myo-lnositol (mIns), a natural component of the human diet and essential precursor of several signalling pathways, including that of G protein-coupled receptors, has also been shown to be effective in the treatment of psychiatric disorders such as depression, obsessive compulsive disorder and panic disorder. Most likely since mlns is a simple isomer of glucose, no serious side effects have been reported with its use, even at high oral doses of mlns. Previous studies suggest that the therapeutic action of mlns may include reduced serotonin 5HTzA and muscarinic acetylcholine receptor function. An important signal transduction system that may possibly be involved in the mechanism of action of antidepressants is phosphoinositide (PI) turnover. In this signalling system PI-phospholipase C (PLCpl), that is implicated in the in the mechanism of action of antidepressants and anxiolytics, is activated. The mechanism of action of mlns, however, still remains elusive and needs further investigation. In this study a possible modulatory role of 24-hour pre-treatment of human neuroblastoma cell line (SH-SY5Y) with mlns on mRNA levels and protein expression of phospholipase C-p1 (PLCP1) and glycogen synthase kinase 3P (GSK3p) was investigated. The effects of mlns were also compared to that of other prototype antidepressants, such as fluoxetine (a selective serotonin reuptake inhibitor), imipramine (a tricyclic antidepressant), lithium and another drug with potential antidepressant effects, sildenafil (phosphodiesterase 5-type (PDE5) inhibitor). Real-time reverse transcription Polymerase Chain Reaction (RTPCR) was performed in order to investigate the mRNA levels, while protein expression in membranes and the cytosol fraction of cells were quantified with Western blots. The expression of PLCPl was decreased after pre-treatments with imipramine or myoinositol in combination with fluoxetine. In addition, sildenafil alone or in combination with myo-inositol, also decreased the expression of membrane-bound PLCp1. However, a 24- hour pre-treatment with lithium did not alter PLCPl expression significantly. Determined mRNA levels for the expression of PLCPl were consistent in these findings, except for the inhibition of the mRNA for the expression of PLCPl also after lithium treatment. The reduced PLCpl mRNA levels after lithium pre-treatment may suggest the involvement of posttranscriptional modification (or delayed translational effects) of PLCpl after lithium treatment. The data from the current study suggest that antidepressant action may include downregulation of PLCPl expression and that modulators of the nitric oxidecGMP pathway (e.g. sildenafil as a PDE5 inhibitor) may exhibit similar properties. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2005.

[Truncated abstract] Auditory hallucinations are some of the most distressing and disabling symptoms of schizophrenia. However very little is known about the exact processes responsible for auditory hallucinations. The aim of this thesis is to provide a new perspective on the nature of the cognitive deficits underlying auditory hallucinations in schizophrenia. As a preliminary study to the investigation of auditory hallucinations in schizophrenia, a factor analysis of a measure of hallucinatory predisposition, the Launay- Slade Hallucination Scale-Revised (Bentall & Slade, 1985), was carried out on data from a large sample of undergraduate students (N = 562). An overlap in characteristics between hallucinatory-like experiences in normal individuals and auditory hallucinations in schizophrenia should draw attention to factors that are important to the hallucinatory experience in general. One of the findings from this study was that intrusiveness is a commonly reported characteristic of hallucinatory-like experiences in normal individuals. Intrusiveness is also one of the defining features of auditory hallucinations in schizophrenia. Since the process of inhibition is essential for suppressing unwanted thoughts, the first set of two studies using patients with schizophrenia (N = 43) investigated the presence of an (intentional) inhibition failure in auditory hallucinations using the Hayling Sentence Completion Test (HSCT; Burgess & Shallice, 1996) and the Inhibition of Currently Irrelevant Memories Task (ICIM; Schnider & Ptak, 1999). It was found that auditory hallucinations were linked to a deficit in intentional inhibition as measured by these tasks. The process of inhibition was further investigated using the Affective Shifting task, but auditory hallucinations were not associated with a deficit on this task. Possible differences in the inhibitory demands of the HSCT, ICIM and Affective Shifting tasks are discussed.

Thesis (M.A.)--University of Toronto, 2005.

Thesis (M.A.)--University of Hong Kong, 1997. / Includes bibliographical references (leaf 47-48).

Thesis (M.A.)--University of Hong Kong, 1997. / Includes bibliographical references (leaf 47-48). Also available in print.

