Inflammation And Oxidative Stress In Emerging Psychotic And Mood Disorders
Funder
National Health and Medical Research Council
Funding Amount
$432,619.00
Summary
We are conducting four large clinical trials testing anti-inflammatory treatments like ?-3 PUFAs and aspirin in young people who are at high-risk for psychosis or have depression. This proposal adds an important component to this research by investigating inflammatory and oxidative stress markers. We aim to determine if the investigated biomarkers predict the course of illness and response to treatments. The findings will facilitate early intervention and targeted treatment.
Interactions Between The Serotonin Transporter And Sympathetic Nervous Activation In Patients With Major Depressive Disorder - Understanding The Link Between The Brain And The Heart
Funder
National Health and Medical Research Council
Funding Amount
$527,109.00
Summary
There is evidence that patients with major depressive disorder (MDD) are at increased risk of developing heart disease. While the mechanisms responsible remain unknown we have previously demonstrated that cardiac sympathetic nervous activity in patients with MDD follows a bimodal distribution, with values in some patients being extraordinarily high. In this project we will determine the physiological consequences of sympathetic activation in patients with MDD.
Network Biomarkers Of Traumatic Stress Resilience And Sensitivity
Funder
National Health and Medical Research Council
Funding Amount
$647,344.00
Summary
Psychosocial stress is a major risk factor for several of the most debilitating mental illnesses including major depression, bipolar disorder, schizophrenia and post-traumatic stress disorder. By understanding the genomic basis of resilience and adverse response to traumatic stress in humans, we may predict and prevent psychopathology. This international collaborative research will use blood from soldiers exposed to extreme combat experience to identify biomarkers of stress and resilience.
Stress Vulnerability In Youth With Borderline Personality Disorder
Funder
National Health and Medical Research Council
Funding Amount
$873,689.00
Summary
Borderline personality disorder (BPD) is a severe mental disorder with adverse long-term outcomes, including suicide. BPD is characterised by vulnerability to stressful life events and catastrophic responses to stress. This study of youth early in the course of BPD examines the baseline biological characteristics of the stress response system, how these characteristics might be influenced by treatment and how this relates to treatment outcome. The findings will inform early intervention for BPD.
The Efficacy Of N-acetylcysteine As An Adjunctive Treatment In Unipolar Depression
Funder
National Health and Medical Research Council
Funding Amount
$443,832.00
Summary
This is evidence that the brain's antioxidant defences, particularly glutathione, are altered in depression. N-acetylcysteine (NAC), a glutathione precursor, increases antioxidant defences and has antidepressant properties in bipolar disorder. The aim of this study is to see if treatment with NAC will precent relapse and improve the symptoms of depression including functioning and quality of life. Participants will be randomly given either NAC or placebo, in addition to standard thereapy.
The Efficacy Of N-acetyl Cysteine As An Adjunctive Treatment For First Episode Psychosis
Funder
National Health and Medical Research Council
Funding Amount
$2,143,069.00
Summary
First episode psychosis may foreshadow devastating, chronic illness. Psychosis follows a staged, progressive pathway. There is evidence to suggest illness progression can be diminished and perhaps even averted if appropriate treatments are given at the early stages of illness. This project will test if N-acetycysteine (NAC) administered to young people who have experienced a first episode of psychosis can help prevent this early psychotic experience from developing into a chronic disorder.
The Effect Of Stress And Hypercortisolaemia On Limbic Epileptogenesis & Affective Disorder.
