Submitted by Jean Medeiros (jeanletras@uepb.edu.br) on 2016-09-09T14:04:14Z No. of bitstreams: 1 PDF - Thyago da Costa Wanderley.pdf: 1142722 bytes, checksum: 59ab00c2674764fd26b76c4ebc9fe32d (MD5) / Approved for entry into archive by Secta BC (secta.csu.bc@uepb.edu.br) on 2016-09-09T18:53:59Z (GMT) No. of bitstreams: 1 PDF - Thyago da Costa Wanderley.pdf: 1142722 bytes, checksum: 59ab00c2674764fd26b76c4ebc9fe32d (MD5) / Made available in DSpace on 2016-09-09T18:55:31Z (GMT). No. of bitstreams: 1 PDF - Thyago da Costa Wanderley.pdf: 1142722 bytes, checksum: 59ab00c2674764fd26b76c4ebc9fe32d (MD5) Previous issue date: 2014-04-08 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Inbreeding is a tradition in populations of northeastern Brazil and is associated with the manifestation of psychiatric disorders such as anxiety disorders, usually treated with benzodiazepines. In this dissertation, two integrative reviews of the literature on use of psychiatric drugs and benzodiazepines in different populations were performed. From these findings and a pilot study, we developed a structured interview schedule to investigate, in a population of 4,543 inhabitants, if there was a higher prevalence of benzodiazepine users in the offspring of consanguineous couples. The users prevalence within the population was estimated to be 4.2%. Within the benzodiazepine users group (n=151), 107 (70.9%) were children of unrelated couples and 44 (29.1%) were consanguineous, whereas in the non-users group (n=251), these values were 177 (70.6%) and 74 (29.4%), respectively; therefore, a significant difference was not observed between the two groups (p=0.94). The users profile was made of women (70.9%), elderly (43.7%) and retired individuals (52.3%). Insomnia (25.8%), "nervousness" (21.9 %) and anxiety (20.5 %) were the main motivations for early usage of these drugs. The majority (97%) of users does not have a clinical diagnosis report and have used such drugs for 8.2 ± 8 years; and a quarter of them did not have an appointment with a physician in the past twelve months. The dependence was observed in 24.5% of the users and 35% of the elderly use these drugs inappropriately, considering the Beers criteria. In the state of Paraíba, it was estimated that R$30 million per year were used to finance the purchase of these drugs; and the users of this medication have not lost their labor capability. / A endogamia é uma tradição mantida em populações do nordeste brasileiro e está associada à manifestação de distúrbios psiquiátricos como os transtornos de ansiedade, usualmente tratados com benzodiazepínicos. Nesta dissertação, foram realizadas duas revisões integrativas da literatura sobre uso de psicofármacos e benzodiazepínicos em diferentes populações. A partir desses achados e de um estudo-piloto, foi desenvolvido um roteiro de entrevista estruturado para investigar, em uma população de 4.543 habitantes, se havia maior prevalência de usuários de benzodiazepínicos na prole de casais consanguíneos. Estimou-se que 4,2% dessa população eram usuários desses medicamentos; sendo que, neste grupo (n=151), 107 (70,9%) eram filhos de casais não consanguíneos e 44 (29,1%) tinham pais aparentados; já no grupo de não usuários (n=251), esses valores foram 177 (70,6%) e 74 (29,4%), respectivamente; não sendo observada, portanto, diferença significativa entre os dois grupos (p=0,94). O perfil dos usuários era de mulheres (70,9%), idosas (43,7%) e aposentadas (52,3%). A insônia (25,8%), o ―nervosismo‖ (21,9%) e ansiedade (20,5%) foram as principais motivações para o início da utilização desses medicamentos. A maioria (97%) dos usuários não possui laudo com diagnóstico clínico e faz uso crônico com média de utilização de 8,2 ± 8 anos; um quarto deles não realizou nenhuma consulta médica nos últimos doze meses. A dependência foi verificada em 24,5% dos usuários e 35% dos idosos fazem uso impróprio desses medicamentos, considerando o critério Beers. Estimou-se que no Estado da Paraíba, anualmente, sejam investidos trinta milhões de reais para financiar a aquisição desses medicamentos; e que o uso desses medicamentos não está relacionado à perda da capacidade laboral.

