Psychiatry - Theses
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Face processing in schizophrenia: an investigation of configural processing and the relationship with facial emotion processing and neurocognition
Cognitive impairment is a key characteristic of schizophrenia and is a clear predictor of functional outcome. This thesis explores the relationship between cognitive ability relating to social and non-social processing. Schizophrenia patients demonstrate an impaired ability to recognise, label and discriminate emotional expression within the face. The underlying mechanisms behind this social cognitive impairment are not yet fully understood. This thesis explores the notion that a basic perceptual impairment in processing facial information adversely impacts on the perception of more complex information derived from faces, such as emotional expression. Face perception relies on processing the featural characteristics of a face as well as the relationship between these features. Information pertaining to the spatial distances between features is referred to as configural information. A group of schizophrenia patients and healthy control participants completed a battery of tasks that assessed basic neurocognition, facial emotion processing and configural face processing. A model of face processing was proposed and used to systematically pinpoint specific deficits that may contribute to impaired face processing in schizophrenia. The results indicated that schizophrenia patients show impairments on three broad constructs; basic neurocognition, facial emotion processing, and most pertinently, deficits in configural processing. It was revealed that although neurocognitive and face processing both explained a significant proportion of the variance in facial emotion processing, the effect of neurocognition was indirect and mediated by face processing. To investigate the diagnostic specificity of these findings, a group of bipolar disorder patients was also tested on the task battery. The results indicated that bipolar disorder patients also show social and non-social cognitive impairments, however, not as severe as that demonstrated by the schizophrenia patients. Furthermore, the effect of neurocognitive performance on facial emotion processing appeared more direct for bipolar disorder patients compared to schizophrenia patients. Although deficits in face processing were observable in bipolar, they were not specific to configural processing. Thus, deficits in emotion processing were more associated to neurocognitive ability in bipolar disorder patients, and more associated to configural face processing in schizophrenia patients. The configural processing deficits in schizophrenia are discussed as a lower-order perception problem. In conclusion, the results of this thesis are discussed in terms of their implication for treatment.
Culture and stigma towards mental illness: a comparison of general and psychiatric nurses of Chinese and Anglo-Australian backgrounds
A sample of 208 nurses (a response rate of 63%) participated in a study by responding to a questionnaire comprising of 170 items which examined nurses’ attitudes towards mental illness, and the association between contact, cultural values, general and practice stigma. General stigma refers to attitudes towards the mentally ill while practice stigma is informed from differential clinical practice approaches towards the care of two case vignettes describing a patient with mental illness and one with diabetes. Subjects were recruited using the snowballing technique and comprised of nurses (83 Anglo Psychiatric, 41 Anglo General, 49 Chinese Psychiatric and 35 Chinese General) currently practising in Victoria. Age ranged from 21 to 65 years. Principal components analyses were conducted on items to develop subscales related to individualism and collectivism, contact types, general and practice stigma. Analyses of variance and covariance were conducted to examine differences between nurse type and ethnicity and respectively, to account for possible differences in background, contact and in the case of practice stigma, general stigma. The key findings revealed differences according to nurse type and ethnicity in several of the subscales. Psychiatric nurses endorsed a higher level of contact than general nurses with mentally ill people on the variables ‘Contact Through Work Situation’, ‘Patient Help Nurses’ and ‘External Socialisation with Patient’, but not on the variable ‘Relative With Mental Illness’. By virtue of more contact, psychiatric nurses also endorsed less general stigma than general nurses, assessed by results from analysing social distancing, but not by negative stereotyping of people with mental illness. With respect to practice stigma, while care and satisfaction did not differ according to patient type and nurse type, psychiatric nurses expressed less authoritarianism and negativity than general nurses towards the mental illness case than general nurses while lesser differences between nurse types were evident for the diabetes case. Chinese nurses when compared with Anglo-Australian nurses, endorsed more highly collectivist values measured by the variables ‘Ingroup Interdependence’ and ‘Ingroup Role Concern’ but there was no difference in individualist values. This may reflect acculturation towards Western values but also retention of Chinese values, interpreted in the light of other results on cultural affiliation, as a bicultural position. Chinese nurses endorsed more highly general stigma towards the mentally ill than Anglo nurses when statistically controlling for differences in background demographics and contact factors. Nursing satisfaction did not differ in ethnicity and patient type. Chinese nurses endorsed more highly care and authoritarianism in their clinical practice approaches than Anglo-Australian nurses, although there was no significant interaction effect between ethnicity and patient type on care and authoritarianism. Chinese nurses endorsed more highly negativity than Anglo-Australian nurses for the mental illness case than the diabetes case, an effect later shown to be mediated by differences in general stigma between the two ethnic groups. Within the Chinese sample, higher contact was associated with lower differential negativity for the mental illness than the diabetes case. Several path analyses suggested Chinese values influenced differential negativity, mediated by general stigma and prior diversified contact with people having a mental illness. It may be concluded from these results that practice stigma is related to cultural values but the relationship is mediated by general stigma and contact. What aspect of the Chinese values specifically correlates with general stigma remains a question for further research, but several possibilities are discussed.
