Home > Science > Autism Tissue Program Reaches Milestone 100th Publication

Autism Tissue Program Reaches Milestone 100th Publication

A journal article published this week studying sex-linked hormones in brain is the 100th paper describing results from brain tissue provided by the Autism Tissue Program. Taken together, the 100 papers, all published in peer-reviewed scientific journals, represent a huge advance in our understanding of the brains of individuals with autism.

The first publications were released in 2001 and built on existing evidence of developmental changes in the brain of those with autism.  The increase to 100 papers in 10 years mirrors the growth of the brain tissue resource from about 20 brains at the start to currently over 100 brains from individuals with a clear diagnosis of autism, ranging in age from 3 to 60.  The papers also show the use of a wide range of specialized resources developed by the Autism Tissue Program including MRI, brain tissue biopsies, genetic material from brain tissue and a large permanent brain library of slides all derived from post mortem brains.

The 100th publication is by Valerie Hu, Ph.D. and colleagues at the George Washington University Medical Center titled: ‘Sex hormones in autism: Androgens and estrogens differentially and reciprocally regulate RORA, a novel candidate gene for autism’.  The aim of the research, funded in part by Autism Speaks, was to examine a particular sex-linked candidate gene found throughout the human body, including brain tissue. This line of research could provide some rationale for the fact that four times more males are affected with autism than females. Dr. Hu’s research shows that both male and female hormones have varying and significant effects on the activity of the RORA gene product.  The RORA gene product regulates an enzyme (aromatase) that converts testosterone into estrogen.

This study offers a molecular mechanism for understanding the sex bias towards males by increasing levels of testosterone. This paper is the first report a sex hormone-responsive candidate gene for ASD. RORA is important for the development of a part of the brain called the cerebellum. The cerebellum is involved in controlling some types of movement, but also plays a role in cognitive tasks such as redirecting attention. RORA also serves to protect neurons against inflammation and oxidative stress.

Dr. Hu and colleagues showed that the female hormone estrogen increases the expression of RORA, while the male hormone androgen (dihydrotestosterone) decreases it. Interestingly, the interaction is somewhat circular as RORA regulates the expression of aromatase, an enzyme that converts testosterone to estrogen.  According to Dr. Hu, “We observed in the brains of individuals with autism a link between decreased in activity of RORA and a reduction of aromatase activity. This reduced activity would lead to build up of testosterone and a decrease in estrogen.”

This study provides a molecular explanation for the higher levels of testosterone observed in some individuals with autism. These findings also suggest a mechanism for the male bias in ASD because female brain tissue may benefit from the protective effects of naturally higher levels of estrogen In addition, the estrogen receptor shares some of the same target genes as RORA, thus compensating for RORA deficiency, which the research team has also observed in some individuals with ASD.

Zeroing in on specific gene effects in the brain is one of several research avenues undertaken by scientists that can only be done through the direct examination of human brain tissue. The value of the study of human brain tissue is the interpretation of the data in the context of the current knowledge about autism. Combined with post mortem imaging and genetic analysis scientists can gain a broader and more thorough understanding of ASD.

Scientists studying brain tissue today need to consider disorders that can co-exist with autism. The Autism Tissue Program takes great care to fully document medical conditions of brain donors.  The informatics portal catalogs over sixty disorders or conditions occurring in those with a diagnosis of autism including epilepsy, Fragile X, Tuberous Sclerosis Complex, Duschenne Muscular Dystrophy, Angleman, Rett and Asperger Syndromes and partial duplications or deletions of several chromosomes.

The Autism Tissue Program has emerged as an important resource of not only brain tissue but also as in informational hub of research results from an international group of scientists.  None of this work would be possible without the dedication of the families who chose to donate brain tissue of loved ones to the Autism Tissue Program. To register you or your family in the brain donor program, please visit www.autismtissueprogram.org for information and online registration, or call 877-333-0999 for information or to initiate a brain donation.

Click here to view the full list of 100 papers the Autism Tissue Program has made possible.

