Medicine & Health

Publication Search Results

Now showing 1 - 10 of 30
  • (2020) Liu, Yue
    Thesis
    Alzheimer’s disease (AD) and cerebrovascular disease (CVD) are the two most prevalent causes of dementia. However, the molecular basis of AD and Vascular dementia (VaD) remains incompletely understood, and effective treatments are still not available. In the last three decades, the interaction(s) between CVD and AD have attracted considerable interest. Mixed AD/CVD pathology is commonly seen in patients with clinically diagnosed AD dementia. Combined vascular and AD pathology is the leading cause of dementia in the very old, and there is a debate on whether this is due to an additive effect of both pathologies on cognitive impairment, and whether it represents an interaction between the two pathologies. This thesis explored the association and interaction between cerebrovascular disease and AD pathology/dementia from the perspectives of plasma lipid profiles, imaging biomarkers, post-mortem pathology, and animal models. In addition, studies on plasma biomarkers of AD and VaD and their independent contribution to dementia and cognitive decline were interpreted. In chapter 2, a systematic review and meta-analyses of several cerebral small vessel disease (CSVD) imaging biomarkers and AD found that CSVDs alone were not able to predict AD incidence but were associated with AD dementia and AD pathology. The strength of relationship increased with the presence of Apolipoprotein E (APOE ε4) genotype. Periventricular and parietal white matter hyperintensities (WMHs) and cortical microbleeds (CMBs) had stronger association with AD than CSVDs in other regions. Microinfarcts were less well studied in related imaging studies. We also further explored CSVDs and other cerebral vascular injuries in the aspect of neuropathology. In chapter 3, a cross-sectional study of autopsy brain pathology from National Alzheimer’s Coordinating Center (NACC) showed that CVD pathology had an additive effect with AD pathology in the development and progression of Alzheimer’s dementia. The relationship between the plasma lipidome and VaD and AD has received little attention. In chapter 4, liquid chromatography mass spectrometry was used to demonstrate that plasma ceramides and cholesterol-esters had the highest accuracy for the classification of VaD from controls, while in chapter 5, I showed that AD could be best discriminated by plasma cholesterols esters, sphingomyelins and triglycerides. The results obtained from clinical samples were supported by my preclinical animal model work which involved the induction of cerebral vascular lesions in AD transgenic mice. These mice were double transgenic rodents containing a chimeric mouse/human amyloid precursor protein (Mo/HuAPP695swe) and a mutant human presenilin 1 (PS1-dE9), both directed to neurons. In chapter 6, neuroinflammation and cognitive deficits were significantly worse in APP/PS1 mice injected with endothelin-1 – a neuropeptide and vasoconstrictor – in the internal capsule compared to APP/PS1 controls. Finally, the neuroprotective effects of the glutathione precursor against biomarkers of oxidative stress, inflammation, Aβ pathology and ferroptosis, and its outcome on spatial memory in APP/PS1 mice were reported in chapter 7. Our findings on imaging and neuropathological biomarkers of cerebral vascular lesions collectively suggested that vascular lesions had a potentially additive effect on AD pathology in Alzheimer’s dementia. The result was supported by our animal study on interaction of induced brain infarcts and AD-like pathological hallmarks in transgenic mice. The two pathologies might have distinct profiles, especially at the lipid level. Strategies aimed at replenishing GSH levels using GGC may have beneficial effects in AD and other neurodegenerative diseases as well as on the ageing brain.