Estrogen and neuropsychiatric disorders in later life
Experimental evidence suggests that estrogen can have both psycho- and neuro-protective effects; however this has not been consistently supported by certain clinical trials and epidemiological studies. This thesis aimed to provide a detailed investigation of the role of estrogen in later-life depression and cognitive functioning by examining serum estrogen levels, estrogen exposure across the lifetime, characteristics of hormone treatment (HT) and the role of estrogen receptor polymorphisms. Data was obtained from two longitudinal population-based studies, the 13-year Melbourne Women’s Midlife Health Project of 438 middle-aged postmenopausal women in Australia, and the seven-year Three City/ESPRIT study of 5644 older French women. Multivariate adjusted regression models showed that endogenous and exogenous hormonal characteristics late in the reproductive life can decrease the risk of late-life depression and a decline in serum estradiol levels increased the risk for recently postmenopausal women. Discontinuing HT increased the risk of depression for older women, as did the use of progestin-containing HT. Estrogen receptor polymorphisms were associated with late-life depression and can interact with HT to modify the risk of depression and mortality. Endogenous reproductive factors linked to higher lifetime estrogen exposure and high levels of estradiol in the early postmenopause were associated with better performance on certain cognitive tasks. Cognitive function also varied according to the characteristics of HT and HT reduced the risk of dementia in genetically susceptible women carrying the apolioprotein ε4 allele. This work brings some important new findings to this field of research, suggesting that the modulation of estrogen levels may be used as a possible therapeutic tool to reduce neuropsychiatric disorders and that certain subgroups of women may be genetically more susceptible to hormone modifications or to the effects of HT.
A neuroendocrine study of chronic combat-related post-traumatic stress disorder
Descriptions of the development of psychiatric symptoms in response to traumatic experience can be found in literature dating back to some of the earliest writings found. Amongst these symptoms there have always been descriptions consistent with what we would now term Post Traumatic Stress Disorder (PTSD). Tomb (1994) describes how such symptoms historically have been most frequently described in relation to combat experience and are contained in such classical texts as Homer’s Iliad. Recognition that such symptoms also occur in association with non combat related trauma is a relatively recent event. This can be seen in description of response to traumas such as The Boston Coconut Grove Fire (Adler 1943) and the Buffalo Creek Dam collapse (Gleser et al 1981). Combined with the massive number of combat veterans with combat experience related to psychiatric disability following the World Wars, significant impetus appears to have developed for separate classification and understanding of trauma related psychiatric symptoms. Together, these forces led to the creation of the diagnostic category of PTSD for the first time in the American Psychiatric Associations DSMIII (APA 1980). In this series of studies, we are thus aiming to further the understanding of the neurobiology of Post Traumatic Stress Disorder by specifically examining a group of male Australian Vietnam veterans with current PTSD, comparing them to two control Vietnam veteran populations, one group of those veterans who previously met criteria for a diagnosis of PTSD and a third group who never have met criteria for a diagnosis of PTSD. We examined these three groups in a number of ways. Firstly, to further understand aspects of central noradrenergic receptor function we utilised a clonidine growth hormone challenge test. Consistent with previous literature on the HPA axis in PTSD from North American we utilised a modified dexamethasone suppression test to investigate feedback within the HPA axis. Finally, we investigated serotonergic receptor function peripherally with a further study of platelet paroxetine binding and performed the first large study examining central serotonergic receptor function using the d-fenfluamine prolactin challenge test. Before describing the methodology and results of these studies I will review relevant findings to these three systems from studies of animal and human models of stress, clinical populations with PTSD and their treatment and previous experimental analysis of relevant biological variables in subjects with PTSD.
