The thesis was designed to gain insight into how Alzheimer’s disease influences selfhood from first-personal accounts of illness. The focus of the study was narrowed further by concentrating on the autobiographies of individuals diagnosed with Early-Onset Alzheimer’s disease (EOAD). The purpose of this thesis was to analyze the autobiographies of individuals with EOAD with the aim of understanding their selfhood. In this thesis I argue that, Alzheimer’s disease may influence a change in self, however, the self is not lost entirely. This thesis draws on the philosophical conception of narrated self as it allows for one perpetually constructed self, whereby a change in self does not necessarily mean the self is lost entirely. Through an interpretive analysis of six autobiographical accounts of Alzheimer’s, this thesis demonstrates that Alzheimer’s disease influences a loss of sense of self but that autobiography enables individuals with Alzheimer’s to (re)construct self.

国立情報学研究所で電子化したコンテンツを使用している。

Doctor of Philosophy / Despite the demonstrated efficacy of cognitive-behavioural therapy for chronic pain, recent research has attempted to identify predictors of treatment outcome in order to improve the effectiveness of such treatments. This research has indicated that variables such as the nature of the onset of the pain and psychopathology are associated with poor adjustment to chronic pain. Accordingly, these variables might also be predictive of poor response to treatment. Individuals who experience a sudden onset of pain following an injury or accident, particularly when the instigating event is experienced as psychologically traumatic, may present for treatment with high levels of distress, including symptoms consistent with a posttraumatic stress response. The impact of this type of onset of pain and posttraumatic stress symptoms on adjustment to chronic pain and treatment outcome is the focus of this thesis. Three studies were conducted to clarify and extend earlier research findings in this area. Using 536 patients referred for treatment in a tertiary referral pain management centre, the first study examined the psychometric properties of a widely used self-report measure of posttraumatic stress symptoms (the PTSD Checklist, or PCL), modified for use in a chronic pain sample. This study provided preliminary support for the suitability of the PCL as a self-report measure of Posttraumatic Stress Disorder (PTSD) symptoms in chronic pain patients. However, the study also highlighted a number of issues with the use of self-report measures of posttraumatic stress symptoms in chronic pain patient samples. In particular, PCL items enquiring about symptoms which are a common aspect of the chronic pain experience (e.g. irritability, sleep problems) appeared to contribute to high mean scores on the PCL Avoidance and Arousal subscales. Furthermore, application of diagnostic cut-off scores and an algorithm recommended for the PCL in other trauma groups suggested that a much larger proportion of the sample was identified as potentially meeting diagnostic criteria for PTSD than would have been expected from previous research. The second study utilised the modified PCL to investigate the impact of different types of onset of pain (e.g. traumatic onset) and posttraumatic stress symptoms on adjustment to chronic pain in a sample of 196 chronic pain patients referred to the same centre. For patients who experienced the onset of pain related to a specific event, two independent experts in the field of PTSD determined whether these events satisfied the definition of a traumatic event according to DSM-IV diagnostic criteria. Adjustment was assessed through a number of validated measures of mood, disability, pain experience, and pain-related cognitions. Contrary to expectations, comparisons between patients who had experienced different types of onset of pain revealed few significant differences between them. That is, analyses comparing patients presenting with accident-related pain, or pain related to other specific events, to patients who had experienced spontaneous or insidious onset of pain revealed no significant differences between the groups on measures of pain severity, pain-related disability, and symptoms of affective distress after adjustment for age, pain duration, and compensation status. Similarly, comparisons between patients who had experienced a potentially traumatic onset of pain with those who had experienced a non-traumatic or spontaneous or insidious onset of pain also revealed no significant differences on the aforementioned variables. In contrast, compensation status, age, and a number of cognitive variables were significant predictors of pain severity, pain-related disability, and depression. The final study investigated the impact of type of pain onset and posttraumatic stress symptoms on response to a multidisciplinary cognitive-behavioural pain management program. Unlike the previous study, this treatment outcome study revealed a number of differences between onset groups. Most notably, patients who had experienced an insidious or spontaneous onset of pain reported greater improvements in pain severity and maintained these improvements more effectively over a one month period than patients who had experienced pain in the context of an accident or other specific incident. There was also limited evidence that improvements in depression favoured patients who had experienced an insidious or spontaneous and non-traumatic onset of pain. Consistent with this, posttraumatic stress symptoms were a significant predictor of treatment outcome, with higher levels of symptoms being associated with smaller improvements in pain-related disability and distress. Notably, this study also revealed that certain cognitive variables (i.e. catastrophising, self-efficacy, and fear-avoidance beliefs) were also significant predictors of treatment outcome, consistent with previous findings in the pain literature. This provided some perspective on the relative roles of both PTSD symptoms and cognitive variables in adjustment to persisting pain and treatment response. These findings were all consistent with expectations and with previous research. Implications for future research and for the assessment and treatment of chronic pain patients who present with posttraumatic stress symptoms are discussed.