  • (2022) Ma, Trevor
    Thesis
    The aim of this study was to estimate the prevalence and identify potential determinants of cardiometabolic disease (CMD) in people with psychotic disorders in secure settings and compare these to people with psychotic disorders in the community. A systematic review of the literature was undertaken to determine existing rates of CMD indicators in people with psychotic disorders in secure settings. Data from a comprehensive health and wellbeing survey, the Forensic Mental Health Patient Survey (FMHPS), were obtained to determine the prevalence and determinants of CMD indicators in a sample of forensic patients. Findings were directly compared to a sample of people with psychotic disorders living in the community using data from the second Australian National Survey of High Impact Psychosis (SHIP). The weighted pooled prevalence rates from the reviewed studies were hypertension 25.0% (N=857, 95% CI 22.1-27.9), dyslipidaemia 29.2% (N=1,135, 95% CI 26.6-31.9), diabetes 11.2% (N=2,582, 95% CI 9.9-12.4), being overweight or obese 72.4% (N=840, 95% CI 69.4-75.5), cardiovascular disease 15.6% (N=1,047, 95% CI 13.4-17.8) and metabolic syndrome 23.5% (N=1,390, 95% CI 21.3-25.7). The prevalence of CMD indicators in the reviewed studies were predominantly higher compared to the general population. When directly compared, the forensic patient sample were older, more likely to be male, and more likely to be of Aboriginal and/or Torres Strait Islander background, than the community-based psychosis sample. The former also had higher rates of polypharmacy, clozapine prescribing, physical activity, and food consumption. However, on multivariate analysis, the forensic patients had a lower prevalence of hypertension (OR 0.36, 95% CI 0.23-0.57) and metabolic syndrome (OR 0.41, 95% CI 0.25-0.67) compared to the community-based psychosis sample. There are clearly important differences in the sociodemographic characteristics, treatment needs and lifestyle practices of forensic patients in secure settings and there may be aspects of secure care that actually reduce CMD risk, however the resultant impact on CMD prevalence is complex. Forensic patients in secure settings require early detection and assertive treatment of CMD indicators and further research to assess the feasibility and effectiveness of these interventions in secure settings is required.

  • (2021) Reilly, Lyndon
    Thesis
    The intervention ‘A trial of a community-based intervention to support the active engagement of Aboriginal and Torres Strait Islander men in parenting, and to improve men’s feelings of empowerment, reduce mental distress and reduce drug and alcohol use’ aimed to increase knowledge of men’s roles as parents, increase feelings of empowerment, decrease mental distress and family conflict, and reduce the use of alcohol or drugs. The study followed the guidelines published by Campbell et al. (2000) on conducting and evaluating complex community-based interventions. In early 2017, the trial started in the Lower Gulf of Carpentaria Aboriginal community of Doomadgee in the Men’s Shed. The findings are based on a Qualitative Description (QD) of measures. The sample size for the control group was substantially smaller than anticipated, and the reasons for withdrawal or drop out are described in the thesis. Given the small sample, it was not empirically sound to compare changes pre and post intervention with pre and post control, even descriptively. The insight and knowledge gathered from this study offers great learning and evidence for the field and the communities that support, or might in the future support, men’s groups, and men’s parenting. As such, the study assumed only small numbers of participants, given the time required and the low level of funding available to the candidate. The intervention aimed, however, to meet the criteria of an exploratory trial, apply a pragmatic community-based design, and ensure feasibility, cultural acceptability, and the potential to sustain the initiative. Finally, the intervention offered to set the stage for future definitive randomised controlled trials (RCTs) in the field.

  • (2021) Foo, Heidi
    Thesis
    As humans age, the functional organisation of their brain networks undergoes complex changes that are associated with observed changes in cognition. Both genetics and the environment play a crucial role in influencing changes in the network topology of the ageing brain. In addition, the network topology is influenced by age-related brain diseases. To date, there is a paucity of population-based studies investigating the contributions of age, genetic and environmental factors, and brain disease to the architecture of the functional brain networks. The broad aim of this thesis, therefore, was to examine the influence of genetics, environmental factors, and disease-states on functional brain networks in older individuals using the United Kingdom (UK) Biobank data (N~18,455; ages 44-80 years). To study functional brain networks, I modelled large-scale brain networks from resting-state functional magnetic resonance imaging (fMRI) scans using graph theory, defined by a collection of nodes (brain regions) and edges (magnitude of temporal correlation in activity on fMRI between two brain regions). Four studies are reported in the thesis. In the first study, I investigated the genetic determinants of functional brain networks. I first estimated single nucleotide polymorphism (SNP) heritability (h2). Subsequently, genome-wide association studies (GWAS) were performed to identify genetic variants associated with each graph theory measure. Gene-based association analysis was carried out to uncover gene-level associations, and the functional consequences of the significant genetic variants were explored. As brain reorganisation of the functional networks has been differentially observed with ageing in the two sexes, I examined in the second study how age and sex are associated with the topology of functional brain networks in association with cognitive performance. In the third study, I examined the association of sleep and other lifestyle factors such as exercise, alcohol, and smoking, with functional network properties. In the final study, I studied how disease phenotypes, in particular depressive symptoms, influence functional network properties. This thesis provides several novel contributions to the literature by identifying important genetic, environmental, and disease-related factors that are associated with measures of functional networks in the ageing brain. The findings highlight biological pathways relevant to the ageing human brain functional network integrity and diseases that affect it.

