7thSpace is the source of this article IS PATERNAL AGE RESPONSIBLE FOR THESE CNVs?

Researchers pinpoint gene mutations responsible for 10 percent of schizophrenia


NEW YORK – Scans of the genome of patients with schizophrenia have revealed rare spontaneous copy number mutations that account for at least 10 percent of the non-familial cases of the disease. Researchers describe specific genetic mutations present in individuals who have schizophrenia, but not present in their biological parents who do not have the disease. These individuals were eight times more likely to have these mutations than unaffected individuals. This new data, reported in the May 30 on-line issue of Nature Genetics, will help researchers account for the persistence of schizophrenia in the population despite low birth rates among people with the disease.

Researchers at Columbia University Medical Center scanned the genome of 1,077 people which included 152 individuals with schizophrenia, 159 individuals without schizophrenia, and both of their biological parents for copy number mutations. They found mutations, either a gain or loss of genes, in 15 individuals diagnosed with schizophrenia that were not present in the chromosomes of either biological unaffected parent. Only two of such mutations were found in those without schizophrenia. Study subjects were from the European-origin Afrikaner population in South Africa, a genetically homogenous population that is ideal for genetic evaluation.

“We now know the cause of around 10 percent of the cases of sporadic schizophrenia,” said Maria Karayiorgou, M.D., professor of psychiatry, Columbia University Medical Center, the senior author on the study. “Schizophrenia is not as much of a ‘big black box’ as it used to be. The identification of these genes lets us know what brain development pathways are involved in disease onset, so that in the future we can look at better ways of treating this devastating disease.”

Schizophrenia affects approximately 1 percent of the population worldwide. About 40 percent of the disease is thought to be inherited, with the other 60 percent sporadically showing up in people whose family history does not include the disease.

One of the new or de novo mutations researchers found in more than one affected individual in this study was a deletion of a region of chromosome 22. Dr. Karayiorgou had previously provided evidence that loss of genes in this region, 22q11.2, was responsible for introducing “new” or sporadic cases of schizophrenia in the population. This confirms 22q11.2 as the only known recurrent such mutation linked to schizophrenia.

“We have already demonstrated 22q11.2 to be involved in sporadic schizophrenia and we have made considerable progress in understanding the underlying biological mechanisms,” said Dr. Gogos. “Now, we have a new set of mutations that we can investigate. The more information we have about the biological basis for this disease, the more information we can provide to those who suffer from it and their families.”

“Such abnormal deletions or duplications of genetic material are increasingly being implicated in schizophrenia and autism,” explains National Institute of Mental Health Director Thomas R. Insel, M.D. “Now we have a dramatic demonstration that genetic vulnerabilities for these illnesses may stem from both hereditary and non-hereditary processes. This line of research holds promise for improved treatments – and perhaps someday even prevention – of developmental brain disorders.”

Karayiorgou and co-senior author Joseph A. Gogos, M.D., Ph.D., associate professor of physiology and neuroscience at Columbia University Medical Center, agree that the goal is for psychiatrists to be able to inform patients that they have a mutation that is causing their disease and ultimately to be able to tailor treatments to individual patients based on their specific mutation. This tailored treatment is a ways off, according to Dr. Karayiorgou, but she says patients and their families are relieved to know that there is a biological cause of their illness.

The researchers plan to extend their screen for additional de novo mutations by using increased resolution scans to study additional families. They also plan to scrutinize further genes affected by the identified mutations through human genetics and animal model approaches.


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The first author of this study, Bin Xu, is also from CUMC. Co-authors include J. Louw Roos from the Department of Psychiatry and Elizabeth J. van Rensburg from the Department of Genetics at the University of Pretoria in Pretoria in South Africa, and Shawn Levy from the Microarray Shared Resource at Vanderbilt University in Nashville, Tenn.