Introdução: O Transtorno de Pânico é um transtorno de ansiedade que se caracteriza pela recorrência de ataques de pânico: crises súbitas de mal-estar e sensação de perigo ou morte iminente, acompanhadas de diversos sintomas físicos e cognitivos. Os indivíduos com Transtorno de Pânico apresentam, caracteristicamente, preocupações acerca das implicações ou consequências dos ataques de pânico. É uma condição clínica complexa que envolve diferentes modalidades ou conglomerados de sintomas. Assim, o foco nas sensações físicas erroneamente interpretadas no transtorno de pânico e na hipocondria, centraliza-se basicamente nas manifestações autonômicas, como taquicardia e dispneia. Há poucos estudos sobre atividade física e transtorno de pânico. Objetivo: O estudo visa verificar a influência do exercício como terapia de exposição nesta população, em comparação a atividades de relaxamento para pacientes com transtorno de pânico isentos de tratamento medicamentoso. Método: Foram incluídos neste estudo 72 pacientes, de ambos os gêneros com idades entre 18 e 55 anos, diagnosticados com TP com ou sem agorafobia. Foram submetidos a diferentes questionários e a uma ergoespirometria para avaliação inicial do transtorno de ansiedade e identificação de risco cardiovascular. Após adequar aos critérios de inclusão os pacientes foram dispostos aleatoriamente em dois grupos para realização dos protocolos. A ideia foi comparar os grupos e avaliar a eficiência do exercício (grupo ETE) e do relaxamento (grupo R) na amenização dos ataques de pânico e consequente aumento da qualidade de vida dos pacientes, através de diferentes testes e questionários. Resultados: Ambos os grupos apresentaram resultados significativos na redução dos sintomas de pânico, aumento da qualidade de vida e diminuição do número de ataques por dia e na intensidade dos ataques, porém o grupo ETE, que utilizou o exercício como terapia de exposição apresentou melhores resultados, comparado ao grupo R e maior eficácia de manutenção. Conclusão: a pesquisa destaca o potencial do exercício como um suporte autônomo ou intervenção complementar para tratamento de transtornos de ansiedade, e se tratando de TP, o exercício também pode ser considerado como uma exposição terapêutica / Introduction: The panic disorder is an anxiety disorder that is characterized by recurrent attacks of panic: sudden crises of malaise and sense of danger or imminent death, accompanied by various physical and cognitive symptoms. Individuals with panic disorder have, characteristically, concerns about the implications or consequences of the attacks of panic. A complex clinical condition involves different modalities or clusters of symptoms. Thus, the focus on physical sensations erroneously interpreted as a panic disorder and hypochondria, is basically centered in the autonomic manifestations such as tachycardia and dyspnea. There are few studies on physical activity and panic disorder. Purpose: The study is to investigate the influence of exercise as interoceptive exposure therapy in this population, compared to the relaxation activities for patients with panic disorder-free drug treatment. Method: We included 72 patients, of both genders aged between 18 and 55 years, diagnosed with PD with or without agoraphobia. They were submitted to different questionnaires and an ergospirometry for initial evaluation of anxiety disorder and cardiovascular risk identification. After adjusting for the inclusion criteria, the patients were randomly placed into two groups for the protocols. The idea was to compare the groups and to evaluate the efficiency of exercise (ETE group) and relaxation (R group) in the mitigation of panic attacks and consequent increase in patients\' quality of life through different tests and questionnaires. Results: Both groups presented significant results in reducing panic symptoms, increased quality of life and a reduction in the number of attacks per day and in the intensity of the attacks, but the TEE group, which used exercise as exposure therapy, presented better results, compared to the R group and greater maintenance effectiveness. Conclusion: the research highlights the potential of exercise as an autonomous support or complementary intervention for the treatment of anxiety disorders, and if it is a question of PD, exercise can also be considered as a therapeutic exposition

