Transgenic Mouse Offers a Window on Gene/Environment Interplay: Prenatal Infection Alters Behavior in Genetically Vulnerable

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Experiments in transgenic mice have provided a novel glimpse of how a prenatal infection could interact with a specific gene variant to cause behavioral and neurologic changes in adults that mirror those seen in major psychiatric disease. The mouse model used offers a means to explore gene/environment interactions and to identify both the mechanisms involved and critical periods of vulnerability.

Background
Research has established that the risk of developing a psychiatric illness and the features of the illness are the outcome of interactions between the environment and genes. Understanding the details of these interactions is a complex task, however. Many genes shape brain development and function, and gene function is in turn influenced by myriad environmental factors unfolding across a lifespan.

Genetic technology has made it possible to create model animals that carry risk genes, providing a way to focus on how single genes or mutations shape function and how specific environmental factors alter it.

This Study
Scientists at the Johns Hopkins University School of Medicine in Baltimore led by Mikhail Pletnikov developed the mouse model used in this study by inserting a gene with a mutation known to be associated in humans with schizophrenia, depression, and bipolar disorder. They used a technique that allows them to turn the gene on and off at desired time points during brain development. In earlier research, mice with the gene, mhDISC1 (mutant human disrupted-in-schizophrenia-1) showed effects on social behavior and mood which differed depending on the sex of the mice, and the age at which the gene was active…….

NIMH Press Office

Reference: Abazyan, B., Nomura, J., Kannan, G., Ishizuka, K., Tamashiro, K.L., Nucifora, F., Pogorelov, V., Ladenheim, B., Yang, C., Krasnova, I.N., Cadet, J.L., Pardo, C., Mori, S., Kamiya, A., Vogel, M.W., Sawa, A., Ross, C.A., and Pletnikov, M.V. Prenatal interaction of mutant DISC1 and immune activation produces adult psychopathology. Biological Psychiatry 2010;68:1172-1181.

http://www.nimh.nih.gov/science-news/2010/transgenic-mouse-offers-a-window-on-gene-environment-interplay-prenatal-infection-alters-behavior-in-genetically-vulnerable.shtml

Disclaimer: Neither SARDAA nor SA, assume any legal liability, responsibility nor does inclusion of articles or comments constitute or imply its endorsement, recommendation, or favoring for the accuracy, completeness, or usefulness of any information, product or process disclosed in the blog.

Upcoming Open Policy Day of the National Advisory Mental Health

You are cordially invited to attend the Friday, January 14, 2011 Open Policy
Session of the National Advisory Mental Health Council (NAMHC). This policy
session is an excellent opportunity for the mental health research and
advocacy communities to become informed about current programs and
priorities of the National Institute of Mental Health (NIMH).

The upcoming Council Session will be held in Building 31C, 6th floor
conference center, conference room 6,
on the National Institutes of Health (NIH) campus, located at 9000 Rockville
Pike, Bethesda, Maryland.
The meeting is scheduled to begin at 8:30 am and conclude by 12:30 p.m.

The agenda will include Dr. Thomas Insel’s report on important activities at
NIMH as well as the biennial report on inclusion in NIMH research. The
agenda also includes a discussion of several potential research initiatives
as well as a presentation by Dr. Karl Deisseroth on the topic of
optogenetics.

Time for public comments is currently scheduled for 12:15 pm, although the
time could change. We recommend that you check the Website for details
concerning the agenda, available soon at
http://www.nimh.nih.gov/NAMHC.

If you plan to attend, please register by noon, Wednesday, January 12 at
http://www.nimh.nih.gov/forms/namhcreg.jsp

Please be advised that NIH has instituted strict security procedures.
Security screening takes place at the campus perimeter and visitor passes
are issued at the NIH Gateway Center. Please consult the security alert Web
site at http://www.nih.gov/about/visitorsecurity.htm.

We look forward to the upcoming Council session and hope that you will be
able to join us.

Disclaimer: Neither SARDAA nor SA, assume any legal liability, responsibility nor does inclusion of articles or comments constitute or imply its endorsement, recommendation, or favoring for the accuracy, completeness, or usefulness of any information, product or process disclosed in the blog.

