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
The cognitive neuroscience of executive control: behavioural, physiological and genetic mechanisms. How genes influence our human abilities to think, reason and control behaviour has puzzled scientists for decades. The human genome project has allowed us to ask how individual genes influence these capacities. Understanding the genetics of these abilities provides a solid platform from which to launch gene discovery projects in clinical disorders where these abilities are compromised. The curr ....The cognitive neuroscience of executive control: behavioural, physiological and genetic mechanisms. How genes influence our human abilities to think, reason and control behaviour has puzzled scientists for decades. The human genome project has allowed us to ask how individual genes influence these capacities. Understanding the genetics of these abilities provides a solid platform from which to launch gene discovery projects in clinical disorders where these abilities are compromised. The current project is directly relevant to the genetics of mental disorders, such as attention deficit hyperactivity (ADHD), that place a large burden, both financially and emotionally, on our society. Understanding the genes and biological pathways that increase risk for mental disorders will ultimately lead to improved treatments for these conditions.Read moreRead less
Models of adolescent drug use and its consequences. Recent concerns surround the impact of drug abuse - particularly binge drinking, inhalant abuse and cannabis use - on the mental health of adolescents. Early drug use is associated with mental health problems although the mechanisms involved are not well characterised. The present proposal aims to use animal models to characterise substance abuse that occurs during the adolescent period and to investigate its effects on brain and behaviour. Inc ....Models of adolescent drug use and its consequences. Recent concerns surround the impact of drug abuse - particularly binge drinking, inhalant abuse and cannabis use - on the mental health of adolescents. Early drug use is associated with mental health problems although the mechanisms involved are not well characterised. The present proposal aims to use animal models to characterise substance abuse that occurs during the adolescent period and to investigate its effects on brain and behaviour. Increasing our knowledge of the causes and consequences of adolescent drug abuse will improve Australia's ability to confront this problem and to develop early interventions and treatments that minimise associated harms.Read moreRead less
Delineating The Anatomical Correlates Of Neurocognitive And Psychomotor Dysfunction In Depression By FMRI
Funder
National Health and Medical Research Council
Funding Amount
$388,340.00
Summary
Severe depression is characterised by slowing of mental and motor abilities. Previous research by our group indicates the role of small frontal and basal brain regions in the regulation of these abilities. This research will extend our previous studies by providing new information detailing the underlying physiology of behavioural and structural abnormalities in patients with severe depression. Emerging research by our group and others suggest that some types of severe depression in later life a ....Severe depression is characterised by slowing of mental and motor abilities. Previous research by our group indicates the role of small frontal and basal brain regions in the regulation of these abilities. This research will extend our previous studies by providing new information detailing the underlying physiology of behavioural and structural abnormalities in patients with severe depression. Emerging research by our group and others suggest that some types of severe depression in later life are due to undetected forms of cerebrovascular disease. If we are able to demonstrate that the key features of severe depression of this type (psychomotor, attentional, memory and executive disturbance and global disability) are related to such brain changes this may lead to a major breakthrough in the prevention and treatment of these disorders. A new type of brain imaging technology called 'functional Magnetic Resonance Imaging' (fMRI) permits simultaneous investigation of the structure and function of small areas of the brain. As the technique does not use radiation and can be performed while the patient is completing mental tasks, it can be used in repeated experiments. Consequently, it permits description of brain changes (areas of activation) that occur during specific mental tasks. Therefore, if we are now able to use this technique to extend our previous clinical and imaging studies we will be able to test whether some forms of late-life depression are due to undetected brain changes.Read moreRead less
Genes, neuroanatomy and family process: Predicting adolescent anxiety and depression. Whilst significant gains in outcomes have been obtained in other areas of health by focusing on early intervention and prevention, in the mental health field this approach has been limited by the paucity of developmentally targeted treatment and prevention strategies. This study will provide unique information regarding the risk processes that are operating during early and late adolescence, and will inform us ....Genes, neuroanatomy and family process: Predicting adolescent anxiety and depression. Whilst significant gains in outcomes have been obtained in other areas of health by focusing on early intervention and prevention, in the mental health field this approach has been limited by the paucity of developmentally targeted treatment and prevention strategies. This study will provide unique information regarding the risk processes that are operating during early and late adolescence, and will inform us about how the family environment can act to modulate the impacts of biological vulnerability on risk for mental disorder. This project will contribute to our understanding of who, and what, to target in early intervention and prevention strategies.Read moreRead less
Studying the effects of repetitive transcranial magnetic stimulation with near Infrared spectroscopy. Repetitive transcranial magnetic stimulation (rTMS) is increasingly being used as a tool in studying human and animal brain function and in the treatment of brain disorders but there are fundamental gaps in our understanding of its basic mechanisms of action and hence our capacity to optimise protocols. This research will use near infrared spectroscopy to study the range of potential ways of alt ....Studying the effects of repetitive transcranial magnetic stimulation with near Infrared spectroscopy. Repetitive transcranial magnetic stimulation (rTMS) is increasingly being used as a tool in studying human and animal brain function and in the treatment of brain disorders but there are fundamental gaps in our understanding of its basic mechanisms of action and hence our capacity to optimise protocols. This research will use near infrared spectroscopy to study the range of potential ways of altering brain activity with rTMS. It will substantially enhance the applicability of the technique ultimately improving our knowledge of human and animal brain function and outcomes for patients with depression and other disorders. It will help reinforce Australia as a leading country in the development of brain stimulation techniques.Read moreRead less
Normal and abnormal processes of social attention orienting. Human beings are capable of rapidly detecting the direction of another person's eye-gaze and shifting attention reflexively in that direction. This project will compare shifts of attention to non-social and social cues of direction to determine whether attentional shifts to gaze-direction are fast because humans are biologically hard-wired to respond to social cues of evolutionary significance (eyes) or because humans are well-practice ....Normal and abnormal processes of social attention orienting. Human beings are capable of rapidly detecting the direction of another person's eye-gaze and shifting attention reflexively in that direction. This project will compare shifts of attention to non-social and social cues of direction to determine whether attentional shifts to gaze-direction are fast because humans are biologically hard-wired to respond to social cues of evolutionary significance (eyes) or because humans are well-practiced at using a number of different signals for direction in their environment. Findings from this work will than be used to investigate whether a selective impairment of responding to gaze-direction contributes to the social impairments so characteristic of people with schizophrenia.
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