Thesis (M.S.)--University of Hawaii at Manoa, 2007. / Includes bibliographical references (leaves 50-51). / viii, 51 leaves, bound ill. (some col.) 29 cm

Thesis (M.S.)--University of Hawaii at Manoa, 2005. / Includes bibliographical references (leaves 37-41). / viii, 41 leaves, bound cil. ill. 29 cm

Thesis (MAppSc in Physiotherapy)--University of South Australia,1997

ABSTRACT Alcoholism inflicts great suffering on individuals and their families and constitutes a huge financial and health burden for society. Current treatments are only partially effective and not adequate because the extraordinary complexity of the condition has, to date, precluded a sufficient level of understanding for specific and successful treatments to be developed. Since alcoholism is a heterogeneous disorder there is unlikely to be a single effective therapeutic, necessitating the development of a range of options. Fortunately addiction neuroscience is a dynamic field and the quality and quantity of information that is now generated gives hope for the development of more useful treatments in the near future. Alcoholism causes long-lasting neuroadaptations resulting in poor health, brain damage, lost productivity, increased incidence of accidents and injury, violence, loss of social and occupational function and premature death. Ethanol alters brain structure and function in numerous and fundamental ways which persist during abstinence. Each of these long-term neuroadaptations is initiated by changes in gene expression which, with repeated alcohol use, become more permanent. The study of alcohol-induced changes in gene expression can aid in the identification of the molecular targets of ethanol and thereby advance our understanding of this disease. The aim of this thesis was to examine differences in gene expression in the brains of alcoholic and non-alcoholic human subjects. The first part involved the investigation of differentially expressed cDNA fragments identified by a PCR-differential display of the cortex of human alcoholics and controls. This led to the unexpected discovery of an upregulated non-coding RNA (ncRNA) in hippocampus, cerebellum and brainstem of human alcoholics and in hippocampus, cerebellum and cortex of alcohol-treated rats. RNA transcripts which do not encode protein but function as ncRNAs play a crucial role in the regulation of gene expression. Thus the increased ncRNA expression suggests that alcohol may influence the regulation of gene expression via its action on ncRNAs. In recent years the crucial importance of the amygdala in drug-seeking and relapse has been increasingly recognized. The wealth of information generated by microarrays can give a more detailed picture of the molecules which participate in the processes underlying the different forms of synaptic plasticity, so that more comprehensive and sophisticated models of the events underlying the development of alcoholism can be formed. For the second part of this work a 19K microarray was used to compare gene expression in the amygdala of alcoholic patients and control cases. The results show that alcoholism affects a broad range of genes and many systems in the amygdala including genes involved in glutamatergic function, synaptic transmission, structural plasticity, metabolism, transcription and RNA processing, energy metabolism, neurodegeneration, chromatin remodeling and the circadian cycle. The glutamate system is profoundly affected by alcoholism and in the amygdala it is involved in associative learning which plays an important role in alcoholism and other addictions. Downregulation of the excitatory amino acid transporters 1 (GLAST) and 2 (GLT-1) and the AMPA glutamate receptor 2 (GluR2) subunit revealed by the microarray were confirmed quantitatively by Western blots and qualitatively by immunohistochemistry. The decreased expression of GLAST, GLT-1 and GluR2 in the alcoholic patients may increase glutamate tone and activity in the amygdala and this may contribute to neurodegeneration as well as the expression of associative memories and anxiety which underlie continued drug-seeking and chronic relapse.

Predominant theories regarding adjustment and adaptation from the 1960s to mid 1980 are examined. Medical literature relating to outcomes after traumatic brain injury is examined. The gloom in major texts is surprising. The lack of definition of the commonly used term ???long-term??? is discussed. The relative lack of research to guide advice about very long-term prognoses remains a major concern. There are a number of ways of defining reality. Some come from an observer???s view of a person???s life. Some come from the reports of a significant other in the life of the person with TBI. Others come from the words or writings of the person who sustained a serious TBI. Quantitative research excels at summarising data and reaching generalisations based on statistical projections. Qualitative research excels at telling the story from the person???s viewpoint, providing the rich descriptive detail that sets quantitative results into their human context. An opportunistic sample of people who suffered a very severe TBI in 1981 was traced and narratives of their experiences since their injury obtained, either written or converted to text from interview. The texts were analysed using a qualitative technique based on grounded theory. The results of the analysis, the fact that a variety of approaches were used by people to deal with their problems, possible reasons for negative prognoses, and the limitations of the study are highlighted. Possible reasons why negativity appears to pervade the thinking of some health professionals involved with people with TBI, and possible directions for the future in therapy and research are discussed.

Predominant theories regarding adjustment and adaptation from the 1960s to mid 1980 are examined. Medical literature relating to outcomes after traumatic brain injury is examined. The gloom in major texts is surprising. The lack of definition of the commonly used term ???long-term??? is discussed. The relative lack of research to guide advice about very long-term prognoses remains a major concern. There are a number of ways of defining reality. Some come from an observer???s view of a person???s life. Some come from the reports of a significant other in the life of the person with TBI. Others come from the words or writings of the person who sustained a serious TBI. Quantitative research excels at summarising data and reaching generalisations based on statistical projections. Qualitative research excels at telling the story from the person???s viewpoint, providing the rich descriptive detail that sets quantitative results into their human context. An opportunistic sample of people who suffered a very severe TBI in 1981 was traced and narratives of their experiences since their injury obtained, either written or converted to text from interview. The texts were analysed using a qualitative technique based on grounded theory. The results of the analysis, the fact that a variety of approaches were used by people to deal with their problems, possible reasons for negative prognoses, and the limitations of the study are highlighted. Possible reasons why negativity appears to pervade the thinking of some health professionals involved with people with TBI, and possible directions for the future in therapy and research are discussed.

Thesis (Ph. D.)--University of Washington. / Bibliography: l. [190]-200.

Thesis (Ph. D.)--Virginia Commonwealth University, 2007. / Prepared for: Dept. of Psychology. Bibliography: leaves 94-108.

Thesis (Ph. D.)--School of Psychology, Faculty of Science, University of Sydney, 2007. / Title from title screen (viewed Aug. 1, 2007). Includes papers co-authored by author. Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the School of Psychology, Faculty of Science, University of Sydney. Includes bibliography. Also issued in print.

Thesis (Ph. D.)--University of Hong Kong, 2007. / Also available in print.