Schizophrenia Genetics Linked to Disruption in How Brain Processes Sound

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Recent studies have identified many genes that may put people with schizophrenia at risk for the disease. But, what links genetic differences to changes in altered brain activity in schizophrenia is not clear. Now, three labs at the Perelman School of Medicine at the University of Pennsylvania have come together using electrophysiological, anatomical, and immunohistochemical approaches — along with a unique high-speed imaging technique — to understand how schizophrenia works at the cellular level, especially in identifying how changes in the interaction between different types of nerve cells leads to symptoms of the disease.

The findings are reported this week in the Proceedings of the National Academy of Sciences.

“Our work provides a model linking genetic risk factors for schizophrenia to a functional disruption in how the brain responds to sound, by identifying reduced activity in special nerve cells that are designed to make other cells in the brain work together at a very fast pace” explains lead author Gregory Carlson, PhD, assistant professor of Neuroscience in Psychiatry. “We know that in schizophrenia this ability is reduced, and now, knowing more about why this happens may help explain how loss of a protein called dysbindin leads to some symptoms of schizophrenia.”

Previous genetic studies had found that some forms of the gene for dysbindin were found in people with schizophrenia. Most importantly, a prior finding at Penn showed that the dysbindin protein is reduced in a majority of schizophrenia patients, suggesting it is involved in a common cause of the disease….

The above story is reprinted from materials provided by University of Pennsylvania School of Medicine.

ScienceDaily

http://www.sciencedaily.com/releases/2011/10/111013153945.htm

Twin Study Reveals Epigenetic Alterations of Psychiatric Disorders

In the first study to systematically investigate genome-wide epigenetic differences in a large number of psychosis discordant twin-pairs, research at the Institute of Psychiatry (IoP) at King’s College London provides further evidence that epigenetic processes play an important role in neuropsychiatric disease.

Published in Human Molecular Genetics, the findings may offer potential new avenues for treatment.

Previous quantitative genetic analyses of schizophrenia and bipolar disorder reveal strong inherited components to both. However, although heritability for schizophrenia and bipolar disorder is estimated at 70%, disease concordance between twin-pairs is far from 100%, indicating that non-genetic factors play an important role in the onset of the diseases.

Dr. Jonathan Mill, lead author of the study at the IoP says, ‘We studied a group of 22 identical twin-pairs, so 44 individuals in all, one of the largest twin studies performed for any complex disease to date. In each twin-pair, one had either schizophrenia or bipolar disorder. Because we know that twins are genetically identical, we can rule out any genetic cause of illness in the affected twin — the aim of our study was to investigate epigenetic variations associated with these disorders.’…

by ScienceDaily staff

ScienceDaily

http://www.sciencedaily.com/releases/2011/09/110921120039.htm

 

Exceptional Opportunities in Translational Neuroscience (Video from One MInd for Research Symposium)

The National Institutes of Health (NIH) has a strong tradition of supporting new approaches for diagnosing, treating, and preventing disease. Despite significant progress, we still lack treatments for many conditions, including conditions affecting the brain and nervous system. One challenge is that the therapeutics development pipeline contains bottlenecks that reduce efficiency and increase costs. To advance the discipline of translational science, NIH has announced plans to create a new center to study the process of therapeutics development, identify bottlenecks that might be re-engineered, and experiment with innovative methods to streamline the process. This presentation will set forth the rationale for establishing the National Center for Advancing Translational Sciences, and discuss how NIH-supported research will benefit people suffering from neurological conditions.

Francis S. Collins is an American physician-geneticist, noted for his landmark discoveries of disease genes and his leadership of the Human Genome Project (HGP) and described by the Endocrine Society as “one of the most accomplished scientists of our time”. He currently serves as Director of the National Institutes of Health. Collins has written a book about his Christian faith. He founded and was president of the BioLogos Foundation before accepting the nomination to lead the NIH. On October 14, 2009, Pope Benedict XVI appointed Francis Collins to the Pontifical Academy of Sciences.

http://thesciencenetwork.org/programs/one-mind-for-research/exceptional-opportunities-in-translational-neuroscience

Serious Neuropsychiatric Diseases Can Be Tackled Through An Innovative, Accelerated, Collaborative Effort (Video from One MInd for Research Symposium)

