Relationship Between Anterior Cingulate Morphology, Neuronal Integrity And Function In Schizophrenia And OCD
Funder
National Health and Medical Research Council
Funding Amount
$312,813.00
Summary
Schizophrenia and obsessive-compulsive disorder (OCD) are extremely disabling psychiatric disorders. Both tend to appear in early adulthood and have a number of important similarities. These include problems with planning and organising thoughts, abnormal brain chemistry, and changed function in the same brain region, the anterior cingulate. The anterior cingulate has been known for some time to be involved in emotion, motivation and attention. However, it is now recognised as the interface betw ....Schizophrenia and obsessive-compulsive disorder (OCD) are extremely disabling psychiatric disorders. Both tend to appear in early adulthood and have a number of important similarities. These include problems with planning and organising thoughts, abnormal brain chemistry, and changed function in the same brain region, the anterior cingulate. The anterior cingulate has been known for some time to be involved in emotion, motivation and attention. However, it is now recognised as the interface between the emotional, feeling part of the brain and the controlling, thinking part. Many, if not all, of the functions performed by the anterior cingulate are disturbed in both schizophrenia and OCD, meaning that studying this region may provide important clues to the nature of the two illnesses. One important characteristic of the anterior cingulate which has not been considered in previous research is its division into three distinct subregions, each with their own specific function. In particular, there is a cognitive region, which deals with response selection and information processing, and an emotional region, which assesses motivational content and controls emotional learning. Because of the nature of the two disorders we intend to study, we believe that schizophrenia will be associated with more abnormalities of the cognitive region, while OCD will be associated with changes in the emotional region. Another important feature of our research design is that we intend to collect data from the same subjects using four separate brain imaging techniques, which provide information about different levels of brain structure and function. This will allow us to interpret our findings from measures of brain chemistry in the context of our findings of brain function. Hopefully this will help us to clarify the pathophysiology of schizophrenia and OCD, and provide potential ways to assess the effect of different treatment strategies in these illnesses.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
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
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
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
A Prospective Study Of Inflammatory Cytokines As Common Factors In The Aetiology Of Both Depression And Osteoporosis.
Funder
National Health and Medical Research Council
Funding Amount
$291,230.00
Summary
Both depression and osteoporosis are common, debilitating and expensive diseases and there is research to suggest that these conditions are related. This study will examine a potential common mechanism, inflammation, which may underlie both diseases. It will focus on circulating proteins which are associated with both depression and fragility fractures, and examine the role they play in both disorders.
ADHD Grown-up: Genetic And Environmental Determinants Of The Adult Outcomes Of Childhood ADHD And Comorbid Conditions
Funder
National Health and Medical Research Council
Funding Amount
$289,542.00
Summary
ADHD remains a controversial issue especially in adulthood. There are many related behavioural problems including substance abuse, anxiety, depression, and personality disorders. Australia is such a focus for twin research that many twin families have taken part in several studies of different aspects of mental health over the years. This grant allows us to link the various datasets to create a unique longitudinal genetic resource and to examine the longterm outcomes.
ADHD And Comorbidity: Implications For Clinical Practice And Molecular Genetics
Funder
National Health and Medical Research Council
Funding Amount
$284,878.00
Summary
ADHD is emerging as the most common, controversial childhood behavioural problem. Previously we have shown that much of the confusion may lie in the fact that ADHD is inherited as a continuum throughout the entire population, only some people having such a strong genetic potential that they warrant the label ADHD. The threshold to achieve this label is partly a community one, leading to the argument over who should be labelled and treated. This grant goes further in examining the possibility tha ....ADHD is emerging as the most common, controversial childhood behavioural problem. Previously we have shown that much of the confusion may lie in the fact that ADHD is inherited as a continuum throughout the entire population, only some people having such a strong genetic potential that they warrant the label ADHD. The threshold to achieve this label is partly a community one, leading to the argument over who should be labelled and treated. This grant goes further in examining the possibility that there is more than one type of ADHD. Some ADHD children have other behavioural problems such as conduct disorder or learning problems. Some have problems throughout their lives while others grow out of it. In Australia we are unique in having developed the most extensive twin databases world-wide and have already studied aspects of ADHD both in the children and their parents. In this grant we shall explore whether there are distinct genetic types of ADHD, characterised not just by their ADHD symptoms but also by the other behavioural problems they experience and by what happens as they grow-up. Such information is invaluable in developing a treatment program dealing with all aspects of the ADHD and also addresses the question of what will happen as they get older. No other study internationally has such extensive data to address these key questions., vital both to clinicians and families. Given the significant genetic component to ADHD, the next possibility is to find the genes involved in the different types. Knowing what these genes do may help in the development of medications more targeted to specific patterns of problems. Recently genes have been identified which may be involved in specific types of ADHD, as well as genes involved in associated problems such as reading disability and substance abuse. This study offers the potential to clearly identify the role of these genes and so assist in improved diagnosis and treatment interventions.Read moreRead less
Posttraumatic Mental Health: Advancing Understanding Of Diagnosis, Treatment And Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$7,590,920.00
Summary
Psychological disorders following exposure to trauma account for a significant proportion of the burden of disease in terms of personal suffering, decreased productivity, occupational dysfunction, and demands on health services. This project will enhance the nation's capacity to reduce psychological problems after trauma. This project will consolidate a critical mass of Australia's leading trauma researchers that will ensure that Australia retains its leading edge in posttraumatic research.