The specificity of morphological changes of the corpus callosum in schizophrenia and related major mental disorders
Schizophrenia is a disabling major mental illness associated with marked impairments in reality testing, organization of speech and behaviour and cognition. Significant evidence points to functional dysconnectivity between cortical and subcortical regions as the major pathophysiological underpinning of the symptoms and disability associated with schizophrenia. Modern neuroimaging techniques have suggested that this dysconnectivity is driven, at least partially, by neuroanatomical changes to connectivity in the brain at the level of white matter tracts, the main connecting “organs” in the brain. This thesis describes the analysis of the structure of the corpus callosum, the brain’s largest white matter fibre tract, with the aim of determining if changes to anatomical connectivity in schizophrenia are associated with a unique callosal shape “signature”. This was undertaken by using a shape analysis methodology that examined regional callosal thickness, using a non-parametric permutation method to determine between-group differences and the relationship between illness variables and callosal shape. This methodology was applied to multiple illness stages: established illness, first-episode psychosis and pre-psychotic patients. It was then applied to other major mental disorders, including multiple cohorts of patients with bipolar disorder and patients with major depression, to determine if any changes seen in schizophrenia patients were specific to schizophrenia-spectrum illness or were more general markers of major mental illness. The results suggest that patients with schizophrenia-illness show specific thickness reductions at the level of the anterior callosum, connecting frontal cortical regions, that are present during the pre-psychotic phase and with first-episode illness. Furthermore, with established illness, these changes are accompanied by additional changes in the callosum connecting cingulate, temporal and parietal regions. Changes seen in healthy individuals as part of the normal ageing process appeared to be disrupted in schizophrenia patients. In bipolar patients, a very different pattern of results emerged, with more global thickness reductions and disproportionate thinning at the level of the posterior callosum. Depressed patients, by contrast, showed state-specific posterior expansions, which bore some homology to changes seen in patients with depressed first-episode psychotic patients and patients with schizoaffective disorder. Furthermore, in the schizophrenia-spectrum group, changes at the level of the genu were strongly predictive of transition to psychosis in those individuals at high-risk for psychosis, and in first-episode individuals were highly predictive of long-term outcome of their psychotic illness. These changes suggest that there are schizophrenia-specific changes at the level of the callosum, marking a unique callosal “signature” for schizophrenia-spectrum illness. These changes show predictive validity for outcome at the earliest stages of illness, and are distinct from changes seen in major affective disorders. These findings suggest that shape changes to white matter structures may be a useful marker to aid diagnosis, in the identification of individuals who may develop a psychotic illness, and in defining the nature of their future illness course.