Background: OCD is a debilitating mental health condition. Poor access to evidence-based psychological treatment has motivated the implementation of low intensity interventions in UK mental health services for OCD. Around one half of those accessing care remain clinically unwell. Service users, providers, and treatment decision-makers could benefit from understanding users' views of low intensity interventions and knowing which users are more likely to benefit from diverse low intensity approaches in order to match individuals with treatments of known efficacy. Aim and objectives: The primary aim of this research was to determine user characteristics associated with engagement and outcome in low intensity interventions for OCD. The objectives of the study were: 1) to review the published literature on predictors of psychological therapy outcome in OCD, 2) to explore individual variation in intervention acceptability, uptake, and engagement, and 3) to identify user characteristics, which moderate intervention engagement and outcome. Methods: This mixed methods thesis was conducted in three parts. Firstly, a systematic review of published trial data was conducted to identify predictors of therapy outcome. Secondly, primary data were collected as part of a large effectiveness trial: 1) qualitative interviews with 36 trial participants, randomised to one of two low intensity interventions (guided self-help; cCBT); and 2) quantitative trial assessments conducted at baseline and at 3-months follow-up. Data from the systematic review and the qualitative study were used to identify possible moderators of outcome. Confirmatory analyses were then conducted on these variables, using data from the quantitative assessments. Results: Objective 1: The systematic review identified 43 studies, examining predictors of outcome. Robust effects were rare and the applied utility of these findings is limited by methodological weaknesses. Objective 2: Six themes were identified from the qualitative study, three relate to the general acceptability of low intensity interventions: 1) Predisposing concepts of high quality psychological therapies, 2) Engaging with low intensity interventions, and 3) The perceived value of therapist support. Three are specific to individuals with OCD: 4) Positive aspects of OCD, 5) Recognition and accommodation of OCD users' needs, and 6) OCD disclosure. Objective 3: User attachment style, expressed emotion, OCD symptom subtype, and prior help seeking for OCD were examined in confirmatory interaction tests. Symmetry/order/exactness symptoms were associated with a greater likelihood of engagement in guided self-help than cCBT. Contamination/washing symptoms were associated with improved outcome in guided self-help over cCBT. Conclusions: This study has made an original contribution through using a mixed methods design to identify individual differences in response to low intensity interventions in OCD. There is significant individual variation in the acceptability of, and engagement with, low-intensity interventions for OCD, linked to the mode and intensity of therapist support preferable to the individual user. However, few moderators could be identified. Future research should focus on maximising the reliability of stratified medicine research to allow related findings to inform clinical decision-making.

No description available.

