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.

Les donneurs de méthyles (B12 et folates) régulent le cycle des monocarbones qui joue un rôle primordial dans les régulations épigénétiques/épigénomiques par méthylation. Une carence en donneurs de méthyles produit un retard de croissance intra-utérine et favorise les anomalies du développement, principalement du système nerveux central. De plus, des taux élevés d'homocystéine associés à une telle carence constituent un facteur de risque pour diverses pathologies neurodégénératives. Nous avons étudié les conséquences d'une carence péri-conceptionnelle et gestationnelle sur le développement cérébral embryonnaire de rats Wistar. L'étude morphométrique a montré un retard de croissance des embryons carencés qui affectait également le cerveau, avec une atrophie de structures telles que l'hippocampe, le cortex et la zone subventriculaire. En raison de la forte sensibilité de l'hippocampe, les effets de la carence ont par ailleurs été étudiés sur un modèle cellulaire de progéniteurs neuronaux hippocampiques. L'utilisation de ces deux modèles a permis de montrer in vivo et in vitro la régulation négative par la carence de la voie Stat3, qui influence prolifération et survie, via une régulation épigénomique post-transcriptionnelle impliquant miR-124. La dérégulation du programme neurogénique impliquant les histones désacétylases affecte la différenciation cellulaire. Par ailleurs, nous avons démontré que la carence en donneurs de méthyles était associée à une modification post-traductionnelle correspondant à une N-homocystéinylation irreversible de protéines neuronales, en particulier associées au cytosquelette. Cette modification induit l'agrégation des protéines, phénomène impliqué dans de nombreuses maladies neurodégénératives. La combinaison de ces différents mécanismes apporte un éclairage nouveau sur les défauts de développement et les troubles cognitifs associés à une carence précoce en donneurs de méthyles, soulignant l'importance de la « programmation foetale » dans la survenue de certaines pathologies neurologiques / Methyl donors (B12 and folate) regulate the one-carbon cycle that plays an important role in the epigenetic/epigenomic regulations by methylation. Methyl donor deficiency (MDD) leads to intrauterine growth retardation and promotes neurodevelopmental abnormalities. Also, high levels of homocysteine associated with such a deficiency are a risk factor for various neurodegenerative diseases. We have studied the consequences of a periconceptional and gestational deficiency on the development of the embryonic brain of Wistar rats. Morphometric studies showed retardation in the development of deficient embryos which also affected the brain, with an atrophy of some structures including hippocampus, cortex and subventricular zone. Given the high sensitivity of the hippocampus, the effects of MDD have been additionally studied in a cellular model of hippocampal neuronal progenitors. Using these two models, we showed both in vivo and in vitro the downregulation of Stat3 pathway regulating cell proliferation and survival, through an epigenomic post-transcriptional process involving miR-124. Disruption of the neurogenic program implying histone deacetylases was shown to alter cell differentiation. Furthermore, we showed that methyl donor deficiency was associated with a post-translational modification corresponding to an irreversible N- homocysteinylation of neuronal proteins, especially those associated with the cytoskeleton. Such a process leads to protein aggregation, a phenomenon involved in many neurodegenerative diseases. The combination of these different mechanisms provides new insights into developmental defects and cognitive impairment associated with an early MDD, highlighting the importance of "fetal programming" in the occurrence of some neurological diseases

No description available.