War experiences: the emotional health and wellbeing of Polish elderly immigrants
Background: Large numbers of Polish refugees arrived in Australia following the end of the Second World War as displaced people, unable to return to their homeland. All had experienced loss of their homeland and many lost loved ones, endured hardship and suffering. Now this group constitutes a significant proportion of the Polish-Australian aged community. The main aim of this thesis is to describe, from a life-span perspective, the relationship between major life events, including war experiences, and psychological and physical health now and in the past. Attention is focused on the factors associated with the longevity of the trauma response. Method: A mixed methods approach was employed using quantitative and qualitative methods along with a detailed historical account of the war and resettlement contexts. The quantitative component involved the recruitment and interview of a convenience sample of 72 Polish elderly migrants from Polish Senior Citizen's clubs across the Melbourne Metropolitan area. Participants who gave informed consent completed a detailed questionnaire and interview about their current physical health, social networks, psychological health, quality of life, posttrauma growth, war-related experiences, traumatic events, migration, and post war life events. Categorical and continuous variables were analysed using a combination of parametric and nonparametric statistics. The qualitative component involved a narrative interview with a subset of 18 people about the war years and early life in Australia. In addition, detailed field notes were compiled from the quantitative questions with the remaining 54 people supplementing their responses with stories and accounts while filling out the questionnaires. This produced a rich source of data that was analysed thematically. Results: Fifty-three per cent of participants were women. Most were aged 75 or older (71%). Just over half were married and a third were living alone. The majority had children (90%). Twenty-one per cent described their physical health and seven per cent their emotional health as poor. During the war, 42% were in Germany as forced labourers, 26% had been exiled to the former Soviet Union, 15% had participated in the Armed Forces, 11% were civilians in Poland and 5% were Concentration Camp Survivors. Every person interviewed had experienced at least two traumatic events during the war. The most commonly reported events were the loss of home and belongings (81%), lack of food and water (79%), bombardment (78%) and forced separation from family (74%). People who had survived the concentration camps and ex-service men experienced the highest number of traumatic events. Number of traumatic events during the war was correlated with life-time PTSD symptoms (r=0.46 p=0.01), current PTSD symptoms (r=0.36) and physical health conditions (r=0.37 p=0.01) but was not associated with current quality of life. Negative worldview was associated with PTSD (lifetime and current), physical health conditions and impact of illness. Trait anxiety and years of residency were associated with depression, anxiety, PTSD (lifetime and current) scores and physical health conditions. Negative worldview, Trait anxiety and years of residency were all independent predictors of psychological distress accounting for 51% of the variance in psychological distress. During their-lifetime, 75% of people identified a period of fear, anxiety and panic, 47% of participants reported feeling depressed, while 7% met criteria for PTSD. In the last six months, 33% reported clinically significant anxiety symptoms, 3% had moderate-severe depressive symptoms and 3% met criteria for current PTSD. Coping strategies mentioned most frequently were use of religion (54%) talking to family and friends (32%) and avoiding any reminders (18%) although none of these strategies were associated with emotional or physical health. Thematic analysis revealed that Polish elderly described their accounts of trauma and physical deprivation in the context of individual, familial and community suffering. Individuals described a range of emotional responses to trauma such as fear, grief and humiliation. These emotions were also experienced by family and community. Survival mechanisms such as acts of defiance, using one’s own skills and having hope were described at an individual level. Family was identified as an important survival resource - a central component to this theme was that of the ‘strong mother’ fending for her children. Community was another resource identified by study participants such as the ‘acts of kindness by strangers’ that often made the difference between life and death. The theme of community and family suffering meant that the individual was not alone in trauma but surrounded by others in a similar situation. Community structures were an important part of the recovery and healing that took place after the war. The cohesive nature of Polonia (Poles abroad) may explain why people who did not return to Poland and migrated to Australia in the late 1940’s and 1950’s had lower rates of psychological distress compared with those who returned to communist Poland and only arrived relatively recently. Conclusions: More than 60 years on from the end of the Second World War Polish elderly people were still affected by these events in some way and that in a small number of cases these events were associated with current emotional and physical health. The main determinant of current emotional and physical health was the type of main experience people endured, the number of traumatic events experienced, having a negative world-view, fewer years of residency and higher Trait-Anxiety scores. The thematic analysis revealed that there is a complex relationship between individuals, families and communities in how they experienced trauma and its aftermath and the resources and mechanisms they used in order to survive.
Outpatient commitment: is it effective?