O transtorno obsessivo-compulsivo (TOC) é uma doença crônica que causa prejuízos para o paciente, bem como para a maioria dos familiares. Frequentemente interfere no funcionamento familiar, pois muitas vezes os membros da família modificam suas rotinas devido aos sintomas do paciente. Esses comportamentos observados nos familiares são chamados de acomodação familiar (AF). Os comportamentos de AF podem reforçar os sintomas do paciente e, consequentemente, contribuir para a manutenção da doença. A AF tem sido correlacionada com maior gravidade dos sintomas obsessivo-compulsivos e está associada a resposta menos satisfatória a tratamento, por exemplo, terapia cognitivo-comportamental. No entanto, estudos que avaliam o impacto de intervenções para o TOC na AF em curto e longo prazos ainda são escassos. Esta tese é composta de três artigos com os seguintes objetivos: 1) analisar as propriedades psicométricas da versão adaptada para o Brasil da Escala de Acomodação Familiar para o TOC – versão pontuada pelo entrevistador (FAS-IR); 2) verificar o impacto da terapia cognitivo-comportamental em grupo (TCCG), com duas sessões destinadas a família, na AF e identificar as variáveis sociodemográficas e clínicas preditoras de redução da AF após as 12 sessões de tratamento (curto prazo); e 3) avaliar o impacto da TCCG na AF 3 anos após o término do tratamento e verificar a correlação entre a gravidade dos sintomas do TOC e AF em longo prazo. Trata-se de um estudo com pacientes com diagnóstico de TOC e seus respectivos familiares. Para a avaliação dos sintomas obsessivo-compulsivos, foram aplicados os seguintes instrumentos: Inventário de Obsessões e Compulsões – Revisado (OCI-R), Escala Obsessivo-Compulsivo de Yale-Brown (Y-BOCS) e Escala de Impressão Clínica Global (CGI). Também foram aplicados os Inventários de Beck para Depressão (BDI) e Ansiedade (BAI), além da Entrevista Clínica Estruturada para Transtornos de Eixo I do DSM-IV, Versão Clínica (SCID-I), para a verificação de possíveis comorbidades. Para a avaliação da AF, a FAS-IR foi aplicada nos familiares. Após o estudo de validação da FAS-IR, foi realizado um ensaio clínico randomizado com alocação aleatória dos pacientes para o grupo intervenção (12 sessões de TCCG, sendo duas com a participação dos familiares) ou para o grupo controle (lista de espera). Por fim, foi realizado um estudo de seguimento naturalístico 3 anos após o término da TCCG. O estudo foi aprovado pelo Comitê de Ética em Pesquisa do Hospital de Clínicas de Porto Alegre. Observou-se que a versão da FAS-IR em português brasileiro apresenta propriedades psicométricas satisfatórias, reforçando que este instrumento se mostra confiável para avaliar a participação e modificação da rotina dos familiares em decorrência dos sintomas dos pacientes. No que se refere ao tratamento realizado, o ensaio clínico randomizado compreendeu uma amostra de 98 pares de pacientes com TOC e seus respectivos familiares, sendo que 52 (53.1%) foram randomicamente alocados para o grupo intervenção e 46 (46.9%) para a lista de espera. Houve melhora significativa de todos os sintomas de TOC e também da AF após TCCG no grupo intervenção quando comparado ao grupo controle (p < 0,001). As seguintes variáveis foram preditoras de redução da AF após a análise multivariada: características dos pacientes – ausência de comorbidade com transtorno unipolar (β = 0,338; p = 0,014), pontuação mais baixa de obsessão (β = 0,244; p = 0,045) e maior nível de escolaridade (β = -0,351; p = 0,006); e características dos familiares – pontuação mais elevada de sintomas de colecionismo (β = -0,461; p = 0,001). O modelo explicou 47,2% da variação na AF após a TCCG. No estudo de seguimento, foi observado que os resultados de redução na AF obtidos ao final da TCCG se mantiveram ao longo do tempo (3 anos). Os resultados do presente estudo somam-se às evidências atuais, não somente confirmando que a TCCG é efetiva na redução dos sintomas do TOC, mas também por mostrar que a TCCG com uma breve participação dos familiares com foco na AF contribui para reduzir os níveis de envolvimento da família nos sintomas do paciente, e que esses resultados se mantêm ao longo do tempo. Algumas características dos pacientes e dos familiares foram preditoras da redução da AF, um resultado que pode contribuir para a qualificação dos protocolos de TCCG atualmente empregados. Este é o primeiro estudo a avaliar o impacto da TCCG (com a participação da família em duas sessões) na AF em curto e longo prazos. A partir dos resultados, pode-se concluir que é importante avaliar a AF permanentemente, assim como incluir a família no tratamento para o TOC. / Obsessive-compulsive disorder (OCD) is a chronic illness that negatively affects the lives of patients and usually of family members as well. It frequently interferes with family functioning, as very often family members modify their routines because of the patient’s symptoms. These behaviors observed among family members are referred to as family accommodation (FA). FA behaviors can reinforce the patient’s symptoms and thus contribute to maintain the disorder. FA has been correlated with an increased severity of obsessive-compulsive symptoms and is associated with poorer response to treatment approaches, e.g., cognitive-behavioral therapy. However, there is a scarcity of studies designed to assess the impact of interventions for OCD on FA in both short and long terms. The present thesis includes three research articles, which had the following objectives: 1) to analyze the psychometric properties of the Brazilian version of the Family Accommodation Scale for OCD – Interviewer-Rated (FAS-IR); 2) to assess the impact of cognitive-behavioral group therapy (CBGT) with the involvement of family members in two sessions on FA and to identify sociodemographic and clinical variables predictive of FA reduction after the 12 treatment sessions (short term); and 3) to assess the impact of CBGT on FA 3 years after completion of the program and to investigate the correlation between severity of OCD symptoms and FA in the long term. The study included patients with a diagnosis of OCD and their family members. Obsessive-compulsive symptoms were assessed using the following instruments: Obsessive-Compulsive Inventory – Revised (OCI-R), Yale-Brown Obsessive Compulsive Scale (Y-BOCS), and Clinical Global Impressions Scale (CGI). Beck Depression (BDI) and Anxiety (BAI) Inventories, as well as the Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version (SCID-I), were also administered to investigate the presence of possible comorbidities. FA was assessed using the FAS-IR, administered to family members. Upon completion of the FAS-IR validation study, a randomized clinical trial was conducted, randomly assigning patients to either the intervention group (12 sessions of CBGT, of which two involved family members) or to a control group (waiting list). Finally, a naturalistic follow-up study was conducted 3 years after completion of the CBGT program. The study was approved by the Research Ethics Committee of Hospital de Clínicas de Porto Alegre. We found that the Brazilian Portuguese version of the FAS-IR had sound psychometric properties, reinforcing that this is a reliable instrument for assessing the participation and modifications of the routines of family members as a result of the patient’s symptoms. With regard to treatment outcomes, the randomized clinical trial included a sample of 98 pairs of patients with OCD and their family members, of which 52 (53.1%) were randomly allocated to the intervention group and 46 (46.9%) to the waiting list. There was a significant improvement of all OCD symptoms and also of FA levels after CBGT in the intervention group when compared to the control group (p < 0.001). The following variables were predictors of FA reduction after the multivariate analysis: patient characteristics – absence of comorbid unipolar disorder (β = 0.338; p = 0.014), a lower obsession score (β = 0.244; p = 0.045), and higher education level (β = -0.351; p = 0.006); and family member characteristics – a higher hoarding score (β = -0.461; p = 0.001). The model explained 47.2% of the variance in FA scores after CBGT. Finally, in the follow-up study, the FA reduction results obtained at the end of CBGT were found to remain in the long term (3 years). These results add to the current body of evidence not only by confirming that CBGT is effective in reducing OCD symptoms, but also by showing that CBGT with a brief family intervention focused on FA contributes to reduce the level of involvement of family members in the patient’s symptoms, and that these results are maintained over time. Some patient and family member characteristics were found to predict FA reduction, a finding that can contribute to qualify the CBGT protocols currently employed. This is the first study to assess the impact of CBGT (with the participation of family members in two sessions) on FA in both short and long terms. These findings underscore the importance of permanently assessing FA, as well as of involving family members in the treatment of patients with OCD.

