An inability to resist a temptation or repeated failures of self-regulation can lead to 'impulsive' and 'compulsive' behaviours that relate to a host of personal and social problems (eg., excessive eating, gambling, and substance use). Despite this, very little research has studied the neural and psychological underpinnings of these behaviours. My research will take advantage of recent innovations and approaches to fill this void and have implications for diagnosis and treatment.
Disruption And Restoration Of Motor Control In Musculoskeletal Pathology: Implications For Physiotherapy Management
Funder
National Health and Medical Research Council
Funding Amount
$210,990.00
Summary
The way in which the nervous system controls muscles and movement may play a role in the development and progression of common musculoskeletal conditions. One of these conditions is patellofemoral pain syndrome which is associated with pain around the knee cap. This condition may result from an imbalance in the activity of the thigh muscles that control movement of the knee cap as the knee bends and straightens. This imbalance is due in part to problems with the control of the muscles by the ner ....The way in which the nervous system controls muscles and movement may play a role in the development and progression of common musculoskeletal conditions. One of these conditions is patellofemoral pain syndrome which is associated with pain around the knee cap. This condition may result from an imbalance in the activity of the thigh muscles that control movement of the knee cap as the knee bends and straightens. This imbalance is due in part to problems with the control of the muscles by the nervous system. Our previous studies have shown that physiotherapy treatment aimed at restoration of the control of the knee muscles results in clinical improvement of the condition. The first part of this project will investigate possible reasons for this muscle imbalance including the effects of pain, swelling and muscle fatigue. Understanding the reasons for the imbalance in muscle activity will help direct and refine more appropriate treatment strategies for this and other musculoskeletal conditions. The second part will assess whether a specific physiotherapy muscle training program for the thigh muscles is more effective in correcting the muscle imbalance than a more generalised thigh strengthening exercise program. The results will help us to better understand why the condition occurs and how we can best assess and treat the problem.Read moreRead less
Gene Expression Signature Technology To Repurpose Drugs For Bipolar Disorder
Funder
National Health and Medical Research Council
Funding Amount
$482,800.00
Summary
In this project we will generate a Gene Expression Signature that best characterises the overall biological effects of a cocktail of drugs currently used to treat bipolar disorder. The Signature will be identified in cells and intact brains, and then validated using human gene expression profiling. The validated Signature will then be used to screen libraries and discover new drugs for treating bipolar disorder.
Genetic Influences On The Comorbidity Between Attention Deficit Hyperactivity Disorder And Substance Use
Funder
National Health and Medical Research Council
Funding Amount
$244,852.00
Summary
Substance use (SU) problems are more common among individuals with a history of ADHD. However, the reasons for this relationship are unclear. Our study will examine the extent to which this relationship is due to shared genetic influences using data collected during interviews about ADHD and SU in a large sample of young adult twins, their siblings and their parents. The results will aid in developing treatments targeting the symptoms of ADHD and SU concurrently.
Bipolar affective disorder (BP), or manic-depressive illness, is a major cause of disability and mortality worldwide. It has a lifetime prevalence of about 1% and suicide risk of about 20%. The disorder is characterised by episodes of mania or hypomania and depression, appearing in varying succession, with or without intermission. Twin, family, and adoptive studies point to a strong genetic component leading to the development of bipolar disorder, with a heritability of the order of 80%. Yet the ....Bipolar affective disorder (BP), or manic-depressive illness, is a major cause of disability and mortality worldwide. It has a lifetime prevalence of about 1% and suicide risk of about 20%. The disorder is characterised by episodes of mania or hypomania and depression, appearing in varying succession, with or without intermission. Twin, family, and adoptive studies point to a strong genetic component leading to the development of bipolar disorder, with a heritability of the order of 80%. Yet the identification of the genetic basis of the disease has proved exceedingly difficult, with numerous studies producing no definitive data. The lack of convincing results has been interpreted as an indication of complex genetic mechanisms and underlying differences between affected families and ethnic groups. Genetically isolated populations, where most individuals descend from a small number of founders, are believed to hold great potential for understanding the genetic basis of complex diseases, such as bipolar disorder. Affected subjects in such populations are likely to share the same predisposing genes, making these genes easier to identify. During the last 10 years, we have been involved in the study of bipolar disorder in one such population, with very promising results. In this project, we propose to take the research further by collecting more affected families, confirming the current positive findings and narrowing down the search to a small region, possibly a single gene. If successful, the study will be a major breakthrough which, by identifying a molecular pathway and disease mechanism, will contribute valuable and generally valid information on the biological basis of mood disorders.Read moreRead less
Understanding The Pathophysiology Of Schizophrenia, Major Depressive Disorder And Bipolar Disorder As A Basis For Improving Treatments
Funder
National Health and Medical Research Council
Funding Amount
$804,106.00
Summary
The Applicant seeks to understand the causes of the schizophrenia, bipolar disorder and major depressive disorder, which affect over 20% of the Australian population. This research is important as drug design, based on chemical remodelling, has not significantly advanced initial breakthroughs in treating psychiatric disorders and there is now a widespread belief that new drugs will only come from understand their causes.
The Neurochemical Basis Of Behavioural Control: Relevance For Addiction, OCD And Tourette Syndrome.
Funder
National Health and Medical Research Council
Funding Amount
$375,225.00
Summary
Both the control of voluntry responses over reflexive habits, and the ability to direct voluntary responses appropriately when there are conflicting choices present in the world, are thought to be important in mental disorders such as drug addiction, tic disorders such as Tourette syndrome and obsessive compulsive disorder. This project will examine the brain neurochemistry that underpins our ability to control voluntary responses, providing insight into potential pharmacological interventions.
Understanding The Role Of Muscarinic Receptors In The Pathophysiology Of Depression And Bipolar Disorder
Funder
National Health and Medical Research Council
Funding Amount
$480,074.00
Summary
The causes of bipolar disorder and major depressive disorder, which effect many Australians, remain unknown. We have recently shown decreases in muscarinic receptors in the brain of people with bipolar disorder and major depressive disorder. Muscarinic receptors are important in maintaining the functions of the brain that seem to be affected in people with bipolar disorder and major depressive disorder. Here we seek to understand how changes in muscarinic receptors occur in both disorders.
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