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
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
Memory, Synaptic Plasticity And Gene Networks In Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$1,142,138.00
Summary
Schizophrenia affects about 1% of the population. Its typical progression over a lifetime leads to long-term impairment of cognition, reality distortion, and an impoverished quality of life. Most likely, multiple genes, interacting together or with environmental factors, are involved. Using a novel approach to its partition, WA researchers aim to unravel complex networks of genes affecting memory and brain function in a cognitive deficit subtype of schizophrenia they have identified recently.
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
A Comparative Structural And Functional Cerebral MRI Study Of First Episode Schizophrenia And Long-term Cannabis Use.
Funder
National Health and Medical Research Council
Funding Amount
$373,125.00
Summary
Cannabis is used for its subjective effects that include euphoria, depersonalisation, somnolence, and altered perceptions of temporal contingency.It is a controlled substance yet one quarter of Australian adolescents and seven percent of adults use cannabis regularly. Chronic use of cannibis can impair frontal brain functioning, affecting the capacities for attention, working memory and concentration.These neurocognitive deficits bear striking similarities to those associated with the negative s ....Cannabis is used for its subjective effects that include euphoria, depersonalisation, somnolence, and altered perceptions of temporal contingency.It is a controlled substance yet one quarter of Australian adolescents and seven percent of adults use cannabis regularly. Chronic use of cannibis can impair frontal brain functioning, affecting the capacities for attention, working memory and concentration.These neurocognitive deficits bear striking similarities to those associated with the negative symptom cluster of schizophrenia,which is related to frontal brain dysfunction. The proposed study will be the first of it's kind to apply sophisticated neuroimaging techniques to investigate how long-term adolescent cannabis use effects the structure and function of the brain and to make comparative analyses with the brain changes associated with first episode schizophrenia. We predict that structural brain abnormalities that are consistent in localisation, if not in degree, will be detected in long-term cannabis using and first episode schizophreniaparticipants and that there will be even more profound abnormalities in the first episode schizophrenia cannabis users. We will use the Tower of London (TOL) task to activate certain areas associated with executive functioning (for instance attention, memory, and strategic planning). Here, we expect lower intensity activation of the prefrontal cortex during TOL performance both in the cannabis and first episode schizophrenia groups and that the activation will be lowest of all for the cannabis using first episode schizophrenia group. The methodology to be applied in this study offers a unique opportunity to enhance our understanding of the structural and functional markers of first episode schizophrenia and cannabis use in the neural substrate.Read moreRead less