Uma série de estudos na literatura vêm demonstrando a necessidade de intervenções voltadas para adultos portadores do transtorno do espectro do autismo, cuja situação de exclusão social somadas às necessidades crescentes do mundo atual de flexibilidade e engajamento podem levar a problemas emocionais, como ansiedade e depressão. O foco deste estudo foi baseado em funções executivas (FEs) real-world, isto é, focado no funcionamento diário bemsucedido e adaptativo. Este estudo pretendeu: 1) apresentar uma revisão bibliográfica para melhor compreensão do desenvolvimento das FEs em indivíduos com TEA; 2) apresentar uma intervenção neurodesenvolvimental global, o método Ramain; 3) apresentar como ilustração um estudo longitudinal de caso de 4 anos e 6 meses de intervenção (1 sessão semanal de 2 hr e 30 min) e de follow-up de 2 e 5 anos, relativo a um jovem adulto portador de TEA atendido por meio desse método. O método buscou ativar as FEs e mobilizar simultaneamente as funções cognitivas, motoras, emocionais e sociais. Concluiu-se através de observação de duas escalas e de marcadores de ganho de autonomia tanto em espaço terapêutico, como na vida cotidiana (por meio dos relatos de pais e profissionais), que houve aprimoramento das FEs e uma evolução significativa na adaptabilidade, no desenvolvimento das habilidades psicossociais, da autonomia e na qualidade de vida desse adulto, o que abre a possibilidade do uso de intervenções globais em casos de indivíduos com TEA / Several studies in literature have indicated the need for interventions targeting adults with autism spectrum disorder, whose social exclusion, coupled with today\'s increasing needs for flexibility and engagement, may lead to emotional problems such as anxiety and depression. The focus of this study was based on real-world (EFs) executive functions, that is, focused on successful and adaptive daily functioning. The purpose of this study was to: 1) present a bibliographical review for better comprehension of the development of EFs in individuals with ASD; 2) present a global neurodevelopmental intervention, i.e., the Ramain method; 3) present, as an illustration, a longitudinal case study of 4 years and 6 months of intervention (1 weekly session of 2 hr and 30 min) and 2- and 5-year follow-up of a young adult ASD patient, through this method. The method sought to activate EFs and simultaneously mobilize cognitive, motor, emotional and social functions. It was concluded through the observation of two scales and markers of autonomy gain both in therapeutic space and in daily life (through reports of parents and professionals) that there was an improvement of EFs and significant evolution in adaptability, in the development of psychosocial skills, autonomy and quality of life of this adult, which opens the possibility of using global interventions in cases of individuals with ASD

Doctor of Philosophy (PhD) / Schizophrenia is a severe mental illness that affects approximately 1% of the population worldwide, and which typically has a devastating effect on the lives of its sufferers. The characteristic symptoms of the disease include hallucinations, delusions, disorganized thought and reduced emotional expression. While many of the early theories of schizophrenia focused on its psychosocial foundations, more recent theories have focused on the neurobiological underpinnings of the disease. This thesis has four primary aims: 1) to use magnetic resonance imaging (MRI) to identify the structural brain abnormalities present in patients suffering from their first episode of schizophrenia (FES), 2) to elucidate whether these abnormalities were static or progressive over the first 2-3 years of patients’ illness, 3) to identify the relationship between these neuroanatomical abnormalities and patients’ clinical profile, and 4) to identify the normative relationship between longitudinal changes in neuroanatomy and electrophysiology in healthy participants, and to compare this to the relationship observed between these two indices in patients with FES. The aim of Chapter 2 was to use MRI to identify the neuroanatomical changes that occur over adolescence in healthy participants, and to identify the normative relationship between the neuroanatomical changes and electrophysiological changes associated with healthy periadolescent brain maturation. MRI and electroencephalographic (EEG) scans were acquired from 138 healthy participants between the ages of 10 and 30 years. The MRI scans were segmented into grey matter (GM) and white matter (WM) images, before being parcellated into the frontal, temporal, parietal and occipital lobes. Absolute EEG power was calculated for the slow-wave, alpha and beta frequency bands, for the corresponding cortical regions. The age-related changes in regional tissue volumes and regional EEG power were inferred with a regression model. The results indicated that the healthy participants experienced accelerated GM loss, EEG power loss and WM gain in the frontal and parietal lobes between the ages of 10 and 20 years, which decelerated between the ages of 20 and 30 years. A