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.
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.
Neurotransmitters mediate the communication between nerve cells in the brain. Once released at the synapse - the contact site between nerve cells - neurotransmitters propagate signals to neighbouring neurons. To allow fast and accurate signal processing in the brain neurotransmitters must be removed rapidly from the site of action. This resets the signal transduction process so that the next nerve impuls can be transmitted. Removal of neurotransmitters is accomplished by transporters, which capt ....Neurotransmitters mediate the communication between nerve cells in the brain. Once released at the synapse - the contact site between nerve cells - neurotransmitters propagate signals to neighbouring neurons. To allow fast and accurate signal processing in the brain neurotransmitters must be removed rapidly from the site of action. This resets the signal transduction process so that the next nerve impuls can be transmitted. Removal of neurotransmitters is accomplished by transporters, which capture the neurotransmitters and bring them back into neurons and astrocytes, the two major cell types in the brain. Malfunction of these transporters can cause mood disorders, Parkinsons's disease and may play a role in the onset of amyotrophic lateral sclerosis and other neurodegenerative disorders. In this project we try to identify novel neurotransmitters transporters, which are likely to play an important role in neurotransmission. Previously, these transporters were assigned as orphan transporters to indicate our lack of understanding. However, recent results from our laboratory now allows to identify the function of these transporters. Elucidation of the physiological role of these transporter will provide the basis to study their function and role in health and disease.Read moreRead less
Self-help For Depressive Symptoms: Finding Messages Suitable For Population-wide Promotion
Funder
National Health and Medical Research Council
Funding Amount
$161,807.00
Summary
Members of the community often use self-help methods to reduce symptoms of depression. In some cases, these may be effective, but in others they may do more harm than good (e.g. self-medication with nicotine or alcohol). The project aims to find out which self-help methods are most likely to be helpful and are easy for the community to use. These methods can then be promoted in educational campaigns to improve how people cope with symptoms of depression. If people can take action to reduce milde ....Members of the community often use self-help methods to reduce symptoms of depression. In some cases, these may be effective, but in others they may do more harm than good (e.g. self-medication with nicotine or alcohol). The project aims to find out which self-help methods are most likely to be helpful and are easy for the community to use. These methods can then be promoted in educational campaigns to improve how people cope with symptoms of depression. If people can take action to reduce milder levels of depression, this may prevent them from progressing to develop a clinical disorder that needs professional treatment.Read moreRead less
Substances that enhance the action of the inhibitory neurotransmitter GABA in the brain are amongst the most widely used drugs. They include many anaesthetics, anxiolytics and sedatives. Their enhancing action is mediated by increasing the effectiveness of GABA acting on GABA receptors, in particular the subtype of GABA receptors known as GABA-A receptors. This action, termed positive modulation, is poorly understood in molecular terms. Our discovery of second order modulators that only act in c ....Substances that enhance the action of the inhibitory neurotransmitter GABA in the brain are amongst the most widely used drugs. They include many anaesthetics, anxiolytics and sedatives. Their enhancing action is mediated by increasing the effectiveness of GABA acting on GABA receptors, in particular the subtype of GABA receptors known as GABA-A receptors. This action, termed positive modulation, is poorly understood in molecular terms. Our discovery of second order modulators that only act in conjunction with first order modulators adds an exciting new dimension to the concept of influencing the ways in which GABA receptors can be modulated. This offers a new approach to the development of therapeutic agents acting on GABA receptors and thus the treatement of important disorders such as anxiety, epilepsy and insomnia.Read moreRead less
The Effect Of High-dose Vitamin-D Supplementation On Mental Health In A Randomised, Controlled Trial Of 1500 Older Women
Funder
National Health and Medical Research Council
Funding Amount
$81,965.00
Summary
Vitamin D is commonly deficient in Western populations, more so in the winter months and in the elderly. A link between depression and vitamin D insufficiency may exist. This study aims to see if vitamin-D supplementation is a practical health intervention for depressive symptoms and may define a public health strategy. In this study participants receive a dose of vitamin D3 or placebo annually for three years. Self-rated psychiatric assessments are administered.
Why Does Early Life Stress Aggravate Limbic Epileptogenesis?
Funder
National Health and Medical Research Council
Funding Amount
$540,116.00
Summary
High rates of anxiety and depression occur in individuals with temporal lobe epilepsy (TLE), the most common form of focal epilepsy in adults. Rats that have experienced early life stress show increased anxiety, decreased seizure thresholds and accelerated epilepsy as adults. We have important leads to mechanisms. The proposed study will better understand the mechanisms connecting early life stress and psychiatric disease to adult TLE, and to test interventions that may counteract these effects.
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
THE NEUROBIOLOGICAL BASIS OF INDIVIDUAL DIFFERENCES IN SUSCEPTIBILITY TO THE CONSEQUENCES OF STRESS
Funder
National Health and Medical Research Council
Funding Amount
$583,875.00
Summary
Stress plays a major role in the development and progression of many different mental health disorders. However, as we all know, the effects of stress on one person can be very different from its effects upon another. This is at least partly explained by differences in individual coping styles. When faced with a stressful situation without a ready solution, people tend to divide into two broad camps: those with an innate tendency to adopt passive coping strategies, such as avoidance, and those t ....Stress plays a major role in the development and progression of many different mental health disorders. However, as we all know, the effects of stress on one person can be very different from its effects upon another. This is at least partly explained by differences in individual coping styles. When faced with a stressful situation without a ready solution, people tend to divide into two broad camps: those with an innate tendency to adopt passive coping strategies, such as avoidance, and those that tend towards active coping strategies, such as attempting to take control of the situation. Previous studies have provided findings that suggest that passive coping is more common amongst sufferers of depression, post-traumatic stress disorder, and chronic pain syndrome than is active coping. But is this cause, or effect? And what are the intervening brain mechanisms? We attempt to address such questions in the present project using an animal model in which social conflict has been shown to trigger depression-like symptoms. In particular we wish to: (i) determine whether the patterns of brain activity triggered by social conflict are different for active vs. passive copers; (ii) determine whether the depression-like consequences of social conflict are more severe in passive than in active copers; (iii) determine whether differences in coping style and vulnerability to social conflict stress are due to the actions of a particular neurotransmitter, dopamine, in the prefrontal cortex of the brain; (iv) determine whether the actions of antidepressants might be attributable changes in prefrontal cortex dopamine function which in turn promote active coping in preference to passive coping. These studies will provide exciting new information about the neurobiological basis of individual differences in vulnerability to the harmful effects of stress, and thus will offer the hope of developing new ways of preventing devastating illnesses such as depression.Read moreRead less
Dopamine Mechanisms Conferring Resilience To Depression: A New Antidepressant Target
Funder
National Health and Medical Research Council
Funding Amount
$560,948.00
Summary
A significant proportion of people who suffer depression fail to obtain effective relief from either drugs or psychotherapy. Accordingly, there is a pressing need to develop new, and more effective, treatments. This project will determine whether certain specific brain pathways that use the transmitter dopamine can be manipulated in their activity so as to increase resilience to depression. This work has potential to provide the foundation for the development a new generation of antidepressants.