Abnormal Auditory System Function In Schizophrenia: An ERP And MEG Study Of Its Origin, Course And Generality.
Funder
National Health and Medical Research Council
Funding Amount
$250,770.00
Summary
In 1991, an Australian group found that schizophrenia patients have a reduced brain response to deviant sounds in a repeating pattern of identical sounds. Deviant sounds produce a brain electrical response known as mismatch negativity which is generated by the auditory cortex in the brain's temporal lobes and by adjacent areas in the frontal lobes. A smaller mismatch negativity in patients has since been replicated in laboratories in the US, Europe and Australia. The importance of this finding i ....In 1991, an Australian group found that schizophrenia patients have a reduced brain response to deviant sounds in a repeating pattern of identical sounds. Deviant sounds produce a brain electrical response known as mismatch negativity which is generated by the auditory cortex in the brain's temporal lobes and by adjacent areas in the frontal lobes. A smaller mismatch negativity in patients has since been replicated in laboratories in the US, Europe and Australia. The importance of this finding is that it had not been previously recognised that patients have low level auditory problems that could potentially have a profound impact on higher level functions. Finnish researchers have gone on to show in healthy individuals that mismatch negativity can reveal important features about how well the auditory system works, e.g., for the brain to respond to a deviant sound, it must have a memory of what happened in the past. Mismatch negativity provides a measure of the integrity of these memory functions. But it also provides an index of how well the auditory system discriminates different aspects of sound, pitch, loudness, and temporal features, such as duration. There are hints in our data and from US researchers that processing of the temporal features of sounds is particularly impaired in schizophrenia. We have also recently discovered that first-degree relatives of patients may have a similar deficit. The aim of this project is to use mismatch negativity to probe what is wrong with the auditory system in schizophrenia and those at risk (first degree relatives). Is it the areas of the brain primarily involved in sound perception (the temporal lobes) that are faulty or is the problem in the frontal lobes? Is it the case that processing of temporal features are particularly compromised and if so, is this a biological marker for schizophrenia. Answers to these questions will greatly enhance our understanding of the nature of the brain dysfunction in schizophrenia.Read moreRead less
The Neurobiology Of Auditory Hallucinations: Characterisation Of Dysfunction Within A Neural Circuitry Model.
Funder
National Health and Medical Research Council
Funding Amount
$299,625.00
Summary
This is a highly innovative research proposal which is based on years of extensive research by our group. Auditory hallucinations are a prominent and potentially disabling symptom of psychosis, however it is extremely difficult to study them scientifically. Past research by our group (and other groups internationally) has indicated that an extensive network in the brain is activated whenever auditory hallucinations occur, but the source of this brain activity is unclear. It was thought that the ....This is a highly innovative research proposal which is based on years of extensive research by our group. Auditory hallucinations are a prominent and potentially disabling symptom of psychosis, however it is extremely difficult to study them scientifically. Past research by our group (and other groups internationally) has indicated that an extensive network in the brain is activated whenever auditory hallucinations occur, but the source of this brain activity is unclear. It was thought that the source may be the same brain circuits that are involved in generating inner speech or monitoring it, but our past research has ruled out these possibilities. Instead, our recent work suggests that auditory hallucinations may be associated with poorly functioning connections within central auditory processing circuits, specifically between left and right auditory association cortical regions. We conceptualise hallucinations as an abnormal and involuntary form of memory retrieval consequent to this dysfunction. Our study will pioneer methods of measuring connectivity in the brain circuits identified in our model, using a combination of functional magnetic resonance imaging (fMRI) and electroencephalographic (EEG) techniques in tandem with tests of central auditory processing. We believe that sufferers may benefit from understanding the physical processes which cause hallucinations. We also believe that a better understanding of hallucinations may lead to a better understanding of schizophrenia and the psychoses, which may in turn help in the development of better ways of treating these illnesses.Read moreRead less
Episodic Memory Dysfunction As A Basis For Auditory Hallucinations In Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$278,517.00
Summary
Auditory hallucinations (AHs) occur frequently in people who suffer from schizophrenia. This symptom usually involves hearing voices that the hallucinator firmly believes originate from other people. The voices are often intrusive, abusive and persecutory. They are a source of significant stress and may result in self harm or harm to others. Our investigations will attempt to provide experimental support for the theory that AHs represent a misremembering of voices which were heard in the past. W ....Auditory hallucinations (AHs) occur frequently in people who suffer from schizophrenia. This symptom usually involves hearing voices that the hallucinator firmly believes originate from other people. The voices are often intrusive, abusive and persecutory. They are a source of significant stress and may result in self harm or harm to others. Our investigations will attempt to provide experimental support for the theory that AHs represent a misremembering of voices which were heard in the past. We will do this by attempting to characterise specific problems that hallucinators have in identifying when they heard verbal fragments and who said them. We plan to conduct our investigations at five levels. First, we will determine how accurate hallucinators' memories are for context by the use of special neuropsychological tests. Second, we will find out if hallucinators form more false memories than comparison subjects using a test in which such incorrect recollections occur commonly. Third, we will determine if hallucinators have a tendency to reconstruct the characteristics of false verbal memories in the same way that they reconstruct the characteristics of their hallucinations. Fourth, we will attempt to suppress these false verbal memories and finally, we will characterise those brain regions which are activated during true and false memory formation by using blood flow analysis technology in order to identify networks of brain activity which preferentially malfunction in hallucinating patients. This study provides the prospect of adding substantially to our understanding of the mechanisms underlying auditory hallucinations and to lead to the development of new cognitively-based treatments for the symptom.Read moreRead less
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.
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