Outcome Prediction, Stratification And Novel Treatments In Individuals At Ultra High Risk Of Psychosis
Funder
National Health and Medical Research Council
Funding Amount
$774,540.00
Summary
The Ultra High Risk (UHR) criteria have been developed to identify people at high risk of psychotic disorders such as schizophrenia so that treatments can be provided early to reduce risk and disability. However the some UHR people are at risk of other difficulties and disorders and others are not at risk of all. We need to improve our ability to distinguish between these groups so that treatment can be tailored according to risk, and develop new treatments that target underlying problems.
The Outcomes Of Adolescents And Young Adults Who Experience Hallucinations: A Birth Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$624,842.00
Summary
A national survey reported that 1 in every 12 Australian adolescents experiences hallucinations. Although hallucinations are relatively common experiences, it remains unclear if hallucinations in adolescence are associated with mental illness, and impairment in social and occupational functioning in later adulthood. This study aims to examine the outcomes at 30 years of age in subjects from an Australian birth cohort study who experienced hallucinations during adolescence and young adulthood.
Clinical And Neurobiological Predictors Of Onset Of Major Mental Disorders (mania, Psychosis, Severe Depression), And Associated Functional Impairment, In Adolescent And Young Adult Twins: A Prospective Longitudinal Study
Funder
National Health and Medical Research Council
Funding Amount
$1,356,103.00
Summary
The Brisbane Twin Study is a prospective twin study tracking the real-time developmental trajectories of the onset of anxiety, mood, psychotic or substance misuse disorders through adolescence and young adulthood. This unique study has now reached the point where reassessment (after 20 years) can be performed. We will now determine the extent to which outcomes are predicted by neurobiological and genetic markers. This information is critical to prevention or early intervention strategies.
A Randomised Control Trial Of A Group-Based Intervention For Substance Abuse In Psychosis.
Funder
National Health and Medical Research Council
Funding Amount
$345,250.00
Summary
The use of alcohol and illicit substances is common amongst people with psychotic illnesses, and is associated with a poor outcome in terms of severity of symptoms, treatment adherence, work-studies, family cohesion, aggression and quality of life. All this adds significantly to the cost of mental health services and society more broadly. The proposed study aims to refine, pilot, and rigorously evaluate a group-based intervention that targets substance use in such individuals at different stages ....The use of alcohol and illicit substances is common amongst people with psychotic illnesses, and is associated with a poor outcome in terms of severity of symptoms, treatment adherence, work-studies, family cohesion, aggression and quality of life. All this adds significantly to the cost of mental health services and society more broadly. The proposed study aims to refine, pilot, and rigorously evaluate a group-based intervention that targets substance use in such individuals at different stages of their illness, and within a number of different treatment settings. The intervention will be informed by an enhanced understanding of the motivations for substance use in people with psychotic illnesses The specific aims are to: Refine, implement and evaluate, using a controlled experimental design, a novel group-based intervention for reducing substance abuse comorbidity in people with psychotic disorders; Determine reasons for substance use by these individuals, to inform the intervention procedures; Pilot the intervention in a series of different treatment settings, including early episode and rehabilitation programs, and non-government organisations dealing with people with psychotic disorders, to ensure generalisability, adaptability, and acceptability; Augment case managers' knowledge and skills in dealing with comorbid drug and alcohol use Enhance detection, motivation to change, ongoing monitoring and relapse prevention of substance misuse in clients with psychotic disorders. It will also be possible, once the treatment intervention is finalised and evaluated, to expand its use to patients with non-psychotic mental illnesses.Read moreRead less
Epigenetic Mechanisms Of Brain Dysfunction In Psychotic And Mood Disorders
Funder
National Health and Medical Research Council
Funding Amount
$617,836.00
Summary
This project investigates the role of epigenetic processes (i.e., functional changes to the genome affecting gene expression) in mediating the long-term effects of childhood trauma in schizophrenia and bipolar-I disorder. We specifically aim to distinguish the effects of trauma-related epigenetic effects on brain structure and function, and on the immune and stress-response systems, and the potential moderation of these effects by structural genetic variants associated with psychosis risk.