Announcing New NIMH Statistics Resource

The National Institute of Mental Health (NIMH) is pleased to announce the
launch of its new statistics section on the web: http://www.nimh.nih.gov/statistics.

This resource represents the best mental health research information from
across the Department of Health and Human Services and other federal
departments, and places it all within an easy-to-navigate format. It is a
vast expansion from NIMH’s previous statistics pages and includes
information on the prevalence of mental disorders and treatment, mental
health-related disability, suicide, and the economic costs associated with
mental illness.

This new section is very much a living resource. It will continue to be
updated regularly as new mental health data from across the federal
government are reported and its format will continue to evolve in order to
ensure the most straightforward usability and clearest presentation of
information. We encourage you to explore this resource, to share it with
your affiliates and members, and to provide us with feedback about what
works and what else might be included or changed. Your thoughts and
feedback may be sent to NIMHstatistics@nih.gov.

Disclaimer: Neither SARDAA nor SA, assume any legal liability, responsibility nor does inclusion of articles or comments constitute or imply its endorsement, recommendation, or favoring for the accuracy, completeness, or usefulness of any information, product or process disclosed in the blog.

WANTED: A FEW GOOD ASSAYS

There has been much concern over the fate of medication development for mental disorders. Some have complained that there are no truly novel medications coming from the pharmaceutical companies in the past three decades. Others have worried that the recent departure of pharmaceutical companies from psychiatric medication development presages a long draught with no new medical treatments likely. Meanwhile results from the large NIMH-funded comparative effectiveness trials, like CATIE and STAR*D, remind us of the need for a new generation of medications. At NIMH, we have been discussing how we might catalyze the next generation of drug discovery and development. One way, we believe, is by creating assays to probe new molecular targets relevant to mental disorders and to screen for new medications. Judging from recent progress, this approach looks hopeful………

Thomas R. Insel, M.D.
NIMH Director
NIMH DIRECTOR BLOG
http://www.nimh.nih.gov/about/director/index.shtml#p118147


Disclaimer
: Neither SARDAA nor SA, assume any legal liability, responsibility nor does inclusion of articles or comments constitute or imply its endorsement, recommendation, or favoring for the accuracy, completeness, or usefulness of any information, product or process disclosed in the blog.

From Cognition to Genomics: Progress in Schizophrenia Research

This week’s issue of Nature has a special section dedicated to research progress on schizophrenia.i There have been few such issues dedicated to any medical disorder, so this is a landmark for schizophrenia research, a follow-up perhaps to an editorial in Nature at the beginning of this year predicting a “decade for psychiatric disorders”.ii But beyond the mere fact that schizophrenia has been singled out for this distinction, the contents document remarkable progress on a disorder that has been such a conundrum for the past century.

For one thing, schizophrenia can now be described as a brain disorder or, more precisely, as a disorder of brain circuits. With neuroimaging, several of the major nodes in the circuit have been identified, especially within the prefrontal cortex. A major advance has been linking changes in circuit function to cognition and behavior. As a result, we are increasingly focusing on the cognitive deficits of schizophrenia as the core problem, preceding and perhaps leading to the more obvious positive symptoms of hallucinations and delusions.

Another area of unambiguous progress has been genomics. Five years ago the field was frustrated by the lack of replicated findings. With the creation of international consortia sharing data from thousands of patients, we can now see several of the major risk genes. They are not the usual suspects, such as genes involved in dopamine or serotonin neurotransmission. Common variants in genes from the MHC complex, which is important for immune self-recognition, a gene for a transcription factor called TCF4, and several genes that encode synaptic proteins have all been found to confer increased risk. The list is probably not complete as together these explain only a fraction of the genetic risk for the disorder. Many rare variants have also been described in the past year, adding to the known major structural lesions like DISC1 and the 22q11 deletion. These rare events may explain only a small fraction of cases, but as with hypertension and cancer, even rare mutations that cause disease can yield important clues to the pathophysiology underlying more common forms of disease.

