INVESTIGATING THE VALIDITY OF PRENATAL INSULTS AS RISK FACTORS FOR SCHIZOPHRENIA.
Funder
National Health and Medical Research Council
Funding Amount
$201,100.00
Summary
Schizophrenia is one of the most devastating of human mental disorders affecting about 1% of the population. The cause of this disorder is not known but it seems certain that it will involve genetic and environmental factors. An adverse environmental factor could be a reduced supply of oxygen and nutrients to a baby during pregnancy. In guinea pigs we aim to investigate whether disruption to the normal supply of oxygen and nutrients to the fetus disrupts the normal fine structure and chemical ma ....Schizophrenia is one of the most devastating of human mental disorders affecting about 1% of the population. The cause of this disorder is not known but it seems certain that it will involve genetic and environmental factors. An adverse environmental factor could be a reduced supply of oxygen and nutrients to a baby during pregnancy. In guinea pigs we aim to investigate whether disruption to the normal supply of oxygen and nutrients to the fetus disrupts the normal fine structure and chemical make up of the brain and gives rise to long-lasting structural and neurochemical changes in adolescent animals, which resemble changes found in the brains of patients with schizophrenia. We will also assess whether behavioural responses of compromised animals are altered in tests that parallel disturbances seen in patients with schizophrenia. Such abnormal brain development could create an underlying vulnerability in the brain, predisposing individuals with risk factors such as genetic inheritance to develop the symptoms of schizophrenia in later life perhaps only after the complete formation of nerve pathways involved in higher brain functioning. If guinea pigs that have been subjected to low oxygen levels during pregnancy show sustained changes in the structure and neurochemistry in regions of the brain that are altered in patients with schizophrenia it would suggest that these long lasting disturbances could result from problems during pregnancy. Thus, this would support the idea that abnormal brain development during pregnancy is one of the underlying causes of schizophrenia.Read moreRead less
Studying The Two Hit Hypothesis Of Psychiatric Illness: Role Of Brain-derived Neurotrophic Factor (BDNF)
Funder
National Health and Medical Research Council
Funding Amount
$469,553.00
Summary
Early environmental factors may play an important role in the development of psychiatric illnesses, such as schizophrenia and depression. We will study an animal model which combines early developmental stress followed by treatment with a stress hormone or chronic cannabis use in adolescence. We will assess behavioural changes and the role of a growth factor in the brain, BDNF. This wil lead to a better understanding of the role of neurodevelopmental stress in psychiatric disease.
The Effects Of Phencyclidine On The NMDA Receptor-neuregulin1 Signalling Complex: Implications For Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$433,872.00
Summary
Phencyclidine is the best known pharmacological agent that can induce schizophrenia-like symptoms in humans and animals. Recent research has strongly suggested that neuregulin1 and ErbB4 signalling are involved in schizophrenia pathology. This study will be the first to determine whether neuregulin1 is altered by phencyclidine, which will further our knowledge by re-evaluating the causal role of neuregulin1 in schizophrenia.
Adolescent Brain Development And Social Cognitive Deficits In Early Psychosis: Can Intervention Improve Outcome?
Funder
National Health and Medical Research Council
Funding Amount
$330,848.00
Summary
This project aims to investigate the origin of impairments in social thinking of young people with first episode psychosis (FEP), and whether social cognitive training can reverse these problems and improve social functioning. We think that slower maturation of particular brain regions during adolescence may be related to these social cognitive deficits. We will also explore whether providing training in these skills can influence the development of these key brain structures.
Examining The Contribution Of The Mirror Neuron System Toward Social Cognitive Impairment In Autism Spectrum Disorders
Funder
National Health and Medical Research Council
Funding Amount
$149,154.00
Summary
Despite a rapidly increasing prevalence, our neurobiological understanding of autism and Asperger's disorder remains limited. Using modern neuroscience techniques, this study investigates whether dysfunction within a specific brain cell, the mirror neuron, underlies social and language impairments in these disorders. This research provides exciting new directions for the understanding, diagnosis, and potential treatment of autism and Asperger's disorder.
