Autism Recovery is possible!

ScienceDaily (May 19, 2012) — Preliminary results from an ongoing, large-scale study by Yale School of Medicine researchers shows that oxytocin -- a naturally occurring substance produced in the brain and throughout the body -- increased brain function in regions that are known to process social information in children and adolescents with autism spectrum disorders (ASD).

A Yale Child Study Center research team that includes postdoctoral fellow Ilanit Gordon and Kevin Pelphrey, the Harris Associate Professor of Child Psychiatry and Psychology, will present the results on May 19 at the International Meeting for Autism Research.

"Our findings provide the first, critical steps toward devising more effective treatments for the core social deficits in autism, which may involve a combination of clinical interventions with an administration of oxytocin," said Gordon. "Such a treatment approach will fundamentally improve our understanding of autism and its treatment."

Social-communicative dysfunctions are a core characteristic of autism, a neurodevelopmental disorder that can have an enormous emotional and financial burden on the affected individual, their families, and society.

Gordon said that while a great deal of progress has been made in the field of autism research, there remain few effective treatments and none that directly target the core social dysfunction. Oxytocin has recently received attention for its involvement in regulating social abilities because of its role in many aspects of social behavior and social cognition in humans and other species.

To assess the impact of oxytocin on the brain function, Gordon and her team conducted a first-of-its-kind, double-blind, placebo-controlled study on children and adolescents aged 7 to 18 with ASD. The team members gave the children a single dose of oxytocin in a nasal spray and used functional magnetic resonance brain imaging to observe its effect.

The team found that oxytocin increased activations in brain regions known to process social information. Gordon said these brain activations were linked to tasks involving multiple social information processing routes, such as seeing, hearing, and processing information relevant to understanding other people.

Other authors on the study include Randi H. Bennett, Brent C. vander Wyk, James F. Leckman, and Ruth Feldman.

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The above story is reprinted from materials provided by Yale University. The original article was written by Karen N. Peart.

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Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

ScienceDaily (May 16, 2012) — What can a fish tell us about human brain development? Researchers at Duke University Medical Center transplanted a set of human genes into a zebrafish and then used it to identify genes responsible for head size at birth.

Researchers at Duke University Medical Center transplanted a set of human genes into a zebrafish and then used it to identify genes responsible for head size at birth.

Head size in human babies is a feature that is related to autism, a condition that recent figures have shown to be more common than previously reported, 1 in 88 children in a March 2012 study. Head size is also a feature of other major neurological disorders, such as schizophrenia.

"In medical research, we need to dissect events in biology so we can understand the precise mechanisms that give rise to neurodevelopmental traits," said senior author Nicholas Katsanis, Ph.D., Jean and George Brumley Jr., MD, Professor of Developmental Biology, and Professor of Pediatrics and Cell Biology. "We need expert scientists to work side by side with clinicians who see such anatomic and other problems in patients, if we are to effectively solve many of our medical problems."

The study was published online in Nature journal on May 16.

Katsanis knew that a region on chromosome 16 was one of the largest genetic contributors to autism and schizophrenia, but a conversation at a European medical meeting pointed him to information that changes within that same region of the genome also were related to changes in a newborn's head size.

The problem was difficult to address because the region had large deletions and duplications in DNA, which are the most common mutational mechanisms in humans. "Interpretation is harrowingly hard," said Katsanis, who is also director of the Duke Center for Human Disease Modeling.

The reason is that a duplication of DNA or missing DNA usually involves several genes. "It is very difficult to go from 'here is a region with many genes, sometimes over 50' to 'these are the genes that are driving this pathology,'" Katsanis said.

"There was a light bulb moment," Katsanis said. "The area of the genome we were exploring gave rise to reciprocal (opposite) defects in terms of brain cell growth, so we realized that overexpressing a gene in question might give one phenotype -- a smaller head, while shutting down the same gene might yield the other, a larger head."

The researchers transplanted a common duplication area of human chromosome 16 known to contain 29 genes into zebrafish embryos and then systematically turned up the activity of each transplanted human gene to find which might cause a small head (microcephaly) in the fish. They then suppressed the same gene set and asked whether any of them caused the reciprocal defect: larger heads (macrocephaly).

The researchers knew that deletion of the region that contained these 29 genes occurred in 1.7% of children with autism.

It took the team a few months to dissect such a "copy number variant" -- an alteration of the genome that results in an abnormal number of one or more sections of chromosomal DNA.

"Now we can go from a genetic finding that is dosage-sensitive and start asking reasonable questions about this gene as it pertains to neurocognitive traits, which is a big leap," Katsanis said. Neurocognitive refers to the ability to think, concentrate, reason, remember, process information, learn, understand and speak.

Many human conditions have anatomical features that are also related to genetics, he said. "There are major limitations in studying autistic or schizophrenic behavior in zebrafish, but we can measure head size, jaw size, or facial abnormalities."

The single gene in question, KCTD13, is responsible for driving head size in zebrafish by regulating the creation and destruction of new neurons (brain cells). This discovery let the team focus on the analogous gene in humans. "This gene contributes to autism cases, and probably is associated with schizophrenia and also childhood obesity," Katsanis said.

Once the gene has been uncovered, researchers can examine the protein it produces. "Once you have the protein, you can start asking valuable functional questions and learning what the gene does in the animal or human," Katsanis said.

Copy number variants, such as the ones this team found on chromosome 16, are now thought to be one of the most common sources of genetic mutations. Hundreds, if not thousands, of such chromosomal deletions and duplications have been found in patients with a broad range of clinical problems, particularly neurodevelopmental disorders.

"Now we may have an efficient tool for dissecting them, which gives us the ability to improve both diagnosis and understanding of disease mechanisms," Katsanis said.

The current study suggests that KCTD13 is a major contributor to some cases of autism, but also points to the synergistic action of this gene with two other genes in the region, named MVP and MAPK3, Katsanis said.

Other authors include lead author Christelle Golzio, Jason Willer and Edwin Oh of the Duke Center for Human Disease Modeling and Department of Cell Biology; Mike Talkowski, Mei Sun and Jim Guzella from the Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital in Boston; Sebastien Jacquemont, Alexandre Reymond and Jacques Beckmann from the Service de Génétique Médicale, Centre Hospitalier Universitaire Vaudois, in Lausanne, Switzerland; and Yu Taniguchi, Akira Sawa and Atsushi Kamiya from the Department of Psychiatry, Johns Hopkins University School of Medicine in Baltimore.

Funding is from a Silvio O. Conte Center grant from the National Institute of Mental Health (NIMH), National Institutes of Health grants, the Simons Foundation, the Autism Consortium of Boston, the Leenaards Foundation Prize, the Swiss National Science Foundation, a National Science Foundation Sinergia grant, an NIMH National Research Service Award, and an academic study award from the University of Lausanne.

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The above story is reprinted from materials provided by Duke University Medical Center.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

1. Christelle Golzio, Jason Willer, Michael E. Talkowski, Edwin C. Oh, Yu Taniguchi, Sébastien Jacquemont, Alexandre Reymond, Mei Sun, Akira Sawa, James F. Gusella, Atsushi Kamiya, Jacques S. Beckmann, Nicholas Katsanis. KCTD13 is a major driver of mirrored neuroanatomical phenotypes of the 16p11.2 copy number variant. Nature, 2012; 485 (7398): 363 DOI: 10.1038/nature11091

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.