Since sildenafil's (Viagra®), a phospodiesterase type 5 (PDE5) inhibitor, approval for the treatment of male erectile dysfunction (MED) in the United States early 1998, 274 adverse event reports were filed by the Food and Drug Administration (FDA) between 4 Jan. 1998 and 21 Feb. 2001 with sildenafil as the primary suspect of various neurological disturbances, including amnesia and aggressive behaviour (Milman and Arnold, 2002). These and other research findings have prompted investigations into the possible central effects of sildenafil. The G protein-coupled muscarinic adetylcholine receptors (mAChRs) and serotonergic receptors (5HT-Rs), have been linked to antidepressant action (Brink et al. 2004). GPCRs signal through the phosphatidylinositol signal transduction pathway known to activate protein kinases (PKs). Since the nitric oxide (NO)-guanylyl cyclase signal transduction pathway is also known to involve the activation of PKs (via cyclic guanosine monophosphate (cGMP)), the scope is opened for sildenafil to possibly modulate the action of antidepressants by elevating cGMP levels. It is generally assumed that excitotoxic delayed cell death is pathologically linked to an increase in the release of excitatory neurotransmitters e.g. glutamate. Glutamate antagonists, especially those that block the define NMDA-receptors, are neuroprotective, showing the importance of the NMDA-NO-cGMP pathway in neuroprotection (Brandt et al., 2003). Sildenafil may play a role in neuroprotection by elevating cGMP levels. Aims: The aims of the study were to investigate any neuroprotective properties of sildenafil, as well as modulating effects of sildenafil pre-treatment on mAChR function. Methods: Human neuroblastoma SH-SY5Y or human epithelial HeLa cells were seeded in 24-well plates and pre-treated for 24 hours in serum-free medium with no drug (control), PDE5 inhibitors sildenafil (100nM and 450 nM), dipiridamole (20 µM) or zaprinast (20 µM), non-selective PDE inhibitor 3-isobutyl-I-methylxanthine (IBMX - ImM), cGMP analogue N2,2'-0-dibutyrylguanosine 3'5'-cyclic monophosphate sodium salt (500 µM), guanylcyclase inhibitor 1H-[1 ,2,4]oxadiazolo[4,3-a]quinoxalin-I-one (ODQ - 3 µM) or sildenafil + ODQ (450 nM and 3 µM respectively). Thereafter cells were used to determine mAChR function by constructing dose-response curves of methacholine or to determine cell viability utilising the Trypan blue, propidium iodide and MTT tests for cell viability. Results: Sildenafil pre-treatments induced a 2.5-fold increase in ,the Emax value of methacholine in neuronal cells but did not show a significant increase in epithelial cells The Trypan blue test suggests that neither the PDE5 inhibitors nor a cGMP analogue show any neuroprotection. Rather, sildenafil 450 nM, dipiridamole and IBMX displayed a neurodegenerative effect. The MTT test was not suitable, since pre-treatment with the abovementioned drugs inhibited the formation of forrnazan. The propidium iodide assay could also not be used, due to severe cell loss. Conclusion: Sildenafil upregulates mAChR function in SH-SY5Y cells and displays a neurodegenerative, and not a protective property, in neuronal cells. This is not likely to be associated with its PDE5 inhibitory action, but may possibly be linked to an increase in cGMP levels via the NO-cGMP pathway. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2005.

The first goal of the current study was to comprehensively assess depressive and anxiety symptomatology, and examine the resultant symptom structures among 206 Caucasian Canadian and 251 Chinese Canadian university student samples in relation to the tri¬partite conceptual model put forth by Clark and Watson (1991). The current study used 14 symptom measures assessing the affective (e.g., low positive affect), the cognitive (e.g., worry), and the somatic aspects (e.g., autonomic hyperarousal) of depressive and anxiety symptomatology. Items that were found to function differently across the current two samples via the techniques of item response theory were considered to be culturally biased and were subsequently removed from these 14 measures so that the true structural relations among measures of depressive and anxiety symptomatology could be illustrated. The current study identified differences in symptom structures between Chinese and Caucasian samples (e.g., worry and autonomic hyperarousal), as well as differences between these two samples' symptom structures and the structures of the original tripartite model (e.g.. lack of depression specific element). After the cross sample differences and similarities in symptom structures of anxiety and depressive symtomatology were identified, the second primary goal of the current study was to further investigate cultural influences on between-group similarities and differences in the resultant symptom structures of anxiety and depression. Symptom factor scores were found to relate only to specific but not generic indicators of an individual's cultural experiences (e.g., Negative Acculturating Experiences). Furthermore. among 201 items of the 14 symptom measures included in the current study, 52 items (about 26%) were found to be culturally biased, with about one half of them being more likely endorsed by the Chinese sample and about the other half more likely endorsed by the Caucasian sample. The phenomenon of cultural bias at an item level was common, because all scales used in the current study contained culturally biased items, and because bias responding tendency was found within both Chinese and Caucasian samples. Cultural contrast response tendency, a composite variable of all cultural biased items. was found to relate to some but not all aspects of cultural orientations (e.g.. Canadian External Orientation). It also showed a greater relation than symptom factors with cultural orientation measures. The third goal of the current study was to explore individuals' cultural and depressive experiences with a qualitative approach using a semi-structured interview, in order to discover new culturally relevant themes that may link individuals' cultural background with psychopathology. Three themes were identified among the interviews of Chinese Canadian university students. portraying the role of Chinese culture in understanding an individual's depression, illustrating the mechanism linking culture with psychopathology, and highlighting the significance of a qualitative research approach in understanding a Chinese individual's experiences. Clinical implications for assessing depression and anxiety symptomatology, especially for individuals with Chinese origin, were discussed.