Doctor of Philosophy / Despite the demonstrated efficacy of cognitive-behavioural therapy for chronic pain, recent research has attempted to identify predictors of treatment outcome in order to improve the effectiveness of such treatments. This research has indicated that variables such as the nature of the onset of the pain and psychopathology are associated with poor adjustment to chronic pain. Accordingly, these variables might also be predictive of poor response to treatment. Individuals who experience a sudden onset of pain following an injury or accident, particularly when the instigating event is experienced as psychologically traumatic, may present for treatment with high levels of distress, including symptoms consistent with a posttraumatic stress response. The impact of this type of onset of pain and posttraumatic stress symptoms on adjustment to chronic pain and treatment outcome is the focus of this thesis. Three studies were conducted to clarify and extend earlier research findings in this area. Using 536 patients referred for treatment in a tertiary referral pain management centre, the first study examined the psychometric properties of a widely used self-report measure of posttraumatic stress symptoms (the PTSD Checklist, or PCL), modified for use in a chronic pain sample. This study provided preliminary support for the suitability of the PCL as a self-report measure of Posttraumatic Stress Disorder (PTSD) symptoms in chronic pain patients. However, the study also highlighted a number of issues with the use of self-report measures of posttraumatic stress symptoms in chronic pain patient samples. In particular, PCL items enquiring about symptoms which are a common aspect of the chronic pain experience (e.g. irritability, sleep problems) appeared to contribute to high mean scores on the PCL Avoidance and Arousal subscales. Furthermore, application of diagnostic cut-off scores and an algorithm recommended for the PCL in other trauma groups suggested that a much larger proportion of the sample was identified as potentially meeting diagnostic criteria for PTSD than would have been expected from previous research. The second study utilised the modified PCL to investigate the impact of different types of onset of pain (e.g. traumatic onset) and posttraumatic stress symptoms on adjustment to chronic pain in a sample of 196 chronic pain patients referred to the same centre. For patients who experienced the onset of pain related to a specific event, two independent experts in the field of PTSD determined whether these events satisfied the definition of a traumatic event according to DSM-IV diagnostic criteria. Adjustment was assessed through a number of validated measures of mood, disability, pain experience, and pain-related cognitions. Contrary to expectations, comparisons between patients who had experienced different types of onset of pain revealed few significant differences between them. That is, analyses comparing patients presenting with accident-related pain, or pain related to other specific events, to patients who had experienced spontaneous or insidious onset of pain revealed no significant differences between the groups on measures of pain severity, pain-related disability, and symptoms of affective distress after adjustment for age, pain duration, and compensation status. Similarly, comparisons between patients who had experienced a potentially traumatic onset of pain with those who had experienced a non-traumatic or spontaneous or insidious onset of pain also revealed no significant differences on the aforementioned variables. In contrast, compensation status, age, and a number of cognitive variables were significant predictors of pain severity, pain-related disability, and depression. The final study investigated the impact of type of pain onset and posttraumatic stress symptoms on response to a multidisciplinary cognitive-behavioural pain management program. Unlike the previous study, this treatment outcome study revealed a number of differences between onset groups. Most notably, patients who had experienced an insidious or spontaneous onset of pain reported greater improvements in pain severity and maintained these improvements more effectively over a one month period than patients who had experienced pain in the context of an accident or other specific incident. There was also limited evidence that improvements in depression favoured patients who had experienced an insidious or spontaneous and non-traumatic onset of pain. Consistent with this, posttraumatic stress symptoms were a significant predictor of treatment outcome, with higher levels of symptoms being associated with smaller improvements in pain-related disability and distress. Notably, this study also revealed that certain cognitive variables (i.e. catastrophising, self-efficacy, and fear-avoidance beliefs) were also significant predictors of treatment outcome, consistent with previous findings in the pain literature. This provided some perspective on the relative roles of both PTSD symptoms and cognitive variables in adjustment to persisting pain and treatment response. These findings were all consistent with expectations and with previous research. Implications for future research and for the assessment and treatment of chronic pain patients who present with posttraumatic stress symptoms are discussed.

