The post COVID-19 syndrome (PCS) is an emerging phenomenon worldwide with enormous socioeconomic impact. While many patients describe neuropsychiatric deficits, the symptoms are yet to be assessed and defined systematically. In this prospective cohort study, we report on the results of a neuropsychiatric consultation implemented in May 2021. A cohort of 105 consecutive patients with merely mild acute course of disease was identified by its high symptom load 6 months post infection using a standardized neurocognitive and psychiatric-psychosomatic assessment. In this cohort, we found a strong correlation between higher scores in questionnaires for fatigue (MFI-20), somatization (PHQ15) and depression (PHQ9) and worse functional outcome as measured by the post COVID functional scale (PCFS). In contrast, neurocognitive scales correlated with age, but not with PCFS. Standard laboratory and cardiopulmonary biomarkers did not differ between the group of patients with predominant neuropsychiatric symptoms and a control group of neuropsychiatrically unaffected PCS patients. Our study delineates a phenotype of PCS dominated by symptoms of fatigue, somatisation and depression. The strong association of psychiatric and psychosomatic symptoms with the PCFS warrants a systematic evaluation of psychosocial side effects of the pandemic itself and psychiatric comorbidities on the long-term outcome of patients with SARS-CoV-2 infection.

N-methyl-D-aspartate (NMDA) receptors are ligand-gated ion channels activated by agonist glutamate and co-agonist glycine. They play a key role in mediating the fast excitatory synaptic neurotransmission in the mammalian central nervous system. To create a functional heterotetrameric receptor, the presence of two GluN1 subunits combined with GluN2 or GluN3 subunits is necessary. Previous studies confirmed the importance of M3 transmembrane helix and extracellularly localized cysteines in regulation of surface expression of functional NMDA receptors. The aim of my thesis is to elucidate an influence of clinically relevant mutations in M3 transmembrane helix and the role of all known cysteines that form disulphide bonds on surface delivery of NMDA receptor expressed in heterologous monkey kidney fibroblasts cell culture (COS-7). Using molecular biology methods, immunocytochemistry and microscopy I found that the clinically relevant mutations M641I and Y647S in GluN1 subunit and also the mutations of particular cysteines forming disulphide bonds caused substantial decrease of surface expression of NMDA receptors. Furthermore, I discovered that the effect of mutated GluN1 subunits on decrease of surface expression depends on the subunit composition. The contribution of my results lies in elucidating the...

Transtornos de humor tais como a depressão e a ansiedade estão entre as desordens psiquiátricas mais comuns na atualidade, com tendência de aumento do número de casos, assim como vêm ocorrendo nas últimas décadas. O Transtorno Depressivo Maior (TDM), uma desordem psiquiátrica dispendiosa e ameaçadora da vida, afeta profunda e negativamente a qualidade de vida dos indivíduos afetados e irá atingir até 20% da população em algum momento ao longo de sua existência. Porém, a descrição de sua patofisiologia segue incompleta e o principal pré-requisito para controlar a doença é entender de forma detalhada as alterações moleculares e comportamentais que a acompanham. O estresse social, como um dos principais indutores da depressão, tem sido alvo de estudos tanto clínicos quanto pré-clínicos, servindo também como um mecanismo laboratorial que auxilia pesquisadores a rastrear alterações moleculares e comportamentais dessa doença. Recentemente, sem deixar de lado as demais hipóteses, o sistema imunológico através de respostas inflamatórias, tem recebido atenção crescente e é investigado por ser potencialmente um indutor e/ou facilitador de estados depressivos, contribuindo para a patofisiologia da depressão. Além disso, considerando que o estresse não afeta a todos os indivíduos da mesma maneira, a compreensão das diferenças individuais que podem resultar em resiliência pode auxiliar pesquisadores quanto aos fatores que afetam o desenvolvimento ou não do transtorno na população. Esta tese é composta por dois artigos, e visa investigar em um modelo pré-clínico, a contribuição do estresse social por subordinação (do inglês, social defeat – SD) ao comportamento tipo-depressivo, relacionando-o com inflamação. No primeiro artigo foi revisada a