Making sense out of the biological matrix of bipolar disorder

Reports new study in Biological Psychiatry

2012-08-20

(Press-News.org) Philadelphia, PA, August 20, 2012 – The more that we understand the brain, the more complex it becomes. The same can be said about the genetics and neurobiology of psychiatric disorders. For "Mendelian" disorders, like Huntington disease, mutation of a single gene predictably produces a single clinical disorder, following relatively simple genetic principals. Compared to Mendelian disorders, understanding bipolar disorder has been extremely challenging. Its biology is not well understood and its genetics are complex.

In a new paper, Dr. Inti Pedroso and colleagues utilize an integrative approach to probe the biology of bipolar disorder. They combined the results of three genome-wide association studies, which examined the association of common gene variants with bipolar disorder throughout the genome, and a study of gene expression patterns in post-mortem brain tissue from people who had been diagnosed with bipolar disorder. The findings were analyzed within the context of how brain proteins relate to each other based on the Human Protein Reference Database protein-protein interaction network.

"None of our research approaches provides us with sufficient information, by itself, to understand the neurobiology of psychiatric disorders. This innovative paper wrestles with this challenge in a creative way that helps us to move forward in thinking about the neurobiology of bipolar disorder," commented Dr. John Krystal, Editor of Biological Psychiatry.

Dr. Pedroso explained, "We combined information about genetic variation from thousands of cases and controls with brain gene expression data and information from protein databases to identify networks of genes and proteins in the brain that are key in the development of bipolar disorder."

The analysis resulted in the ability to define risk gene variants that were deemed functional, by virtue of the association with changes in gene expression levels, and to group these functional gene variants in biologically meaningful pathways.

The results implicated genes involved in several neural signaling pathways, including the Notch and Wnt signaling pathways. These pathways are key processes in neurotransmission and brain development and these findings indicate they are also likely to be involved in causing this severe disorder. The authors noted that three features stand out among these genes: i) they localized to the human postsynaptic density, which is crucial for neuronal function; ii) their mouse knockouts present altered behavioral phenotypes; and iii) some are known targets of the pharmacological treatments for bipolar disorder.

Dr. Gerome Breen, senior author on the study and Senior Lecturer at King's College London Institute of Psychiatry, said, "Our study provides some of the first evidence to show the biochemical and developmental processes involved in causing risk for developing this life-long and costly illness. We have highlighted potential new avenues for new drug treatments and intervention."

### The article is "Common Genetic Variants and Gene-Expression Changes Associated with Bipolar Disorder Are Over-Represented in Brain Signaling Pathway Genes" by Inti Pedroso, Anbarasu Lourdusamy, Marcella Rietschel, Markus M. Nöthen, Sven Cichon, Peter McGuffin, Ammar Al-Chalabi, Michael R. Barnes, and Gerome Breen (doi: 10.1016/j.biopsych.2011.12.031). The article appears in Biological Psychiatry, Volume 72, Issue 4 (August 15, 2012), published by Elsevier.

Notes for editors Full text of the article is available to credentialed journalists upon request; contact Rhiannon Bugno at +1 214 648 0880 or Biol.Psych@utsouthwestern.edu. Journalists wishing to interview the authors may contact Seil Collins at +44 0207 848 5377 or seil.collins@kcl.ac.uk.

The authors' affiliations, and disclosures of financial and conflicts of interests are available in the article.

John H. Krystal, M.D., is Chairman of the Department of Psychiatry at the Yale University School of Medicine and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available here.

About Biological Psychiatry Biological Psychiatry is the official journal of the Society of Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal publishes both basic and clinical contributions from all disciplines and research areas relevant to the pathophysiology and treatment of major psychiatric disorders.

The journal publishes novel results of original research which represent an important new lead or significant impact on the field, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Reviews and commentaries that focus on topics of current research and interest are also encouraged.

Biological Psychiatry is one of the most selective and highly cited journals in the field of psychiatric neuroscience. It is ranked 5th out of 129 Psychiatry titles and 16th out of 243 Neurosciences titles in the Journal Citations Reports® published by Thomson Reuters. The 2011 Impact Factor score for Biological Psychiatry is 8.283.

About Elsevier Elsevier is a world-leading provider of scientific, technical and medical information products and services. The company works in partnership with the global science and health communities to publish more than 2,000 journals, including The Lancet and Cell, and close to 20,000 book titles, including major reference works from Mosby and Saunders. Elsevier's online solutions include ScienceDirect, Scopus, Reaxys, ClinicalKey and Mosby's Nursing Suite, which enhance the productivity of science and health professionals, and the SciVal suite and MEDai's Pinpoint Review, which help research and health care institutions deliver better outcomes more cost-effectively.

A global business headquartered in Amsterdam, Elsevier employs 7,000 people worldwide. The company is part of Reed Elsevier Group PLC, a world-leading publisher and information provider, which is jointly owned by Reed Elsevier PLC and Reed Elsevier NV. The ticker symbols are REN (Euronext Amsterdam), REL (London Stock Exchange), RUK and ENL (New York Stock Exchange).

Media contact Rhiannon Bugno
Editorial Office, Biological Psychiatry
+1 214 648 0880
biol.psych@utsouthwestern.edu

ELSE PRESS RELEASES FROM THIS DATE:

No evidence that drug used for preventing life-threatening bleeding in women during labor works

2012-08-20

There is insufficient evidence for the effectiveness of a drug that is being used increasingly to prevent life-threatening bleeding in women after giving birth in community settings in low income countries, according to a review of all the available research published today (Monday) in the Journal of the Royal Society of Medicine. [1] Misoprostol (brand name Cytotec) was originally developed for treating gastric ulcers, but is increasingly used in low- and middle-income countries for preventing postpartum haemorrhage (PPH). It is given to women during labour to prevent ...

