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.

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.)--University of Alberta, 2009. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Department of Psychology. Title from pdf file main screen (viewed on November 6, 2009). 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.