Outpatient Commitment (OPC) is a legal procedure that allows for involuntary psychiatric treatment in the community. Legislation for OPC first emerged in the 1970s in the USA in an attempt to provide a legal remedy for the problems posed by ideological reforms to institutional psychiatry and mental health law. OPC in particular attempts to address the difficulties presented by persons with chronic relapsing forms of serious mental illness and poor compliance with outpatient treatment - persons whose disadvantage is now particularly visible in the streets of our large cities. OPC sits awkwardly between the developing and expanding frameworks of community mental health services and mental health law. It potentially overlaps with guardianship laws, enduring medical power of attorney and court orders. Despite the growing provision for OPC and its increasing frequency of use in North America, the Antipodes, and most recently on the boarders of the European continent, there remains little understanding of the conceptual mechanisms involved in its application. Even less is known about the group of patients who might respond best to its implementation. Without taking stock of its potential adverse effects, societies run the risk of enthusiastically embracing this rather crude legal mechanism of persuasion, instead of exploring or supporting the development of potentially more effective and sophisticated clinical interventions to address the problem of non-compliance with outpatient psychiatric treatment. Given the current limitations of clinical interventions for serious mental illness and treatment non-compliance, OPC may provide a very useful role in enhancing the efficacy of these interventions/treatments through its effects on the way a treatment service is provided as well as on the patient's treatment adherence. With this aim in mind, many different forms of OPC have now emerged. However, without adequate research evidence, it is not possible to advocate strongly for the development of one form of OPC legislation over another. Nor is it possible to argue for its use in preference to other legal mechanisms of treatment orders e.g., guardianship orders. The final decision about which form of OPC legislation is chosen appears to have relatively little to do with any empirical evidence of clinical efficacy but more to do with historical and legal concerns. This thesis attempts to go some way to further bridge the gap between evidence based psychiatry and the application of mental health law with respect to Outpatient Commitment. Chapters 1 and 2 describe a brief account of the historical context within which OPC has emerged both internationally and in Australia. Chapter 3 provides a review of clinical outcome studies in the USA and elsewhere, concluding that on simple clinical measures of outcome, OPC appears to be associated with significant benefits. It is of note that all these studies have considerable limitations, and none provide a useful comparison of patients' objective clinical ratings with patients' subjective ratings of the "persuasiveness" or "coerciveness" of OPC. Chapters 4 and 5 of this thesis outline the results of a retrospective controlled study of the clinical outcome of all patients on a form of OPC in a sector of metropolitan Melbourne, Victoria, Australia, between 1987-1992. The characteristics of the patients selected has already been reported in a previous study which describes the sample as being mainly those with chronic relapsing forms of psychotic illness complicated by a history of violence and noncompliance with outpatient treatment. In Chapter 4, the results of an analysis of the clinical outcome of this group of patients suggests that the majority of these patients benefit from the application of OPC. In Chapter 5, the results of the control group comparison also indicate that though these OPC patients have evidence of higher levels of morbidity than other involuntary patients discharged directly into the community, OPC patients improve relatively better while on OPC orders. However, a minority of OPC patients do not seem to benefit or even deteriorate with the application of OPC. The study attempts to identify the characteristics that might predict better or worse clinical outcomes associated with OPC. It is important to note that the study, because of its retrospective design, suffers from limitations similar to those evident in other studies and, in particular, it does not account for influence of patients' subjective experiences of OPC. Finally in Chapters 6 & 7, based on the experience of this study and on a review of the literature, a conceptual model is proposed in order to assist with an understanding of how OPC might work. This model focuses on the nature of the impact of OPC on treatment adherence, through its effect on the patient and on the system within which the patient is being treated. It suggests that a balance needs to be struck between the persuasiveness versus the coerciveness of the Outpatient Commitment procedure. An ineffectual mechanism may discredit the procedure as a persuasive aid to treatment adherence. Conversely, an overly coercive mechanism may actually deter patients from accepting any form of assistance for their illness. This model forms the basis of recommendations for future research to test the effectiveness of OPC and to compare or contrast different forms of OPC with each other and with other less formal mechanisms of coerced community psychiatric treatment. Australia, given its relatively uniform structure and administration of mental health services, is in a good position to compare the benefits or otherwise of the rather disparate forms of OPC being introduced into each of its various states and territories. With a multi-centre randomised controlled trial of OPC in this setting, it may then be possible to make recommendations about which form of OPC most effectively and collaboratively assists in the improvement of poor treatment compliance, and which group of patients with serious mental illness are likely to benefit most from its application. It may also assist with determining OPC's relative clinical merit when compared with other less formal coercive/persuasive clinical interventions for treatment non-compliance. Without attempts to study and confirm the empirical evidence for the 'clinical efficacy' of OPC, this increasingly internationally accepted model of OPC oriented community psychiatric care runs the risk of being prematurely challenged in some future wave of mental health reform. As in the example of de-institutionalisation, the ultimate future of OPC may, however, rest not with the law but with the advent of better and more effective treatments for psychotic disorders.
