Understanding The Molecular Basis Of Bipolar Affective Disorder
Funder
National Health and Medical Research Council
Funding Amount
$812,250.00
Summary
Bipolar disorder (manic depressive illness) is a severe mood disorder, with a lifetime prevalence of up to 1.6%. The illness is characterised by aberrant mood swings resulting in periods of mania and depression with reversion to normal behaviour between episodes. The condition has a severe impact on sufferers, being demonstrated to be the sixth most disabling disorder in the WHO Global Burden of Disease report and increasing the risk of suicide fifteen-fold. There is a pressing need to define mo ....Bipolar disorder (manic depressive illness) is a severe mood disorder, with a lifetime prevalence of up to 1.6%. The illness is characterised by aberrant mood swings resulting in periods of mania and depression with reversion to normal behaviour between episodes. The condition has a severe impact on sufferers, being demonstrated to be the sixth most disabling disorder in the WHO Global Burden of Disease report and increasing the risk of suicide fifteen-fold. There is a pressing need to define more clearly the biological basis of bipolar disorder as a necessary prerequisite to improved diagnosis and treatment. The underlying causes of bipolar disorder remain unknown. However, family studies reveal the high heritability of bipolar disorder and this familial clustering provides an opportunity to use genetic approaches to identify the predisposing genes. The long-term aim of our research is to investigate the biology of those genes that either cause or predispose to bipolar disorder. We have previously reported strong evidence for a novel bipolar disorder susceptibility gene on chromosome 4, a finding which has subsequently been reproduced in several independent studies. Consequently, we hypothesise that there is a gene located on chromosome 4 that predisposes to bipolar disorder. The aim of this proposal is to identify the chromosome 4 bipolar susceptibility gene and understand how the gene causes bipolar disorder. Identifying the genes responsible for bipolar disorder will allow us to define and understand the biological basis of this severe psychiatric condition. This will ultimately lead to major improvements in the ability to diagnose, treat and prevent the illness.Read moreRead less
High-Throughput Screening Of The Genome And Proteome In Postmortem CNS From Subjects With Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$553,190.00
Summary
Schizophrenia is a serious psychiatric illness that effects ~1% of the Australia population. The underlying pathology of the illness remains unknown. This application seeks funding to use new technologies to screen approximately 60% of the expressed human genome and proteome to determine which genes are being differentially expressed in two regions thought to be important in generating the symptoms of the illness, the frontal cortex and hippocampus. This project will generate a large amount of d ....Schizophrenia is a serious psychiatric illness that effects ~1% of the Australia population. The underlying pathology of the illness remains unknown. This application seeks funding to use new technologies to screen approximately 60% of the expressed human genome and proteome to determine which genes are being differentially expressed in two regions thought to be important in generating the symptoms of the illness, the frontal cortex and hippocampus. This project will generate a large amount of data, however by comparing the data from subjects with schizophrenia to that from control subjects and subjects with bipolar disorder who were psychotic and being treated with antipsychotic drugs close to death will allow us to identify changes that are specific to schizophrenia. Genes that are expressing different levels of mRNA and protein will become prime targets for future investigations as they are likely to be central to the pathology of the illness.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
Anti-Estrogens - A Potential Treatment For Bipolar Affective Disorder In Women?
Funder
National Health and Medical Research Council
Funding Amount
$239,250.00
Summary
Bipolar Affective Disorder (BPAD) or Manic-Depressive Illness is a serious mental illness with high morbidity and mortality. The cause of the illness is still unclear and the underlying neurochemical changes are different for the manic phase compared with the depressive phase. The current treatments for BPAD are limited in scope and not biochemically well understood. There are gender differences in the presentation and outcomes for BPAD which adds to the complexity of the illness. We are proposi ....Bipolar Affective Disorder (BPAD) or Manic-Depressive Illness is a serious mental illness with high morbidity and mortality. The cause of the illness is still unclear and the underlying neurochemical changes are different for the manic phase compared with the depressive phase. The current treatments for BPAD are limited in scope and not biochemically well understood. There are gender differences in the presentation and outcomes for BPAD which adds to the complexity of the illness. We are proposing a study to develop a new type of treatment for the manic phase of BPAD and are exploring the use of anti-estrogens in women with mania. The background to our proposed study comes from a few case reports suggesting that anti-estrogen agents such as progesterone and tamoxifen may be useful adjuncts to treatment. We conducted a small pilot study comparing the addition of oral tamoxifen with oral progesterone and placebo in 10 women with mania and found that the women who received tamoxifen made significantly better improvements in their manic symptoms over a 28-day trial. The research study we are now proposing is a larger, three-arm, double blind, placebo controlled, 28-day adjunctive study in women with mania to expand and clarify our pilot study findings. Patients in our proposed study would receive either 40mg per day tamoxifen or 20mg per day progesterone or placebo in addition to standardised lithium medication. We will measure enzyme activity (protein kinase C) and estrogen-progesterone levels to understand more about the mechanisms of action by these new hormone treatments. BPAD is a crippling disorder and if we are successful, then tamoxifen treatment may be an important new treatment. This proposed study will also shed new light on some of the neurochemical mechanisms underlying BPAD as well as opening up the new area of hormone treatments for serious mental illness.Read moreRead less
A Double-blind Placebo Controlled Trial Of Transcranial Magnetic Stimulation In The Treatment Of Depression.
