NIMH Grants Focus on Innovative Autism Research

December 30, 2008 • Science Update

Autism is a complex brain disorder involving communication and social difficulties as well as repetitive behavior or limited interests. Autism is often grouped with similar disorders, such as Asperger’s syndrome and pervasive developmental disorder, all of which may be referred to collectively as autism spectrum disorders (ASD). The underlying causes of ASD are unclear. Currently, there is no cure for the disorders and treatments are limited.

NIMH is committed to reducing the burden of autism and related disorders through research that can lead to methods of prevention, recovery, and cure. To accomplish this goal, the Institute recently funded nine research projects that focus on ASD:

• Greg Allen, Ph.D., of the University of Texas Southwestern Medical Center of Dallas, is using a variety of brain imaging methods—such as diffusion tensor imaging and functional connectivity magnetic resonance imaging—together with conventional neuropsychological assessments to study anatomic and functional connections in key areas of the brain that have been implicated in autism, including the cerebellum. According to Allen, the cerebellum is one of the most widely connected structures in the central nervous system and the most consistent site of brain abnormality in autism. Abnormal connections between the cerebellum and associated brain regions may disrupt the cerebellum’s ability to coordinate certain behaviors and result in abnormal strengthening of functions in other brain regions to compensate. These changes could account for some of the symptoms of autism. This study will help researchers better understand connectivity in autism-related brain areas, which in turn may lead to better-informed treatments.
• David Amaral, Ph.D., and Melissa Bauman, Ph.D., of the University of California Davis, seek to expand and enhance their previous work on an animal model of ASD. Early findings with this model showed that rhesus monkeys exposed to certain antibodies in the womb showed more autism-like symptoms than monkeys that had not been exposed. Further studies with this model may help researchers develop a diagnostic test to screen for these antibodies in pregnant women, and potentially to develop treatments to reduce this risk factor.
• Tal Kenet, Ph.D., of Massachusetts General Hospital, proposes an innovative use of magnetoencephalography (MEG) to study brain functioning during listening tasks in children with autism. MEG is a type of brain imaging technology that allows researchers to see what happens in the brain when a person feels, thinks or moves. In this study, Kenet and colleagues are building on an ongoing study that is gathering structural brain imaging and corresponding behavioral data in boys with autism and in matched, healthy controls. The researchers will also gather corresponding functional brain imaging data to further the understanding of how the brain responds during listening tasks. These studies could provide key information about the language and communication problems that are hallmark symptoms of autism. This understanding, in turn, may help in the development of more effective treatments and earlier methods of diagnosis.
• Ami Klin, Ph.D., of Yale University, is studying the development of vision-related behaviors in high risk infants who have an older sibling diagnosed with autism, infants at high risk for developmental delays but who do not have a family history of ASD, and infants at low risk for ASD or developmental delays. Past research on teens and young children showed that those with ASD had abnormal patterns of eye contact when looking at video scenes of social interaction; instead these children preferred looking at the mouths of people in the video. These patterns were strong predictors of social impairments. With the current study, Klin and colleagues aim to extend their findings by following these very young infants over time. They will be the first researchers to begin a study in infants as young as two months old to determine whether early differences in eye tracking behaviors may predict later diagnosis of an ASD. Results from this work will provide information on some of the earliest possible indicators of ASD.
• Rick Lin, Ph.D., of the University of Mississippi, was awarded an Exceptional, Unconventional Research Enabling Knowledge Acceleration (EUREKA) grant to study the possible role of altered serotonin production in causing ASD. Serotonin is a brain chemical important in early brain development, as well as the target of popular antidepressant medications, namely selective serotonin reuptake inhibitors (SSRIs). Findings from this study could affect not only the way that autism is detected and treated, but also the way that depression is treated in pregnant women or nursing mothers.
• Catherine Lord, Ph.D., of the University of Michigan, aims to expand on previous work with young children with ASD to study the natural course of the disorder through adolescence and adulthood and to examine early predictors of outcome. The researchers will study a large group of adolescents and young adults with ASD, ages 16–23, who have been followed in previous studies since age 2. The study will focus on how co-occurring mental disorders and an individual’s coping methods affect quality of life. By studying the natural course of ASD, Lord and colleagues aim to determine factors that can help predict a child’s ability to adapt to increasing independence as he or she grows into an adult living with ASD.
• David Mandell, Sc.D., of the University of Pennsylvania, is leading a randomized controlled field trial of a school-based autism intervention in a large public school system. Half of the teachers and aides within the Philadelphia School District will be randomly assigned to receive training in Strategies for Teaching Based on Autism Research (STAR), a program that uses techniques designed to encourage desired behaviors and to reduce unwanted behaviors. The other half of teachers and aides will receive equally intense training in Structured Teaching and then in STAR. Structured Teaching is the current standard of care used in the Philadelphia School District and is based on the Treatment and Education of Autistic and Related Communication Handicapped Children (TEACCH) model, which focuses on using the physical, social and communicating environment to encourage learning and independence in children with ASD. Assessing these interventions in a real-world setting provides critical knowledge on the implementation and effectiveness of these programs, which will help inform practice and policy.
• Allan Reiss, M.D., of Stanford University, aims to use novel brain imaging techniques to study the brain as a whole, focusing on the complexity of the cerebral cortex—the outermost layer of the brain involved in a variety of functions, including memory, attention, language, and thought. In this study, Reiss and colleagues are comparing 27 pairs of siblings where one of the siblings has autism and the other does not with control participants, matched for age and gender. The researchers will also assess the link between cortical complexity and behaviors or symptoms in participants with autism, which will then be compared with similar assessments in younger children (17–40 months old) and age-matched controls. These findings will help researchers to understand the course of development in cortical complexity from roughly 2 to 12 years of age. This study will help to pinpoint the brain regions associated with autism and how they change and develop throughout childhood.
• Stephen Sheinkopf, Ph.D., of Women and Infants Hospital of Rhode Island, is testing the feasibility of studying some of the earliest signs of possible developmental differences in high-risk fetuses and newborns. Children are considered high-risk if their mothers have previously given birth to a child diagnosed with ASD. Since the disorder is highly heritable, siblings of people with ASD are at higher risk for also developing ASD, compared with the general population. Research shows that fetal behaviors can predict later behaviors and temperament, and that fetuses can tell the difference between familiar voices. Using sound and vibrations (commonly used in prenatal care), such as music or a recording of the mother’s voice or of a stranger’s voice, the researchers will measure fetal responses, such as movement and heart rate. They will also assess differences in newborn behaviors between high-risk and low-risk babies. Findings from this study will provide a unique look at the early beginnings of ASD and may lead to more extensive studies of this type.