Diss. Linköping : Univ., 1999.

Thesis (Ph. D.)--State University of New York at Binghamton, Department of Psychology, 2006. / Includes bibliographical references.

Thesis (Ph. D.)--Rutgers University, 2009. / "Graduate Program in Psychology." Includes bibliographical references (p. 51-66).

Title from second page of PDF document. Includes bibliographical references (p. 103-109).

Thesis (Ph. D.)--University of New South Wales, 2006. / "May 2006." Title taken from title screen (viewed October 25, 2007). Includes bibliographical references (p. 188-206) and appendices.

Esta dissertação é composta por quatro estudos acerca de instrumentos para a avaliação de sintomas de ansiedade. O objetivo do Estudo 1 foi realizar uma revisão sistemática dos instrumentos disponíveis para avaliar sintomas de ansiedade e transtornos de ansiedade (TA) em população brasileira. O objetivo do Estudo 2 foi realizar o processo de adaptação transcultural da Spence Children’s Anxiety Scale (SCAS) para o Brasil. O objetivo do Estudo 3 foi examinar a sensibilidade e especificidade da Screen for Child Anxiety Related Emotional Disorders (SCARED) para o diagnóstico de TA em uma amostra comunitária de crianças e adolescentes brasileiros. O objetivo do Estudo 4 foi investigar as propriedades psicométricas da SCAS em amostras comunitária e clínica de crianças e adolescentes brasileiros. Os resultados do Estudo 1 fornecem um panorama das características e evidências de adequação dos instrumentos disponíveis para avaliar sintomas de ansiedade e TA em população brasileira. Os resultados dos Estudos 2, 3 e 4, em conjunto, apresentam a versão brasileira da SCAS como um instrumento adequado para avaliar sintomas de ansiedade infantil em contextos comunitário e clínico no Brasil. Implicações para a avaliação e o tratamento psicológico e psiquiátrico de TA são discutidas. / This Master Thesis encompasses four studies about instruments to the assessment of anxiety symptoms. The aim of the Study 1 was to conduct a systematic review of the instruments available to assess anxiety symptoms and anxiety disorders (AD) in Brazilian population. The aim of the Study 2 was to perform the cross-cultural adaptation process of the Spence Children’s Anxiety Scale (SCAS) to Brazil. The aim of the Study 3 was to examine the sensitivity and specificity of the Screen for Child Anxiety Related Emotional Disorders (SCARED) to the diagnosis of AD in a community sample of Brazilian children and adolescents. The aim of the Study 4 was to investigate the psychometric properties of the SCAS in a community and a clinical sample of Brazilian children and adolescents. Results from Study 1 provide an overview of the characteristics and the adequacy evidences of the instruments available to assess anxiety symptoms and AD in Brazilian population. Results from Studies 2, 3, and 4, altogether, present the Brazilian version of the SCAS as an instrument suitable to assess pediatric anxiety symptoms in Brazilian community and clinical settings. Implications for the psychological and psychiatric assessment and treatment of AD are discussed.