  • (2020) Nicolopoulos, Alexandra
    Thesis
    In the quest to effectively understand what motivates adolescents and young adults to attempt suicide, it is imperative to examine the interplay between factors pertaining to suicide risk, suicidal ideation, and suicide attempt. While current psychological models of suicide have captured this interplay proficiently, they have predominantly been informed by research undertaken in adult populations. Further, these studies have largely been epidemiological and/or clinical in nature, with a diminutive focus on capturing the lived experience of suicide via qualitative methods. The first study in this thesis systematically reviewed and examined qualitative studies conducted between 1995 and 2015, which had investigated motives for suicide in individuals aged 12-25. Results indicated disparity between current suicide models and participants’ lived experience accounts of suicide. Additionally, the review found a lack of research rigour and comprehensiveness among studies which were identified. The second study in this thesis undertook a rigorous, comprehensive qualitative study informed by the findings of the first. Robust theoretical underpinnings, rigorous analytical frameworks, and novel approaches to recruitment and data collection, were employed to explore the multiple complex factors which motivate young individuals to take their own lives. An extensive thematic network analysis revealed interpersonal dysfunction, environmental factors and compromised identity served as the highest risks for suicide in this population. Further investigation of thoughts, emotions and feelings present while ideating, and at the time of attempt, highlighted different themes to those reported in existing suicide models, particularly regarding the linearity of the suicide trajectory endorsed by the models. The overall findings of this research suggest the frameworks of current suicide models - predominantly informed by quantitative studies and investigating adult populations - have not reflected some of the vital themes which characterise the suicide experience of younger populations. Further identified is the capacity of comprehensive qualitative inquiry to highlight richly detailed lived experience and contextual factors, not accessible via clinical and epidemiological studies. Drawing upon qualitative inquiry to inform both extant and future theoretical models, can provide important new insights into understanding suicide in adolescent and young adult populations.

  • (2021) Rahman, Tasnim
    Thesis
    N-methyl-D-aspartate receptor (NMDAR) hypofunction mimics many symptoms of schizophrenia, yet our molecular knowledge about how NMDARs are changed in the dorsolateral prefrontal cortex (dlPFC) and caudate is incomplete. NMDARs are affected by neuroinflammation, and recent research shows evidence of neuroinflammation in schizophrenia pathophysiology — however whether there is a relationship between the neuropathological changes in NMDARs in schizophrenia and neuroinflammation in schizophrenia is not known. I therefore sought to elucidate whether deficits in NMDARs were exacerbated when the brain was in a state of heightened neuroinflammation in dlPFC and caudate in people with schizophrenia. I also determined whether maternal immune activation (MIA) — a risk factor for schizophrenia — could cause molecular changes in NMDARs. For my human studies, I used two matched case/control postmortem cohorts [dlPFC (n=74), caudate (n=88)]. The dlPFC cohort has an identified ‘inflammatory biotype’ previously stratified into ‘high’ or ‘low’ clusters based on the gene expression of inflammatory markers. I found decreased ratio of GluN2A:GluN2B binding and decreased ratio of GRIN2A:GRIN2B mRNA levels in dlPFC in schizophrenia, which were most apparent in cases with high inflammatory status. Next, I found that an inflammatory biotype was identifiable in caudate tissue, where the high inflammatory cluster had more schizophrenia cases (41%) than controls (17%). I then found decreased GRIN1 mRNA in the caudate in schizophrenia, which was most apparent in cases with high inflammatory status. Finally, I used coronal tissue of rats (58) that were offspring of dams injected with either a viral mimic (MIA offspring) or saline (controls) during their pregnancy. I found increased GluN2A:GluN2B binding in the cortex of male MIA offspring, increased NMDAR channels and GluN2A binding in the striatum of male MIA offspring, and decreased GRIN1 mRNA in the striatum of female MIA offspring versus controls. My results suggest a link between neuroinflammation and NMDAR hypofunction in both the dlPFC and caudate in schizophrenia, and that MIA is a factor sufficient to cause NMDAR hypofunction in the striatum at adulthood. My results support the notion that some molecular changes in NMDARs may have a neurodevelopmental origin emanating from foetal-exposure to an inflammatory agent.