Serious neuropsychiatric diseases are among the most devastating illnesses affecting mankind. Nevertheless, while staggering advances are being made in the field of neuroscience as a whole, scientific expertise is scattered and the approach to research is fragmented. Our knowledge base and data are largely siloed, and incentives for research and collaboration are lacking. In addition, federal and industry support for funding brain research is declining, leading to fewer new experimental treatments. This presentation describes a plan to expand the boundaries of science. By sharing data and knowledge platforms, individual researchers and organizations can make groundbreaking advances. This would entail developing a major private-public partnership that will include universities, government, advocacy groups, industry, and private citizens. Much is at stake in terms of human capital, for as a society, we have a moral imperative to break through current barriers to smash stigma, develop better treatments, and ultimately cure brain disorders.

Husseini Manji is the Global Therapeutic Area Head of Neuroscience at Johnson and Johnson Pharmaceuticals.

http://thesciencenetwork.org/programs/one-mind-for-research/serious-neuropsychiatric-diseases-can-be-tackled-through-an-innovative-accelerated-collaborative-effort

Imagining the Future: A 10-Year Plan for Neuroscience (Video from One Mind for Research Symposium)

Teen Brains Over-Process Rewards, Suggesting Root of Risky Behavior, Mental Ills

University of Pittsburgh researchers have recorded neuron activity in adolescent rat brains that could reveal the biological root of the teenage propensity to consider rewards over consequences and explain why adolescents are more vulnerable to drug addiction, behavioral disorders, and other psychological ills.

The team reports in the Journal of Neuroscience that electrode recordings of adult and adolescent brain-cell activity during the performance of a reward-driven task show that adolescent brains react to rewards with far greater excitement than adult brains. This frenzy of stimulation occurred with varying intensity throughout the study along with a greater degree of disorganization in adolescent brains. The brains of adult rats, on the other hand, processed their prizes with a consistent balance of excitation and inhibition.

The extreme difference in brain activity provides a possible physiological explanation as to why teenagers are more prone than adults to rash behavior, addiction, and mental diseases, said lead researcher Bita Moghaddam, a professor of neuroscience in Pitt’s School of Arts and Sciences. She and coauthor David Sturman, a Pitt neuroscience doctoral student, observed the disparate reactions to reward in individual neurons in the orbitofrontal cortex, a brain region that weighs payoff and punishment to plan and make decisions.

“The disorganized and excess excitatory activity we saw in this part of the brain means that reward and other stimuli are processed differently by adolescents,” Moghaddam said. “This could intensify the effect of reward on decision making and answer several questions regarding adolescent behavior, from their greater susceptibility to substance abuse to their more extreme reactions to pleasurable and upsetting experiences.”

In addition, malfunctions in the orbitofrontal cortex have been observed in cases of schizophrenia, mood disorders, and other psychological disturbances, Moghaddam said. The type of erratic activity in the cortex that she and Sturman observed could aggravate these conditions at a time when the maturing brain is vulnerable…..

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by University of Pittsburgh.

http://www.sciencedaily.com/releases/2011/01/110126121732.htm

New Research May Lead to Treatment of a Variety of Mental Disorders

One of the first studies published from the University of Missouri Brain Imaging Center (BIC) gives researchers insight into the brain and memory and may provide researchers clues to treating a variety of debilitating disorders.

Nelson Cowan, director of the BIC and Curator’s Professor in the Department of Psychological Sciences, used the BIC’s magnetic resonance imaging (MRI) to produce graphics that depict the structure and function of the brain during various mental tasks in an effort to understand abstract working memory. People use their abstract working memories to assign meaning when trying to recall facts — for example, when someone dials a set of phone numbers, their abstract memory brings forth an image of the person they are calling.

Previous studies identified an area of the brain responsible for holding abstract working memory, although it was assumed by some researchers to hold only visual information. At the BIC, Cowan found that this same part of the brain can hold auditory information as well. For example, when people hear “Jingle Bells” they relate it to the Christmas season and retain the meaning of the song temporarily.

“This research has given us better understanding of an area of the brain that may be affected in people with various learning disabilities, autism and schizophrenia,” said Cowan. “For example, recent research has shown that people with schizophrenia simply hold fewer items in their working memories, rather having an inability to disregard unimportant items, as previously thought. Thus, discovering more about working memory will enable scientists to better target schizophrenia, among other disorders.”