O objetivo do presente projeto foi traduzir e adaptar o Obsessional Beliefs Questionnaire – OBQ-44 ao Português Brasileiro e verificar suas propriedades psicométricas em pacientes com Transtorno Obsessivo-Compulsivo (TOC). Na primeira etapa, traduziu-se e adaptou-se o OBQ-44 ao Português Brasileiro, aplicou-se essa versão inicial a 20 pacientes com TOC, observando sua compreensão e adequações linguísticas. Retro-traduzido, gerou-se uma versão final aprovada pela autora. Sua versão brasileira mostrou-se de fácil compreensão e apto a pacientes de classes sócioeconômicas diversas e na identificação dos domínios de crenças em pacientes com TOC, auxiliando na compreensão da origem e manutenção do transtorno. Na segunda etapa, avaliaram-se suas propriedades psicométricas em 104 pacientes com TOC, dos quais 48 realizaram 12 sessões semanais de Terapia Cognitivo Comportamental em Grupo (TCCG) e 56 permaneceram em lista de espera, no Hospital de Clínicas de Porto Alegre. Pela análise fatorial, identificaram-se 3 domínios de crenças da escala original, consistência interna muito boa e reprodutibilidade boa. Após intervenção, a sensibilidade à mudança foi boa e quanto ao tamanho de efeito padronizado, verificouse forte intensidade. A versão brasileira do OBQ-44 apresentou boas propriedades psicométricas, mostrando-se útil ao estudo de crenças disfuncionais em pacientes com TOC e sua modificação com o tratamento. / The aim of this present Project was to translate and adapt the Obsessional Beliefs Questionnaire – OBQ-44 to the Brazilian Portuguese, and to verify its psychometric properties in patients with Obsessive-Compulsive Disorder (OCD). During the first stage, the OBQ-44 was translated and adapted to the Brazilian Portuguese, and it was administrated to 20 patients with OCD to observe its comprehension and linguistic accuracies. After being back-translated, a final version was developed and approved by the author. Its Brazilian version presents to be easily comprehended and suitable to be used with patients belonging to several socio-economic classes, and to identify the belief domains in patients with OCD, assisting the understanding of the origin and maintenance of the disorder. During the second stage, its psychometric properties were evaluated in 104 patients with OCD, of whom 48 underwent 12 weekly sessions of cognitive-behavioral group therapy (CBGT), and 56 remained on the waiting list, at Hospital de Clínicas de Porto Alegre. Through factor analysis, 3 belief domains from the original scale were identified, very good internal consistence, and good reproducibility. After intervention, the sensitiveness to changes was good and, regarding the standardized measures of effect, a strong intensity was verified. The Brazilian version of the OBQ-44 presented good psychometric properties and value to the study of dysfunctional beliefs in patients with OCD and the alterations after treatment.