literatura mais recente sobre a contribuição do SD para a ativação microglial, o principal elemento neuroinflamatório do sistema nervoso central (SNC), e sua relação com o desenvolvimento dos comportamentos tipo-ansioso e tipo-depressivo. No segundo artigo investigou-se o papel de um estressor social contínuo (21 dias consecutivos de derrota social crônica) em um grupo de ratos Wistar adultos, relacionando respostas comportamentais a alterações de marcadores imunológicos periféricos e a duas estratégias de coping. O modelo de estresse por derrota social tem sido utilizado em diversos estudos de transtornos psiquiátricos e é uma das principais formas de indução de estados tipo-depressivos em animais de laboratório. Ademais, vêm demonstrando ser útil na indução de alterações do sistema 11 imunológico, tanto centrais quanto periféricas. Exposição ao estresse por derrota social induz em células microgliais um estado de hiperativação que, dependendo do tempo de exposição, pode levar ao desenvolvimento de desordens psiquiátricas como a ansiedade e a depressão. Além disso, o protocolo de 21 dias de derrota social contínua revelou dois estilos comportamentais em ratos Wistar. As estratégias de coping passivo e ativo observadas estão relacionadas a vulnerabilidade e a resiliência, respectivamente, e foram correlacionadas com distintos perfis imunológicos periféricos. Animais resilientes apresentam comportamentos e perfil imunológico periférico que os protegem do desenvolvimento de psicopatologias associadas ao estresse. / Humor disorders such as depression and anxiety are among the currently most common disorders, with a trend to an increasing number of cases, like in the past few decades. Major Depressive Disorder (MDD) is an expensive and life-threatening psychiatric disorder that profoundly and negatively affects individual´s quality of life and will affect up to 20% of the population at some point throughout life. However, the pathophysiology of MDD remains incompletely described, and a detailed description of its molecular and behavioral alterations is one of the core prerequisites for disease control. Social stress, one of the main inducers of depression, has been the subject of both clinical and preclinical studies, and has been used as a laboratory tool to help researchers track molecular and behavioral changes of this disease. Recently, without leaving other hypotheses aside, the immune system through inflammatory responses has received increasing attention and is investigated as a potential contributor in the pathophysiology of depression. Furthermore, considering that stress does not affect all individuals to de same extend, understanding individual differences that can turn into resilience may help researchers unravel the factors that influence the development of this disorder in the population. The present dissertation is composed of two articles, aiming to investigate in a preclinical model the contribution of social defeat stress (SD) to depressive-like behavior and correlate it to inflammation. In the first article, we reviewed the most recent literature on the contribution of SD to microglial activation, the main neuroinflammatory element of the central nervous system (CNS), and its relation to the development of anxiety and depressive-like behaviors. In the second paper, we investigated the role of a continuous social stressor (21 consecutive days of chronic social defeat) in a group of adult male Wistar rats, relating behavioral responses and two different coping strategies to changes in peripheral immune markers. The social defeat stress model has been used in several studies of psychiatric disorders and is one of the main forms to induce depressive-like states in laboratory animals. Additionally, it has been shown to be useful in inducing central and peripheral immune alterations. Exposure to stress due to social defeat induces microglial cells into a state of hyperactivation that, depending on the time of exposure, can lead to the development of psychiatric disorders such as anxiety and depression. Furthermore, the 21-day protocol of continuous social defeat revealed two behavioral 13 styles in Wistar rats. The observed passive and active coping strategies are related to vulnerability and resilience, respectively, and have been correlated with different peripheral immunological profiles. Resilient animals present behaviors and a peripheral immune profile that protect them from the development of stress-associated psychopathologies.