Diss. (sammanfattning) Stockholm : Karol inst., 2002. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Στην εποχή της συστημικής βιολογίας, οι υψηλής απόδοσης (-ομικές) τεχνικές βιομοριακής ανάλυσης επέτρεψαν την ολιστική ανάλυση των διαφόρων μοριακών επιπέδων κυτταρικής λειτουργίας μέσω της ταυτόχρονης μέτρησης εκατοντάδων έως χιλιάδων αντιπροσωπευτικών μοριακών ποσοτήτων. Η μεταβολομική αναφέρεται στην ποσοτικοποίηση του (σχετικού) προτύπου συγκέντρωσης των ελεύθερων μικρών μεταβολιτών. Λαμβάνοντας υπ’ όψιν, το ρόλο των μεταβολιτών ως, αντιδρώντα ή/και προϊόντα των μεταβολικών αντιδράσεων, το πρότυπο συγκέντρωσης τους επηρεάζει και επηρεάζεται από την κατανομή των μεταβολικών ροών, αποτελώντας επομένως ένα αποτύπωμα της μεταβολικής κατάστασης ενός βιολογικού συστήματος. Μεταξύ των πλεονεκτημάτων της μεταβολομικής ανάλυσης είναι ότι μπορεί να χρησιμοποιηθεί σε μεταβαλλόμενη κατάσταση φυσιολογίας, ενώ δεν απαιτεί ολοκληρωμένη γνώση του μεταβολικού δικτύου ενός οργανισμού. Αυτά τα χαρακτηριστικά είναι ιδιαίτερα πλεονεκτικά για τη μελέτη της μεταβολικής ενεργότητας του εγκεφάλου, λαμβάνοντας υπ’όψιν την ανατομική, μορφολογική και φαινοτυπική πολυπλοκότητα αυτού του οργάνου και την έως τώρα κατανόηση των μεταβολικών του μηχανισμών. Πιο συγκεκριμένα για την επίδραση του ενήλικου υποθυρεοειδισμού στον μεταβολισμό του εγκεφάλου, η μέχρι σήμερα γνώση παραμένει αποσπασματική, ενώ προέρχεται από διαφορετικά πειράματα και διάφορες εγκεφαλικές περιοχές. Μια ολιστική θεώρηση του μεταβολισμού σε συνθήκες υποθυρεοειδισμού σε συγκεκριμένες εγκεφαλικές περιοχές αναμένεται να αυξήσει σημαντικά τη γνώση μας για την ασθένεια αυτή. Σε μια πρόσφατη μελέτη της ερευνητικής μας ομάδας, που ήταν η πρώτη μεταβολική ανάλυση εγκεφαλικού ιστού σε ζωικό μοντέλο μακρόχρονου υποθυρεοειδισμού, η πολυπαραμετρική στατιστική ανάλυση των μεταβολικών προτύπων της παρεγκεφαλίδας μυός έδειξε διαφορές στη μεταβολική φυσιολογία του ιστού στα ευ- σε σχέση με τα υποθυρεοειδικά ζώα, παρέχοντας ισχυρές ενδείξεις ότι ο μεταβολισμός της παρεγκεφαλίδας θηλαστικών επηρρεάζεται από τον μακρόχρονο υποθυρεοειδισμό. Στην παρούσα εργασία, συγκρίθηκε η επίδραση του μακρόχρονου υποθυρεοειδισμού στη μεταβολική φυσιολογία της παρεγκεφαλίδας μεταξύ αρσενικών και θηλυκών Balb/cJ μυών, αφού επεκτάθηκε για επιπλέον μεταβολίτες η αυτοματοποιημένη μέθοδος προσδιορισμού κορυφών στο χρωματογράφημα. Ο μακρόχρονος υποθυρεοειδισμός επήχθη με χορήγηση 1% υπερχλωρικού καλλίου για 64 μέρες στο πόσιμο νερό των ζώων. Αυτή είναι και η πρώτη μελέτη της επίδρασης του ενήλικου υποθυρεοειδισμού στην μεταβολομική φυσιολογία του 4 εγκεφάλου των θηλυκών μυών. Τα μεταβολικά πρότυπα αναλύθηκαν με το λογισμικό ανοικτού κώδικα ΤΜ4/ MEV(www.tm4.org/MEV) για την πολυπαραμετρική στατιστική ανάλυση των -ομικών δεδομένων. Τα αποτελέσματα συζητήθηκαν στο πλαίσιο ενός κατάλληλα ανακατασκευασμένου μεταβολικού δικτύου για την παρεγκεφαλίδα μυός με βάση τις μεταβολικές βάσεις δεδομένων KEGG και EXPASY και δεδομένα από τη βιβλιογραφία. Η ανάλυση των προτύπων έδειξε ότι η επίδραση της δίμηνης χορήγησης υπερχλωρικού καλλίου στη μεταβολική φυσιολογία της παρεγκεφαλίδας ήταν πιο οξεία στα αρσενικά απ’ότι στα θηλυκά ζώα. Αυτή η παρατήρηση υποστηριζόταν και απο την σημαντικά μικρότερη μείωση του μέσου βάρους των υποθυρεοειδικών σε σχέση με αυτό των ευθυρεοειδικών ζώων στο τέλος της δίμηνης χορήγησης στα θηλυκά σε σχέση με τα αρσενικά. Τέος, σύγκριση των μεταβολικών προτύπων της παρεγκεφαλίδας των ευθυρεοειδικών αρσενικών και θηλυκών μυών έδειξε τους μισούς από τους μεταβολίτες στην παρεγκεφαλίδα των αρσενικών να έχουν σημαντικά μεγαλύτερη συγκέντρωση απ’ ότι στον ιστό των θηλυκών. Αυτή η παρατήρηση καταδεικνύει την ανάγκη της παρεγκεφαλίδας των θηλυκών σε μικρότερες συγκεντρώσεις ελεύθερων μικρών μεταβολιτών για την εύρυθμη λειτουργία της ως ένα πιθανό παράγοντα «προστασίας» του μεταβολισμού της από την