frequentemente têm início na infância e adolescência, podendo persistir até a idade adulta. O objetivo da pesquisa foi estudar a prevalência, os fatores de risco e a continuidade dos transtornos psiquiátricos no início da adolescência (11 anos) na Coorte de Nascimentos de 2004 do Município de Pelotas-RS. Métodos. Estudo 1: O presente estudo teve como objetivos avaliar a prevalência de transtornos psiquiátricos no início da adolescência, examinar a distribuição dos transtornos psiquiátricos conforme características maternas e infantis e avaliar a ocorrência de comorbidades psiquiátricas. Todos os adolescentes de 11 anos, que participaram da Coorte de Nascimentos de 2004 de Pelotas-RS, foram convidados a participar deste estudo. O instrumento utilizado para avaliar a presença de transtornos psiquiátricos foi o Development and Well-Being Assessment (DAWBA). Foram avaliados 3.562 indivíduos e a prevalência de transtornos psiquiátricos de acordo com os critérios do DSM-5 foi de 13,2% (IC95% 12,1-14,4); 15,6% entre os meninos e 10,7% entre as meninas. Os distúrbios mais comuns foram transtornos de ansiedade (4,3%), transtorno de déficit de atenção/hiperatividade (4,0%) e transtorno de conduta/oposição (2,8%). Baixa escolaridade materna, tabagismo durante a gestação, presença de sintomas de humor durante a gestação ou sintomas depressivos crônicos e graves maternos nos primeiros anos de vida do adolescente, sexo masculino, Apgar < 7 no nascimento e parto prematuro foram associados a uma maior chance de distúrbio psiquiátrico aos 11 anos. Comorbidades psiquiátricas foram observadas em 107 indivíduos (22,7%), dos quais, 73, 24 e 10 tinham dois, três e quatro diagnósticos psiquiátricos, respectivamente. Nossos resultados ressaltam a importância dos transtornos psiquiátricos como condição prevalente no início da adolescência, o que repercute diretamente no planejamento de políticas públicas e serviços específicos de atenção à saúde mental nessa faixa etária. Estudo 2: Os objetivos deste estudo foram investigar a incidência de transtornos psiquiátricos entre as idades de seis e 11 anos e avaliar a continuidade homotípica e heterotípica desses transtornos, entre os membros da Coorte de Nascimentos de 2004 de Pelotas-RS. Todos os nascidos vivos na cidade de Pelotas no ano de 2004 foram localizados e 4.231 recém-nascidos foram incluídos no estudo (recusas < 1%), sendo acompanhados em diferentes idades ao longo do tempo. Aplicou-se o Strengths and Difficulties Questionnaire (SDQ) em 3.585 indivíduos com seis anos e em 3.563 indivíduos com 11 anos. Os resultados do SDQ para as quatro subescalas (sintomas emocionais, problemas de conduta, hiperatividade/falta de atenção e problemas de relacionamento com os pares) foram categorizados como normais ou anormais (indivíduos nas categorias limítrofe e anormal) conforme manual do instrumento. Para examinar as associações entre transtornos mentais ao longo do tempo, os transtornos aos seis anos foram inseridos na regressão logística como variáveis independentes e aqueles aos 11 anos foram inseridos como variáveis dependentes. Entre os seis e 11 anos, houve um aumento de 50% na prevalência de sintomas emocionais e um aumento de 45% dos transtornos de hiperatividade/falta de atenção. Entre as crianças que tinham \"qualquer dificuldade no SDQ\" aos seis anos, esse status persistiu em 81% dos indivíduos aos 11 anos. Durante a transição da infância para o início da adolescência, houve continuidade homotípica para sintomas emocionais, problemas de conduta, hiperatividade/falta de atenção e problemas de relacionamento com pares. Nossos resultados indicam que os transtornos mentais nessa faixa etária são moderadamente estáveis, com taxas de transtornos e padrões de continuidade semelhantes aos observados em outros estudos / Psychiatric disorders often begin in childhood and adolescence and may persist into adulthood. The objective of the study was to study the prevalence, risk factors and continuity of psychiatric disorders in early adolescence (11 years) in the 2004 Birth Cohort of the Municipality of Pelotas, RS. Methods. Study 1: The present study aimed to evaluate the prevalence of psychiatric disorders in early adolescence, to examine the distribution of psychiatric disorders according to maternal and infant characteristics and to evaluate the occurrence of psychiatric comorbidities. All 11-year-old adolescents who participated in the 2004 Pelotas-RS Birth Cohort were invited to participate in this study. The instrument used to evaluate the presence of psychiatric disorders was the Development and Well-Being Assessment (DAWBA). A total of 3,562 individuals were evaluated and the prevalence of psychiatric disorders according to DSM-5 criteria was 13.2% (95% CI 12.1-14.4); 15.6% among boys and 10.7% among