Depressive Illness And The Heart: Identifying The Relation Between Affective Disorders And Coronary Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$503,625.00
Summary
Major depression is ranked fourth among the 10 leading causes of the global burden of disease and, if epidemiological projections are correct, by 2020 it will reach second place. Patients with depression are at increased risk of developing coronary heart disease. This elevated risk is independent of conventional risk factors such as smoking, obesity, hyperlipidaemia, diabetes and hypertension. Also conclusively demonstrated is the adverse effect of depression in patients following myocardial inf ....Major depression is ranked fourth among the 10 leading causes of the global burden of disease and, if epidemiological projections are correct, by 2020 it will reach second place. Patients with depression are at increased risk of developing coronary heart disease. This elevated risk is independent of conventional risk factors such as smoking, obesity, hyperlipidaemia, diabetes and hypertension. Also conclusively demonstrated is the adverse effect of depression in patients following myocardial infarction (MI), which materially increases mortality. The mechanism of increased cardiac risk attributable to depressive illness is at present uncertain but activation of the sympathetic nervous system, exaggerated platelet reactivity and-or altered baroreflex function are likely to be of prime importance. Preliminary data from our laboratory indicates that whole body and cardiac sympathetic nervous activity and cardiac baroreflex sensitivity are modified following antidepressant therapy. Identifying the underlying neurochemical mechanisms responsible for alterations in affective behaviour, and quantifying cardiac and whole body sympathetic activity directly and indirectly, and testing whether therapeutic and behavioural interventions can influence brain neurotransmitter turnover and modify cardiac sympathetic tone, platelet reactivity, and baroreflex function in a fashion likely to reduce cardiac risk, will be an important step forward in alleviating the burden of depressive illness on the community.Read moreRead less
Behavioural And Neuropsychiatric Aspects Of Transition To Severe Conduct Disorder In Adolescence.
Funder
National Health and Medical Research Council
Funding Amount
$343,100.00
Summary
Conduct disorder represents an enormous cost to Australian society directly via the mental health and forensic systems, and indirect costs via its associations with other mental health problems, relationship problems, impaired social functioning, and substance use problems. Behavioural-family-based treatment have good success rates with young children with cooperative parents, however, there are a minority who progress to chronic problems despite this. Risk and resilience factors identifying chr ....Conduct disorder represents an enormous cost to Australian society directly via the mental health and forensic systems, and indirect costs via its associations with other mental health problems, relationship problems, impaired social functioning, and substance use problems. Behavioural-family-based treatment have good success rates with young children with cooperative parents, however, there are a minority who progress to chronic problems despite this. Risk and resilience factors identifying chronic patterns in early childhood are the key to early intervention. In previous research, this research team showed for the first time that callous-unemotional traits, a feature of chronic psychopathy, could be measured in children as young as 4 years, and was predictive of a range of negative outcomes. However, it was also found that the key neuropsychiatric markers characteristic of psychopathy, including reward dominance-punishment insensitivity and deficits in affective empathy, did not exist in conduct problem children prior to adolescence. Around the time of puberty, it appears that important changes occur in cognitive-affective processing styles that are associated with the adult form of psychopathy and antisocial behaviour. Thus, this research raises critical questions about the development of severe antisocial behaviour (or psychopathy) through the childhood to adolescent years. Our evidence indicates that early adolecence may be the period when intrapsychological characteristics representing chronic risk become concrete. The current research will be the first to map the development common neuropsychiatric markers (affective empathy, punishment insensitivity) of severe antisocial processes through the late childhood-adolescent period. The findings will have clear implications for models of antisocial behaviour and clinical approaches to working with conduct problem children and adolescents.Read moreRead less
Risk Factors For Compliance With Command Hallucinations In Psychotic Disorders
Funder
National Health and Medical Research Council
Funding Amount
$180,290.00
Summary