Transtornos de humor tais como a depressão e a ansiedade estão entre as desordens psiquiátricas mais comuns na atualidade, com tendência de aumento do número de casos, assim como vêm ocorrendo nas últimas décadas. O Transtorno Depressivo Maior (TDM), uma desordem psiquiátrica dispendiosa e ameaçadora da vida, afeta profunda e negativamente a qualidade de vida dos indivíduos afetados e irá atingir até 20% da população em algum momento ao longo de sua existência. Porém, a descrição de sua patofisiologia segue incompleta e o principal pré-requisito para controlar a doença é entender de forma detalhada as alterações moleculares e comportamentais que a acompanham. O estresse social, como um dos principais indutores da depressão, tem sido alvo de estudos tanto clínicos quanto pré-clínicos, servindo também como um mecanismo laboratorial que auxilia pesquisadores a rastrear alterações moleculares e comportamentais dessa doença. Recentemente, sem deixar de lado as demais hipóteses, o sistema imunológico através de respostas inflamatórias, tem recebido atenção crescente e é investigado por ser potencialmente um indutor e/ou facilitador de estados depressivos, contribuindo para a patofisiologia da depressão. Além disso, considerando que o estresse não afeta a todos os indivíduos da mesma maneira, a compreensão das diferenças individuais que podem resultar em resiliência pode auxiliar pesquisadores quanto aos fatores que afetam o desenvolvimento ou não do transtorno na população. Esta tese é composta por dois artigos, e visa investigar em um modelo pré-clínico, a contribuição do estresse social por subordinação (do inglês, social defeat – SD) ao comportamento tipo-depressivo, relacionando-o com inflamação. No primeiro artigo foi revisada a literatura mais recente sobre a contribuição do SD para a ativação microglial, o principal elemento neuroinflamatório do sistema nervoso central (SNC), e sua relação com o desenvolvimento dos comportamentos tipo-ansioso e tipo-depressivo. No segundo artigo investigou-se o papel de um estressor social contínuo (21 dias consecutivos de derrota social crônica) em um grupo de ratos Wistar adultos, relacionando respostas comportamentais a alterações de marcadores imunológicos periféricos e a duas estratégias de coping. O modelo de estresse por derrota social tem sido utilizado em diversos estudos de transtornos psiquiátricos e é uma das principais formas de indução de estados tipo-depressivos em animais de laboratório. Ademais, vêm demonstrando ser útil na indução de alterações do sistema 11 imunológico, tanto centrais quanto periféricas. Exposição ao estresse por derrota social induz em células microgliais um estado de hiperativação que, dependendo do tempo de exposição, pode levar ao desenvolvimento de desordens psiquiátricas como a ansiedade e a depressão. Além disso, o protocolo de 21 dias de derrota social contínua revelou dois estilos comportamentais em ratos Wistar. As estratégias de coping passivo e ativo observadas estão relacionadas a vulnerabilidade e a resiliência, respectivamente, e foram correlacionadas com distintos perfis imunológicos periféricos. Animais resilientes apresentam comportamentos e perfil imunológico periférico que os protegem do desenvolvimento de psicopatologias associadas ao estresse. / Humor disorders such as depression and anxiety are among the currently most common disorders, with a trend to an increasing number of cases, like in the past few decades. Major Depressive Disorder (MDD) is an expensive and life-threatening psychiatric disorder that profoundly and negatively affects individual´s quality of life and will affect up to 20% of the population at some point throughout life. However, the pathophysiology of MDD remains incompletely described, and a detailed description of its molecular and behavioral alterations is one of the core prerequisites for disease control. Social stress, one of the main inducers of depression, has been the subject of both clinical and preclinical studies, and has been used as a laboratory tool to help researchers track molecular and behavioral changes of this disease. Recently, without leaving other hypotheses aside, the immune system through inflammatory responses has received increasing attention and is investigated as a potential contributor in the pathophysiology of depression. Furthermore, considering that stress does not affect all individuals to de same extend, understanding individual differences that can turn into resilience may help researchers unravel the factors that influence the development of this disorder in the population. The present dissertation is composed of two articles, aiming to investigate in a preclinical model the contribution of social defeat stress (SD) to depressive-like behavior and correlate it to inflammation. In the first article, we reviewed the most recent literature on the contribution of SD to microglial activation, the main neuroinflammatory element of the central nervous system (CNS), and its relation to the development of anxiety and depressive-like behaviors. In the second paper, we investigated the role of a continuous social stressor (21 consecutive days of chronic social defeat) in a group of adult male Wistar rats, relating behavioral responses and two different coping strategies to changes in peripheral immune markers. The social defeat stress model has been used in several studies of psychiatric disorders and is one of the main forms to induce depressive-like states in laboratory animals. Additionally, it has been shown to be useful in inducing central and peripheral immune alterations. Exposure to stress due to social defeat induces microglial cells into a state of hyperactivation that, depending on the time of exposure, can lead to the development of psychiatric disorders such as anxiety and depression. Furthermore, the 21-day protocol of continuous social defeat revealed two behavioral 13 styles in Wistar rats. The observed passive and active coping strategies are related to vulnerability and resilience, respectively, and have been correlated with different peripheral immunological profiles. Resilient animals present behaviors and a peripheral immune profile that protect them from the development of stress-associated psychopathologies.

