Zhang, Dexing = 階梯式治預防焦慮癥和抑鬱癥的效果和可性的研究 / 張德杏. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 181-205). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese; appendixes includes Chinese. / Zhang, Dexing = Jie ti shi zhi yu fang jiao lü zheng he yi yu zheng de xiao guo he ke xing de yan jiu / Zhang Dexing.

Excessive Reassurance Seeking (ERS) is an under-researched and poorly understood behaviour that resembles the compulsive behaviours that are typically seen in obsessional problems. ERS can be complex, persistent, extensive, debilitating and may dominate the interactions of those involved. In addition to resembling compulsive checking in Obsessive-Compulsive Disorder (OCD) it may have the effect of transferring responsibility to another person. However, it could be seen as a type of support. Both ERS and support are defined and key questions about these concepts are considered in five studies which examine ERS from the perspectives of non-clinical samples, sufferers of anxiety problems, caregivers and therapists. Study 1 qualitatively examines interpersonal components of ERS in OCD and identified the experience of frustration in caregivers as being particularly pervasive. Study 2 examines the diagnosis specific/transdiagnostic elements of ERS in OCD and health anxiety contrasted with support using mixed methods. Results revealed some limited diagnosis specificity of ERS. Strikingly, people with health anxiety did not seek support; reassurance seeking may be their default response. Study 3 uses a larger sample to quantitatively evaluate therapists’ perception of ERS and its treatment, with results suggesting that there is considerable room for improvement. Study 4 examined therapeutic intervention for ERS in treatment refractory OCD using a single case experimental design; Cognitive Behavioural Treatment (CBT) that focuses on treating ERS had beneficial effects. Study 5 tackled the diagnosis specific/transdiagnostic issues in a questionnaire by considering ERS across different anxiety problems. ERS may represent a final common pathway of multiple processes; some processes appear transdiagnostic; others may indicate disorder specificity. Overall, findings reveal the complexity of ERS and its likely nature as a safety-seeking behaviour which requires attention in treatment. Engendering support as an alternative to reassurance in CBT may be particularly promising.

Orientadora: Telma Gonçalves Carneiro Spera de Andrade / Banca: Camila Marroni Roncon / Banca: Lucinéia dos Santos / Resumo: Fármacos antidepressivos como os inibidores seletivos de recaptação de serotonina são utilizados no tratamento da ansiedade, pânico e outros transtornos mentais. Os efeitos desejados ocorrem somente após administração crônica, em torno de 3 a 4 semanas após o início do tratamento, com aumento dos sintomas de ansiedade no início da terapia farmacológica, ocasionando a descontinuidade do uso desses fármacos. Além disso, há relatos de resistência a esse tipo de tratamento. Visando encontrar soluções para tais problemas, fundamentados em estudos que mostraram que mecanismos opioides favorecem a atividade inibitória da serotonina em neurônios da Substância Cinzenta Periaquedutal Dorsal que modulam a fuga/pânico, o presente estudo teve por objetivo investigar o efeito da Buprenorfina, um agonista parcial de receptores μ-opioide e antagonista de receptores κ-opioide, como agente ansiolítico e anti-pânico, como também avaliar se o efeito ansiolítico e antipânico da Fluoxetina seriam antecipados pela associação com a Buprenorfina. Foram realizados 3 experimentos utilizando ratos machos Wistar com peso médio de 200g no início das sessões experimentais: 1. Tratamento agudo com Buprenorfina IP nas doses (0,015mg/Kg, 0,03mg/Kg e 0,3mg/Kg), tendo como controle positivo o Alprazolam IP (4mg/Kg); 2. Tratamento subcrônico 3 dias com Buprenorfina IP (0,3mg/Kg); 3. Tratamento agudo com Buprenorfina (0,3mg/Kg) - associado ao tratamento subcrônico com Fluoxetina 3 dias IP (10mg/Kg)... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Antidepressant drugs such as selective serotonin reuptake inhibitors are used in the treatment of anxiety, panic and other mental disorders. The desired effects occur only after chronic administration, around 3 to 4 weeks after starting treatment, with increased anxiety symptoms at the beginning of pharmacological therapy, causing the discontinuation of the use of these drugs. In addition, there are reports of resistance to this type of treatment. Aiming to find solutions for such problems, based on studies that showed that opioid mechanisms favor the serotonin inhibitory activity in SCPD neurons that modulate scape/panic, the present study aimed to investigate the effect of Buprenorphine, a partial agonist of μ receptors-opioid and antagonist κ receptor-opioid as anxiolytic and anti-panic agents as well as assessing whether the anxiolytic and antipanic effect of Fluoxetine would be antecipated by association with Buprenorphine.Three experiments were performed using male Wistar rats weighing 200g at the beginning of the experimental sessions: 1. Acute treatment with Buprenorphine IP at doses (0,015mg/kg, 0,03mg /kg and 0,3mg/kg) or Alprazolan IP (4mg/kg); 2. Subchronic treatment 3 days with Buprenorphine IP (0,3mg/kg); 3. Acute treatment with Buprenorphine (0,3mg/kg) - associated to the subchronic treatment with Fluoxetine 3 days IP (10mg/kg). After the treatments, the animals were submitted to behavioral evaluation in the Elevated T Maze (ETM) and subsequently to the Open Field and the Light-Dark Transition Test. In experiment 1 the behavioral test was repeated 24 hours after the first behavioral evaluation. The results showed that Buprenorphine in the larger doses decreased the manifestation of the avoidances, without alterations of the scapes in the ETM, differently from what was (Complete abstract click electronic access below) / Mestre

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

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.

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 involvement of corticotropin-releasing hormone (CRH) and neuropeptide Y (NPY) in the pathophysiology of anxiety and anxiety-related disorders is well established. The objective of this study is to explore the genetic variations in the CRH and NPY genes in a well-documented behavioral animal model, the vervet monkey (Chlorocebus aethiops sabaeus), in order to uncover a possible association between these polymorphisms and behavioral traits quantitatively extracted following analysis of social behavior and responses to novelty challenges. / The vervet CRH and NPY genes were amplified and sequenced; the priority was given to the regions expanding from -1kb upstream of the transcription initiation site (where most of the regulatory elements are found in both genes) through the second exon. / Polymorphism discovery analysis revealed the presence of 9 vervet CRH SNPs and 9 vervet NPY SNPs; the SNPs are relatively evenly distributed across the regions covered. An association between one intronic NPY SNP and "defensive aggression" was detected. / These results are coherent with other reports implicating NPY in defensive aggressive behavior, and support the notion that fear responses are fundamental behavioral traits for the dissection of anxiety.