girls. The most common disorders were anxiety disorders (4.3%), attention deficit/hyperactivity disorder (4.0%) and conduct/opposition disorder (2.8%). Low maternal schooling, smoking during pregnancy, presence of mood symptoms during pregnancy, or chronic and severe maternal depressive symptoms in the first years of the adolescent life, male sex, Apgar < 7 at birth and premature delivery were associated with a greater chance of psychiatric disorder at age 11 years. Psychiatric comorbidities were observed in 107 subjects (22.7%), of whom, 73, 24 and 10 had two, three and four psychiatric diagnoses, respectively. Our results highlight the importance of psychiatric disorders as a prevalent condition in early adolescence, which directly affects the planning of public policies and specific services for mental health care in this age group. Study 2: The objectives of this study were to investigate the incidence of psychiatric disorders between the ages of six and 11 years and to evaluate the homotypic and heterotypic continuity of these disorders among members of the 2004 Pelotas-RS Birth Cohort. All live births in the city of Pelotas in the year 2004 were located and 4,231 newborns were included in the study (refusals < 1%), being followed at different ages over time. The Strengths and Difficulties Questionnaire (SDQ) was applied in 3,585 subjects aged 6 years and 3,563 subjects aged 11 years. The SDQ scores for the four subscales (emotional symptoms, behavioral problems, hyperactivity/inattention and peer relationship problems) were categorized as normal or abnormal (individuals in the borderline and abnormal categories) according to the instrument´s manual. To examine the associations between mental disorders over time, disorders at six years were inserted into the logistic regression as independent variables and those at 11 years were entered as dependent variables. Between six and 11 years, there was a 50% increase in the prevalence of emotional symptoms and a 45% increase in hyperactivity/inattention disorders. Among children who had \"any difficulty\" according to the SDQ at age six, this status persisted in 81% of individuals at age 11. During the transition from childhood to early adolescence, there was homotypic continuity for emotional symptoms, conduct problems, hyperactivity/inattention, and peer relationship problems. Our results indicate that mental disorders in this age group are moderately stable, with rates of disorders and patterns of continuity similar to those observed in other studies

Neuropsykiatriska funktionsnedsättningar är en grupp diagnoser som påverkar hur hjärnan hanterar information och kan ge svårigheter med koncentration, reglera uppmärksamhet, minne m.m. En metod som används för att ge stöd till personer NPF är Tydliggörande pedagogik. Tydliggörande pedagogik går ut på att beskriva händelser och omgivningen på ett sätt som personer med NPF lätt kan förstå. Metoder som används inom tydliggörande pedagogik är visuella scheman, arbetsordningar och visualisering av tid. Det här projektet har vidareutvecklat applikationen Vardag åt uppdragsgivaren Altran. Vardag implementerar ett visuellt schema för att ge stöd till personer med NPF. Denna uppsats beskriver utvecklingen av applikationen och vilka funktioner som finns i applikationen. Uppsatsen beskriver också funktioner som kan vidareutvecklas i applikationen. Applikationen kommunicerar med ett webb-API på en server för att synkronisera aktiviteter och bilder som tillhör schemat. De funktioner som har implementerats i applikationen under projektet är bilder som synkas till server, underaktiviteter, visuella teman, token autentisering till webb-API:et och datum för aktiviteter. Vardag är implementerad med React Native för att göra applikationen kompatibel med Android och IOS. / Neurodevelopmental disorders affect the way the brain handles information and can result in difficulties with concentration, shifting attention, memory and processing the surrounding environment. Clarifying pedagogy is a method that is used to support people with neurodevelopmental disorders.  Clarifying pedagogy aims to describe the environment and events clearly to the people with neurodevelopmental disorders. Aid included in clarifying pedagogy is schedules, checklist and time visualisations. This project is continuing the development of the Vardag-application for the company Altran. Vardag implements schedules in an application to help people with neurodevelopmental disorders. Vardag is implemented with React Native to make the application compatible with IOS and Android. A web API was developed and used to communicate between the application and the server.  During this project the features upload image, sub activities, visual themes and activities on a specific date was implemented.