Transtornos de humor tais como a depressão e a ansiedade estão entre as desordens psiquiátricas mais comuns na atualidade, com tendência de aumento do número de casos, assim como vêm ocorrendo nas últimas décadas. O Transtorno Depressivo Maior (TDM), uma desordem psiquiátrica dispendiosa e ameaçadora da vida, afeta profunda e negativamente a qualidade de vida dos indivíduos afetados e irá atingir até 20% da população em algum momento ao longo de sua existência. Porém, a descrição de sua patofisiologia segue incompleta e o principal pré-requisito para controlar a doença é entender de forma detalhada as alterações moleculares e comportamentais que a acompanham. O estresse social, como um dos principais indutores da depressão, tem sido alvo de estudos tanto clínicos quanto pré-clínicos, servindo também como um mecanismo laboratorial que auxilia pesquisadores a rastrear alterações moleculares e comportamentais dessa doença. Recentemente, sem deixar de lado as demais hipóteses, o sistema imunológico através de respostas inflamatórias, tem recebido atenção crescente e é investigado por ser potencialmente um indutor e/ou facilitador de estados depressivos, contribuindo para a patofisiologia da depressão. Além disso, considerando que o estresse não afeta a todos os indivíduos da mesma maneira, a compreensão das diferenças individuais que podem resultar em resiliência pode auxiliar pesquisadores quanto aos fatores que afetam o desenvolvimento ou não do transtorno na população. Esta tese é composta por dois artigos, e visa investigar em um modelo pré-clínico, a contribuição do estresse social por subordinação (do inglês, social defeat – SD) ao comportamento tipo-depressivo, relacionando-o com inflamação. No primeiro artigo foi revisada a literatura mais recente sobre a contribuição do SD para a ativação microglial, o principal elemento neuroinflamatório do sistema nervoso central (SNC), e sua relação com o desenvolvimento dos comportamentos tipo-ansioso e tipo-depressivo. No segundo artigo investigou-se o papel de um estressor social contínuo (21 dias consecutivos de derrota social crônica) em um grupo de ratos Wistar adultos, relacionando respostas comportamentais a alterações de marcadores imunológicos periféricos e a duas estratégias de coping. O modelo de estresse por derrota social tem sido utilizado em diversos estudos de transtornos psiquiátricos e é uma das principais formas de indução de estados tipo-depressivos em animais de laboratório. Ademais, vêm demonstrando ser útil na indução de alterações do sistema 11 imunológico, tanto centrais quanto periféricas. Exposição ao estresse por derrota social induz em células microgliais um estado de hiperativação que, dependendo do tempo de exposição, pode levar ao desenvolvimento de desordens psiquiátricas como a ansiedade e a depressão. Além disso, o protocolo de 21 dias de derrota social contínua revelou dois estilos comportamentais em ratos Wistar. As estratégias de coping passivo e ativo observadas estão relacionadas a vulnerabilidade e a resiliência, respectivamente, e foram correlacionadas com distintos perfis imunológicos periféricos. Animais resilientes apresentam comportamentos e perfil imunológico periférico que os protegem do desenvolvimento de psicopatologias associadas ao estresse. / Humor disorders such as depression and anxiety are among the currently most common disorders, with a trend to an increasing number of cases, like in the past few decades. Major Depressive Disorder (MDD) is an expensive and life-threatening psychiatric disorder that profoundly and negatively affects individual´s quality of life and will affect up to 20% of the population at some point throughout life. However, the pathophysiology of MDD remains incompletely described, and a detailed description of its molecular and behavioral alterations is one of the core prerequisites for disease control. Social stress, one of the