Funder
National Health and Medical Research Council
Funding Amount
$366,775.00
Summary
Depression is a severe and often disabling illness that occurs frequently in the general population. Depression is a treatable illness and the majority of patients will respond to anti-depressant medication, a form of psychotherapy or a combination of these. However, a significant percentage of patients with depression fail to respond to these therapies and currently require electroconvulsive therapy (ECT). This entails the complications and costs of multiple anaesthetics, memory impairment and ....Depression is a severe and often disabling illness that occurs frequently in the general population. Depression is a treatable illness and the majority of patients will respond to anti-depressant medication, a form of psychotherapy or a combination of these. However, a significant percentage of patients with depression fail to respond to these therapies and currently require electroconvulsive therapy (ECT). This entails the complications and costs of multiple anaesthetics, memory impairment and substantial social stigma. Transcranial magnetic stimulation is being researched as a potential alternative for these patients. It is administered to patients who are awake and alert and appears to have fewer side effects. TMS uses the unique properties of a magnetic field to produce or disrupt electrical activity in superficial areas of the brain, targeted to the areas thought to be involved in the cause of depression. Our research study will compare the two most promising types of TMS with an inactive or placebo condition. This is important to establish that the effects of TMS arise from the actual stimulation and to investigate whether one of two types of TMS administered is superior. We will administer this treatment for between 2 and 4 weeks and assess the response. We anticipate that our research will contribute to the development of TMS as a treatment methodology for this important patient group. It is crucial that a new treatment be thoroughly evaluated prior to wide dissemination of it in clinical practice. We will help define the effectiveness of this treatment and the most appropriate way in which it can be administered.Read moreRead less
A Double-blind Controlled Trial Of RTMS In The Treatment Of Bipolar Depression
Funder
National Health and Medical Research Council
Funding Amount
$401,605.00
Summary
Bipolar affective disorder (BPAD) is a serious mental illness of substantive impact but there has been relatively sparse investigation of treatments for it. One of the only substantially new treatments developed for depression in recent years has been rTMS. Repetitive TMS has been evaluated in over 30 trials conducted, but no substantive trials have explored its use in bipolar depression. We propose to do this, conducting a large scale clinical trial.
Ocular Motility In Autism And Asperger S Disorder: Dissociation Of Motor Deficits.
Funder
National Health and Medical Research Council
Funding Amount
$131,235.00
Summary
We will use ocular motor technology to investigate motor dysfunction in autism and Asperger's disorder, to advance our understanding of the neurobiological bases of these disorders. This will help clarify whether neural networks are differentially disrupted in these disorders, as our previous clinical research suggests. This dissociation and the subsequent development of an ocular motor clincal screen may improve diagnosis, and potentially treatment, of these devastating conditions.
Examining The Contribution Of The Mirror Neuron System Toward Social Cognitive Impairment In Autism Spectrum Disorders
Funder
National Health and Medical Research Council
Funding Amount
$149,154.00
Summary
Despite a rapidly increasing prevalence, our neurobiological understanding of autism and Asperger's disorder remains limited. Using modern neuroscience techniques, this study investigates whether dysfunction within a specific brain cell, the mirror neuron, underlies social and language impairments in these disorders. This research provides exciting new directions for the understanding, diagnosis, and potential treatment of autism and Asperger's disorder.
The Role Of Stress, HPA-axis Dysfunction And CNS Structural And Functional Change In The Development Of Psychosis.
Funder
National Health and Medical Research Council
Funding Amount
$345,538.00
Summary
This research will further understanding of the processes underlying the development of serious mental illnesses such as schizophrenia and may lead to the development of strategies to prevent these devastating disorders. Although there have been advances in the management of psychotic disorders in recent years, their underlying causes remain largely unknown. We aim to investigate the potential roles of stress, HPA-axis function and structural and functional brain changes. The neurodevelopmental ....This research will further understanding of the processes underlying the development of serious mental illnesses such as schizophrenia and may lead to the development of strategies to prevent these devastating disorders. Although there have been advances in the management of psychotic disorders in recent years, their underlying causes remain largely unknown. We aim to investigate the potential roles of stress, HPA-axis function and structural and functional brain changes. The neurodevelopmental model of psychosis suggests that small structural CNS changes occur very early in life conferring a degree of vulnerability on the affected individual. We propose that the psychological and neurobiological processes listed above interact with the pre-existing vulnerability, resulting in the development of psychotic symptoms. This is in line with the stress-vulnerability model of psychosis. We aim to investigate this model by monitoring the level of stress reported by young people at risk of psychosis over 12 months. We will also obtain measures of their biological response to stress by assessing cortisol levels over time and brain structure and functioning will be assessed. By monitoring these processes in the high risk group, we will be able to identify any changes that occur if a psychotic illness develops. This research also has practical applications in the identification of young people at high risk of developing a psychotic disorder, Moreover it will inform the development of medical and psychological strategies aimed at preventing or delaying the onset of schizoprenia and related illnesses in the high risk population.Read moreRead less
Advanced Paternal Age: Behavioural, Neuroanatomical And Genomic Correlates In The Offspring Of Older Fathers
Funder
National Health and Medical Research Council
Funding Amount
$501,565.00
Summary
The offspring of older fathers have an increased risk of developing disorders such as autism and schizophrenia. This is thought to be due to mutations in the developing sperm. Our group has shown in a mouse model that the offspring of older fathers have changes in brain shape and in behaviour, similar to some findings in autism. In this grant we will refine this animal model and explore the brain, behavioural and genetic correlates of advanced paternal age.