[News release] Closer than ever to a personalized treatment solution for intellectual disability — ScienceDaily

Closer than ever to a personalized treatment solution for intellectual disability 

From the press release

JUPITER, FL – January 21, 2015 – Scientists from the Florida campus of The Scripps Research Institute (TSRI) have produced an approach that protects animal models against a type of genetic disruption that causes intellectual disability, including serious memory impairments and altered anxiety levels.

The findings, which focus on treating the effects of mutations to a gene known as Syngap1, have been published online ahead of print by the journal Biological Psychiatry.

“Our hope is that these studies will eventually lead to a therapy specifically designed for patients with psychiatric disorders caused by damagingSyngap1 mutations,” said Gavin Rumbaugh, a TSRI associate professor who led the study. “Our model shows that the early developmental period is the critical time to treat this type of genetic disorder.”

Damaging mutations in Syngap1 that reduce the number of functional proteins are one of the most common causes of sporadic intellectual disability and are associated with schizophrenia and autism spectrum disorder. Early estimates suggest that these non-inherited genetic mutations account for two to eight percent of these intellectual disability cases. Sporadic intellectual disability affects approximately one percent of the worldwide population, suggesting that tens of thousands of individuals with intellectual disability may carry damaging Syngap1 mutations without knowing it.

In the new study, the researchers examined the effect of damagingSyngap1 mutations during development and found that the mutations disrupt a critical period of neuronal growth—a period between the first and third postnatal weeks in mouse models. “We found that a certain type of cortical neuron grows too quickly in early development, which then leads to the premature formation of certain types of neural circuits,” said Research Associate Massimilano Aceti, first author of the study.

The researchers reasoned that this process might cause permanent errors in brain connectivity and that they might be able to head off these effects by enhancing the Syngap1 protein in the newborn mutant mice. Indeed, they found that a subset of neurons were misconnected in the adult mutant mice, suggesting that early growth of neurons can lead to life-long neural circuit connectivity problems. Then, using advanced genetic techniques to raise Syngap1 protein levels in newborn mutant mice, the researchers found this strategy completely protected the mice only when the approach was started before this critical developmental window opened.

As a result of these studies, Rumbaugh and his colleagues are now developing a drug-screening program to look for drug-like compounds that could restore levels of Syngap1 protein in defective neurons. They hope that, as personalized medicine advances, such a therapy could ultimately be tailored to patients based on their genotype.

In addition to Rumbaugh and Aceti, other authors of the study, “Syngap1 Haploinsufficiency Damages a Postnatal Critical Period of Pyramidal Cell Structural Maturation Linked to Cortical Circuit Assembly,” include Thomas K. Creson, Thomas Vaissiere, Camilo Rojas, Wen-Chin Huang, Ya-Xian Wang, Ronald S. Petralia, Damon T. Page and Courtney A. Miller of TSRI. For more information, seehttp://www.biologicalpsychiatryjournal.com/article/S0006-3223%2814%2900593-9/abstract

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[Press release] Connection between childhood adversity and psychiatric disorders seen at cellular level | EurekAlert! Science News

Connection between childhood adversity and psychiatric disorders seen at cellular level | EurekAlert! Science News.

Logo for mitochondrial DNA (Photo credit: Wikipedia)

From the 20 January 2015 press release

PROVIDENCE, R.I. – In a new study published online in Biological Psychiatry on January 16, 2015, researchers from Butler Hospital identify an association between biological changes on the cellular level and both childhood adversity and psychiatric disorders. These changes in the form of telomere shortening and alterations of mitochondrial DNA (mtDNA), are important in the aging process, and this new research provides evidence that psychosocial factors–specifically childhood adversity and psychiatric disorders– may also influence these cellular changes and could lead to accelerated aging.

Mitochondria convert molecules from food into energy that can be used by cells and also play a key role in cellular growth, signaling, and death. Telomere shortening is also a measure of advanced cellular aging. Recent studies have examined the possible connection between mitochondria and psychiatric disorders, but the research is very limited, and no prior work has examined the relationship of mitochondrial DNA to psychosocial stress. “We are interested in these relationships because there is now clear evidence that stress exposure and psychiatric conditions are associated with inflammation and health conditions like diabetes and heart disease. Identifying the changes that occur at a cellular level due to these psychosocial factors allows us to understand the causes of these poor health conditions and possibly the overall aging process.” said Audrey Tyrka, MD, PhD, Director of the Laboratory for Clinical and Translational Neuroscience at Butler Hospital and Associate Professor of Psychiatry and Human Behavior at Brown University.

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