Modeling The Two-hit Hypothesis Of Schizophrenia: Combined Neonatal Stress And Postnatal Corticosterone In Rats
Funder
National Health and Medical Research Council
Funding Amount
$318,500.00
Summary
Schizophrenia is a severe mental illness defined by a number of symptoms including hallucinations, delusions, social withdrawal and cognitive impairment. Factors very early in development have been suggested to induce an increased vulnerability to this illness. Recently, it was suggested that another major event, later in life, would be needed before vulnerable individuals would develop schizophrenia. The aim of this project is to model this two-hit hypothesis in rats. We will compare the effect ....Schizophrenia is a severe mental illness defined by a number of symptoms including hallucinations, delusions, social withdrawal and cognitive impairment. Factors very early in development have been suggested to induce an increased vulnerability to this illness. Recently, it was suggested that another major event, later in life, would be needed before vulnerable individuals would develop schizophrenia. The aim of this project is to model this two-hit hypothesis in rats. We will compare the effect of various neonatal maternal separation protocols as an early stressful event, followed by chronic treatment with the stress hormone corticosterone at various stages later in life. We will also perform a detailed anatomical study of the hippocampus of these rats. This brain area has been implicated in the development of schizophrenia in humans. We will also investigate if treatment with antipsychotic drugs can prevent or reverse behavioural and neuroanatomical changes seen in the rats. This will be the first comprehensive study to model this two-hit neurodevelopment hypothesis of schizophrenia and will provide an experimental verification of a clinical concept which is very difficult to prove in patients.Read moreRead less
The Developmental Vitamin D Model (DVD) As An Animal Model For Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$258,075.00
Summary
Most Australians have the opportunity to enjoy the natural benefits of sunlight, however many Australians lack vitamin D. We have shown that even in Queensland, the so-called Sunshine State, vitamin D levels in the middle of winter are below World Health Organisation recommended levels. We are exploring low maternal vitamin D as a biological explanation for the universal phenomena worldwide of a 7-10% increase in the incidence of patients born with schizophrenia in the colder months of the year. ....Most Australians have the opportunity to enjoy the natural benefits of sunlight, however many Australians lack vitamin D. We have shown that even in Queensland, the so-called Sunshine State, vitamin D levels in the middle of winter are below World Health Organisation recommended levels. We are exploring low maternal vitamin D as a biological explanation for the universal phenomena worldwide of a 7-10% increase in the incidence of patients born with schizophrenia in the colder months of the year. Schizophrenia is a developmental disease that presents in adolescence and affects about 1% of the world's population. To date we have shown increased amounts of schizophrenia in offspring from mothers that had low blood vitamin D levels during pregnancy or who had inadequate vitamin D intake. Early signs therefore appear promising but obviously more research is required to confirm this idea. Our studies in animals have revealed that by restricting vitamin D intake in pregnant rats, newborns have brains that develop differently. Most notably lateral ventricle volume is increased, a key anatomical finding in patients with schizophrenia. When these animals become adults the increase in lateral ventricles persists. Also when we explore the behaviour of these animals we find a deficit in learning and memory similar to that seen in many schizophrenic patients. Furthermore when we expose these animals to agents that induce psychosis or agents that block psychosis in patients we see a heightened sensitivity in animals that were deprived of this vitamin in utero particularly in locomotion. These behavioural findings are consistent with the best animal models for schizophrenia. At a mechanistic level they indicate an abnormality in the two major neurotransmitters in the brain that have been consistently linked with this disease, dopamine and glutamate. The experiments outlined in this application will attempt to establish the neurochemical basis for these altered behaviours.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.
Social Behaviour In Rats Developmentally Deficient In Vitamin D: Modelling The Negative Symptoms Of Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$360,927.00
Summary
We are exploring low maternal vitamin D as a biological explanation for a 7-10% increase in the incidence of patients born with schizophrenia in the colder months of the year world wide. Developmental vitamin D (DVD) deficiency in rats leads to long term changes in brain development and behaviour. The aim of this research is to examine social behaviour in DVD deficient rats as a model of negative symptoms of schizophrenia and establish the neurochemical basis for this altered behaviour
The Role Of Cannabis In An Nrg1 Animal Model Of Genetic Vulnerability To Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$455,323.00
Summary
The link between psychosis and cannabis use has been discussed for decades. As the majority of users do not develop schizophrenia, it seems that other risk factors are necessary to trigger psychosis. Adolescence may be a time of particular vulnerability to the effects of cannabis use. We aim to use an animal model for schizophrenia to clarify cannabis' impact on the development of schizophrenia when interacting with the risk factors genetic vulnerability and age of onset of cannabis use.
Alcohol, Angry Rumination, And Aggression: The Role Of Acute Impairment Of Executive Functioning
Funder
National Health and Medical Research Council
Funding Amount
$341,780.00
Summary
In Australia, alcohol-induced aggression imposes substantial psychological, public health, social, and economic burdens on victims, perpetrators, and society. When people drink and brood over interpersonal transgresssions, they are at increased risk of violence, even toward the innocent. The goal of the proposed research is to identify neuropsychological mechanisms that account for this increased aggression.