επίδραση του μακρόχρονου ενήλικου υποθυρεοειδισμού. Καθώς η παρεγκεφαλίδα των αρσενικών χρειάζεται μεγαλύτερες ποσότητες ελεύθερων μικρών μεταβολιτών, η αναμενώμενη μείωση της συγκέντρωσης των μεταβολιτών που λαμβάνει ο εγκέφαλος μέσω του αιματοεγκεφαλικού φραγμού λόγω του υποθυρεοειδισμού θα την επηρεάσει πιο γρήγορα και πιο δραστικά από αυτή των θηλυκών. Αυτές οι σημαντικές παρατηρήσεις χρειάζονται περαιτέρω διερεύνηση μέσω κατάλληλα σχεδιασμένων αναλύσεων μεταβολομικής και φυσιολογίας και άλλων εγκεφαλικών περιοχών, συνδυάζοντας επίσης μετρήσεις των επιπέδων των θυρεοειδικών ορμονών με μεταβολομική ανάλυση του εγκεφαλικού ιστού με Υγρή Χρωματογραφία- Φασματομετρίας Μάζας, καθώς και μετρήσεις ομικών αναλύσεων από άλλα επίπεδα κυτταρικής λειτουργίας, κυρίως της πρωτεωμικής. / In the systems biology era, the high-throughput “omic” technologies have enabled the holistic analysis of the various molecular levels of cellular function through the simultaneous measurement of hundreds to thousands of relevant molecular quantities. Metabolomics refers to the quantification of the (relative) concentration profile of the free small metabolites. Taking into consideration the role of the metabolites as reactants and products of the metabolic reactions, their concentration profile affects and is affected by the metabolic pathway flux distribution. Thus, the metabolic profile provides a fingerprint of the metabolic state of a biological system. Among the advantages of the metabolomic analysis is that it can be easily used to monitor transient metabolic conditions without requiring extensive knowledge of the structure and regulation of the investigated metabolic networks. This characteristic is especially advantageous for the analysis of brain metabolism, considering the anatomical, morphological and phenotypic complexity of this organ and our current shortages in understanding its metabolic mechanisms. For the effect of adult onset hypothyroidism (AOH) on brain metabolism in particular, the current knowledge remains fragmented, concerning different experimental setups and recovered from various brain regions. A holistic view of metabolism under AOH in particular brain regions is expected to significantly enhance the current knowledge about the disease. In a recent study of our group, which was the first metabolomic analysis of brain tissue in a prolonged AOH mouse model, multivariate statistical analysis of the metabolic profiles of the mouse cerebella indicated differences in the metabolic physiology of the tissue in the eu- compared to the hypo- thyroid animals, providing strong evidence that the mammalian cerebellum is metabolically responsive to prolonged AOH. In the present work, we compared the effect of prolonged AOH on the cerebellar metabolic physiology between male and female Balb/cJ mice, after enhancing the metabolite peak identification method to include additional metabolites. The prolonged AOH was induced by a 64-day treatment with 1% potassium perchlorate in the drinking water of the animals. This is the first reported analysis of the effect of AOH on the brain metabolic physiology of female mice. The raw metabolic profiles were normalized and appropriately filtered. The normalized metabolic profiles were analyzed using the open-source TM4/MeV software (www.tm4.org/MeV) for the multivariate statistical analysis of “omic” data. The acquired results were interpreted in the context of an appropriately reconstructed metabolic network for the mouse cerebellum based on the metabolic databases, KEGG and Expasy, and a plethora of information mined from the literature. The analysis of the metabolic profiles 6 indicated that the effect of the 2-month potassium perchlorate treatment on the metabolic physiology of the cerebellum is more acute in the male with respect to the female mice. The time profile of the body