Increased attention towards threatening stimuli in both the external and internal environments is thought to be a factor in the causation and maintenance of pathological anxiety. Attentional biases for threatening information have been demonstrated in anxiety disorders, however the cortical mechanisms involved remain unclear. In this investigation, an Emotional Stroop task consisting of neutral, positive, depression-related and anxietyrelated words, was used to investigate attentional biases in 14 Panic Disorder patients and 32 psychiatrically healthy controls. The standard colour-word Stroop was also performed to determine whether any general cognitive deficits exist in Panic Disorder. Steady-state probe topography (SSPT), a brain electrical activity imaging methodology, was used to investigate participants' brain activity during performance of the tasks. It was hypothesised that Panic Disorder is associated with specific biases for disorder-specific information and thus patients would exhibit increased interference for anxiety-related words only, compared to neutral words. Mean reaction times for the Standard Stroop was similar for the two groups. For the Emotional Stroop task, neither group showed an interference effect for any emotional category. However, Panic Disorder patients performed the Emotional Stroop significantly more slowly than the Controls. The SSPT data suggest that the Standard and Emotional Stroop tasks are associated with different patterns of brain activity in the Control and Panic Disorder groups despite the similarities in the reaction time data. Specifically, the Standard Stroop was marked by strong temporo-parietal excitation in the Panic Disorder group only. In addition, anterior SSVEP patterns further differentiated between the Control and Panic Disorder groups. The most striking finding for the Emotional Stroop was strong sustained bilateral temporo-parieto-occipital excitation in the Panic Disorder group. In addition, a subgroup of the Controls exhibited increased interference for anxiety-related words and therefore the brain activity for this group and the remainder of Controls who did not show interference was analysed separately. It was found that the presence of interference for anxiety-related words was associated with right prefrontal inhibition prior to response. Other time-varying changes in the SSVEP further distinguished between the subgroup of Controls who showed an interference effect and those who did not.

Aus der Einleitung: A wide range of epidemiological community studies worldwide converge on several incontrovertible facts regarding anxiety disorders: they occur frequently, begin at an early age, significantly impair multiple areas of development and life, and are associated with numerous adverse correlates and consequences. Furthermore, evidence clearly points to the fact that the majority of patients who have anxiety disorders still go undetected and undertreated, despite considerable efforts over the last two decades to improve this situation. Less than half receive any treatment at all and only a fraction of those receive what can be considered even "minimally adequate treatment."

The relationship between DSM-IV anxiety disorders and their clinical characteristics in mothers and anxiety in offspring was examined in 933 mother-child pairs from a longitudinal community study. Offspring of mothers with an anxiety disorder had an elevated risk of developing any anxiety disorder, compared with offspring of mothers with no anxiety disorder. Increased risk of anxiety in the offspring was especially associated with maternal social phobia and generalised anxiety disorder, and with maternal diagnoses of early onset, greater number and more severe impairment. These results suggest that the type of maternal anxiety disorder and its severity of manifestation contribute to mother-offspring aggregation of anxiety.

Der Beitrag diskutiert kritische theoretische und praktische Aspekte der Komorbidität auf der Grundlage von klinischen und epidemiologischen Befunden zur Komorbidität. Angststörungen weisen statistisch hochsignifikante Assoziationen untereinander sowie mit affektiven, psychotischen Störungen, Eβstörungen sowie Substanzstörungen und Persönlichkeitsstörungen auf. Sie gehen zumeist eindeutig den komorbiden Störungen voraus, so daβ Angststörungen als Risikofaktoren für viele andere Formen psychischer Störungen angesehen werden können. Die möglicherweise kausalen pathogenetischen Mechanismen sind jedoch nach wie vor umstritten und sind offensichtlich vielfältig. Der Beitrag diskutiert vor diesem Hintergrund besonders die möglicherweise kritische Bedeutung von Panikattacken als zentraler «Vulnerabilitätsmarker» nicht nur für die Entwicklung von Angststörungen, sondern auch für affektive Erkrankungen. Hier konnte z.B. nachgewiesen werden, daβ initiale Panikattacken nicht nur die Wahrscheinlichkeit für Rückfälle sekundärer Depressionen erhöhen, sondern auch signifikant die Häufigkeit und Länge depressiver Phasen beeinflussen. Die Vielzahl differenzierter Befunde legt nahe, Komorbidität bei der Eingangs- und Verlaufsdiagnostik ebenso wie bei der Indikationsstellung umfassender zu berücksichtigen.

