Novel insights into the role of the GABAB receptor in depression and anxiety

The GABAB receptor is a functional heterodimer comprising the GABAB1 and GABAB2 subunits, with the GABAB1 subunit displaying two major isoforms, GABAB(1a) and GABAB(1b). Preclinical findings have strongly implicated the GABAB receptor in stress-related psychiatric disorders, however, the precise contribution of the GABAB receptor in depression and anxiety disorders remains unknown. Emerging data suggest that the interaction between adverse environmental conditions, such as early life stress, and a specific genetic composition can increase the risk to develop psychiatric disorders in adulthood. This thesis investigated the role of the GABAB receptor alone or in combination with early-life stress (maternal separation), in modulating antidepressant like and anxiety-related behaviours. Pharmacological blockade of the GABAB receptor with CGP52432 had antidepressant-like behavioural effects. Moreover, mice lacking the GABAB(1b) receptor subunit isoform exhibited antidepressant-like behaviours in adulthood but anxiety-like behaviour in early-life. In response to maternal separation, GABAB(1a)-/- mice exhibited early-life stress-induced anhedonia, a core symptom of depression, while GABAB(1b)-/- mice exhibited a more resilient phenotype. Moreover, when compared with wildtype or GABAB(1a)-/- mice, GABAB(1b)-/- mice that underwent maternal separation exhibited enhanced stressinduced neuronal activation in the hippocampus and in the nucleus accumbens (NAcc), a critical area for anhedonia thus suggesting that enhanced stress-induced neuronal activation in the hippocampus and NAcc in GABAB(1b)-/- mice may be important for their antidepressant-like phenotype and their resilience to stress-induced anhedonia. Pharmacological blockade of GABAB receptor and GABAB(1b) receptor subunit isoform loss of function increased adult hippocampal cell proliferation, thus suggesting that increased hippocampal neurogenesis could be a potential mechanism for the antidepressant-like effects of GABAB receptor antagonists and GABAB(1b) receptor subunit isoform disruption. Finally, this thesis investigated whether the expression of several genes involved in hippocampal neurogenesis or the antidepressant response were altered in the mouse hippocampus following chronic treatment with a GABAB receptor antagonist.

Caring and anxiety among registered nurses in an acute hospital setting

Background: Even though caring remains the essence of nursing it is still an ambiguous concept as the lens through which each nurse perceives caring differs. The differences are due to multiple factors including the setting in which the nurse works. Nurses experience high levels of anxiety when caring for patients in acute settings. Despite an abundance of published studies on caring there is a dearth of research available that focuses on the relationship between caring and anxiety. Aim: The aim of this research study was to investigate caring and anxiety in a sample of registered nurses working in an acute hospital and to determine the relationship between these and other variables. Method: A quantitative descriptive study using a correlational design was employed, with a sample of 280 registered nurses. The Caring Behaviours Inventory-24 was used to measure caring and the State Trait Anxiety Inventory to measure Anxiety. The study was guided by the Theory of Human Caring (Watson 2008). Findings: Nurses reported high levels of caring and low levels of anxiety. A statistical significant relationship was found between caring and anxiety and between caring and supportive work environment and job satisfaction. A statistical significant relationship was found between anxiety and work environment, job satisfaction gender, age, relationship status and education. Conclusion: This is the first study to investigate the relationship between caring and anxiety in an acute hospital setting. This research contributes to advancing nursing knowledge by providing evidence of the relationship between caring and anxiety among nurses in an acute hospital setting. Despite nurses reporting high levels of caring and low levels of anxiety, it is important to further enhance caring and reduce anxiety levels among all nurses. Thus, educators and managers need to explore strategies for the alleviation of anxiety among nurses, practising in acute care settings.

Nurses' knowledge of advance directives and perceived confidence in end-of-life care: a cross-sectional study in five countries

Nurses' knowledge regarding advance directives may affect their administration and completion in end-of-life care. Confidence among nurses is a barrier to the provision of quality end-of-life care. This study investigated nurses' knowledge of advance directives and perceived confidence in end-of-life care, in Hong Kong, Ireland, Israel, Italy and the USA using a cross-sectional descriptive design (n = 1089). In all countries, older nurses and those who had more professional experience felt more confident managing patients' symptoms at end-of-life and more comfortable stopping preventive medications at end-of-life. Nurses in the USA reported that they have more knowledge and experience of advance directives compared with other countries. In addition, they reported the highest levels of confidence and comfort in dealing with end-of-life care. Although legislation for advance directives does not yet exist in Ireland, nurses reported high levels of confidence in end-of-life care.