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.
Dissecting The Role Of Cortico-striatal Circuitry On Habit Formation
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
Decisions are made based on actions and outcomes, but over time repeated actions become habits. They are no longer determined by outcomes and are dysfunctional in many disorders such as OCD, addiction and Tourette’s syndrome. How the brain changes during habit formation is not known. I will characterise the role of a specific neural circuit to determine how it influences habit development. This will improve our knowledge of normal learning processes and help us understand habitual dysfunction.
Dopamine Neuron Ontogeny: Convergent Neurobiological Pathway For Risk Factors Of Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$337,214.00
Summary
Schizophrenia is associated with changes in dopamine (a signalling molecule in the brain). These changes are present prior to psychosis, suggesting they begin early in development. Our aims are to manipulate key factors in the development of brain dopamine systems to clarify their role in psychosis and schizophrenia. This work has the potential to identify early brain changes that lead to schizophrenia, which in turn may generate better diagnoses and outcomes for people with this disorder.
Developmental Vitamin D Deficiency And Prefrontal Cortical Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$355,570.00
Summary
The cause of schizophrenia is unknown but is believed to be due to abnormal brain development. Dopamine abnormalities are central to schizophrenia. We have developed a model of maternal vitamin D deficiency in rats, based on disease epidemiology that shows individuals that have low levels of vitamin D at birth have an increased risk of developing schizophrenia later in life. We now also show dopamine systems in regions associated with cognition may develop abnormally in our animal model.
Do The Developmental Vitamin D-deficiency And Maternal Immune Activation Animal Models Of Schizophrenia Have Convergent Early Pathways ?
Funder
National Health and Medical Research Council
Funding Amount
$669,580.00
Summary
The etiology of schizophrenia is unknown but it is generally considered to have a neurodevelopmental basis and involve altered dopamine signaling. Using two distinct developmental animal models of schizophrenia we have shown convergent gestational abnormalities in how dopamine systems develop. This is possibly a convergent early etiological mechanism in schizophrenia.
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
Role Of Brain Serotonin In Animal Models Of Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$175,550.00
Summary
There is increasing evidence that deficiencies in the release of a brain chemical called serotonin play an important role in the development of schizophrenia. Post-mortem studies have shown changes in the levels of 'receptors' (keyholes for messenger chemicals in the brain) for serotonin in schizophrenia. In addition, in the treatment of schizophrenia, the more recently introduced 'atypical' antipsychotic drugs are superior to the more traditional 'typical' antipsychotics in terms of efficacy an ....There is increasing evidence that deficiencies in the release of a brain chemical called serotonin play an important role in the development of schizophrenia. Post-mortem studies have shown changes in the levels of 'receptors' (keyholes for messenger chemicals in the brain) for serotonin in schizophrenia. In addition, in the treatment of schizophrenia, the more recently introduced 'atypical' antipsychotic drugs are superior to the more traditional 'typical' antipsychotics in terms of efficacy and side-effect profile. Typical antipsychotic drugs act mainly through blockade of receptors for a brain chemical called dopamine. Atypical drugs appear to have additional actions, in particular blocking the effect of serotonin in the brain. This evidence is mostly circumstancial, relying to a large extent on biochemical analysis of brain regions and 'receptors' on which antipsychotics MAY act. It is currently unclear exactly how and where in the brain changes in serotonin activity influence behavioural processes causing schizophrenia. It is also unclear how and where typical and atypical antipsychotic drugs interact with the role of serotonin in schizophrenia. In this project we intend to inactivate specific parts of the serotonin system of otherwise intact, freely moving rats. Using behavioural observation methods relevant for schizophrenia, we will analyze if and how these interventions influence the behaviour of these rats. The results can have important implications for our fundamental understanding of the involvement of serotonin in the brain in schizophrenia.Read moreRead less