  • (2020) Yee, Natalia Yen Lin
    Thesis
    Past research investigating the relationship between psychosis and risk of criminal offending has typically focused on individuals with chronic psychotic disorders and on violent offending. However, contact with the criminal justice system is not constrained to the most unwell or those accused of violent crimes. Therefore, there is a need for research to consider the full spectrum of illness and criminality in order to better understand the association between psychosis and criminal offending and to improve outcomes for mentally ill individuals in the criminal justice system. This thesis adopts a clinical staging approach to psychosis by considering the full illness spectrum, from the at-risk mental state (ARMS) to the early and chronic stages of psychosis, in relation to any type of criminal offending. In Study 1, using a meta-analysis approach, psychosis was positively associated with risk of any type of criminal offending (pooled OR = 2.65, 95% CI = 2.19-3.21, p < .001). The association was slightly stronger in women than men (OR = 2.81 vs. 2.42) although not statistically significant. In Study 2, only a small proportion of adult prisoners referred to prison mental health services for possible psychotic or at-risk symptoms were either in their first episode of psychosis (FEP; 6%) or determined to be at ultra-high risk (UHR; 6%). The majority of referred prisoners had established psychotic illness likely due to the selected nature of the sample. Study 3 involved an unselected sample of prisoners recruited at prison entry. Among those with no prior history of psychosis (n = 155), 24.5% met UHR criteria and 3.2% were in their FEP. Across both Study 2 and 3, psychosis spectrum prisoners had greater disadvantage across key sociodemographic, clinical, and offending indicators when compared to non-psychotic prison controls, but the psychosis spectrum was not associated with a greater risk of violent offending. The illness burden and complex disadvantage associated with psychosis exists across the illness spectrum, including during the early and at-risk stages, regardless of offence type. This highlights the need for specialised early identification and intervention services to improve outcomes for mentally ill offenders, especially those with psychosis. Overall, this doctoral research supports an association between psychosis and criminality that extends across the full spectra of psychotic illness and criminal offending.

  • (2021) Marshall, Ruth
    Thesis
    Background The mental health of first responders is an area of growing concern, with recent studies indicating significantly higher rates of PTSD, anxiety and depression than found in the general population (Berger et al., 2012; Syed et al., 2020). Many organisations use mental health screening to identify individuals at risk of developing posttraumatic stress disorder (PTSD) or other mental health conditions, though its effectiveness conducted pre- or post-employment is unclear. Aims This research aims to investigate the role that mental health screening may have in predicting PTSD and other types of psychological injury in first responders. Methods A systematic review of the research literature related to pre-employment screening of personality and other factors which may be predictive of later depression or PTSD symptoms in first responders was conducted. Nested case-control studies of 300 serving police officers with pre-employment personality screening (MMPI-2) data linked to information on long-term sick leave for psychological injury was analysed. A separate set of linked mental health surveys was conducted to examine variance in the number and severity of symptoms reported. Results Measures of dynamic factors including physiological responses to simulated trauma and maladaptive coping styles had stronger evidence as predictors of psychological vulnerability than assessments of static factors such as trauma history or pre-existing psychopathology. With the nested case control studies, conditional logistic regression analyses found no associations between any of the MMPI-2 scale scores, either in isolation or combination, and later psychological injury (OR = 0.89; 95% CI 0.78-1.02). Possible reasons for these findings are discussed, one being the under-reporting of symptoms. This hypothesis was tested by comparing responses on identical validated questionnaires (DASS-21 and PCL-5) administered by different organisations. As expected, police officers reported significantly lower levels of anxiety (p < 0.05) and PTSD (p < 0.001) symptoms on the employer-administered survey compared to the anonymous independent survey. Conclusions The available research evidence does not support the type of pre-employment mental health screening conducted by many first responder organisations. The under-reporting of symptoms in employer-administered surveys is a major barrier to the effectiveness of any screening.