There is widespread public concern about the danger individuals with schizophrenia or related disorders pose to themselves and to the community. Whilst a number of violence risk factors such as being male, exhibiting hostility, and having a prior history of violence are well established, they are of limited use to clinicians in making management decisions. Our study will investigate a different approach to identify individuals and occasions when a sufferer might require more intensive care or ob ....There is widespread public concern about the danger individuals with schizophrenia or related disorders pose to themselves and to the community. Whilst a number of violence risk factors such as being male, exhibiting hostility, and having a prior history of violence are well established, they are of limited use to clinicians in making management decisions. Our study will investigate a different approach to identify individuals and occasions when a sufferer might require more intensive care or observation. Most individuals with schizophrenia experience auditory hallucinations. Amongst these hallucinations, voices that command the individual to undertake a particular action are common; many of these involve significant potential harm to the hallucinator or to other persons. We will attempt to identify those factors that are associated with an individual obeying command hallucinations. Variables to be examined include the characteristics of the hallucinated voices, and the beliefs of the subject about the power of the voices. Subjects will be interviewed to find out whether they have delusions that are consistent with their hallucinations, whether they suffer from Antisocial Personality Disorder, or are dependent on alcohol or drugs. We will also determine whether subjects who report being raised by authoritarian parents, who are dependent on the approval of others, or who see external factors as determining the occurrence of major events in their lives, are more likely to act on their hallucinations. Two groups of 100 patients will be studied. One group will be representative of people living in the community with schizophrenia. The other group will be people with schizophrenia who have been treated by the State Forensic Psychiatric Services. Statistical models will be developed in order to determine the accuracy with which compliance with command hallucinations can be predicted. These models with also reveal which risk factors are the most important.Read moreRead less
Psychosocial Predictors Of Developing Breast Cancer In Women From High Risk Breast Cancer Families
Funder
National Health and Medical Research Council
Funding Amount
$593,875.00
Summary
Over the past 20 years, studies have highlighted the possible roles of stressful life events and distress, possibly mediated by social support and personality, in causing or speeding up the development of breast cancer. This possibility is of strong concern to consumers. To date, there have been few well designed, prospective studies of this issue. Furthermore, no previous studies have specifically targeted women at increased risk because of their family history. Over the past 7 years, it has be ....Over the past 20 years, studies have highlighted the possible roles of stressful life events and distress, possibly mediated by social support and personality, in causing or speeding up the development of breast cancer. This possibility is of strong concern to consumers. To date, there have been few well designed, prospective studies of this issue. Furthermore, no previous studies have specifically targeted women at increased risk because of their family history. Over the past 7 years, it has become possible to identify 2 breast cancer genes (BRCA1 and BRCA2). Female carriers of mutations in these genes with a strong family history have an estimated lifetime risk of between 35% and 85%. The Kathleen Cuningham Consortium for Research into Familial Breast Cancer (KConFab) was established 7 years ago to coordinate the collection of genetic, epidemiological and clinical data in Australian families with a dominantly inherited predisposition to breast cancer. Due to the high rate of breast cancer diagnoses in this group, and the systematic recruitment of large numbers of high risk women by KConFab, there is a unique and temporary opportunity to conduct a rigorous study to resolve this question, with sufficient numbers involved. The study is a world first, and will provide the best data to date in this area. If the study demonstrates a relationship between psychosocial factors and the development of breast cancer in women from high risk breast cancer families, subsequent identification of vulnerable individuals and the implementation of appropriate interventions may have a real impact on reducing morbidity and mortality in this population. Furthermore, the results may have implications for all women in reducing breast cancer incidence.Read moreRead less
A Comparative Structural And Functional Cerebral MRI Study Of First Episode Schizophrenia And Long-term Cannabis Use.