From genomics have come clues to the importance of reconceptualizing schizophrenia as a neurodevelopmental disorder. Many of the genetic factors are involved with neurodevelopment; hardly surprising as thousands of genes must be expressed in a carefully choreographed sequence to develop a healthy brain. What is unexpected is that many of the genetic variations associated with schizophrenia appear to disrupt fragments of proteins expressed only in fetal development……

Dr. Thomas Insel
NIMH Director
NIMH’s Director Blog
http://www.nimh.nih.gov/about/director/index.shtml#p115270

Disclaimer: Neither SARDAA nor SA, assume any legal liability, responsibility nor does inclusion of articles or comments constitute or imply its endorsement, recommendation, or favoring for the accuracy, completeness, or usefulness of any information, product or process disclosed in the blog.

BRAIN SCANS – NOT QUITE READY FOR PRIME TIME

http://www.nimh.nih.gov/about/director/2010/brain-scans-not-quite-ready-for-prime-time.shtml

Dr. Thomas Insel
Director’s Blog
NIMH Director

Submitted by Anna

Disclaimer: Neither SARDAA nor SA, assume any legal liability, responsibility nor does inclusion of articles or comments constitute or imply its endorsement, recommendation, or favoring for the accuracy, completeness, or usefulness of any information, product or process disclosed in the blog.

NATIONAL SURVEY CONFIRMS THAT YOUTH ARE DISPROPORTIONATELY AFFECTED BY MENTAL DISORDERS

About 20 percent of U.S. youth during their lifetime are affected by some type of mental disorder to an extent that they have difficulty functioning, according to a new NIMH survey published in the October 2010 issue of the Journal of The American Academy of Child and Adolescent Psychiatry. The data support the observation from surveys of adults that mental disorders most commonly start in early life.

http://www.nimh.nih.gov/science-news/2010/national-survey-confirms-that-youth-are-disproportionately-affected-by-mental-disorders.shtml

DIRECTOR’S BLOG POSTING: TAKING CLINICAL RESEARCH TO THE NEXT LEVEL

Last year, NIMH asked its National Mental Health Advisory Council to help the Institute consider how it could best develop new interventions. A workgroup of the Council met through the winter to discuss opportunities and challenges in treatment development. To inform the process, they developed a report, From Discovery to Cure: Accelerating the Development of New and Personalized Interventions for Mental Illness. Among their many suggestions was: (a) a call to develop the next generation of interventions, based on a better understanding of the disorders and (b) a call to optimize the use of current treatments based on a better understanding of individual differences in response.

Thomas Insel, M.D.
NIMH Director
http://www.nimh.nih.gov/about/director/index.shtml#p91707

Submitted by Anna

DIRECTOR’S BLOG POSTING: MICROBES AND MENTAL ILLNESS

Hints that some mental illness may be linked to infectious agents and/or autoimmune processes date back to at least the early 20th Century. In the 21st Century, the field of microbiomics, which is mapping the microbial environment of the human organism, may transform the way we think about human physical and mental development. It is already clear that 90% of “our DNA” is microbial, not human. “We” are, in fact, “super-organisms” made up of thousands of species, many of which are being identified for the first time. And there are persistent individual differences in our microbial ecology established early in life.

Thomas Insel, M.D.
NIMH Director
http://www.nimh.nih.gov/about/director/index.shtml#p98381

Submitted by Anna

MEETING SUMMARY–CLOSING THE GAPS: THE ROLE OF RESEARCH IN REDUCING MENTAL HEALTH DISPARITIES IN THE U.S.

On May 5, 2010, the Office for Research on Disparities and Global Mental Health in the Office of the Director of NIMH convened a meeting of representatives of key federal agencies and thought leaders from a range of fields—including genetics, cultural neuroscience, epidemiology, psychology, clinical psychiatry, and community-based services and intervention research—to discuss novel directions that, if investigated empirically, could foster the reduction of mental health disparities across race/ethnicity, socioeconomic status, and geography. http://www.nimh.nih.gov/research-funding/scientific-meetings/2010/closing-the-gaps-the-role-of-research-in-reducing-mental-health-disparities-in-the-us.shtml

Submitted by Anna