Chinese-Australian families' help-seeking behaviours for mental illness
This thesis includes two studies: a survey of Melbourne's Chinese community and a family interview study. The survey was based on 418 respondents while twenty-eight caregivers participated in the family interview study. The survey explores how depression and schizophrenia are understood and are dealt with in a migrant Chinese community. The purpose of the family interview study was to examine the pathways to care for mental disorders, the social representation of illness and families' experiences of illness. Social knowledge about mental illness, physical illness and the concepts of normal human experiences of distress influenced the labelling of experienced conditions. Disorders were labelled as ‘a mental illness’, ‘a physical illness’, ‘a normal problem’ or ‘an abnormal problem’. Results indicated that schizophrenia was likely to be labelled as a mental illness and psychiatrists were seen as the main form of help. On the other hand, depressive disorder, anxiety disorder and post traumatic stress disorder were likely to be labelled as a ‘normal problem’, an ‘abnormal problem’ or a ‘physical illness’ and were likely to be treated by family members, friends, a traditional Chinese medicine physician or a Western physician. Labels given determined initial responses to the problem but the work also indicates a dynamic relabelling process developed by exposure to the social and professional systems. Pathways to care are intimately related to illness understandings which in themselves are in some respects relatively dynamic. The present study suggests that health professionals and the health institutions need to take into account patients' and family members’ explanations of illness in order to improve access to their services and in order to improve the quality of the services they deliver to the community.
A population-based study of alcohol use in elderly men: associations with physical and mental health
Considerable attention has been paid to the prevalence and outcomes of alcohol use disorders in both in population-based and clinical samples, and also to the harms associated with alcohol intake in young adults. However less attention has been paid to alcohol consumption in elderly men. The aims of this population-based study were to investigate the patterns of alcohol consumption and the associations between different levels of alcohol intake and demographic, lifestyle, physical and mental health outcomes in a representative sample of elderly men. Five hundred and fifty five participants aged at least 65 years and enrolled in the Geelong Osteoporosis Study reported their usual alcohol consumption for the prior 12-months, had their BMD measured and completed a comprehensive range of medical and lifestyle assessments. Alcohol consumption was common, the majority (48.7%) consumed alcohol moderately (≤2 drinks/day), with a further 19.7% consuming 3-4 drinks and 13.5% consuming ≥5 drinks/day. Almost one in five elderly men in this sample were a non-drinker at the time of assessment. The alcohol consumption groups were compared on demographic and lifestyle variables, and also on key physical and mental health outcomes. The median alcohol consumption increased with increasing socio-economic status. The heaviest alcohol consumption groups were more likely to report current or past cigarette smoking and were also more likely to have low leisure-time physical activity levels in age adjusted models (OR=1.74 95% CI 1.01-3.00), and more likely to have impaired mobility as measured by the Timed Up & Go test (OR=3.01 95% CI 1.41-6.43) when compared to moderate alcohol consumers. Current non-drinkers were more likely to have low leisure-time physical activity levels (OR=1.75 95% CI 1.05-2.91) and were less likely to be current participant in sport (OR=0.52 95% CI 0.29-0.94) than moderate alcohol consumers, independently of age, cigarette smoking and current use of five or more medications. In comparison to non-drinkers, consumers of ≥5 drinks/day had mean differences in adiposity of +4.8% (BMI), +20.1% (FMI), +5.0% (waist