This study was supported by the National Institutes of Health’s (NIH) National Institute of Mental Health (NIMH) and the Lieber Center for Schizophrenia Research at Columbia University Medical Center.


Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future health care leaders at the College of Physicians & Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia’s College of Physicians & Surgeons was the first in the country to grant the M.D. degree. CUMC is home to the largest medical research enterprise in New York state and one of the largest in the United States. Visit www.cumc.columbia.edu.

Columbia Psychiatry is ranked among the best departments and psychiatric research facilities in the nation and has contributed greatly to the understanding of and current treatment for psychiatric disorders including depression, suicide, schizophrenia, bipolar and anxiety disorders, and childhood psychiatric disorders. Located at the New York State Psychiatric Institute on the NewYork-Presbyterian Hospital/Columbia University Medical Center campus in the Washington Heights community of Upper Manhattan, the department enjoys a collaborative relationship with physicians in various disciplines at Columbia University’s College of Physician and Surgeons. Visit http://columbiapsychiatry.org/.


Susan Craig
sc2756@columbia.edu
212-305-9746
Columbia University Medical Center


Published on: 2008-05-31


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National Institute of Mental Health Has No Interest in Prevention of Autism

Somehow I cannot believe that Harry and Laura Slatkin would not want future parents to know what the real risk factors are for having an autistic child. They know very well the true horror of autism. David is getting the finest help imaginable but money cannot buy a way to ameliorate his condition. I do believe that if it had been made very clear to them that fathering babies past 40 (33-35 and up) was a strong risk for autism and how the risk grows with increasing with paternal age, Harry and Laura Slatkin might have made different decisions regarding parenthood. If all men knew the truth about the male biological clock, and more precise information was added to what is already known, men might be convinced not to father babies past the age of 35. They might realize the extent of the problem of gene DNA mutations in sperm. Life studies of children of men 34 and over should be done and the true extent of genetic disorders exposed.



In 2003 Slatkin and his wife co-founded the New York Center for Autism (NYCA), a not-for-profit organization dedicated to increasing the availability and quality of intensive, science-based educational programs for children with autism living in New York City, consisting of a school, an outreach program and a research facility.


. Insel oversees the NIMH’s $1.3 billion research budget that provides support to investigators at universities throughout the country in the areas of basic science; clinical research, including large-scale trials of new treatments; and studies of the organization and delivery of mental health services. The Institute also administers an in-house research program at the NIH Bethesda. NIMH was authorized in 1946 as one of the first NIH institutes. The Institute’s mission is to reduce the burden of mental illness and behavioral disorders through research on mind, brain, and behavior.


Comments
An Interview with Thomas Insel,
Director of the National Institute of Mental Health



He is so focused on biomedical research he doesn't go near behavioral biological genetic reasons for autism or schizophrenia. It is why he got the job.

THEY ARE NOT COMBATING AUTISM UNLESS THEY SHOW HOW INCREASING PATERNAL AGE AND AUTISM GO HAND IN HAND

NO ONE AT THE CDC IS INTERESTED IN COMBATING/PREVENTING AUTISM


FATHERING BABIES BEFORE 35 WOULD CUT THE RATE OF SPORADIC AUTISM WAY DOWN WHY DOESN'T THE CDC MENTION PATERNAL AGE?

THE MEETING IS FOR THOSE WHO PROFIT FROM AUTISM - NO ONE IS TRYING TO PREVENT AUTISM



Surprise Senate Hearing on Combating Autism - Community Not Notified

We learned for the first time Thursday that the Senate has scheduled a hearing Tuesday, April 17, 2007 entitled "Combating Autism: Undertaking a Coordinated Response". There was no notice of this hearing to the many autism organizations other than Autism Speaks and possibly ASA. We learned of it only because one of our CAA Watch A-CHAMP District Leaders inadvertently heard of the hearing from a highly placed source.

Many of us have placed calls to Subcommittee Chair Sen. Harkin's staff, including members of our strong Iowa contingent. None of us have had the courtesy of a return phone call.