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by University of Missouri-Columbia.

Journal Reference: Nelson Cowan, Dawei Li, Amanda Moffitt, Theresa M. Becker, Elizabeth A. Martin, J. Scott Saults, Shawn E. Christ. A Neural Region of Abstract Working Memory. Journal of Cognitive Neuroscience, 2011; : 1 DOI: 10.1162/jocn.2011.21625

http://www.sciencedaily.com/releases/2011/01/110125152522.htm

Neuronal Migration Errors: Right Cells, Wrong Place

Normally, cortical nerve cells or neurons reside in the brain’s gray matter with only a few scattered neurons in the white matter, but some people with schizophrenia have a higher number of neurons in the white matter. Neuronal migration errors may arise in schizophrenia as a consequence of both genetic and environmental factors.

The phenomenon of aberrant cellular localization has now been studied in detail in a paper by Yang and colleagues, published in the current issue of Biological Psychiatry.

Using a specialized technique that involves staining cells, the researchers were able to determine the distribution of nerve cells in brain tissue from people who had been diagnosed with schizophrenia in comparison to tissue from people who did not carry this diagnosis prior to their death.

Their results linked two main findings emerging from analyses of brain tissue in schizophrenia: abnormalities in the inhibitory neurons within the cortex and increases in neurons in white matter below the cortex…..

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Elsevier, via AlphaGalileo.

Journal Reference: Yang Yang, Samantha J. Fung, Alice Rothwell, Si Tianmei, Cynthia Shannon Weickert. Increased Interstitial White Matter Neuron Density in the Dorsolateral Prefrontal Cortex of People with Schizophrenia. Biological Psychiatry, 2011; 69 (1): 63 DOI: 10.1016/j.biopsych.2010.08.020

http://www.sciencedaily.com/releases/2011/01/110104082412.htm

Targeting Nicotine Receptors to Treat Cognitive Impairments in Schizophrenia

Smoking is a common problem for patients with schizophrenia. The increased tendency of patients diagnosed with this disorder is to not only smoke, but to do so more heavily than the general public. This raises the possibility that nicotine may be acting as a treatment for some symptoms of schizophrenia.

Nicotine acts through two general classes of brain receptors, those with high and low affinity for nicotine. The low affinity class of nicotinic receptors contains the alpha-7 subunit, which is present in reduced numbers in people with schizophrenia.

Two papers published in the January 1st issue of Biological Psychiatry suggest that drugs that stimulate these alpha-7 subunit-containing nicotinic receptors might enhance cortical function and treat cognitive impairments associated with schizophrenia.

In their study of healthy monkeys, Graham Williams and colleagues at Yale University and AstraZeneca found that very low doses of AZD0328, a novel drug that acts as an alpha-7 agonist, produced both acute and persistent improvements in their performance on a spatial working memory task……

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Elsevier, via AlphaGalileo.

Journal References:
1. Jason R. Tregellas, Jody Tanabe, Donald C. Rojas, Shireen Shatti, Ann Olincy, Lynn Johnson, Laura F. Martin, Ferenc Soti, William R. Kem, Sherry Leonard. Effects of an Alpha 7-Nicotinic Agonist on Default Network Activity in Schizophrenia. Biological Psychiatry, 2011; 69 (1): 7 DOI: 10.1016/j.biopsych.2010.07.004
2. Stacy A. Castner et al. Immediate and Sustained Improvements in Working Memory After Selective Stimulation of α7 Nicotinic Acetylcholine Receptors. Biological Psychiatry, (in press)

http://www.sciencedaily.com/releases/2011/01/110111084220.htm

NIH-LED STUDY IDENTIFIES GENETIC VARIANT THAT CAN LEAD TO SEVERE IMPULSIVITY

A multinational research team led by scientists at the National Institutes of Health (NIH) has found that a genetic variant of a brain receptor molecule may contribute to violently impulsive behavior when people who carry it are under the influence of alcohol. A report of the findings, which include human genetic analyses and gene knockout studies in animals, appears in the December 23, 2010 issue of Nature.

http://www.niaaa.nih.gov/NewsEvents/NewsReleases/Pages/NIH-ledstudyidentifiesgeneticvariantthatcanleadtosevereimpulsivity.aspx

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