circumference), +15.2% (%body fat), +5.3% (% trunk fat) and had a mean difference in lean tissue mass of -5.0%. Furthermore, they had a 2.8-fold increased risk of being classified as obese according to BMI (≥30 kg/m2) and a 3.4-fold increased risk of having a waist circumference of at least 102 cm. While the groups differed in total energy intake, they did not differ in energy intake obtained from food suggesting unregulated supplementation of energy intake from alcohol. Aside from a difference at the mid-forearm site BMD was not associated with alcohol consumption, however bone quality as measured by quantitative ultrasound at the heel decreased with increasing alcohol consumption. Overall, 14.8% of this sample met criteria for a lifetime history of a mental illness, and 3.1% were identified as having a current psychiatric illness, most commonly major depressive disorder. Non-drinkers (OR=2.58 95% CI 1.20-5.56) and consumers of ≥3 drinks/day (OR=1.73 95% CI 0.85-3.51) were more likely to have a lifetime history of any psychiatric illness than moderate alcohol consumers after adjustment for age and mobility. There was a low prevalence of alcohol use disorders in this sample, 2.6% for a lifetime history and 0.8% for a current disorder. One third of elderly men currently drink at a level in excess of the Australian government recommendations for safe alcohol consumption, which in combination with medical comorbidities and high levels of medication use places this group at increased risk of harm. Furthermore, both heavy alcohol consumption and current non-drinking was associated with negative physical and mental health outcomes, this highlights the importance of routinely screening for alcohol consumption within the elderly, and extending the investigation into other important correlates when indicated. Although causality cannot be inferred, these findings provide an insight into the association between alcohol intake, lifestyle and physical and mental health.
The effects of catecholamine depletion and acute psychosocial stress on neurocognition
Extensive research has clearly established that neurocognition is negatively impacted by various stressors. While the extant research has focused on the effects of cortisol on declarative memory, little attention has been given to the role of the catecholamines in the deterioration of neurocognitive performance following psychosocial stress. Forty healthy male (n = 21) and female (n = 19) volunteers aged between 18-47 years who had been screened for eligibility participated in the study. Heart rate, blood pressure and salivary cortisol were measured at baseline, pre-stress, post stress (immediate) and after one hour of rest (post stress recovery). Neurocognitive assessment included immediate and delayed verbal recall, spatial learning and strategy, attention and working memory (spatial and non-spatial) at the same four phases. Participants randomly received an L-tyrosine and L-phenylalanine depleted (DEP) or a nutritionally balanced (BAL) amino acid drink in a randomised, double blind, placebo-controlled parallel group design 5 hrs before exposure to the Trier Social Stress Test (TSST). The ratio of L-tyrosine and L-phenylalanine to the sum of other large neutral amino acids (ΣLNAAs) in plasma were both significantly reduced by -80% at the post-ingestion period (5 h) compared to baseline. Exposure to the TSST for both ATPD and balanced-treated participants resulted in the robust stimulation of the sympathomedullary (SAM) and hypothalamic-pituitary adrenocortical (HPA) axes. This was demonstrated by significant increases in heart rate and blood pressure immediately after stress exposure compared to baseline in both ATPD and balanced conditions. Salivary cortisol levels significantly increased immediately after the completion of the TSST compared to pre-stress levels. There were a limited number of effects of the TSST combined with ATPD on measures of neuropsychological performance. These outcomes suggest that neurocognition is not severely impacted by acute social stress under conditions of catecholamine depletion.
