Autism BrainNet: A network of postmortem brain banks established to facilitate autism research.

Autism spectrum disorder (ASD or autism) is a neurodevelopmental condition that affects over 1% of the population worldwide. Developing effective preventions and treatments for autism will depend on understanding the genetic perturbations and underlying neuropathology of the disorder. While evidence from magnetic resonance imaging and other noninvasive techniques points to altered development and organization of the autistic brain, these tools lack the resolution for identifying the cellular and molecular underpinnings of the disorder. Postmortem studies of high-quality human brain tissue currently represent the only viable option to pursuing these types of studies. However, the availability of high-quality ASD brain tissue has been extremely limited. Here we describe the establishment of a privately funded tissue bank, Autism BrainNet, a network of brain collection sites that work in a coordinated fashion to develop an adequate library of human postmortem brain tissues. Autism BrainNet was initiated as a collaboration between the Simons Foundation and Autism Speaks, and is currently funded by the Simons Foundation Autism Research Initiative. Autism BrainNet has collection sites (nodes) in California, Texas, New York, and Massachusetts; an affiliated, international node is located in Oxford, England. All donations to this network become part of a consolidated pool of tissue that is distributed to qualified investigators worldwide to carry out autism research. An essential component of this program is a widespread outreach program that highlights the need for postmortem brain donations to families affected by autism, led by the Autism Science Foundation. Challenges include an outreach campaign that deals with a disorder beginning in early childhood, collecting an adequate number of donations to deal with the high level of biologic heterogeneity of autism, and preparing this limited resource for optimal distribution to the greatest number of investigators.

Mortality in individuals with autism, with and without epilepsy.

Previous studies show higher mortality rates among individuals with autism than the general population. Comorbidity with epilepsy is an assumed, often ill-defined factor in the increased mortality rates of individuals with autism. Data from the Autism Tissue Program, a tissue donation program established to support biomedical research on autism, show that approximately one-third of its brain donors with autism also had epilepsy. Analysis of new data from the California State Department of Developmental Services is consistent with past reports showing that there is a higher than expected rate of mortality in individuals with autism and epilepsy than autism alone. Accurate, complete and accessible records on cause of death are necessary not just for brain research, but also for understanding risk factors that contribute to early death in individuals with autism spectrum disorders. Various national health care and state developmental disability agency initiatives to reduce risk of mortality are described.

A genotype resource for postmortem brain samples from the Autism Tissue Program.

The Autism Tissue Program (ATP), a science program of Autism Speaks, provides researchers with access to well-characterized postmortem brain tissues. Researchers access these tissues through a peer-reviewed, project-based approval process, and obtain related clinical information from a secure, online informatics portal. However, few of these samples have DNA banked from other sources (such as a blood sample from the same individual), hindering genotype-phenotype correlation and interpretation of gene expression data derived from the banked brain tissue. Here, we describe an initiative to extract DNA from Brodmann Area 19, and genotype these samples using both the Affymetrix Genome-Wide Human SNP Array 6.0 and the Illumina Human1M-Duo DNA Analysis BeadChip genome-wide microarray technologies. We additionally verify reported gender, and infer ethnic background from the single nucleotide polymorphism data. We have also used a rigorous, multiple algorithm approach to identify genomic copy number variation (CNV) from these array data. Following an initial proof of principle study using two samples, 52 experimental samples, consisting of 27 subjects with confirmed or suspected autism and related disorders, 5 subjects with cytogenetically visible duplications of 15q, 2 with epilepsy and 18 age-matched normal controls were processed, yielding high-quality genotype data in all cases. The genotype and CNV data are provided via the ATP informatics portal as a resource for the autism research community.

Autism brain tissue banking.

One avenue of progress toward understanding the neurobiological basis of autism is through the detailed study of the post-mortem brain from affected individuals. The primary purpose of autism brain tissue banking is to make well-characterized and optimally preserved post-mortem brain tissue available to the neuroscience research community. In this paper we discuss our current understanding of the criteria for optimal characterization and preservation of post-mortem brain tissue; the pitfalls associated with inadequate clinical and neuropathological characterization and the advantages and disadvantages of post-mortem studies of the brain. We then describe the current status of the brain tissue bank supported by the Autism Tissue Program, including the demographic characteristics of the tissue donors, post-mortem interval, sex, age and the method of preservation. Finally, we provide information on the policies and procedures that govern the distribution of brain specimens by this bank and the nature of the studies that are currently being supported directly by this program.

Autism post-mortem neuroinformatic resource: the autism tissue program (ATP) informatics portal.

The Autism Tissue Program (ATP) was established to oversee and manage brain donations related to neurological research in autism. The ATP Informatics Portal (www.atpportal.org) is an integrated data access system based on Oracle technology, developed to provide access for researchers to information on this rare tissue resource. It also permits sorting of existing cases based on donor ante-mortem history as well as agonal states and post-mortem tissue conditions. Phase II of development established administrative tracking of registrants intending to donate, as well as management of tissue requests and the awarding and tracking of tissue. Phase III is the ongoing assimilation of data sets derived from research on a core group of donors with searchable access by investigators.

The neuropathology of autism: a review.

Presented is a review of recent progress in the understanding of autism based on investigations of donated human brain tissue. Autism is a pervasive developmental disorder by the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria, manifesting by age 3 and characterized by impairments in social interaction and communication, as well as restricted, repetitive, stereotyped patterns of behavior. Based on reported neuropathologic findings, these characteristic behaviors are clinical manifestations of both pre- and postnatal alterations. This review summarizes the current data obtained from postmortem brain studies in the areas of stereology, neurotransmitter systems/synaptic processes, molecular mechanisms, and neuroimmunology. In addition, we discuss current research strategies designed to facilitate translational research and maximize the yield of precious resources (e.g. the Autism Tissue Program), highlight barriers to research, and consider future trends.