main inducers of depression, has been the subject of both clinical and preclinical studies, and has been used as a laboratory tool to help researchers track molecular and behavioral changes of this disease. Recently, without leaving other hypotheses aside, the immune system through inflammatory responses has received increasing attention and is investigated as a potential contributor in the pathophysiology of depression. Furthermore, considering that stress does not affect all individuals to de same extend, understanding individual differences that can turn into resilience may help researchers unravel the factors that influence the development of this disorder in the population. The present dissertation is composed of two articles, aiming to investigate in a preclinical model the contribution of social defeat stress (SD) to depressive-like behavior and correlate it to inflammation. In the first article, we reviewed the most recent literature on the contribution of SD to microglial activation, the main neuroinflammatory element of the central nervous system (CNS), and its relation to the development of anxiety and depressive-like behaviors. In the second paper, we investigated the role of a continuous social stressor (21 consecutive days of chronic social defeat) in a group of adult male Wistar rats, relating behavioral responses and two different coping strategies to changes in peripheral immune markers. The social defeat stress model has been used in several studies of psychiatric disorders and is one of the main forms to induce depressive-like states in laboratory animals. Additionally, it has been shown to be useful in inducing central and peripheral immune alterations. Exposure to stress due to social defeat induces microglial cells into a state of hyperactivation that, depending on the time of exposure, can lead to the development of psychiatric disorders such as anxiety and depression. Furthermore, the 21-day protocol of continuous social defeat revealed two behavioral 13 styles in Wistar rats. The observed passive and active coping strategies are related to vulnerability and resilience, respectively, and have been correlated with different peripheral immunological profiles. Resilient animals present behaviors and a peripheral immune profile that protect them from the development of stress-associated psychopathologies.

L’identification de biomarqueurs des maladies mentales telles que l’autisme, la schizophrénie ou la maladie d’Alzheimer, est d’une importance capitale non seulement pour établir un diagnostic objectif, mais aussi pour suivre l’effet des traitements. La création et le maintien de fonctions neuronales sub-cellulaires, telle que la plasticité synaptique, sont fortement dépendants du transport intraneuronal, essentiel pour acheminer d’importants composants à des positions spécifiques. Un transport actif défaillant semble être partiellement responsable d’anomalies de la plasticité synaptique et de la morphologie neuronale présentes dans de nombreuses maladies neuropsychiatriques. Cette thèse décrit (i) la mise au point d’une méthode de quantification du transport intraneuronal reposant sur le suivi de nanoparticules de diamants fluorescents (fNDs); (ii) l’application de cette technique simple et faiblement invasive à l’analyse fonctionnelle de variants génétiques associés à des maladies neuropsychiatriques. Ce manuscrit comporte quatre chapitres. Le premier détaille l’architecture polygénique complexe des maladies mentales et démontre la pertinence d’étudier le transport intraneuronal. Les deuxième et troisième chapitres sont dédiés à la méthode et détaillent les stratégies d’internalisation des fNDs, les outils de quantification du transport intraneuronal et la validation de la technique. La forte brillance, la photo-stabilité parfaite et l’absence de toxicité cellulaire font des fNDs un outil de choix pour étudier la dynamique du