O Transtorno Obsessivo-Compulsivo (TOC) é um transtorno crônico que causa prejuízos significativos tanto para o paciente como para os seus familiares. De um modo geral, interfere no funcionamento familiar, pois muitas vezes leva os membros de uma família a modificar suas rotinas em função dos sintomas do paciente. As mudanças de comportamentos dos familiares em decorrência desses sintomas são chamadas de Acomodação Familiar (AF). O presente estudo teve como objetivos: primeiramente traduzir e adaptar para o português a Family Accommodation Scale for Obsessive-Compulsive Disorder: Interviewer-Rated (FAS-IR) e, em segundo lugar, examinar se fatores sociodemográficos e clínicos estão ou não associados à AF. Após realizada a tradução e adaptação da escala, foi realizada a segunda etapa do trabalho com uma amostra ambulatorial constituída de 114 pacientes com TOC e seus respectivos familiares. Para avaliação dos sintomas obsessivo-compulsivos (OC) nos pacientes, foram aplicadas as seguintes escalas: DY-BOCS, Y-BOCS e CGI. Para analisar sintomas de depressão e ansiedade, foram aplicados o BDI e o BAI, e para a verificação de possíveis comorbidades, o SCID. Nos familiares, para avaliar a AF foi aplicada a FAS-IR, e para verificação de sintomas OC, a Y-BOCS e a OCI-R. Dois modelos de regressão linear múltipla foram utilizados: o primeiro modelo foi utilizado para avaliar a relação entre as variáveis do paciente e a AF; já o segundo foi utilizado para avaliar as variáveis do familiar e a AF. Averiguou-se que a AF era altamente prevalente entre os familiares na população em estudo. O fator do paciente associado positivamente com a AF foi gravidade do TOC, enquanto AF estava associada inversamente a pior dimensão do paciente ser obsessões com conteúdo agressivo. As características dos familiares associadas positivamente com AF foram sintomas OC nos familiares e o familiar ser o cônjuge do paciente. A AF é muito comum nas famílias de portadores do TOC, mas ainda são pouco conhecidas as razões que levam os familiares a mudarem seu comportamento. É importante estar atento a esse fato, pois tais comportamentos de acomodação podem servir de reforço aos sintomas do paciente e consequentemente contribuir para sua manutenção. / Obsessive-Compulsive Disorder (OCD) is a chronic disorder that causes significant impairments both to patient and his/her family members. Generally, it interferes with familiar functioning, since it frequently drives family members to modify their routines because of the patient‟s symptoms. Changes on family members‟ behaviors as a consequence of these symptoms are termed as Family Accommodation (FA). The present study aimed at: firstly translate into and adapt to Portuguese the Family Accommodation Scale for Obsessive-Compulsive Disorder: Interviewer-Rated (FAS-IR) and, secondly, to examine whether or not socio-demographic and clinical factors are associated to FA. After the scale was translated and adapted into Portuguese, the second step of the research was performed with an outpatient sample comprised 114 patients with OCD and their respective family members. To evaluate the obsessive-compulsive (OC) symptoms on patients, the following scales were applied: DY-BOCS, Y-BOCS, and CGI. To analyze depressive and anxiety symptoms, the BDI and BAI scales were used, and to verify possible comorbidities, the SCID. On family members, to evaluate the FA, FAS-IR was applied, and to verify the OC symptoms, the Y-BOCS and OCI-R scales. Two multiple linear regression models were used: the first one was used to evaluate the relationship between patient‟s variables and the FA; and the second one, to evaluate the relationship between family member‟s variables and the FA. It was noted that FA was highly prevalent among the family members in the studied population. The patient‟s factor positively associated with FA was OCD severity, whereas FA was inversely associated with the patient‟s worst dimension being obsessions with aggressive content. Family members‟ characteristics positively associated with FA were OC symptoms in family members and the family member being the patient‟s spouse. The FA is highly common among OCD carriers‟ families, but the reasons that drive family members to modify their own behaviors are not yet well known. It is important to be aware of this fact, since these accommodation behaviors may serve as a reinforcer of the patient‟ symptoms, and, consequently, contribute in keeping them.