The list of witnesses is pasted below.

On the second panel are two representatives of Autism Speaks and Dr. Judy Favell, former President of the American Psychological Association, Division 33. Dr. Favell is a behaviorist who received a large Dept of Education grant to research the provision of services to children with autism by interactive video. The program, called "telehealth" involves installing a video camera in one's home so that families may engage in therapy sessions at long distrance by video.

Dr. Favell appears to be closely associated with three for-profit ventures. One is Advoserv (www.advoserv.com), a Florida corporation that provides residential and other services in Florida, Delaware, Maryland and New Jersey. The second is Cnow, billed as committed to being the "nation's premier telehealth solutions provider." (http://www.cnowinc.com/) The third venture is the National Institute of Telehealth, which develops the behavioral treatment plan that is implemented via video. Telehealth and telemedicine research is being funded by NIMH, headed by Dr. Insel, one of the witnesses at the hearing. (http://tinyurl.com/2uzyje)



No stakeholders are participating in this hearing.
Welcome to the BRAVE NEW WORLD of autism.

Senate Committee on Appropriations
Hearing Schedule for the Week of April 13, 2007

For more information, media should contact (202) 224-3904.

Tuesday April 17, 2007
2:00 p.m. Labor, Health and Human Services, and Education SD-124
Agenda: Combating Autism: Undertaking a Coordinated Response

Witnesses: Panel I:
Dr. Julie Gerberding, Director
Centers for Disease Control and Prevention
Atlanta, Georgia
Dr. Thomas R. Insel, Director
National Institute of Mental Health
Bethesda, Maryland

Panel II:
Robert C. Wright
Vice Chairman and Executive Officer
General Electric Foundation
Fairfield, Connecticut
Dr. Judith E. Favell
Chief Executive Officer, AdvoServ
Executive Director, The Celeste Foundation
Mount Dora, Florida
Bradley Whitford
Volunteer Spokesperson
for Autism Speaks Organization
New York, New York



Is Thomas Insel serious that he doesn't know that advancing paternal age causes autism and so does a mother with an older father at her birth? Thomas Insel doesn't know that a family history of autoimmume disorders such as type 1 diabetes and Hashimoto's thyroiditis is a major risk factor for having a child with autism. Does Thomas Insel not know that childhood schizophrenia and autism are associated with older and especially older fathers? This is not credible. Does Thomas Insel not know that a public health warning on paternal age over 33 would greatly reduce sporadic autism? I am sure he knows.




Keynote Address #1
Autism: What do we know? What do we need?
Thomas Insel, NIMH/NIH
Since the first IMFAR meeting in 2001, autism has received increased commitment from the
research community, increased cooperation among advocacy groups, and increased awareness in
the public. Nevertheless, we still know very little about the pathophysiology of this illness. Autism
is a developmental brain disease, but we do not know what the ‘lesion’ looks like. Autism is a
genetic disorder, but we have not identified genes of major effect nor have we found many of the
associated alleles. Recent reports document increased prevalence (not incidence) for autism, but
we have yet to identify a single environmental risk factor to explain this increase. And finally,
autism is considered by many experts to be a cluster of disorders, but we have no consistent
approach for sub-typing the various ‘autisms’ into valid syndromes.
While advances are being made on all of these fronts, to maximize progress we will need a
coordinated, strategic effort. In spite of flat budgets at NIH, the research community will need (a)
to expand to include developmental neurobiologists and others who can bring powerful new tools
to autism research, (b) to build cooperative research networks that can share protocols and data
across labs via a common database, and (c) to partner with advocacy groups and families to ensure
that research is relevant and results are disseminated. We There is also an urgent need for studies
to delineate the biological and behavioral subtypes of this complicated disorder so that we can
identify the genetic, environmental, and interactive etiologies of autism, and develop new
treatments and preventive strategies.