transport intraneuronal sur une durée d’observation de plusieurs heures avec une haute résolution spatiotemporelle et une bonne puissance statistique. Enfin, dans le quatrième chapitre, nous appliquons cette nouvelle méthode d’analyse fonctionnelle pour étudier l’effet de variants génétiques associés à l’autisme et à la schizophrénie. Pour cela, nous utilisons des lignées de souris transgéniques ayant une faible surexpression des gènes MARK1 et SLC25A12, ainsi que des AAV-shRNA pour induire une haplo-insuffisance du gène AUTS2. Notre méthode de diagnostic moléculaire s’avère suffisamment sensible pour déceler des variations fines de la dynamique du transport intraneuronal, ouvrant la voie à de futurs développements en nanomédecine translationnelle. / The identification of molecular biomarkers of brain diseases as diverse as autism, schizophrenia and Alzheimer’s disease, is of crucial importance not only for an objective diagnosis but also to monitor response to treatments. The establishment and maintenance of sub-cellular neuronal functions, such as synaptic plasticity, are highly dependent on intracellular transport, which is essential to deliver important materials to specific locations. Abnormalities in such active transport are thought to be partly responsible for synaptic plasticity and neuronal morphology impairment found in many neuropsychiatric and neurodegenerative diseases. This thesis reports (i) the development of a quantification technic of intraneuronal transport based on fluorescent nanodiamonds (fNDs) tracking; (ii) the application of this simple and minimally invasive approach to the functional analysis of neuropsychiatric disease-related genetic variants.This manuscript falls into four chapters. The first one details the complex polygenic architecture of mental disorders and demonstrates the disease relevance of monitoring the intraneuronal transport. The second and the third chapters are dedicated to the nanodiamond-tracking assay and describe the fNDs internalisation strategies, the spatiotemporal quantitative readouts and the validation of the technic. The high brightness, the perfect photostability and the absence of cytotoxicity make fNDs a tool of choice to perform high throughput long-term bioimaging at high spatiotemporal resolution. Finally, in the fourth chapter, we apply this new functional analysis method to study the effect of genetic variants associated to autism and schizophrenia. We established transgenic mouse lines in which MARK1 and SLC25A12 genes were slightly overexpressed, and AAV-shRNA to induce AUTS2 gene haploinsufficiency. Our molecular diagnosis assay proves sufficiently sensitive to detect fine changes in intraneuronal transport dynamic, paving the way for future development in translational nanomedicine.

I denna kvalitativa intervjustudie undersöktes hur barn med neuropsykiatriska funktionsnedsättningar beskriver flytten från en vanlig skola till en specialutformad skola. Det undersöktes i vilken utsträckning barnets perspektiv beaktades under processen av skolbytet. Studiens övergripande fynd visar att elever med neuropsykiatriska funktionsnedsättningar har begränsat aktörskap och låg delaktighet i skolan och att bytet till en specialutformad skola har konsekvenser för barnens identitetsformering. Med hjälp av den narrativa analysen framkom att eleverna upplever en dålig situation i den gamla skolan, där de inte får den hjälp de behöver. Elevernas delaktighet och inflytande åsidosätts och de har svag röst i fråga om bytet till en annan skola och de sällan deltar i beslut som berör dem. Studiens resulat tyder på behovet att reflektera om hur skolans verksamheter skulle organiseras så att alla barn får den hjälp de behöver, beakta barns rätt att själv utöva makt över sitt eget liv och att delta i beslutsfattande processer som rör dem samt att beakta barnets perspektiv vid alla skolrelaterade överväganden.