linear relationship was also observed between the maturational changes in regional GM volumes and EEG power in the frontal and parietal lobes. These results indicate that the periadolescent period is a time of great structural and electrophysiological change in the healthy human brain. The aim of Chapter 3 was to identify the GM abnormalities present in patients with FES, both at the time of their first presentation to mental health services (baseline), and over the first 2-3 years of their illness (follow-up). MRI scans were acquired from 41 patients with FES at baseline, and 47 matched healthy control subjects. Of these participants, 25 FES patients and 26 controls returned 2-3 years later for a follow-up scan. The analysis technique of voxel-based morphometry (VBM) was used in conjunction with the Statistical Parametric Mapping (SPM) software package in order to identify the regions of GM difference between the groups at baseline. The related analysis technique of tensor-based morphometry (TBM) was used to identify subjects’ longitudinal GM change over the follow-up interval. Relative to the healthy controls, the FES patients were observed to exhibit widespread GM reductions in the frontal, parietal and temporal cortices and cerebellum at baseline, as well as more circumscribed regions of GM increase, particularly in the occipital lobe. Furthermore, the FES patients lost considerably more GM over the follow-up interval than the controls, particularly in the parietal and temporal cortices. These results indicate that patients with FES exhibit significant structural brain abnormalities very early in the course of their illness, and that these abnormalities progress over the first few years of their illness. Chapter 4 employed the same methodology to investigate the white matter abnormalities exhibited by the FES subjects relative to the controls, both at baseline and over the follow-up interval. Compared to controls, the FES patients exhibited volumetric WM deficits in the frontal and temporal lobes at baseline, as well as volumetric increases at the fronto-parietal junction bilaterally. Furthermore, the FES patients lost considerably more WM over the follow-up interval than did the controls in the middle and inferior temporal cortex bilaterally. While there is substantial evidence indicating that abnormalities in the maturational processes of myelination play a significant role in the development of WM abnormalities in FES, the observed longitudinal reductions in WM were consistent with the death of a select population of temporal lobe neurons over the follow-up interval. The aim of Chapter 5 was to investigate the clinical correlates of the GM abnormalities exhibited by the FES patients at baseline. The volumes of four distinct cerebral regions where 31 patients with FES exhibited reduced GM volumes relative to 30 matched controls were calculated and correlated with patients’ scores on three primary symptom dimensions: Disorganization, Reality Distortion and Psychomotor Poverty. The results indicated that the greater the degree of atrophy exhibited by the FES patients in three of these four ‘regions-of-reduction’, the less severe their degree of Reality Distortion. These results suggest that an excessive amount of GM atrophy may in fact preclude the formation of hallucinations or highly systematized delusions in patients with FES. The aim of Chapter 6 was to identify the relationship between the longitudinal changes in brain structure and brain electrophysiology exhibited by 19 FES patients over the first 2-3 years of their illness, and to compare it to the normative relationship between the two indices reported in Chapter 2. The methodology employed for the parcellation of the MRI and EEG data was identical to Chapter 2. The results indicated that, in contrast to the healthy controls, the longitudinal reduction in GM volume exhibited by the FES patients was not associated with a corresponding reduction in EEG power in any brain lobe. In contrast, EEG power was observed to be maintained or even to increase over the follow-up interval in these patients. These results were consistent with the FES patients experiencing an abnormal elevation of neural synchrony. Such an abnormality in neural synchrony could potentially form the basis of the dysfunctional neural connectivity that has been widely proposed to underlie the functional deficits present in patients with schizophrenia. The primary aim of Chapter 7 was to assimilate the findings from the preceding empirical chapters with the theoretical framework provided in the literature, into an integrated and testable model of schizophrenia. The model emphasized dysfunctions in brain maturation, specifically in the normative processes of synaptic ‘pruning’ and axonal myelination, as playing a key role in the development of disintegrated neural activity and the subsequent onset of schizophrenic symptoms. The model concluded with the novel proposal that disintegrated neural activity arises from abnormal elevations in the synchrony of synaptic activity in patients with first-episode schizophrenia.