weight of the female compared to the male mice indicated a significantly smaller decrease in the mean weight of the hypothyroid compared to the euthyroid mice in the female compared to the male population at the end of the KClO4 treatment, an observation that further supports the metabolic profiling results. Finally, comparison between the metabolic profiles of the euthyroid male and female cerebellum indicated a significantly higher concentration in half of the measured free metabolites in the male compared to the female animals. This indicates the “leanness” of the metabolic profile of the female cerebellum as a potential “protective” parameter to the effect of AOH on its metabolic physiology, in the sense that the expected due to AOH decrease in the concentrations of the metabolites that are transferred to the brain through the blood brain barrier may affect more the male cerebellum that requires higher levels of free metabolites for its regular activity. These significant observations are in need of further investigation through appropriately designed physiological and metabolomic studies, integrating also thyroid hormone measurements from Liquid Chromatography-MS metabolomic analysis of brain tissue as well as omic measurements from other molecular levels of cellular function, mainly from proteomics.

Neurobehavioural problems (i.e. cognitive impairment/behaviour problems) are common in childhood epilepsy. There are very limited data in children with early-onset epilepsy (CWEOE; onset ≤4 years). This study: (1) estimated the incidence of early-onset epilepsy, (2) described the spectrum and prevalence of neurobehavioural problems in CWEOE, and their risk factors, and (3) explored eye-gaze behaviour as a marker of neurobehavioural problems. This two year, prospective, population-based, case-controlled study identified newly diagnosed CWEOE in South East Scotland using active multi-source capture-recapture surveillance. CWEOE and controls completed detailed age-appropriate neuropsychological assessment - including Bayley III/WPPSI III, NEPSY II and social-emotional behaviour questionnaires. Children completed five eye-tracking tasks which assessed memory, attention, and social cognition. 59 CWEOE were identified (36M:23F); ascertainment-adjusted incidence 62/100,000 ≤4yrs/yr (95%CI 40-88). Asian and White-European children were at increased risk of epilepsy. 46 CWEOE (95%CI 62-84, 27M:19F) and 37 sex-age matched controls (18M:19F) underwent neuropsychological assessment. CWEOE had poorer general cognitive ability (p < .001, η²=.24), and increased parent reports of abnormal behaviour – significantly so in adaptive behaviour, ASD behaviours, hyperactivity/inattention, and atypical social behaviour. Overall 63% of CWEOE met criteria for neurobehavioural problems across multiple domains, vs 27% of controls (p < .001). Risk factors varied by domain. Prematurity and symptomatic/cryptogenic aetiology were common risk factors but other seizure-related variables were not. CWEOE with social problems exhibited abnormal eye-gaze behaviour toward social stimuli. Subtle atypicalities in sustained attention were noted in CWEOE, and an unexpected absence of antisaccade production was seen in all children. This is the first population-based study to describe the neurobehavioural profile, and explore eye-gaze behaviour, in CWEOE. Neurobehavioural problems are present, detectable, and highly prevalent in CWEOE, with implications for medical, psychosocial and educational resource provision, and provides an argument for early intervention. Eye-tracking may be a viable marker of neurobehavioural problems, and this study provides impetus for future eye-tracking investigations in CWEOE. Lastly, certain ethnic groups may be at increased risk of early-onset epilepsy in Scotland, providing opportunity for targeted intervention.

