Office for People With Developmental Disabilities

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Highlights of Autism Research at IBR


IBR’s integrated approach to diagnosing, preventing, and treating developmental disabilities—combining the results of genetic and environmental studies—targets genetic and metabolic pathways that are responsive to intervention and consequently improves prevention and treatment. Following are some of the studies IBR has conducted on autism.

Early autism diagnosis:

Results of a recently published IBR study indicate that neonatal intensive care unit (NICU) graduates later diagnosed with autism have a unique behavioral profile starting in early infancy. IBR researchers, in collaboration with physicians from Richmond University Medical Center, conducted a developmental follow-up study of infants who spent time in an NICU who were later diagnosed with autism. They found that these children had unique characteristics at as early as one month old, including abnormal muscle tone and abnormalities in visual processing. These behaviors occur more frequently in this group of NICU graduates than in other NICU graduates. Compared to similar children who did not develop autism, NICU graduates with autism showed slower improvements of abnormal neonatal behaviors, atypical visual functioning, and lack of change in development to higher levels during the first six months. These results indicate that NICU graduates later diagnosed with autism may have a unique behavioral profile starting in early infancy.

Gene that determines severity of autism:

In a collaborative research project on the genetic basis of autism, IBR researchers identified a gene that codes for an important brain enzyme known as MAOA and found it to be an important determinant of the severity of autism in young affected children. They found that this gene predicts which children will be low functioning or high functioning and correlated highly with the severity of their autism. These are important observations, since IQ and autism severity are both important predictors of later functioning. The fact that MAOA appears to be a risk gene has important implications for predicting response to drug treatment. It may be that these MAOA alleles can be used to predict which children will have a beneficial or adverse response to treatment.

Possible mechanisms involved in the pathogenesis of autism:

IBR researchers have investigated the possible causes contributing to the pathogenesis of autism at the cellular/molecular level. They have found that levels of the inflammatory cytokines TN-a, IL-6, IL-*, GM-CSF, and IFN-y are increased in the brains of children with autism. In addition, they observed that apoptosis-related proteins such as Bc12 and p53 and Cathepsin D are altered in the autistic brain. These findings suggest that abnormal immune responses and programmed cell death may contribute to the pathogenesis of autism.

Autism brain analysis:

A complex study of 38 regions in the brains of individuals with autism revealed significantly smaller neurons in children with autism and an increase in neuronal volume that is close to normal size in teenagers and adults with autism. This increase is a result of metabolic and structural alterations rather than a delayed correction of developmental structural and functional deficits. This study provides a new standard for neuropathological diagnosis of autism. In contrast to previous criteria, the new standard defines not only the type but also the topography of changes and their age-associated modifications. The other novelty of this diagnostic approach is its separation of pathology contributing to the autistic clinical phenotype from pathology responsible for epilepsy observed in more than 30% of individuals with autism.

Definition of the spectrum of autism neuropathology:

Autism diagnosis is based on a pattern of behavioral developmental anomalies, but diagnostic neuropathological criteria are missing. A complex study, supported by New York State, the Department of Defense, and Autism Speaks, was conducted by neuropathologists from eight research centers of the largest postmortem collection of brains preserved at IBR for research.  Using the same standards across the eight research centers, the neuropathologists revealed a global and region-specific pattern of developmental neuropathological changes and dynamic alterations throughout the lifespan. Several groups detected minicolumn abnormalities and reduced size of neurons in the neocortex and brainstem nuclei. IBR researchers revealed a global pattern of defects of neuronal migration, abnormal neuronal proliferation with subependymal nodular dysplasia, dysplastic changes in the cortex, subcortical structures and cerebellum; reduced size of neurons in the majority of examined regions in children with autism; and an increase in the size of neurons in teenagers and adults with autism. Focal agenesis and diffuse deficit of axons in the corpus callosum of subjects with autism revealed developmental deficits in long-distance connectivity. Metabolic abnormalities are represented with excessive accumulation of neuronal amyloid-β and reduced expression of fragile X mental retardation protein 1 (FMRP1) in neurons. Increased FMRP level in a population of astrocytes infiltrating white and gray matter is a marker of glial pathology affecting neuron structure and function. The similar type and topography of neuropathological changes in subjects with autism of unknown etiology and autism caused by chromosome 15 reveals clinical and neuropathological commonalities regardless of autism etiology. The detected broad spectrum of developmental neuropathological changes affecting numerous brain structures, neuronal populations, and neuronal circuits, as well as glial cells contributes to a broad spectrum of clinical autism manifestations and common comorbidities, including intellectual deficits and epilepsy. On the other hand, interindividual differences in the type, topography, and severity of neuropathological changes explain the interindividual differences reported in clinical studies. 