Funder
National Health and Medical Research Council
Funding Amount
$380,714.00
Summary
This project has the potential to provide novel insights about the causal connections between stress, psychiatric illness (specifically anxiety and depression) and temporal lobe epilepsy (TLE) - the most common form of medical refractory epilepsy in the community. Up to 50% of patients with TLE suffer from anxiety and-or depression. Until relatively recently it had been widely assumed that this was a consequence of the chronic epileptic condition. However, recent evidence suggests that there is ....This project has the potential to provide novel insights about the causal connections between stress, psychiatric illness (specifically anxiety and depression) and temporal lobe epilepsy (TLE) - the most common form of medical refractory epilepsy in the community. Up to 50% of patients with TLE suffer from anxiety and-or depression. Until relatively recently it had been widely assumed that this was a consequence of the chronic epileptic condition. However, recent evidence suggests that there is a bi-directional relationship, with the psychiatric conditions and stress also acting to aggravate the seizures and even predispose to the development of the epilepsy itself. Apart from gaining insights into causes of TLE, anxiety and depression, this framework has potential public health relevance suggesting approaches to the eventual primary and secondary prevention of both MTLE and its associated psychiatric co-morbidities, a neglected area at present. The use of an animal model allows investigation of aetiological processes that extend over the lifetime, which is exceptionally difficult to achieve in humans. Retrospective studies, such as case-control studies, although an indispensable research methods, are subject to bias and imprecision when it comes to measuring remote past exposures to stress, abuse, and deprivation. If the results of these experiments are consistent with our hypotheses, a very strong case would exist for exploring this relationship in human studies. The data would also provide a strong rationale for more aggressive detection and treatment of these psychiatric co-morbidities in TLE patients, in order to potentially modify the progression of the disorder as well as improve the quality of life of sufferers. The results of intervention studies in animal models may suggest specific mode of treatment to achieve this.Read moreRead less
Brain Control Of The Thermoregulatory Cutaneous Circulation: A Window To The Mind, And To The Neurobiology Of Clozapine
Funder
National Health and Medical Research Council
Funding Amount
$561,396.00
Summary
Patients suffering from schizophrenia benefit from medication. Discovering the brain mechanisms whereby the medications work is most important. Action of many important drugs have been established in experimental animals. This is a difficult task for anti-schizophrenia drugs because it is difficult to establish what animals are thinking or feeling, and it is doubtful whether animals ever suffer from schizophrenia. Thus it would be very advantageous to discover a physiological response, measurabl ....Patients suffering from schizophrenia benefit from medication. Discovering the brain mechanisms whereby the medications work is most important. Action of many important drugs have been established in experimental animals. This is a difficult task for anti-schizophrenia drugs because it is difficult to establish what animals are thinking or feeling, and it is doubtful whether animals ever suffer from schizophrenia. Thus it would be very advantageous to discover a physiological response, measurable in, for example, rats, that can serve as a marker of the animal s emotional responses to situations that would normally prove anxiety-provoking. The present grant is based on the discovery, in my laboratory, that stressful stimuli cause sudden falls in blood flow to the tail in rats. My laboratory is the first in the world to measure pulsatile blood flow to the tail in conscious rats, and this is why we made our discovery. My laboratory also discovered that clozapine, a drug of major theoretical and practical importance for the treatment of schizophrenia inhibits fright-induced constriction of the tail artery. Clozapine interacts with many potential neurotransmitters in the brain. Some very complex combinations of these interactions are presumably responsible for the drug s unique psychotherapeutic action in schizophrenia. Our discovery that clozapine inhibits fright-induced constriction of the tail artery means that we will be able to investigate clozapine s mechanisms of action. Results of our findings are genuinely likely to increase our understanding of how clozapine works in schizophrenia. This information should also provide clues as to the nature of the presently mysterious brain malfunctions that result in schizophrenia.Read moreRead less
Phase-Based Treatment For Posttraumatic Stress Disorder In Traumatized Refugees
Funder
National Health and Medical Research Council
Funding Amount
$1,003,340.00
Summary
Refugees report high rates of posttraumatic stress disorder (PTSD). Low response rates to psychological interventions for PTSD in refugees may be explained by their failure to target co-morbid emotion regulation difficulties. In this project, we will test the efficacy of a phase-based intervention that first targets emotion regulation difficulties before implementing trauma-focused therapy to reduce PTSD in refugees. Findings will advance knowledge and inform clinical interventions for refugees.
The Efficacy Of N-acetylcysteine As An Adjunctive Treatment In Bipolar Depression: A Double-blind, Randomised, Placebo-controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$970,090.00
Summary
The brain's antioxidant defences, particularly glutathione, are reduced in bipolar disorder. Treatment with N-acetylcysteine (NAC), a naturally occurring and well-tolerated glutathione precursor, has been shown by our research group to be effective at reducing depression in people with bipolar disorder during a 6-month pilot trial. In this definitive placebo controlled randomised study, we aim to see if add-on treatment with NAC can reduce depression in participants in the depressive phase of bi ....The brain's antioxidant defences, particularly glutathione, are reduced in bipolar disorder. Treatment with N-acetylcysteine (NAC), a naturally occurring and well-tolerated glutathione precursor, has been shown by our research group to be effective at reducing depression in people with bipolar disorder during a 6-month pilot trial. In this definitive placebo controlled randomised study, we aim to see if add-on treatment with NAC can reduce depression in participants in the depressive phase of bipolar disorder.Read moreRead less