The purpose of the current project is to illustrate the application of advanced statistical techniques to address research questions about depression and anxiety in patients with an acute coronary syndrome (ACS). The first study, using data from 100 patients who were randomized into a clinical trial of cognitive behavioral therapy, used bivariate mixed models to determine trajectories of depression and anxiety after an ACS, to examine the effects of cognitive behavioral therapy (CBT) on depression and anxiety, and to determine if anxiety and depression symptoms change at the same rate with CBT treatment as indicated by joint modeling of these two psychiatric disorders. The findings suggest that depression and anxiety are highly correlated and persistent in patients with an ACS both at baseline and over time. The intervention used in the present investigation does not appear to uncouple the association between anxiety and depression, suggesting that CBT has comparable effects on both psychiatric disorders. The second study used latent transition analysis to identify symptomatology profiles of depression, anxiety, and functional impairment in patients with an ACS, describe changes over time (two, three and six-month follow-up) in patient’s acute symptom profiles, and determine if patients receiving CBT showed signs of remission in depression, anxiety and impaired function earlier than patients that received usual care. A three-class model was selected to identify and describe these acute symptom profiles. One class was characterized by patients with both psychiatric disorders and impaired function, the second by patients with psychiatric disorders but normal function, and the third by patients with anxiety but without depression, and having normal function. There was moderate improvement in depression, anxiety and functional status for control patients, but this improvement was less evident than in the treatment group. Women showed a better response to CBT than men. The third study used latent class and latent transition analysis to determine symptom profiles of depression and anxiety in patients with an ACS using the Hospital Anxiety Depression Scale; a secondary study goal was to examine the effects of age and gender on these symptom patterns. A two-class model was selected to describe depression and anxiety symptomatology profiles. Class I (76% of patients at baseline) was labeled as “severe depression and some anxiety” whereas Class II (24% of patients at baseline) was labeled as “mild depression and distress anxiety”. More than 70% of older patients continued to have severe depression and anxiety at follow-up and a large proportion of these patients who reported mild depression and anxiety at baseline showed worsening of symptoms at follow-up. The current study demonstrates that patients with depression and anxiety after an ACS can be identified on the basis of the symptoms that they present. This is particularly important to identifying individuals at potential risk for developing clinical complications after an ACS.