An Empirical Framework For Assessing Mortality And Morbidity In People With Psychotic Disorders: A 7-year Prospective And 10-year Retrospective Follow-up Of 2075 Participants In The Survey Of High Impact Psychosis (SHIP) Using Linked Registers
Funder
National Health and Medical Research Council
Funding Amount
$751,876.00
Summary
Our study is designed to fill a knowledge gap on mortality and morbidity in people with a psychotic disorder. It will: 1. Estimate rates of 7-year mortality and morbidity in people with a psychotic disorder. 2. Examine the impact of sets of risk factors on mortality and morbidity. 3. Develop predictive risk equations for CVD for use with people with psychotic disorders. 4. Calculate the economic burden of severe and acute physical morbidity in addition to mental health impacts.?
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
A Study Of The Medial Temporal Lobe In High-risk And Established Schizophrenia Using T2 Relaxometry
Funder
National Health and Medical Research Council
Funding Amount
$358,245.00
Summary
Neurodevelopmental models of schizophrenia suggest that this disorder is associated with a structural brain abnormality present from very early life. This model predicts that brain changes are present before the onset of schizophrenia, and do not change. Our work supports the idea that damage is present from the outset of illness - however, this damage was not evident in a high-risk group of individuals who later developed psychosis. When these patients were rescanned after the onset of the illn ....Neurodevelopmental models of schizophrenia suggest that this disorder is associated with a structural brain abnormality present from very early life. This model predicts that brain changes are present before the onset of schizophrenia, and do not change. Our work supports the idea that damage is present from the outset of illness - however, this damage was not evident in a high-risk group of individuals who later developed psychosis. When these patients were rescanned after the onset of the illness, they exhibited reductions in the volumes of structures that are regarded as critical to the symptoms of schizophrenia. The lack of structural changes in this group before the onset of psychosis may have a number of possible explanations. However, it may be that a number of factors produce the observed changes in the temporal lobe in schizophrenia. Thus, high-risk subjects may have a vulnerability to hippocampal damage that becomes apparent during the transition to psychosis. In order to explore this, our study will examine changes in the hippocampi in three groups of patients, and compare them with matched normal control subjects. The patient groups are: (i) individuals at high-risk, (ii) first-episode psychosis patients and (iii) patients with chronic schizophrenia. The study will rescan the high-risk group to examine hippocampal changes once they have become psychotic. T2 relaxometry is a non-invasive way to examine whether changes in the brain are present in patients with schizophrenia from the outset of illness. T2 will also let us examine the high-risk individuals to see whether such changes are also apparent premorbidly. Using T2 we will be able to examine the nature of these structural changes and assess what processes are in evidence. Our MRI findings present a challenge to the neurodevelopmental hypothesis of schizophrenia. The use of T2 in this study will allow a thorough examination of these findings and will have major implications for this hypothesis.Read moreRead less
Structural And Functional Studies On Glutamate Decarboxylase.
Funder
National Health and Medical Research Council
Funding Amount
$500,460.00
Summary
This proposal aims to determine the molecular structure of the two known isoforms of Glutamate Decarboxylase (GAD65 and GAD67). GAD in an essential human enzyme that is responsible for synthesising the primary inhibitory neurotransmitter gamma-aminobutyric acid (GABA). GABA functions in the human Central Nervous System (CNS) to dampen down excitatory signals. Proper control of GABA synthesis is important and perturbations in GABA levels lies behind human diseases such as intractable epilepsy, de ....This proposal aims to determine the molecular structure of the two known isoforms of Glutamate Decarboxylase (GAD65 and GAD67). GAD in an essential human enzyme that is responsible for synthesising the primary inhibitory neurotransmitter gamma-aminobutyric acid (GABA). GABA functions in the human Central Nervous System (CNS) to dampen down excitatory signals. Proper control of GABA synthesis is important and perturbations in GABA levels lies behind human diseases such as intractable epilepsy, depression and schizophrenia. As a result of this role, numerous common therapeutics (for example benzodiazepines) target proteins involved in the GABA neurotransmitter system. The goal of this proposal is to use the molecular structures of GAD to understand how to achieve fine control of GABA production. In addition to its role in the CNS, GAD is an important human autoantigen. Antibodies to one isoform of GAD, GAD65, are found in most patients with type I diabetes as well as certain patients with the movement disorder stiff person syndrome and related diseases of the CNS. It is suggested that the development of auto-antibodies may play a key role in the pathophysiology of these conditions. Despite sharing >80% sequence similarity with GAD65, autoantibodies to the other isoform of GAD, GAD67, are rarely found in patients with disease. The aim of this grant is to characterise the region of GAD that is targetted by autoantibodes. These data will allow us to understand why certain autoantibodes are able to inhibit GAD enzyme activity and why GAD65, but not GAD67 is recognised by autoantibodes.Read moreRead less