2008 Environmental Factors Awards
2008 Basic and Clinical Awards (Winter)
2008 Basic and Clinical Awards (Summer)
2008 Epidemiology Awards
2008 High Risk, High Impact Projects
2008 Pilot Awards (Winter)
2008 Pilot Awards (Summer)
2008 Treatment Awards
Maternal Infection and Autism: Impact of Placental Sufficiency and Maternal Inflammatory Responses on Fetal Brain Development
Maternal infections during pregnancy have been linked to an increased risk of autism and other neurological disorders in the child. Dr. Palmer’s laboratory has found that giving a mild infection to rats and mice during pregnancy causes changes in the production of brain cells in the developing offspring, a process which might also contribute to the development of autism in humans. Maternal infection is likely to affect fetal development via proteins that are produced as part of the mother’s immune response. These proteins could affect fetal development in several ways, including by acting directly on the developing fetal brain, or by impairing the ability of the mother’s placenta to supply blood and oxygen to the fetus.
In this study, Dr. Palmer and colleagues will evaluate these two hypotheses to determine how maternal immune proteins affect both the placenta and fetal brain development. If placental function is found to be impaired by the immune response, they will test several clinical strategies aimed at preserving placental function to determine whether these therapies allow the fetal brain to develop properly even in the presence of infection.
This research should provide new insight into the mechanisms of how the maternal immune system affects fetal brain development, and may suggest new therapeutic avenues for reducing the risk of neurological disorders during pregnancy.
Investigation of the link between early brain enlargement and abnormal functional connectivity in autism spectrum disorders
People with autism have been found to have abnormalities in brain growth, characterized by an enlargement of the brain early in development, followed by premature growth arrest. In the present study, researchers will test the hypothesis that early changes in brain growth in autism has long-term consequences for neural connectivity, or communication between different regions of the brain, as changes in connectivity are thought to underlie the symptoms of autism.
Dr. Kleinhans and colleagues will examine this proposed relationship between early brain growth and later brain connectivity. They will gather previously collected measurements of brain size and volume from 3 to 5 year old children with low-functioning autism. When these children are 15 years old, they will be asked to participate in a brain imaging study using functional magnetic resonance imaging (fMRI), a non-invasive method of imaging patterns of brain activity and neural connectivity.
These data should determine whether an increase in brain size during childhood is correlated with weakened or changed patterns of connections between brain regions in teenagers with autism, and contribute to our understanding of the developmental basis of behavioral impairment and clinical outcomes in autism spectrum disorders.
MEG investigation of the neural substrates underlying visual perception in autism
Sensory perception abnormalities in autism spectrum disorders (ASDs) have been documented for decades. Reports on sensory perception in ASDs have been variable, with some studies finding inferior performance and some finding superior performance in people with ASDs compared to normally developing individuals. While a great deal of data on sensory performance in ASDs has accumulated, the underlying causes for the abnormalities in ASDs remain unknown. Current hypotheses suggest that these perceptual changes are caused by changes in connectivity, or communication between neurons in different regions of the brain.
The present study aims to uncover the neural pathways in the cerebral cortex that underlie sensory processing abnormalities in individuals with ASDs. Dr. Kenet and colleagues will test the hypothesis that in ASDs, the short-range connections between cortical neurons that are involved in sensory processing are functionally weaker, or are underconnected. They will focus on the activity of these connections during visual processing, as how these pathways function in normal individuals is relatively well understood. Neural activity in individuals with ASDs will be observed and measured by magnetoencephalography (MEG) while the subjects are engaged in visual tasks. MEG is a noninvasive method of visualizing neural activity which allows researchers to examine the relative strength of the neuronal connections in a specific brain region.
Comparing neural activity during visual processing in individuals with ASDs to that of typical individuals may help us to further understand the nature and cause of sensory perception abnormalities in ASDs.
Effect of oxytocin receptor inhibitor (Atosiban) during the perinatal period and prevalence of autism spectrum disorders
Among environmental factors that may confer risk for autism, perinatal factors are prominent. Based on multiple lines of research, it has been hypothesized that activity of the hormone oxytocin – a ‘social’ hormone that mediates affiliative behaviors in many species including humans – may be a perinatal factor that impacts the risk of autism spectrum disorders (ASDs). An increasing number of women in the US and abroad receive Pitocin (a synthetic form of oxytocin) during childbirth to induce or augment labor. In some areas such as Israel and Europe, women may receive an oxytocin receptor inhibitor (Atosiban) to delay preterm labor.
This study will take an epidemiological approach to determining the roles of Pitocin and Atosiban in ASD. Dr. Ebstein and colleagues will recruit mother and child pairs from four categories: mothers having received Atosiban during pregnancy, mothers having received Nifedipine, a drug used to prevent preterm labor that does not affect oxytocin signaling, mothers that received Pitocin during labor, and a matched control group of mothers who received no drugs and delivered at term. Children of these mothers will be screened for neurodevelopmental delays, and those testing positive will undergo further evaluations for ASD.
If the use of drugs affecting oxytocin activity during the perinatal period is found to be associated with neurodevelopmental problems, it will have profound implications for a widely used obstetrical practice that may inadvertently confer additional risk for ASD and related disorders.
Sleep, neuropsychological, mood, behavior, learning, and developmental problems in children with autism
Many children with autism have problems with sleep, learning, mood, and behavior, as well as developmental and neuropsychological issues. The present study will attempt to address the relationships between these issues, and estimate the frequency and types of these problems in the autistic population.
Dr. Mayes and colleagues will analyze two large existing datasets: a general population sample of 500 children from a National Institute of health funded sleep study, and a clinically diagnosed sample of 1250 children evaluated in a psychiatry diagnostic clinic, including 250 children with autism. Each of these samples includes detailed data collected on sleep problems, neuropsychological measures of attention, memory, language, and reasoning, IQ scores, reading and math test achievement scores, parent rating scores assessing behavior, and developmental and medical histories of the children participating. Using statistical methods, this study will try to untangle the relationships between these measures, to determine which are associated with each other, and which are specific to various forms of autism (low-functioning versus high-functioning). For example, are there specific types of sleep problems associated with age, gender, or IQ? Do factors during pregnancy, labor, or the neonatal period correlate with particular kinds of problems with memory, attention, or language?
This large-scale analysis should help to inform clinicians, educators, and medical practitioners about the frequency and types of problems in autism. Understanding the relationships between these problems may also help to guide intervention programs, and identify subgroups of children with autism who are at risk for particular problems.