Os transtornos de ansiedade estão entre os mais comumente observados, tanto na população em geral, quanto nos serviços de atenção primária à saúde. Acometem entre 5 a 18% de crianças e adolescentes e se associam a altas taxas de psicopatologia na adolescência e na vida adulta. Apesar da alta prevalência e da substantiva morbidade associada, os transtornos de ansiedade infanto-juvenis ainda são subdiagnosticados e subtratados, mesmo com evidências de tratamentos efetivos, como a farmacoterapia e a terapia cognitivo-comportamental (TCC). No Brasil, a TCC tem uma aplicação restrita devido ao pequeno número de terapeutas habilitados e, sobretudo, à falta de protocolos elaborados, considerando as características socioculturais do país. A presente pesquisa tem por objetivo descrever a elaboração, o desenvolvimento das sessões de TCC em grupo para o tratamento de transtornos de ansiedade de pré-adolescentes (10 a 13 anos) e avaliar a resposta à terapia, considerando as características da cultura brasileira. A TCC em grupo elaborada nesta pesquisa baseou-se no programa reconhecido para o tratamento de crianças e adolescentes com transtornos de ansiedade, o Cognitive-behavioral therapy for anxious children: therapist manual for group treatment, e o Coping Cat workbook, ambos de Kendall e Hedtke (2006), em bibliografias atuais sobre o tema e na experiência das terapeutas e supervisoras. As sessões foram elaboradas uma a uma e, para verificar se cada sessão estava adequada em relação aos procedimentos e ao tempo proposto, foi realizado um grupo piloto com quatro pré-adolescentes. A versão final do protocolo de TCC em grupo, após o ajuste das sessões, de acordo com as considerações subjetivas e objetivas da equipe e dos pacientes, foi definida em 14 sessões semanais de 90 minutos cada e mais duas sessões concomitantes com os pais: uma na sétima semana do tratamento e outra na última semana do mesmo. Cento e trinta e oito estudantes de escolas públicas da área de abrangência do Hospital de Clínicas de Porto Alegre foram diagnosticados com transtorno de ansiedade e 45 preencheram os critérios de inclusão para testar a resposta ao protocolo final. Os diagnósticos foram determinados por psiquiatras da infância e adolescência, através de uma entrevista semi-estruturada, o Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (KDSADS-PL). A eficácia do tratamento foi avaliada pelas seguintes escalas: Clinical Global Impression (CGI), Pediatric Anxiety Rating Scale (PARS) e Children’s Global Assessment Scale (CGAS), para mensurar a melhora clínica; Screen for Child Anxiety Related Emotional Disorders (SCARED) e Children’s Depression Inventory (CDI), para avaliar a intensidade dos sintomas de ansiedade e de depressão, respectivamente; a SNAP-IV que avalia os sintomas externalizantes; e Youth Quality of Life Instrument-Research Version (YQOL-R), que avalia a qualidade de vida. As avaliações dos pacientes foram realizadas por avaliadores independentes e aplicadas no início, meio e término do tratamento. Em relação à elaboração do manual, observou-se que vários procedimentos do protocolo original não eram viáveis nesta população, em função do nível socioeconômico e por razões culturais. Os pacientes se mostraram mais motivados em fazer atividades lúdicas e divertidas, assim como, requisitaram mais oportunidades para falarem sobre seus sentimentos e pensamentos ao invés de escrever no manual de terapia. Dos 41 pré-adolescentes que preencheram os critérios de inclusão no estudo, 28 (68%) aceitaram fazer o tratamento e entraram em um dos quatro grupos de TCC. Houve um predomínio do sexo feminino (n = 22; 79%), com média de idade (desvio padrão) de 12(DP=0,77) anos. O diagnóstico mais freqüente foi transtorno de ansiedade generalizada (n = 23; 82%) e todos os pacientes apresentaram pelo menos mais de uma comorbidade, principalmente com outro transtorno de ansiedade. Considerando a resposta ao tratamento, houve diminuição significativa nos sintomas de ansiedade (p <0,001), e melhora nos sintomas externalizantes, com tamanho de efeito de moderado a grande (0,59 a 2.06), porém, não houve diminuição dos sintomas depressivos e melhora da qualidade de vida ao longo do tempo. Os resultados confirmaram que a utilização de um protocolo de TCC requer adaptação cultural. A melhora significativa nos sintomas de ansiedade e não dos sintomas de depressão e da qualidade de vida reforçam a importância de intervenções precoces para jovens. Finalmente, é necessário um estudo de seguimento para avaliar a resposta ao tratamento em longo prazo. / Anxiety disorders are among the most commonly observed, both in the general population and in the services of primary health care. Anxiety disorders affect between 5 and 18% of children and adolescents and are associated with high rates of psychopathology in adolescence and adulthood. Despite the high prevalence and substantial associated morbidity, anxiety disorders in children and adolescents are still underdiagnosed and undertreated, despite evidence of effective treatments, like CBT and pharmacotherapy. In Brazil, CBT has limited application due to the small number of qualified therapists, and especially the lack of protocols devised by considering the sociocultural characteristics of the country. The objectives of the present research are to describe the design and development of the session’s group CBT for the treatment of youths (10 to 13 years old) with anxiety disorders and to evaluate the final response to therapy, considering the characteristics of Brazilian culture. The CBT group developed in this research was based on the recognized program for the treatment of children and adolescents with anxiety disorders, The Coping Cat program - Cognitive-behavioral therapy for anxious children: therapist manual for group treatment, and The Coping Cat workbook, both by Kendall and Hedtke (2006), in current bibliographies on the subject and the experience of therapists and supervisors. The sessions were designed one by one, and to verify that each session was appropriate for the procedures and the proposed time, a pilot group was created with four youths. The final version of the group CBT protocol, after adjustment of the sessions and according to the subjective and objective considerations of staff and patients, was defined in 14 weekly sessions of 90 minutes each and an additional two concurrent sessions with parents: one in the seventh week of treatment and another in the last week. One hundred and thirty-eight students selected from public schools in the area covered by Hospital de Clínicas de Porto Alegre were diagnosed with anxiety disorder and 45 fulfilled inclusion criteria to test the response of the final protocol. Diagnoses were made by childhood and adolescence psychiatrists, through a semi-structured interview Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (KDSADS-PL). Treatment efficacy was evaluated through the following scales: Clinical Global Impression (CGI), Children’s Global Assessment Scale (CGAS) and Pediatric Anxiety Rating Scale (PARS), to measure clinical improvement; Screen for Child Anxiety Related Emotional Disorders (SCARED) and Children’s Depression Inventory (CDI), which assess the severity of anxiety and depression symptoms, respectively; SNAP-IV, which assesses the externalizing symptoms; and Youth Quality of Life Instrument-Research Version (YQOL-R), which measures quality of life. Patient assessments were performed by independent evaluators at the beginning, middle and end of treatment. Regarding the manual, several of the original protocol procedures were not feasible in this population, due to socioeconomic and cultural reasons. Patients showed to be more motivated in playful activities while also requesting more opportunities to talk about their feelings and thoughts instead of continuously writing in the therapy manual. All 41 subjects selected according to the inclusion criteria were invited to take part in therapy. A total of 28(68%) patients entered one of four therapy groups and the remaining candidates (32%) were refused for a number of reasons. Concerning response to therapy, there was a significant decrease in anxiety symptoms (p < 0.001), and an improvement in externalizing symptoms (p=.003), with a moderate to large effect size (0.59 to 2.06), but not in depressive symptoms or quality of life over time. The results confirmed that the use of a CBT protocol requires cultural adaptation. The significant improvement in anxiety symptoms and not the symptoms of depression and quality of life emphasize the importance of early intervention for youths. Finally, it is necessary to implement a follow-up study to assess response to treatment in the long term.