  • (2020) Murphy, Michael
    Thesis
    The introduction identifies that depression and anxiety are common in patients affected by cancer and when left untreated cause high morbidity. Face-to-face psychological therapy is the current mainstay treatment for patients. However, many cancer patients are unable to access face-to-face clinicians. Cognitive Behavioural Therapy (CBT) is evidence based for the treatment of anxiety and/or depression in cancer survivors. CBT is also one of the therapy modalities utilised to assist people with advanced, or incurable, cancer. Internet-delivered CBT (iCBT) has the potential to allow people undertake treatment in their own home, without geographical concerns and without stigma. iCBT use is expanding in the general community. However, the modality is only emerging in cancer research and there is a dearth of research for those with clinical range depression and/or anxiety. The aim of this thesis was to investigate the acceptability and efficacy of transdiagnostic (i.e. addressing depression and anxiety simultaneously) iCBT in cancer patients. The thesis firstly reviews key factors relating to depression in cancer, from diagnosis to management principles. This enables better development of any future cancer-specific online intervention(s). Three empirical studies are then presented. Study 1 outlines the results of focus groups evaluating a prototype iCBT intervention. Participants found it acceptable and gave guidance on future development. Subsequently, two iCBT interventions were developed and tested, each for a different population. Study 2 was a randomised controlled trial of an iCBT intervention versus treatment-as-usual in cancer survivors. iCBT was highly acceptable and very successful in treating their psychological symptoms. Study 3 was a pilot trial of a second iCBT intervention, addressing clinical depression and/or anxiety in people living with advanced cancer. This group found the intervention acceptable and the early results are promising; however, iCBT was commonly harder to use due to physical health problems. The three studies were novel and indicate that iCBT is acceptable to cancer patients and show it has a future role in the treatment of clinical depression and/or anxiety in the cancer setting. The specifics of the type (guided versus unguided) and method (standalone, blended and/or stepped care) of administrating iCBT requires further research.

  • (2021) Chinnappa-Quinn, Lucia Nallamma Premilla
    Thesis
    This thesis investigates the association of acute illness hospitalisation (AIH) with posthospitalisation cognitive decline (PHCD). It includes a systematic review which summarises 24 reports with samples exposed to mixed diagnosis AIH. Eleven of these concluded that cognition was worse following AIH, both in the short term and long term. Three specifically reported an accelerated rate of decline in cognition following AIH. Meta-analysis (MA) of seven of the 24 studies (41,453 participants), demonstrated a Cohen s d value for poorer cognition of 0.25 standard deviation units for hospitalised compared with non-hospitalised participants. Although several methodological challenges limited the generalisability of the MA, it suggested there is a long-term risk of PHCD following AIH exposure. The association of AIH exposure and cognition was investigated using the Sydney Memory and Ageing study (MAS) sample. Latent growth modelling was used to estimate global cognition latent intercept and slope from neuropsychological data in four biennial waves. Electronically linked hospitalisation data were computed in time intervals to clarify recency effects. Overall AIH effect, as well as surgical, medical and AIH with delirium exposures were investigated. A novel approach was taken to include concurrent hospitalisation variables in the same model to allow effects to overlap, and use continuous variables to quantify effects accurately. The sample had a mean age of 78.8 years, a mean Mini-Mental State Examination score of 28.7 and was functionally independent. Over ten years, 82% were hospitalised with a mean of 1.7 medical and 1.6 surgical hospitalisations. Their mean global cognition z-score decline per year was -0.105. Recent AIH exposure was associated with an increased rate of decline (-0.014 ± 0.005 p = .008). AIH episodes had a greater association with cognitive decline than length of stay. This association was greater for medical admissions and especially so for AIH complicated by delirium, even with non-neurological acute illness. Conversely, surgical AIH were not associated with cognitive decline. This confirms emerging evidence that post-operative cognitive dysfunction is a mild subset of PHCD. Delirium, however, emerged as the most potent association with accelerated decline and warrants further investigation and more proactive intervention to reduce its incidence.