A consideração da idade de início de sintomas, como parte do diagnóstico de TDAH, é controversa e tem sido um tema revisitado com o surgimento das novas classificações de Psiquiatria. O objetivo deste estudo é comparar pacientes com sintomas de TDAH de início precoce e tardio em termos de características neuropsicológicas e de personalidade. Pacientes adultos com TDAH (n = 415) foram avaliados no ambulatório de TDAH do Hospital de Clínicas de Porto Alegre, Brasil. O processo de diagnóstico de TDAH e comorbidades foi baseado nos critérios do DSM-IV. A comparação entre os dois grupos de idade de início (antes de 7; n = 209 e de 7 a 12 anos; n = 206) foi realizada com ANOVA, seguido de análises de regressão Stepwise forward para restringir o número de comparações e acessar o possível efeito de confundidores múltiplos. Adultos com TDAH de início precoce apresentam escores mais altos em busca de novidade em ambas as análises (respectivamente p = 0,016 e p = 0,002), mas as características cognitivas e de atenção são similares em comparação com o grupo de início tardio. Estes dados acrescentam evidências anteriores de que apesar de um perfil mais externalizante do TDAH de início precoce, o desempenho geral é semelhante, reforçando a necessidade da conscientização e inclusão deste grupo nos critérios diagnósticos do DSM-V. / The consideration of age of onset of impairment as part of the ADHD diagnosis is controversial and has been a revisited issue with the emergence of the new classifications in Psychiatry. The aim of this study is to compare patients with early and late onset of ADHD impairment in terms of neuropsychological and personality characteristics. Adult patients with ADHD (n=415) were evaluated in the ADHD outpatient program at Hospital de Clínicas de Porto Alegre, Brazil. The diagnostic process for ADHD and comorbidities was based on DSM-IV criteria. The comparison between the two age of onset groups (before 7; n=209 or from 7 to 12 years; n=206) was performed with ANOVA, followed by Stepwise forward regression analyses to restrict the number of comparisons and access the possible effect of multiple confounders. Patients with early onset ADHD present higher scores in novelty seeking in both analyses (respectively p = 0.016 and p = 0.002), but similar cognitive and attention features as compared with the late onset group. These data add to previous evidence that despite a more externalizing profile of early onset ADHD, the overall performance is similar reinforcing the need for awareness and inclusion of the late onset group in DSM-V diagnostic criteria.

Esta tese trata do estatuto silábico das consoantes finais /r, l, s, n/ no Português. Partimos, inicialmente, da proposta de Harris e Gussmann (1998), segundo a qual as consoantes finais não ocupam a coda silábica, mas são onsets de sílabas com núcleos vazios. Essa proposta baseia-se em uma concepção de estrutura silábica independente da estrutura segmental e que obedece às condições próprias (condições de licenciamento), as quais determinam a boa formação silábica. Nesse sentido, a estrutura silábica pode ser bem formada independentemente da estrutura segmental que a preenche. Assim se explica a ideia de Harris e Gussmann (1998) de núcleos vazios, isto é, de sílabas bem-formadas em termos de estrutura silábica, mas com núcleo não preenchido. Para procedermos a esta discussão, o trabalho foi subdividido em quatro capítulos. No primeiro, apresentamos a abordagem de que consoantes finais são onsets, buscando entender as implicações dessa abordagem e seus desdobramentos. Fazemos também uma comparação com abordagens alternativas, como a da extraprosodicidade e das semissílabas. Noções como a de licenciamento e outros detalhes da perspectiva adotada por Harris e Gussmann (1998) são explicitadas no capítulo 2, no qual também buscamos abordar os principais pressupostos da tese. Embasamo-nos na perspectiva de que a gramática é regida por princípios e parâmetros, admitindo marginalmente a existência de condições e regras específicas à língua. Adotamos também a perspectiva da existência de mais de um nível representacional. A abordagem considera tanto níveis derivacionais, como proposto pela Fonologia Lexical, Kiparsky (1982), quanto a de representação abstrata das estruturas fonológicas, com vários níveis (tiers) estruturais independentes, hierarquicamente organizados. Dessa forma, o núcleo vazio é criado no Léxico e pode ser preenchido, ainda nesse nível, por vogais introduzidas pela sufixação e pela flexão. Por outro lado, uma sílaba com núcleo vazio pode prosseguir até o nível pós-lexical sem precisar ser preenchido com conteúdo segmental. No capítulo 3, trazemos algumas línguas para as quais foi defendida na literatura a existência de consoante final como onset de um núcleo vazio, que denominamos línguas NV. Diferentes