Funder
National Health and Medical Research Council
Funding Amount
$373,125.00
Summary
Cannabis is used for its subjective effects that include euphoria, depersonalisation, somnolence, and altered perceptions of temporal contingency.It is a controlled substance yet one quarter of Australian adolescents and seven percent of adults use cannabis regularly. Chronic use of cannibis can impair frontal brain functioning, affecting the capacities for attention, working memory and concentration.These neurocognitive deficits bear striking similarities to those associated with the negative s ....Cannabis is used for its subjective effects that include euphoria, depersonalisation, somnolence, and altered perceptions of temporal contingency.It is a controlled substance yet one quarter of Australian adolescents and seven percent of adults use cannabis regularly. Chronic use of cannibis can impair frontal brain functioning, affecting the capacities for attention, working memory and concentration.These neurocognitive deficits bear striking similarities to those associated with the negative symptom cluster of schizophrenia,which is related to frontal brain dysfunction. The proposed study will be the first of it's kind to apply sophisticated neuroimaging techniques to investigate how long-term adolescent cannabis use effects the structure and function of the brain and to make comparative analyses with the brain changes associated with first episode schizophrenia. We predict that structural brain abnormalities that are consistent in localisation, if not in degree, will be detected in long-term cannabis using and first episode schizophreniaparticipants and that there will be even more profound abnormalities in the first episode schizophrenia cannabis users. We will use the Tower of London (TOL) task to activate certain areas associated with executive functioning (for instance attention, memory, and strategic planning). Here, we expect lower intensity activation of the prefrontal cortex during TOL performance both in the cannabis and first episode schizophrenia groups and that the activation will be lowest of all for the cannabis using first episode schizophrenia group. The methodology to be applied in this study offers a unique opportunity to enhance our understanding of the structural and functional markers of first episode schizophrenia and cannabis use in the neural substrate.Read moreRead less
Psychosocial Predictors Of Developing Breast Cancer In Women From High Risk Breast Cancer Families
Funder
National Health and Medical Research Council
Funding Amount
$337,018.00
Summary
Systematic review of the literature on psychosocial predictors of developing breast cancer has highlighted the possible roles of life events and distress, possibly mediated by social support and personality. To date there has been little prospective assessment of psychosocial factors in the development of breast cancer. Furthermore, no research in this area has specifically targeted women at increased risk because of their family history, nor explored whether the impact of psychosocial factors s ....Systematic review of the literature on psychosocial predictors of developing breast cancer has highlighted the possible roles of life events and distress, possibly mediated by social support and personality. To date there has been little prospective assessment of psychosocial factors in the development of breast cancer. Furthermore, no research in this area has specifically targeted women at increased risk because of their family history, nor explored whether the impact of psychosocial factors systematically varies according to genetic mutation status. Over the past 5 years it has become possible to isolate two breast cancer genes (BRCA1 and BRCA2). Female carriers of mutations in these susceptibility genes have an estimated lifetime risk of breast cancer of between 37% and 85%. The Kathleen Cuningham Consortium for Research into Familial Breast Cancer (KConFab) was established four years ago to co-ordinate the collection of genetic, epidemiological and clinical data in Australian families with a dominantly inherited predisposition to breast cancer. The systematic recruitment of large numbers of high risk women by KConFab provides a unique and temporary opportunity to address questions concerning psychosocial predictors of disease development in a prospective design with sufficient power, due to the higher rates of breast and ovarian cancer events in this population. We will also be able to explore interactions with genetic mutation status. The study will be a world first, and provide the most rigorous data to date in this area. If this study demonstrates a relationship between psychosocial factors and the development of breast cancer in women from high risk families, subsequent identification of vulnerable individuals and the implementation of appropriate interventions may have a real impact on reducing morbidity and mortality in this population. Furthermore, the results may have implications for all women in reducing breast cancer incidence.Read moreRead less
Children Of Parents With Mental Illness: A Population-based Study
Funder
National Health and Medical Research Council
Funding Amount
$774,715.00
Summary