Nearly 80% of children treated for cancer are expected to survive, but not without cost. Survivors face unprecedented challenges associated with long-term consequences of treatment, also called late effects. Approximately half of children treated for cancer are at risk for experiencing cognitive late effects, which typically emerge several years post diagnosis. The nature and extent of cognitive late effects appear to be developmental and related to patient, disease, and treatment variables. However, the relationships between these variables is not well understood because there have been few prospective and longitudinal studies that report on the contributions of these variables over time. This dissertation examined the effects of patient, disease, and treatment variables, as well as their interactions over time on neurocognitive functioning in childhood cancer survivors. It comprises part of a large prospective, randomized clinical trial designed to examine changes in cognitive function over three years as a function of different levels of monitoring of school-based intervention based on individual educational plans (IEPs). This dissertation uniquely contributed a new measure (the Treatment Intensity Rating Scale) that was used to systematically classify treatment severity across different types of cancer and cancer treatments. Participants included 61 children ages 7 to 12 years at enrollment who were two to five years from completion of treatment for a brain tumor, leukemia, or lymphoma. Participants received yearly neuropsychological evaluations for a follow-up period of 3 years. Results of these evaluations were used to develop IEPs. Participants were randomized to have their IEPs monitored on a quarterly or annual basis for the duration of the study. Contrary to the progressive decline in neurocognitive functioning that is typically anticipated in pediatric cancer survivors, analyses revealed relative stability of performance on neurocognitive measures over time. Higher neurocognitive performance was noted in children whose IEPs were monitored more frequently versus less frequently. Results also supported gender-specific risk for late effects, with lower performance on select neurocognitive measures in females compared to males. Results of this study provide encouraging evidence of the positive effects of school-based interventions and their close monitoring. This has important implications for quality of life as these children survive well beyond childhood into adulthood.

Aim: The aim of the study is to gain deeper understanding into the lived experiences of parents at a stimulation centre in KwaZulu-Natal, South Africa, and the coping strategies they employ in caring for their children with Autism Spectrum Disorder (ASD). Significance: As literature has focused on international studies this study has provided deeper understanding of the lived experiences and coping strategies of parents of children with ASD in a local setting within South Africa. Experiences across the age spectrum of children, gendered differences in coping and the meaning behind having a child with ASD provides a unique outlook on ASD as opposed to literature that focuses on other areas. Methods: Eleven parents participated in semi-structured interviews. These interviews were triad, dyad or one-on-one interviews. Interviews were audiotaped and transcribed verbatim once completed. Thematic analysis was used to analyze the data and extract themes. Findings: The lived experiences of parents included stressful and devastating experiences as well as positive meaning. Daily challenges were navigated by positive and negative coping strategies with gendered differences in coping being evident. Parents expressed mixed feelings about the benefits of support groups and provided a road map of advice for other parents of children with ASD. Conclusion: Parents of children with ASD undergo enormous stress and emotional upheaval in caring for their children. However in addition to negative experiences, they gain some positive meaning and see it as character building. Their experiences provide useful information for other parents undergoing the same journey. / Thesis (M.O.T.)-University of KwaZulu-Natal, Durban, 2013.

Doctor of Philosophy (PhD) / Schizophrenia is a severe mental illness that affects approximately 1% of the population worldwide, and which typically has a devastating effect on the lives of its sufferers. The characteristic symptoms of the disease include hallucinations, delusions, disorganized thought and reduced emotional expression. While many of the early theories of schizophrenia focused on its psychosocial foundations, more recent theories have focused on the neurobiological underpinnings of the disease. This thesis has four primary aims: 1) to use magnetic resonance imaging (MRI) to identify the structural brain abnormalities present in patients suffering from their first episode of schizophrenia (FES), 2) to elucidate whether these abnormalities were static or progressive over the first 2-3 years of patients’ illness, 3) to identify the relationship between these neuroanatomical abnormalities and patients’ clinical profile, and 4) to identify the normative relationship between longitudinal changes in neuroanatomy and electrophysiology in healthy participants, and to compare this to the relationship observed between these two indices in patients with FES. The aim of Chapter 2 was to use MRI to identify the neuroanatomical changes that occur over adolescence in healthy participants, and to identify the normative relationship between the neuroanatomical changes and electrophysiological changes associated with healthy periadolescent brain maturation. MRI and electroencephalographic (EEG) scans were acquired from 138 healthy participants between