Does Caffeine Affect The Development Of The Very Immature Brain: Dose Response Relationship?
Funder
National Health and Medical Research Council
Funding Amount
$668,386.00
Summary
Premature birth is a major health problem worldwide. Preterm babies often develop apnoea of prematurity (AOP), which is commonly treated with caffeine. Trials indicate that preterm babies treated with low dose caffeine have less neurodevelopmental disabilities at 18 months. Higher doses of caffeine are often needed to reduce AOP but the risk of this is unknown. We will study the short and long-term effects of increasing doses of caffeine on the developing brain in a long-gestation species.
Why Does Early Life Stress Aggravate Limbic Epileptogenesis?
Funder
National Health and Medical Research Council
Funding Amount
$540,116.00
Summary
High rates of anxiety and depression occur in individuals with temporal lobe epilepsy (TLE), the most common form of focal epilepsy in adults. Rats that have experienced early life stress show increased anxiety, decreased seizure thresholds and accelerated epilepsy as adults. We have important leads to mechanisms. The proposed study will better understand the mechanisms connecting early life stress and psychiatric disease to adult TLE, and to test interventions that may counteract these effects.
Neuroactive Steroids In The Developing Brain: Potential For Preventing Perinatal Brain Damage
Funder
National Health and Medical Research Council
Funding Amount
$481,500.00
Summary
Complications during pregnancy, birth asphyxia or premature birth can lead to serious neurological impairment in the newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neuroactive steroids are a group of neuromodulators that are derived from the hormone progesterone. These steroids fall into two groups, those that appear to protect brain cells from damage caused by an inadequate supply of oxygen and those that may increase cell death. We have shown tha ....Complications during pregnancy, birth asphyxia or premature birth can lead to serious neurological impairment in the newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neuroactive steroids are a group of neuromodulators that are derived from the hormone progesterone. These steroids fall into two groups, those that appear to protect brain cells from damage caused by an inadequate supply of oxygen and those that may increase cell death. We have shown that protective neuroactive steroids are present in very large amounts in the fetal brain. Steroids produced by the placenta are converted to these neuroactive products by enzymes in the brain leading to the high levels that are seen during fetal life. Certain adverse conditions during pregnancy as well as preterm birth may cause marked changes in the balance of steroids that could increase susceptibility to brain injury. We have found that areas of the brain, where damage most often occurs, normally contain the highest amount of protective steroids, but only in late pregnancy. This suggests that disturbances that lower steroid production in these areas could contribute to the death of cells, particularly in mid-pregnancy and after premature birth. In the proposed studies, we will examine whether a toxic balance of steroids develops following adverse events in pregnancy as well as the areas of the brain where this is most pronounced. We will examine the changes in the expression of enzymes that can potentially cause the accumulation of protective steroids in the brain. We will then examine treatments that can raise the concentration of steroids and determine which combination of steroids best reduces cell death and brain injury following complications during pregnancy. The findings of this work will indicate the best therapeutic approach that may be adopted to modify the concentration of certain steroids so as to reduce the risk of brain damage in the fetus and neonate.Read moreRead less
Neurosteroid Mediated Protection After Birth: Approaches For Maximising Protective Steroid Levels In The Neonatal Brain
Funder
National Health and Medical Research Council
Funding Amount
$450,703.00
Summary
Complications during pregnancy, birth asphyxia or premature birth can lead to neurological impairment in the newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neurosteroids are a group of steroids that regulate brain activity. These steroids protect brain cells from damage caused by an inadequate supply of oxygen by suppressing toxicity caused by excessive activity. We have shown that the levels of these protective steroids are remarkably high in the ....Complications during pregnancy, birth asphyxia or premature birth can lead to neurological impairment in the newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neurosteroids are a group of steroids that regulate brain activity. These steroids protect brain cells from damage caused by an inadequate supply of oxygen by suppressing toxicity caused by excessive activity. We have shown that the levels of these protective steroids are remarkably high in the fetal brain and levels rise further in response to fetal stress. The placenta contributes steroid precursors that help maintain these high neurosteroid levels. This placenta-fetal brain interaction comprises an internal mechanism that protects the fetal brain from adverse events during pregnancy. At birth, however, there is a dramatic decline in neurosteroid concentrations in the brain after the loss of the placental precursor supply. The fall in concentrations is even greater in animals that are born growth restricted. This suggests that newborns, particularly those from compromised pregnancies, are at increased risk of brain damage due to low neurosteroid levels. We believe that certain commonly used steroid therapies may also lower steroid levels in the brain and result in increased vulnerability to brain damage during birth or in the early neonatal period. Alternatively, we propose that replacement of neurosteroid precursors in the newborn may raise brain neurosteroid levels and protect against brain damage. In the proposed studies we will evaluate treatments that can raise the concentration of steroids and determine the best strategy for reducing brain injury following complications during pregnancy, at birth and during the early newborn period. This work will determine the best therapeutic approaches for maximising neurosteroid-induced brain protection and for reducing the risk of brain damage.Read moreRead less
Environmental Influences On Allergic Airways Disease From Birth To 8yrs: Long-term Outcomes Of A Randomised Trial (CAPS)
Funder
National Health and Medical Research Council
Funding Amount
$530,000.00
Summary
The prevalence of asthma in Australia is among the highest in the world yet no trials of primary prevention have been conducted which address the most common known causative agent (housedust mite allergens) and the most common known protective factor (dietary omega-3 fatty acids). Until the effectiveness of interventions which address these factors is certain, it will not be possible to give confident advice about how to prevent asthma. We are applying to continue follow up of the cohort of the ....The prevalence of asthma in Australia is among the highest in the world yet no trials of primary prevention have been conducted which address the most common known causative agent (housedust mite allergens) and the most common known protective factor (dietary omega-3 fatty acids). Until the effectiveness of interventions which address these factors is certain, it will not be possible to give confident advice about how to prevent asthma. We are applying to continue follow up of the cohort of the Childhood Asthma Prevention Study (CAPS) which has been underway since mid-1997. CAPS is a randomised controlled trial in which 616 infants at high risk of developing asthma because of a family history have been enrolled. The interventions include allergen reduction and dietary supplementation with omega-3 fatty acids. The interventions are designed to have maximum effect but be simple to implement by parents. Objective and subjective measurements of exposures, atopy, diet and asthmatic symptoms are being collected at 3 month intervals and at medical assessments when the children are 18 months, 3 and 5 years old. The interventions are stopped at age 5 years. The continued follow up of the cohort to age 8 will enable us to test conclusively if the interventions have had a positive effect. If so, CAPS will form the basis for a nationwide public health campaign which will have the potential to reduce the incidence of childhood asthma in Australia.Read moreRead less
Contribution Of Disturbed Blood Flow And Cerebral Metabolism To White Matter Damage In The Perinatal Brain
Funder
National Health and Medical Research Council
Funding Amount
$369,375.00
Summary
It has been known for some time that the white matter regions of the developing brain are particularly vulnerable to damage. These regions are deep in the brain near the ventricles, and are rich in myelin sheaths wrapped around the nerve fibres running from cell-rich areas in the outer layers of the brain to other regions, and down into the spinal cord. Damage to white matter usually leads to behavioural, learning and motor problems in the newborn infant - in its severest form, seen as cerebral ....It has been known for some time that the white matter regions of the developing brain are particularly vulnerable to damage. These regions are deep in the brain near the ventricles, and are rich in myelin sheaths wrapped around the nerve fibres running from cell-rich areas in the outer layers of the brain to other regions, and down into the spinal cord. Damage to white matter usually leads to behavioural, learning and motor problems in the newborn infant - in its severest form, seen as cerebral palsy. Such outcomes are often associated with the presence of asphyxia and infection during pregnancy, leading to the belief that the damage first arises while the baby is still in utero. In this application we suggest that asphyxia and-or infection during pregnancy cause prolonged disturbances in the regulation of blood flow and integrity of the blood-brain barrier in the developing brain, together with changes in metabolism that result in accumulation of prostaglandins and the toxic hydroxyl radical, leading irreversibly to cell death. If this series of events proves to be true, we have suggested and will test several protocols for protecting the fetal brain, which should be readily translatable to clinical practice.Read moreRead less
A Parent Education And Skills Training Early Intervention For Children With Autism
Funder
National Health and Medical Research Council
Funding Amount
$305,674.00
Summary
Autism is a severely handicapping disorder adversely affecting social interaction, communication, and behaviour, interests and activities. Over the past 9 years our team has conducted a follow-up study of a large group of 111 Australian children and adolescents with autism. The young people have continued to have very high levels of emotional and behavioural disturbance and generally do not improve. Parents of children with autism are under significant amounts of stress; reporting high levels of ....Autism is a severely handicapping disorder adversely affecting social interaction, communication, and behaviour, interests and activities. Over the past 9 years our team has conducted a follow-up study of a large group of 111 Australian children and adolescents with autism. The young people have continued to have very high levels of emotional and behavioural disturbance and generally do not improve. Parents of children with autism are under significant amounts of stress; reporting high levels of disturbed family functioning and mental health problems. Although there is no cure, children benefit most when early help is provided (under 5 years). There are several promising interventions based on intensive behaviour and educational management, for example requiring 40 hours per week of therapist contact over 2 years. Such programs are costly and impractical as widely available treatment options. Training parents to understand and manage their child also shows promise. This study will evaluate the effectiveness of a parent skills training and education treatment program compared to supportive therapy, and to generally available community services. The therapists will follow a treatment manual that will ensure a consistent and replicable approach. The progress of the children with autism and their families will be reassessed immediately after treatment, and at 1 and 2 years post-treatment in order to ascertain immediate and long-term effects of the treatment. If treatment proves to be of use, we will have established a defined, cost efficient, practical and effective model of early treatment that can be easily taught to professionals and widely disseminated throughout early childhood services.Read moreRead less
RISK AND PROTECTION FACTORS FOR NORMAL AND ABNORMAL BRAIN AGEING: A LONGITUDINAL EPIDEMIOLOGICAL MRI STUDY
Funder
National Health and Medical Research Council
Funding Amount
$153,020.00
Summary
Brain is considered the last frontier of medicine, and ageing the major challenge to health care in the 21st century. In this proposal, we bring these two challenges together in a major new longitudinal study of ageing in Canberra that has recently been initiated. This is a longitudinal study of a random community sample covering 3 age groups - 20-24 years, 40-44 years and 60-64 years, with at least 2000 participants in each age group - who are being assessed in 1999-2001, and will be followed u ....Brain is considered the last frontier of medicine, and ageing the major challenge to health care in the 21st century. In this proposal, we bring these two challenges together in a major new longitudinal study of ageing in Canberra that has recently been initiated. This is a longitudinal study of a random community sample covering 3 age groups - 20-24 years, 40-44 years and 60-64 years, with at least 2000 participants in each age group - who are being assessed in 1999-2001, and will be followed up at 4-yearly intervals for 20 years. The focus of the study is on neuropsychiatric disorders (anxiety, depression, substance use and cognitive disorders). In this application, we propose to perform MRI scans and blood tests on a quarter (n-500) of the 60-64 sample to obtain an epidemiological sample for brain morphology. Not only will we be able to study changes in brain morphology over time, and relate it with cognitive function and psychiatric disorder, we will also be able to assess the role of risk and protection factors. We are particularly interested in brain reserve, dietary factors (anti-oxidants, omega 3, wine and folate) and drugs (anti-inflammatory drugs, hormone replacement and vitamin supplements) as protection factors, and hypertension, homocysteine levels, white matter lesions on MRI and low hippocampal volumes as risk factors for cognitive impairment and dementia. We also want to study the brain morphological correlates of Depression in a community sample. The study will enhance our understanding of the ageing brain, both in health and disease, and identify factors that increase or decrease the risk of cognitive impairment and psychiatric disorder in old age.Read moreRead less
Early Intervention For Anxiety And Phobic Disorders In Young Children With Intellectual Disability
Funder
National Health and Medical Research Council
Funding Amount
$305,674.00
Summary
Children with intellectual disability (ID) are 2-3 times more likely to have behavioural and emotional disturbance, including anxiety and fears, than children of normal intellectual ability. Anxiety problems are a source of distress for the child, impair their ability to learn and are a cause of family burden and community cost. Therefore, effective interventions are urgently required. Research with non-disabled children has demonstrated the effectiveness of teaching parents to manage their chil ....Children with intellectual disability (ID) are 2-3 times more likely to have behavioural and emotional disturbance, including anxiety and fears, than children of normal intellectual ability. Anxiety problems are a source of distress for the child, impair their ability to learn and are a cause of family burden and community cost. Therefore, effective interventions are urgently required. Research with non-disabled children has demonstrated the effectiveness of teaching parents to manage their child's anxiety, however the effectiveness of this approach in children with ID has not yet been established. This project aims to compare the relative effectiveness of two intervention conditions compared to a waiting list group, for highly anxious children aged 4-7 years with ID. One intervention will teach parents to help their child deal with anxiety problems, and develop skills to overcome their own associated emotional upset and family and social problems. The other intervention will provide non-directive counselling and support to help the parents understand the nature and causes of ID, associated anxiety problems in the child, and parent and family stress. The long term outcome of these two interventions will be assessed by following the children and their families for two years. A manual of each treatment is produced. This project aims to provide evidence for a relatively inexpensive, feasible and effective early intervention program for young children with ID at risk for developing anxiety problems that can be easily taught to professionals and is acceptable to parents. Widespread use of this intervention has the potential to reduce the added burden and cost to families and the community of persistent severe anxiety in young people with ID.Read moreRead less
Immunising Aboriginal Mothers With Pneumococcal Polysaccharide Vaccine To Prevent Infant Ear Disease And Carriage
Funder
National Health and Medical Research Council
Funding Amount
$1,131,530.00
Summary
Aboriginal children experience the highest rates of acute and chronic ear infections in the world, with resultant permanent ear damage, hearing loss and educational disadvantage. These infections are mainly bacterial, and Streptococcus pneumoniae (pneumococcus) is the predominant pathogen. Pneumococcal colonisation and infection begins within days of birth, many months before any potential immunological protection from infant pneumococcal conjugate vaccine may be expected. New strategies are nee ....Aboriginal children experience the highest rates of acute and chronic ear infections in the world, with resultant permanent ear damage, hearing loss and educational disadvantage. These infections are mainly bacterial, and Streptococcus pneumoniae (pneumococcus) is the predominant pathogen. Pneumococcal colonisation and infection begins within days of birth, many months before any potential immunological protection from infant pneumococcal conjugate vaccine may be expected. New strategies are needed to eliminate, or at least delay, this early-onset pneumococcal colonisation. One such strategy is the administration to the mother of pneumococcal vaccine, which may protect the newborn infant by leading to higher titres of transplacental or breast milk pneumococcal antibodies and-or by reducing carriage (and transmission to the infant) of maternal pneumococci. Previous small studies using this strategy have been encouraging, but there have been no studies properly evaluating carriage or disease endpoints in infants. The polysaccharide pneumococcal vaccine is currently recommended for all Aboriginal and Torres Islander persons aged 15 years or more in the Northern Territory but uptake of the vaccine has been poor. We propose to conduct a pilot study to determine if maternal immunisation with this vaccine, either in the third trimester of pregancy of immediately following delivery, can reduce pneumococcal carriage and the prevalence of middle ear disease among Aboriginal infants at seven months of age. We aim to recruit 210 Aboriginal women who have uncomplicated pregnancies from Darwin and remote communities in the Top End of the Northern Territory. Each subject and their infant offspring will be followed-up after vaccination and at birth, one , two and seven months after birth.Read moreRead less