Schizophrenia, bipolar disorder and major depression account for about 16% of the global burden of disease, according to estimates by the World Health Organization and the World Bank. These disorders tend to run a chronic or recurrent course, with devastating impact on sufferers and their families. We know today that part of their causes are genetic and may be transmitted to the next generation. However, another part of the causation is likely to be environmental, involving maternal pregnancy co ....Schizophrenia, bipolar disorder and major depression account for about 16% of the global burden of disease, according to estimates by the World Health Organization and the World Bank. These disorders tend to run a chronic or recurrent course, with devastating impact on sufferers and their families. We know today that part of their causes are genetic and may be transmitted to the next generation. However, another part of the causation is likely to be environmental, involving maternal pregnancy complications, as well as psychosocial adversity and stressful events impacting children who happen to carry a genetic susceptibility to such disorders. To disentangle and understand better such effects, our research is focusing on families where genetic risk to the offspring is present, due to a mother suffering from one of these disorders. By linking data available on population databases in WA, we aim to follow up the childhood development and young adult health outcomes of all children born to women with schizophrenia, bipolar disorder or depression. Few studies of this kind have been done worldwide, and we expect that the WA study will answer many unresolved questions, leading to preventative and treatment interventions that would reduce adverse outcomes and improve the quality of life of families at risk.Read moreRead less
Studying The Two Hit Hypothesis Of Psychiatric Illness: Role Of Brain-derived Neurotrophic Factor (BDNF)
Funder
National Health and Medical Research Council
Funding Amount
$469,553.00
Summary
Early environmental factors may play an important role in the development of psychiatric illnesses, such as schizophrenia and depression. We will study an animal model which combines early developmental stress followed by treatment with a stress hormone or chronic cannabis use in adolescence. We will assess behavioural changes and the role of a growth factor in the brain, BDNF. This wil lead to a better understanding of the role of neurodevelopmental stress in psychiatric disease.
Selective Estrogen Receptor Modulators (SERMs) A Potential Treatment For Psychotic Symptoms Of Schizophrenia?
Funder
National Health and Medical Research Council
Funding Amount
$701,276.00
Summary
Schizophrenia is a serious disease with increasing social and economic costs. We need new treatments to improve the life and functioning of people with schizophrenia. We have published studies showing that estrogen is potentially a new treatment for schizophrenia. New brain estrogens called Selective Estrogen Receptor Modulators have fewer side-effects than standard estrogen. We will conduct a controlled clinical trial of a SERM in 180 postmenopausal women with schizophrenia.
Efficacy Of Treatment For Resistant Command Hallucinations.
Funder
National Health and Medical Research Council
Funding Amount
$343,875.00
Summary
Auditory hallucinations (AHs), often described as voices, are a common symptom of schizophrenia and psychoses. Command hallucinations (CHs) are a type of AH in which the voice heard by the patient commands him or her to perform a particular action. The nature of the directive may vary from inconsequential actions to commands to harm the patient or others. There is widespread public concern about the danger individuals with schizophrenia or related disorders pose to themselves and to the communit ....Auditory hallucinations (AHs), often described as voices, are a common symptom of schizophrenia and psychoses. Command hallucinations (CHs) are a type of AH in which the voice heard by the patient commands him or her to perform a particular action. The nature of the directive may vary from inconsequential actions to commands to harm the patient or others. There is widespread public concern about the danger individuals with schizophrenia or related disorders pose to themselves and to the community. There is firm evidence pointing to the important role that CHs play in propelling psychotic individuals into serious and damaging actions. We have found, however, that most individuals who comply with dangerous CHs do so, not because they are angry, violent, antisocial or wish to cause harm, but because they feel powerless to resist. Though CHs are one of the most disturbing symptoms of psychosis, standard treatment has proved to be of limited benefit. This study will evaluate the effectiveness of Treatment of Resistant Command Hallucinations (TORCH), an innovative treatment for CHs. TORCH is an extension of an existing treatment for psychosis that we previously developed. TORCH aims to reduce the distress, worry and harmful or self-defeating behaviour associated with CHs by arming the patient with effective strategies that will enhance resistance and reduce compliance. The project has clear implications for improved clinical and therapeutic management of CHs with major public health, clinical and forensic repercussions. The consequences of being formally assessed as being at risk of acting violently result in the potential for substantial restrictions on the freedom of the individual. The availability of TORCH may prompt a less restrictive management of individuals at risk of dangerous behaviour and promote a more optimistic attitude amongst clinicians. Relatives and carers also stand to benefit through reduction in perplexing and fear-inducing behaviours.Read moreRead less