processos ilustram a existência dessas categorias após uma consoante na posição final. A observação das evidências para os núcleos não preenchidos foneticamente em distintos idiomas reforça a ideia de que eles sejam estruturas representacionais possíveis; além disso, traz informações para a construção da argumentação da análise de núcleos vazios para o Português. No capítulo 4, argumentamos pela análise das consoantes finais /l, r, s/ como onsets de sílabas com núcleos vazios. Para essa argumentação, trazemos inicialmente a análise do estatuto silábico das consoantes finais no Português Europeu, com base em Mateus e D’Andrade (2000). Em seguida, analisamos argumentos baseados na literatura sobre o Português Brasileiro para cada um dos segmentos finais, mostrando que a análise como onset final é compatível com o comportamento observando para essas consoantes. A nasal final, por sua vez, não pode ser considerada onset como as outras, pois se trata do processo de nasalização da vogal, em que não há um segmento consonantal, mas um glide nasal, conforme Battisti (1997). Por fim, propomos a representação de uma estrutura CVC] como constituída silabicamente como CV.CØ]. A análise adota, ainda, a existência do Parâmetro da Consoante Final que estaria ativado no Português Brasileiro. / This thesis focuses on the syllabic status of word-final consonants /r, l, s, n/ in Portuguese. We had as initial proposal the one presented by Harris and Gussmann (1998), according to which word-final consonants do not occupy the syllable coda, but the onset of a syllable containing an empty nucleus. Such proposal is based on a conception of syllable structure independent of the segmental structure and obeys constraints (licensing constraints) that determine the syllable well-formedness. Following this assumption, the syllable structure can be well-formed independently of the segmental structure that fills it. This explains the authors’ idea of empty nuclei, i.e. of well-formed syllables in terms of syllable structure despite an unfilled nucleus. To proceed to this discussion, this work was divided into four chapters. On the first chapter, we present the approach of C] as onsets, as a way of understanding the implications of this approach and their unfolding. We also compare it to alternative approaches, such as the extraprosodicity and the semisyllable ones. The notion of licensing, among other notions, and some other details of the perspective adopted by Harris e Gussmann (1998) are presented on Chapter 2, on which we also try to make the main presuppositions of this thesis explicit. We adopted the perspective of a grammar ruled by principles and parameters, assuming marginally the existence of specific conditions and rules to the language. We also adopted the perspective that assumes the existence of more than one representational level. This approach considers both the derivational levels, as proposed by Lexical Phonology, Kiparsky (1982), and the abstract representation of phonological structures, with independent structural tiers, hierarchically organized. Thus the empty nucleus is created on the Lexicon and can be filled, on this same tier, by vowels inserted through suffixation and inflection. On the other hand, an onset of a syllable containing an empty nucleus can proceed up to the pos-lexical level without being necessary to be filled by any segmental content. On chapter 3, we mention some languages to which it was assumed the existence of word-final consonant as the onset of an empty nucleus. These languages are named NV languages. Different processes show the existence of empty nucleus after a word-final consonant. The observation of evidences to empty nuclei in different languages reinforces the idea that these empty nuclei are possible representational structures; besides, it carries information to the argumentation construction of the empty nucleus analysis in Portuguese. On chapter 4, we argue for the word-final consonants /l, r, s/ analysis as onsets of syllables containing empty nuclei. For this argument, we bring up the analysis of the syllabic status of word-final consonants in the European Portuguese, based on Mateus e D’Andrade (2000). Then we analyze arguments based on the literature about Brazilian Portuguese to each word-final segment, showing that the word-final onset analysis is compatible with the behavior observed to these consonants. The word-final nasal, however, cannot be considered syllable onset as the other consonants, because this represents the vowel nasalization process, in which there is no consonantal segment, but a nasal glide instead, according to Battisti (1997). Finally, we propose the representation of a CVC] structure as CV.CØ]. This analysis adopts the existence of Word-final Consonant Parameter that would be active in the Brazilian Portuguese.