Schizophrenia is a group of brain disorders that affects approximately 1 in 100 people. The symptoms can include delusions (false beliefs), hallucinations (e.g., hearing voices), blunted emotions, poor planning ability and reduced motivation. Because these disorders often start in early adulthood, and can be chronic, schizophrenia contributes substantially to the burden of disease across the globe. The causes of schizophrenia are poorly understood, but it is clear that both genetic factors and e ....Schizophrenia is a group of brain disorders that affects approximately 1 in 100 people. The symptoms can include delusions (false beliefs), hallucinations (e.g., hearing voices), blunted emotions, poor planning ability and reduced motivation. Because these disorders often start in early adulthood, and can be chronic, schizophrenia contributes substantially to the burden of disease across the globe. The causes of schizophrenia are poorly understood, but it is clear that both genetic factors and environmental factors can contribute to the risk of developing schizophrenia. As part of an integrated program of research searching for novel environmental risk factors for schizophrenia, this application examines the impact of low prenatal vitamin D on brain development. Vitamin D is a steroid hormone mostly derived from the action of bright sunshine on the skin. Our past research (based on population studies, cell culture studies and animal experiments) have provided tantalizing clues about the impact of low prenatal vitamin D on brain development. This project will explore two important areas. We will explore mechanims by which LOW vitamin D may cause LESS programmed cell death (apoptosis). Programmed cell death is a crucial feature in brain development, and any alteration to the orderly sequence of brain development may leave the person vulnerable to adult-onset brain disorders like schizophrenia. Secondly, we will compare the behaviour and brain markers of adult rats born of mothers depleted of vitamin D versus normal mothers. Finally, we will examine the impact of vitamin D on neural tissue cultures obtained from nasal biopsy. If low prenatal vitamin D is a risk factor for schizophrenia, then it may be possible to reduce the incidence of schizophrenia by providing pregnant women with a safe and cheap vitamin tablet (similar to how folate supplements have reduced the incidence of spina bifida) .Read moreRead less
Stress And HPA Axis Function In First-episode Psychosis: Relationship With Clinical Features And Dynamic Brain Changes
Funder
National Health and Medical Research Council
Funding Amount
$182,378.00
Summary
This research examines the role of stress in the progression of psychotic disorders- a group of severe mental illnesses that include schizophrenia. We will investigate whether patients with psychosis who have an abnormal response to stress experience more severe and distressing symptoms as well as brain volume changes during the initial phase of illness. The results of this research could have important implications for the development of more effective treatments for these disorders.
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
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
Longitudinal Brain Changes In First-episode Psychosis: A 10 Year Follow-up MRI Study
Funder
National Health and Medical Research Council
Funding Amount
$165,250.00
Summary
It is now widely accepted that schizophrenia is associated with changes in the structure of the brain. Until recently these structural changes were considered to predate the onset of illness and to remain static. However, our own work has suggested an alternative model, which relates schizophrenia to brain changes at specific life stages. In order to demonstrate this, we intend to acquire repeat brain images on 100 patients who were initially scanned 10 years ago at the start of their psychotic ....It is now widely accepted that schizophrenia is associated with changes in the structure of the brain. Until recently these structural changes were considered to predate the onset of illness and to remain static. However, our own work has suggested an alternative model, which relates schizophrenia to brain changes at specific life stages. In order to demonstrate this, we intend to acquire repeat brain images on 100 patients who were initially scanned 10 years ago at the start of their psychotic illness. This would be the largest follow-up study of first episode psychosis in the world, with the longest interval between the first and second brain scan. Further, for a proportion of patients we will have 3 MRI scans, at illness onset, 2-4 years post-onset, followed by a third scan at 10 years, thereby providing unique follow-up brain imaging data. Based on our own and other research, we intend to explore the relationship between progressive brain change over a ten year period and: (i) the diagnosis of the patient (schizophrenia or other disorder), (ii) the clinical and functional outcome of the patient (still chronically ill or with no further episode of psychosis), and (iii) the cognitive state of the patient (their ability to perform well on tests of memory, planning and so on). We are able to conduct this study because of the existence of an infrastructure developed to follow-up patients, with a recontact rate of 70% of those patients admitted in 1992 and 1993. In this study we seek to implement these strategies for the patients identified after 1994. The results of this study will test our ideas derived from our model of the major psychotic illnesses and may identify the structural brain changes which are associated with the development of chronic schizophrenia and other psychoses. A further novel outcome will be the inclusion of patients who have remained well and identiifying the structural correlates of a good prognosis.Read moreRead less