IBR scientists have developed a Pervasive Developmental Disorder- Behavior Inventory (PDD-BI), and a rapid screening version, that can be used to identify and assess the progress of children with ASDs. No such rating scales for people with autism previously existed. Completed by parents and teachers, it is much faster to complete than current tests and will assist in both diagnosis and treatment monitoring.

Applied behavior analysis:

IBR’s Applied Behavior Analysis (ABA) Laboratory is conducting a school-based program entitled The Behavioral Assessments and Intervention Evaluation Program. This program is designed to provide intensive, individualized functional behavioral assessment and intervention to students with developmental disabilities who present with severe behavior problems by identifying the conditions under which target behavior occurs and devising interventions using that information. Challenging behaviors are replaced by adaptive behaviors (e.g., functional communication skills) that have equivalent functions in the school and home environment. Assessment and treatment to address challenging problem behavior is conducted in the student’s natural environment in collaboration with teachers, staff, and caregiver.

Excessive folic acid supplementation:

IBR studies are indicating that excessive folic acid (FA) supplementation during pregnancy may lead to abnormal gene expression during early brain development and may contribute to autism. These findings suggest a need for careful monitoring of FA supplementation in women who are pregnant or are planning a pregnancy.

Mitochondrial abnormalities in ASD:

IBR scientists who conducted the first study of mitochondria—the powerhouses of the cell—in postmortem brain tissue from individuals with ASD found significant abnormalities in mitochondria function in some regions of the brain. Further work will deepen our understanding of ASD and may lead to treatments.

Validity of neural network methodology in classification of autism:

IBR researchers assessed the ability of neural network modeling of the diagnostic process to classify and predict individuals who have autism or intellectual disability. They found that it has validity for identifying and understanding not only persons with autism, but also individuals with any condition in which a unique behavioral pattern is expected (e.g., learning disorders, schizophrenia).

Prevalence of autism on Staten Island:

In response to the alarm expressed by many parent groups and physicians on Staten Island about the numbers of children with autism here, IBR researchers conducted a collaborative epidemiological study of autism on Staten Island. Results showed that the prevalence of autism on Staten Island was very similar to that in recent CDC surveys.

Association between males with autism and fragile X syndrome:

IBR scientists were the first to define an association between fragile X syndrome and autism, finding that 1–2% of individuals with autism have the fragile X mutation. They observed that males with autism who have fragile X syndrome display characteristic social avoidance with unfamiliar adults.

Relationship between genotypes of autism and fragile X syndrome:

The recognition of the relationship between the genotypes of autism and fragile X syndrome by IBR researchers has led to increased understanding of the correlation between the genetic basis of these conditions and their clinical expression.

Effects of parental depression on toddlers with autism:

IBR researchers determined that unlike boys with both autism and fragile X syndrome, children with autism who do not have fragile X, but whose mothers and mothers’ relatives have a history of repeated episodes of depression, are markedly higher functioning than children with autism whose mothers do not have a history of depression. Behaviorally, these children are reported by their mothers to be more anxious and fearful, but the children’s teachers do not note these problems. Taken together, these data indicate yet another difference between children with autism who have fragile X syndrome and children with autism who do not have fragile X syndrome. The researchers also noted a higher prevalence of pervasive developmental disorder in the siblings of children with autism whose mother, or her family, had a history of depression. These data suggest that the genes responsible for depression and anxiety may, in part, also contribute to a form of autism associated with familial depression.

Targeted treatment trials:

Exciting new research developments at IBR and elsewhere have scientists feeling hopeful about the possibilities of new, effective, psychotropic drug treatment trials being conducted at IBR and elsewhere for people with fragile X syndrome and people with ASD. Fragile X syndrome is the most common inherited cause of intellectual disability and is associated with ASD in about 50% of cases; most affected males evidence some autistic-like behaviors.

Fragile X Clinical & Research Consortium:

IBR—the lead site in a consortium of 27 US Fragile X clinics—has developed a clinical registry, is conducting a longitudinal study of Fragile X, and has received funding from the CDC to continue the project for 4 more years.

Improved testing for fragile X:

IBR scientists are developing a new, extremely more sensitive test for the fragile X protein, using a monoclonal antibody approach that will allow for implementation of low-cost newborn screening across the US, resulting in greater prevention and commercial development.