  1. Richard Fauth
    February 22, 2011 at 6:13 pm | #1

    Thank you Dr. Hu for your work. Thank you AS for publishing this article. It is my hope that many more parents will recognize the critical importance of the work you are doing. Unfortunately it is a shame how many People who call themselves Autism Advocates will be oblivious to this kind of research. This is one parent who also considers himself an advocate- who isnt one of them. Thank you again.

  2. February 22, 2011 at 8:52 pm | #2

    Angleman, Rett and Asperger Syndromes and partial duplications or deletions of several chromosomes.

  3. Katie Wright
    February 22, 2011 at 9:16 pm | #3

    I just wish this meant something for my son.
    10 years of ATP and it is still up to me, the internet and a handful of doctors to treat kids like mine.
    How many ATP publications have specific causation or treatment outcomes?

    • Richard Fauth
      February 24, 2011 at 11:36 pm | #4

      There is good news Katie. Research is now pointing at two distinct directions for treatment out comes-irregardless of causation. Glutamate up regulation and glutamate down regulation. IGF-1 and several other compounds on one side and the compounds investigated at seaside therapeutics and others on the other. I know you think it’s cause is environmental-The likilihood that environment plays a role is high-finding what- far more difficult.

      Push for pluripotent stem cell research beyond genetics. They can grow your childs neurons in a dish-from skin cells. They are already growing my child’s. Please do not misunderstand-the advantage is not to grow neurons and then somehow plant them-while that may be possible someday-far more likely is the ability to try different compounds on the grown neurons to see improvements. The atp research is helpfull as it shows what is a good neuron and what is not. Unfortunately, up until now we had to wait for people to die to study tissues-pluripotent stems cells push beyond that to the sea change needed.

      The current pluripotent cell research focuses on genetics only because the genetic causes are easier to see. I know you dont want to hear about genetics as you are convinced it is only for the few diseases in which they can show causation. But genetic association studies can point the way to which of the distinct directions your child’s issues lie and therefore what help could work. A micro array and a few fish studies aren’t good enough-sequencing of Autism suspect genes is crucial-and within reach- very soon.

      If some unknown Environmental factor has caused damage-they wont know what to do about it-unless they know what to do already via ongoing testing for Rhet and fragile x. If they know the risk factors genetically-they will know the proteins that are likely damaged-and not only what environmental agents could do the harm you describe-but what to do about it.

      The end game isn’t what caused it so much as its what wrong and how to fix it. They arent going to fix the genes-there going to fix what the genes did or didn’t do. Push for better imaging. Push for protein protein interaction studies, push for better genetic testing of the now many autism suspect genes and the proteins transcribed.

      The energy to make the push is there-it needs direction.

  4. February 23, 2011 at 8:53 pm | #5

    The informatics portal catalogs over sixty disorders or conditions occurring in those with a diagnosis of autism including epilepsy, Fragile X, Tuberous Sclerosis Complex, Duschenne Muscular Dystrophy, Angleman, Rett and Asperger Syndromes and partial duplications or deletions of several chromosomes.

  5. March 11, 2011 at 10:01 pm | #6

    We just wanted to post a note of thanks and laud the work of the ATP and professionals like Dr. Jane Pickett. We first met Dr. Pickett in 1999 and became involved within support of the ATP as parents of a son who was diagnosed in 1993 after having suffered an injury from several vaccinations in one day.

    We do believe in genetic predisposition as well as environmental factors and particpated as a family in many research studies over the years in our quest to obtain answers to not only causation, but what can be done to assist those individuals living with ASD who may benefit from a variety of interventions as our son has.

    We’d also like to note that our family made a donation to the ATP when our loved one Mark Coriaty passed in Nov. of 1999. A adult living with ASD and Epilepsy, a sibling, son, and uncle to our son with ASD, he was a person who was often misunderstood and his AS not previously diagnosed. His death, one which should have not occured, has also driven us within advocacy efforts to ensure others do not have such a fate.

    Overall however we as a community do need to communicate to our federal agencies how valuable such research is and if we are seeking other options, what those can and should be.

    With much appreciation for the ATP,
    The Gammichia Family

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