Les variants du nombre de copies (CNV) offre un cadre riche pour étudier les mécanismes neurobiologiques qui sous tendent la vulnérabilité aux troubles neuropsychiatriques. Notamment, les délétions du 16p11.2 et 22q11.2 sont parmi les facteurs génétiques les plus fréquents associés au trouble du spectre de l’autisme (TSA) et à la schizophrénie (SCZ). À l’heure actuelle, les perturbations fonctionnelles cérébrales qui sous-tendent cette vulnérabilité cognitive restent mécomprises. Récemment, l’analyse par gradient du connectome humain a révélé une réorganisation le long de l’axe dominant sensorimoteur à transmodal dans le TSA et la SCZ. Dans cette étude, nous avons cherché à étendre cette approche analytique aux porteurs d’une délétion du 16p11.2 et du 22q11.2 conférant un risque élevé pour de mêmes conditions. À cette fin, nous avons utilisé les données d’imagerie par résonance magnétique au repos combinant les données de deux cohortes génétiques, pour un total de 180 sujets incluant 61 porteurs. Par le biais d’un paradigme cas-contrôle, nous rapportons la première évidence d’une compression du gradient fonctionnel sensorimoteur à transmodal chez les porteurs de telles délétions. En dernier lieu, nous présentons une étude exploratoire d’association endophénotype-phénome dans la population générale du UK Biobank. Nous démontrons que la ressemblance aux profils de compression corticale des délétions est reliée à plusieurs traits humains complexes, en concordance avec les dimensions cliniques impactées par ces mêmes CNV. / Copy number variants (CNVs) present a unique opportunity to study the neural mechanisms underlying vulnerability to neuropsychiatric disorders. Notably, deletions of the 16p11.2 and 22q11.2 region are among the most common genetic variations associated with autism spectrum disorder (ASD) and schizophrenia (SCZ). However, brain functional disruptions underlying this cognitive vulnerability remains unclear. Recent gradient analysis framework developed to study parsimonious connectome dimensions at the system-level have reported disruptions along the overarching sensorimotor-to-transmodal gradient in ASD and SCZ. In this study, we sought to extend this gradient approach to carriers of a deletion at the 16p11.2 and 22q11.2 region. To achieve this, we pooled resting-state functional magnetic resonance imaging data from a total of 180 subjects, including 61 carriers, distributed among two genetic cohorts. By the means of a case-control study design, we provide the first evidence of a compressed cortical functional gradient in CNV carriers compared to healthy controls. Finally, we provide an exploratory endophenotype-phenome association study in the general UK Biobank population. We demonstrate that resemblance to 16p11.2 and 22q11.2 deletion profiles of cortical compression is related to several complex human traits, in concordance with clinical dimensions known to be impacted by the same CNV.

The aim of this study is to examine social workers’ experiences of how the ADHD-diagnosis affects their work with children and youths living in foster care and how it affects the individuals and families themselves. The study is built upon five qualitative interviews and the results are analyzed through a theoretical framework that constitutes ADHD as not only the symptoms and the medical disorder but also as a social phenomenon where the disorder is socially constructed by the current society, norms, and knowledge. The study shows that the social workers’ do not rely on the sole ADHD-diagnosis in the understanding and guidance of the children and their foster parents, but rather see the individual needs of each children. The social workers’ experiences shows that the diagnosis can act as a relief and explanation for both children and their foster parents but can also be a stigma. My overall conclusions are that the diagnosis seems to have only minor significance for these social workers’ daily work and is rather more relevant for obtaining medical treatment or extra support in school for the children. / Syftet med den här studien är att undersöka socialsekreterares erfarenheter av hur ADHD hos barn och unga som är familjehemsplacerade påverkar socialsekreterarnas arbete och hur diagnosen påverkar barnen och de unga samt familjehemmen. Studien bygger på fem kvalitativa intervjuer och resultaten är analyserade genom ett teoretiskt ramverk som betraktar ADHD som inte bara symtomen och den medicinska störningen utan också som ett socialt fenomen där diagnosen är socialt konstruerad genom samhället, normer och aktuell kunskap. Studien visar att socialsekreterarna inte förlitar sig enbart på ADHD-diagnosen för att förstå och hjälpa barnen och deras familjehemsföräldrar utan snarare ser varje barns individuella behov. Socialsekreterarnas erfarenheter visar att diagnosen kan ge lättnad och förklaring för både barnet och familjehemsföräldrarna men att den också kan vara stigmatiserande. Mina slutsatser är att diagnosen tycks spela mindre roll för socialsekreterarnas dagliga arbete med barnen utan är mer relevant för att erhålla medicinsk behandling eller för att få extra stöd i skolan.