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2009. / Härtill 5 uppsatser.

Most cases of lung cancer have a commonly-understood behavioral etiology. Thus, individuals with lung cancer are often blamed for their illness by others and may therefore seek to avoid this blame by concealing their diagnosis from others. This study sought to determine the prevalence of diagnosis concealment, examine potential predictors of concealment, and test parts of a cognitive-affective-behavioral model of the effects of concealing a concealable stigma among individuals receiving treatment for lung cancer. With regard to predictors of concealment, it was hypothesized that concealment would be positively associated with male gender, introversion, and trait social anxiety and would be negatively associated with social support and the use of seeking guidance and support as a coping strategy. Hypothesized correlates of concealment included poorer self-esteem as well as greater anxiety, cancer-specific distress, and social avoidance. A sample of 117 participants receiving chemotherapy or radiation for stage I-IV non-small cell lung cancer and limited to extensive stage small cell lung cancer was recruited during routine outpatient visits. A medical chart review was conducted to assess clinical factors and participants completed a standard demographic questionnaire as well as measures of coping strategies, introversion, trait social anxiety, social avoidance, social support, anxiety, depression, cancer-specific distress, self-esteem, perceived stigma, public self-consciousness, and private self-consciousness. Results indicated that 31% of participants concealed their diagnosis from others since their diagnosis and 26% concealed their diagnosis in the month preceding their participation in the study. Hypotheses regarding predictors and correlates of concealment were not supported. However, exploratory analyses identified use of alcohol, recency of a recurrence of lung cancer, use of positive reappraisal as a coping strategy, and social support as predictors of concealment as well as internalized shame as a correlate of concealment. These findings serve to extend existing literature on concealing a concealable stigma and support parts of an existing model on the effects of concealment. Future research should aim to test the impacts of concealment in the context of certain social situations to examine longitudinal relationships between predictors and consequences of concealment.

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.

Postnatal handling of rat litters during the first week of life greatly decreases behavioural fearfulness to novelty in the adult offspring. Our first question was to what extent the Benzodiazepine/GABAA receptor complex, a system critical for the expression of fear, might be involved in mediating the observed reduced fearfulness in handled animals (H). Benzodiazepine receptor (BZ) binding was reduced in the amygdala and locus coeruleus (LC), regions important for the expression of fear in non-handled (NH) and maternally separated animals (MS). Moreover, levels of the mRNA for the gamma2 sub-unit of the GABAA receptor complex, which confers high affinity BZ binding, were higher in the amygdaloid nuclei as well as in the LC of handled compared with both NH and MS animals. / Studies with the handling paradigm have lead to the idea that variations mother-pup interactions may actually be the cause of the handling effects. As adults, the offspring of mothers which exhibited high levels of licking/grooming and arched-back nursing (LG-ABN) showed substantially reduced behavioral fearfulness in response to novelty compared to the offspring of low LG-ABN mothers. In addition, the adult offspring of the high and low LGABN mothers showed the same receptor and molecular profiles as H and NH adult offspring. Corticotropin releasing factor (CRF) and alpha2 norepinephrine receptor levels, additional receptor systems thought to be important in the expression of fearfulness, differed in these animals too. Adoption studies give further support to the maternal hypothesis in the finding that the expression mRNA for the gamma2 sub-unit of the GABAA receptor complex can be differentially expressed as a result of different offspring to mother combinations. / Taken together, these findings suggest that early life events (ie: naturally occurring differences in maternal care) during the first few days of life have long-term effects on the development of central neurotransmitter systems, which mediate the expression of fearfulness to novelty.