Understanding the role of frontotemporal brain structures in schizophrenia through magnetic resonance imaging and neuropathological studies
Section 1: The first two chapters describe my initial hippocampal volumetric work in patients with first-episode psychosis and chronic schizophrenia that identified hippocampal changes early in the course of psychosis. Chapter 3 explores in detail the theoretical basis for hippocampal involvement in schizophrenia and introduces for the first time the concept that the hippocampal volume changes observed in patients with first episode psychosis and chronic schizophrenia may not be present in patients at high risk of psychosis. Chapters 4 to 6 describe a series of cross sectional studies showing that hippocampal volumes are normal in high risk patients who later develop psychosis (Chapter 4 and 6), normal in patients with schizophreniform psychosis (Chapter 6), reduced on the left side in patients with first-episode schizophrenia (Chapter 6) and bilaterally reduced in patients with chronic schizophrenia (Chapter 6). These findings suggest that right hippocampal volume reduction occurs with increased illness duration, a finding supported by a voxel based morphometry study of patients with chronic schizophrenia (Chapter 5). Finally in contrast to our original findings (Chapter 1) that hippocampal volumes were equally reduced in patients with first-episode schizophrenic and non schizophrenic psychoses, our study of a much larger first-episode cohort (Chapter 6) showed that hippocampal volume reduction was specific to schizophrenic psychoses while amygdala enlargement was specific to non schizophrenic first-episode psychoses. These findings suggested either that (i) patients who make the transition from high-risk to first-episode or first-episode to chronic schizophrenia already have hippocampal changes and/or (ii) that hippocampal volume changes occurred progressively over the course of the illness. Section 2: Chapters 7 and 8 describe follow-up longitudinal imaging studies in a first-episode cohort and a high-risk cohort respectively. We did not identify hippocampal volume change over a two-year period (Chapter 7) but observed whole brain changes over time in first-episode and chronic schizophrenia cohorts. We hypothesised that structural changes may have occurred prior to or over the transition to active psychotic illness. Chapter 8 describes parahippocampal and frontal changes in high-risk patients who developed a psychotic illness and not in those who did not develop a psychotic illness. These findings provided support for the concept that some patients with a psychotic illness exhibit progressive structural brain changes. Section 3: Chapters 1 to 8 describe evidence for the presence of structural brain changes in the hippocampi of patients with schizophrenia. Structural MRI cannot determine the neurobiological correlates of such brain changes i.e what is causing the changes or which elements of brain tissue are involved. The neurobiology of diseases that mimic schizophrenia (‘secondary schizophrenias’) has provided insights into schizophrenia. Chapter 9 describes a previously unrecognised association between young onset frontotemporal dementia and schizophrenia-like psychosis and specific hippocampal pathology in these cases. Chapter 10 describes similar pathological abnormalities in the hippocampus of patients with schizophrenia and bipolar disorder, who had never been suspected of having dementia earlier in life. The identification of clinical and neuropathological associations between FTD and schizophrenia / bipolar disorder is of significant clinical relevance and provide new avenues for research into the underlying neurobiology of major mental disorders. Section 4: The concluding section discusses how the work in this thesis can be understood within the context of neuroimaging work that has emanated from this large dataset and the current schizophrenia literature. The association between schizophrenia and FTD identified in Chapters 9 and 10 is explored further in this final section with reference to the literature and some illustrative case reports.
Psychosocial mechanisms underlying cultural differences in depressive and anxiety illness symptom reporting and presentation: comparison of Greek-born immigrants and Anglo-Australians
The current research included three studies: a survey exploring psychological factors that may underly cultural differences in illness reporting and presentation; and a qualitative and a quantitative study exploring cultural differences in illness schemas. The purpose of the work is to examine the importance of a wide variety of factors that may underly cultural differences in the presentation and reporting of depression and anxiety. The total sample of respondents consisted of 221 Greek-born and 239 Anglo-Australian people (mean age 65 yrs). First, Greek-born people reported higher levels of depression (as measured by the Beck Depression Inventory-2, BD1-2) and anxiety (as measured by the State Trait Anxiety Inventory, STAI) and higher levels of stress, trait negative affectivity, illness concern, impression management, self-focused attention and stigma. Hierarchical regression analyses indicated that all explanatory variables were significant unique predictors of at least one BDI-2 and/or STAI measure when controlling for confounding variables such as socio-economic status, age and gender. Overall, Trait Negative Affectivity (TNA) was the most stable and consistent predictor of the BDI-2 and STAI scores for both birthplace groups. Conceptual similarities appear to exist for the causes and important symptoms components of illness schemas between mental and physical problems for the Greek-born. For the Anglo-Australians, similarities exist for the course and development, consequences and therapy components of illness schemas between mental, physical and social problems. The propensity to report particular types of symptoms to a doctor appeared to also be affected by illness schemas. Findings suggest that different presentation of depression and anxiety across cultures may be better understood by the degree to which processes underlying symptom reporting may be salient in different cultures.