the ages of 10 and 30 years. The MRI scans were segmented into grey matter (GM) and white matter (WM) images, before being parcellated into the frontal, temporal, parietal and occipital lobes. Absolute EEG power was calculated for the slow-wave, alpha and beta frequency bands, for the corresponding cortical regions. The age-related changes in regional tissue volumes and regional EEG power were inferred with a regression model. The results indicated that the healthy participants experienced accelerated GM loss, EEG power loss and WM gain in the frontal and parietal lobes between the ages of 10 and 20 years, which decelerated between the ages of 20 and 30 years. A linear relationship was also observed between the maturational changes in regional GM volumes and EEG power in the frontal and parietal lobes. These results indicate that the periadolescent period is a time of great structural and electrophysiological change in the healthy human brain. The aim of Chapter 3 was to identify the GM abnormalities present in patients with FES, both at the time of their first presentation to mental health services (baseline), and over the first 2-3 years of their illness (follow-up). MRI scans were acquired from 41 patients with FES at baseline, and 47 matched healthy control subjects. Of these participants, 25 FES patients and 26 controls returned 2-3 years later for a follow-up scan. The analysis technique of voxel-based morphometry (VBM) was used in conjunction with the Statistical Parametric Mapping (SPM) software package in order to identify the regions of GM difference between the groups at baseline. The related analysis technique of tensor-based morphometry (TBM) was used to identify subjects’ longitudinal GM change over the follow-up interval. Relative to the healthy controls, the FES patients were observed to exhibit widespread GM reductions in the frontal, parietal and temporal cortices and cerebellum at baseline, as well as more circumscribed regions of GM increase, particularly in the occipital lobe. Furthermore, the FES patients lost considerably more GM over the follow-up interval than the controls, particularly in the parietal and temporal cortices. These results indicate that patients with FES exhibit significant structural brain abnormalities very early in the course of their illness, and that these abnormalities progress over the first few years of their illness. Chapter 4 employed the same methodology to investigate the white matter abnormalities exhibited by the FES subjects relative to the controls, both at baseline and over the follow-up interval. Compared to controls, the FES patients exhibited volumetric WM deficits in the frontal and temporal lobes at baseline, as well as volumetric increases at the fronto-parietal junction bilaterally. Furthermore, the FES patients lost considerably more WM over the follow-up interval than did the controls in the middle and inferior temporal cortex bilaterally. While there is substantial evidence indicating that abnormalities in the maturational processes of myelination play a significant role in the development of WM abnormalities in FES, the observed longitudinal reductions in WM were consistent with the death of a select population of temporal lobe neurons over the follow-up interval. The aim of Chapter 5 was to investigate the clinical correlates of the GM abnormalities exhibited by the FES patients at baseline. The volumes of four distinct cerebral regions where 31 patients with FES exhibited reduced GM volumes relative to 30 matched controls were calculated and correlated with patients’ scores on three primary symptom dimensions: Disorganization, Reality Distortion and Psychomotor Poverty. The results indicated that the greater the degree of atrophy exhibited by the FES patients in three of these four ‘regions-of-reduction’, the less severe their degree of Reality Distortion. These results suggest that an excessive amount of GM atrophy may in fact preclude the formation of hallucinations or highly systematized delusions in patients with FES. The aim of Chapter 6 was to identify the relationship between the longitudinal changes in brain structure and brain electrophysiology exhibited by 19 FES patients over the first 2-3 years of their illness, and to compare it to the normative relationship between the two indices reported in Chapter 2. The methodology employed for the parcellation of the MRI and EEG data was identical to Chapter 2. The results indicated that, in contrast to the healthy controls, the longitudinal reduction in GM volume exhibited by the FES patients was not associated with a corresponding reduction in EEG power in any brain lobe. In contrast, EEG power was observed to be maintained or even to increase over the follow-up interval in these patients. These results were consistent with the FES patients experiencing an abnormal elevation of neural synchrony. Such an abnormality in neural synchrony could potentially form the basis of the dysfunctional neural connectivity that has been widely proposed to underlie the functional deficits present in patients with schizophrenia. The primary aim of Chapter 7 was to assimilate the findings from the preceding empirical chapters with the theoretical framework provided in the literature, into an integrated and testable model of schizophrenia. The model emphasized dysfunctions in brain maturation, specifically in the normative processes of synaptic ‘pruning’ and axonal myelination, as playing a key role in the development of disintegrated neural activity and the subsequent onset of schizophrenic symptoms. The model concluded with the novel proposal that disintegrated neural activity arises from abnormal elevations in the synchrony of synaptic activity in patients with first-episode schizophrenia.

No description available.