Canine tail chasing resembles human obsessive compulsive disorders

2012-08-20

The genetics research group, based at the University of Helsinki and the Folkhälsan Research Center and led by Professor Hannes Lohi, has in collaboration with an international group of researchers investigated the characteristics and environmental factors associated with compulsive tail chasing in dogs. A questionnaire study covering nearly 400 dogs revealed several similarities between compulsive behavior in dogs and humans: early onset, recurrent compulsive behaviors, increased risk for developing different types of compulsions, compulsive freezing, the beneficial effect ...

Big Bang theory challenged by big chill

2012-08-20

The start of the Universe should be modeled not as a Big Bang but more like water freezing into ice, according to a team of theoretical physicists at the University of Melbourne and RMIT University. They have suggested that by investigating the cracks and crevices common to all crystals - including ice - our understanding of the nature of the Universe could be revolutionised. Lead researcher on the project, James Quach said current theorising is the latest in a long quest by humans to understand the origins and nature of the Universe. "Ancient Greek philosophers wondered ...

EARTH: Do-it-yourself lava flows

2012-08-20

Alexandria, VA – It's not every day that lava flows through a college campus parking lot. But, since January 2010, Syracuse University has been bringing the lava to Central New York. Using commercially available basalt gravel and a coke-fired furnace, the geologists involved with the Syracuse University Lava Project are able to produce a wide range of flow morphologies and other features at a scale comparable to natural flows. Although one of the most common and voluminous types of lava flows, basaltic lava is still not completely understood. The majority of basaltic ...

As smart electric grid evolves, Virginia Tech engineers show how to include solar technologies

2012-08-20

An economically feasible way to store solar energy in existing residential power networks is the subject of an award winning paper written by two Virginia Tech electrical engineers and presented at an international conference. Reza Arghandeh of Blacksburg, Va., a doctoral candidate in the Bradley Department of Electrical and Computer Engineering at Virginia Tech http://www.ece.vt.edu/ , won the best student paper award at the 20th International Conference on Nuclear Engineering, held in conjunction with the American Society of Mechanical Engineering Power 2012 Conference ...

Savvy tots to grown-ups: 'Don't be such a crybaby'

2012-08-20

WASHINGTON -- Children as young as 3 apparently can tell the difference between whining and when someone has good reason to be upset, and they will respond with sympathy usually only when it is truly deserved, according to new research published by the American Psychological Association. "The study provides the first evidence that 3-year-olds can evaluate just how reasonable another person's distressed reaction is to a particular incident or situation, and this influences whether they are concerned enough to try to do something to help," said the study's lead author, ...

Neural interface for prosthesis can restore function in motor control brain areas

2012-08-20

Amsterdam, NL, August 20, 2012 – Amputation disrupts not only the peripheral nervous system but also central structures of the brain. While the brain is able to adapt and compensate for injury in certain conditions, in amputees the traumatic event prevents adaptive cortical changes. A group of scientists reports adaptive plastic changes in an amputee's brain following implantation of multielectrode arrays inside peripheral nerves. Their results are available in the current issue of Restorative Neurology and Neuroscience. "We found that a neurally-interfaced hand prosthesis ...

Scientists report promising new direction for cognitive rehabilitation in the elderly

2012-08-20

Amsterdam, NL, August 20, 2012 – Research has found that declines in temporal information processing (TIP), the rate at which auditory information is processed, underlies the progressive loss of function across multiple cognitive systems in the elderly, including new learning, memory, perception, attention, thinking, motor control, problem solving, and concept formation. In a new study, scientists have found that elderly subjects who underwent temporal training improved not only the rate at which they processed auditory information, but also in other cognitive areas. ...

Next generation 3-D theater: Optical science makes glasses a thing of the past

2012-08-20

WASHINGTON, Aug. 20—From the early days of cinema, film producers have used various techniques to create the illusion of depth – with mixed results. But even with digital technology, the latest Hollywood blockbusters still rely on clunky glasses to achieve a convincing 3-D effect. New optics research by a team of South Korean investigators offers the prospect of glasses-free, 3-D display technology for commercial theaters. Their new technique, described in a paper published today in the Optical Society's (OSA) open-access journal Optics Express, can bring this added ...

How well is depression in women being diagnosed and treated?

2012-08-20

New Rochelle, NY, August 20, 2012—Major depression affects as many as 16% of reproductive-aged women in the U.S. Yet pregnant women have a higher rate of undiagnosed depression than nonpregnant women, according to a study published in Journal of Women's Health, a peer-reviewed publication from Mary Ann Liebert, Inc., publishers. The article is available free on the Journal of Women's Health website at http://www.liebertpub.com/jwh. Jean Ko, PhD and coauthors from the Centers for Disease Control and Prevention (CDC), Atlanta, GA, found that more than 1 in 10 women ages ...

Climate policy must consider cross-border pollution “exchanges” to address inequality and achieve health benefits, research finds

Bipartisan members of congress relaunch Congressional Peripheral Artery Disease (PAD) Caucus with event that brings together lawmakers, medical experts, and patient advocates to address critical gap i

Making sense out of the biological matrix of bipolar disorder

ELSE PRESS RELEASES FROM THIS DATE:

LAST 30 PRESS RELEASES: