Scientists breed first mentally ill mouse

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Now ya can test yer mice at home...

Home bipolar disorder test causes stirs
Sat Mar 22, `08 - Dr. John Kelsoe has spent his career trying to identify the biological roots of bipolar disorder. In December, he announced he had discovered several gene mutations closely tied to the disease, also known as manic depression.

Then Kelsoe, a prominent psychiatric geneticist at the University of California, San Diego, did something provocative for the buttoned-down world of academic medical research: He began selling bipolar genetic tests straight to the public over the Internet last month for $399. His company, La Jolla-based Psynomics, joins a legion of startups racing to exploit the boom in research connecting genetic variations to a host of health conditions. More than 1,000 at-home gene tests have burst onto the market in the past few years.

The proliferation of these tests troubles many public health officials, medical ethicists and doctors. The tests receive almost no government oversight, even though many of them are being sold as tools for making serious medical decisions. Health experts worry that many of these products are built on thin data and are preying on individuals' deepest anxieties.

"People are always rushing to the market on the basis of one or two studies," said Dr. Muin Khoury, director of the National Office of Public Health Genomics at the Centers for Disease Control and Prevention. "We have very little evidence that telling people their genetic information is going to make any difference." Tests have become available claiming to help predict and diagnose everything from serious illnesses like cancer and Alzheimer's to athletic ability and a person's ideal diet. Psynomics' offering is one of the first psychiatric gene tests on the market.

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Schizophrenia suspected as genetic disorder...

Genetic underpinnings of schizophrenia revealed
Thu Mar 27, 2008 WASHINGTON - The devastating mental illness schizophrenia may be caused by many different mutations in many different genes that disrupt biological pathways vital to normal brain development, scientists said on Thursday.

Schizophrenia is a complex disorder marked by delusions, hallucinations and disordered thinking that appears in about 1 percent of all adults. Experts long have struggled to grasp its causes and the role of genetics and environmental factors. Two teams of researchers published new genetic insights in the journal Science. Their findings suggest that instead of one crucial gene or a handful, a myriad of different glitches in many genes could be responsible for schizophrenia.

DNA deletions and duplications that disrupt genes are far more common in schizophrenics, the researchers found. These disrupted genes often are related to pathways critical for brain development. They involve creating the infrastructure in which neurons communicate, as well as such functions as neuronal growth and migration and cell death. "You're basically screwing up the way that the regulation of brain growth occurs," said Dr. Jon McClellan of the University of Washington in Seattle, one of the researchers.

Researchers at the University of Washington and Cold Spring Harbor Laboratory in Cold Spring Harbor, New York, looked at DNA from 150 schizophrenics and from 268 healthy people. These genetic deletions and duplications were present in 15 percent of schizophrenics and only 5 percent of healthy people.

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UW study finds surprising genetic causes of schizophrenia
March 27, 2008 - Errors in DNA don't seem to follow pattern

As if the science of how genetics leads to disease isn't already complex enough, researchers in Seattle and Long Island, N.Y., say individuals appear to develop schizophrenia from a varying smorgasbord of bad genes rather than common genetic flaws. Scientists at the University of Washington and Cold Spring Harbor Laboratory report in Friday's edition of the magazine Science that multiple errors or deletions in a person's genetic code, or DNA, can lead to schizophrenia -- a psychiatric illness characterized by delusions and disordered thinking that today affects one of every 100 people.

The finding that multiple genes are involved is, by itself, not surprising, since other diseases or disorders are, or strongly appear to be, the result of many flaws rather than just a single bad gene. That fits nicely within the standard dogma of genetics. What is surprising, challenging to the dogma and perhaps confusing to many experts who study the interplay between genetics and neuroscience, is that the UW-Cold Spring Harbor team found strong evidence that it's usually not the same set of genes going bad in people who develop schizophrenia.

"It's different genes in different people," said Dr. Jon "Jack" McClellan, a UW psychiatrist and a co-author of the report. This is a big challenge to the conventional wisdom, McClellan said, adding that he believes this could turn out to be the same for most other complex psychiatric diseases -- if not for all diseases that arise without a simple genetic flaw. "The standard dogma is that any complex trait (such as mental illness) is going to be caused by the cumulative effect of multiple, common defects," said Dr. Mary-Claire King, a world-renowned geneticist and also one of the UW co-authors on the report. "But that's not what we found."

More UW study finds surprising genetic causes of schizophrenia

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Too many bipolar diagnoses?

Is bipolar disorder overdiagnosed?
May 6, 2008 - A new study by Rhode Island Hospital and Brown University researchers reports that fewer than half the patients previously diagnosed with bipolar disorder received a diagnosis of bipolar disorder based on a comprehensive, psychiatric diagnostic interview--the Structured Clinical Interview for DSM-IV (SCID).

The study concludes that while recent reports indicate that there is a problem with underdiagnosis of bipolar disorder, an equal if not greater problem exists with overdiagnosis. The study was published online by the Journal of Clinical Psychiatry. Principle investigator Mark Zimmerman, M.D., will present the findings at the annual meeting of the American Psychiatric Association on Wednesday, May 7.

The study method involved 700 psychiatric outpatients who were interviewed using the SCID and completed a self-administered questionnaire between May 2001 and March 2005. The questionnaire asked patients whether they had been previously diagnosed with bipolar or manic-depressive disorder by a health care professional. Family history of bipolar disorder was used as an index of diagnostic validity.

Of the 700 patients, 145 reported they had been previously diagnosed as having bipolar disorder; however, fewer than half of the 145 patients (43.4 percent) were diagnosed with bipolar disorder based on the SCID. Further, the study showed that patients diagnosed with bipolar disorder based on the SCID had a significantly higher morbid risk of bipolar disorder in first-degree relatives.

Unnecessary side effects are a significant concern of overdiagnosis. Because mood stabilizers are the treatment of choice for bipolar disorder, overdiagnosing can unnecessarily expose patients to serious medication side effects, including possible impact to renal, endocrine, hepatic, immunologic and metabolic functions.

More Is bipolar disorder overdiagnosed? | Science Codex

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Child's autism linked to parents' mental illness
Mon., May. 5, 2008 - Having a schizophrenic parent roughly doubles risk of disorder, study finds

In another sign pointing to an inherited component to autism, a study released on Monday found that having a schizophrenic parent or a mother with psychiatric problems roughly doubled a child's risk of being autistic. "Our research shows that mothers and fathers diagnosed with schizophrenia were about twice as likely to have a child diagnosed with autism," said Julie Daniels of the University of North Carolina, Chapel Hill, who worked on the study.

"We also saw higher rates of depression and personality disorders among mothers, but not fathers," she said in a statement. The study of families in Sweden with children born between 1977 and 2003 involved 1,227 children diagnosed with autism. They were compared with families of nearly 31,000 children who did not have autism. Sweden's detailed health registry provides a wealth of data for such studies.

Autism, which is marked by impaired social interaction and communication, or a related disorder like Asperger's syndrome, affects an estimated one out of every 150 U.S. children, the U.S. Centers for Disease Control and Prevention estimates. Asperger's is marked by mild social awkwardness. No one knows what causes autism, but researchers think it is likely that several genes and possibly environmental factors contribute. Some autism advocates believe childhood vaccinations play a role, although most medical experts say it is extremely unlikely.

Which genes lie behind various mental illnesses are also poorly understood, according to the researchers, whose study appeared in the journal Pediatrics, published by the American Academy of Pediatrics. "Earlier studies have shown a higher rate of psychiatric disorders in families of autistic children than in the general population," Daniels said.

More Child's autism linked to parents' mental illness - Mental health - MSNBC.com

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Missing DNA link to schizophrenia...

Missing DNA chunks tied to schizophrenia risk
Wed., July. 30, 2008 - Huge international gene screen ties batch of deletions to 15-fold higher risk

Two huge international studies show that people who lack certain chunks of DNA run a dramatically higher risk of getting schizophrenia, a finding that could help open new doors to understanding and diagnosing the disease. These deletions are rare, each found in less than 1 percent of schizophrenia patients. But each one boosts the risk of disease by as much as 15-fold, by one estimate.

Scientists said studying such abnormalities may help them find new medications by shedding light on what causes the disease. And if enough rare aberrations can be found eventually, they may be combined into a test to help in diagnosis, said Kari Stefansson, chief executive officer of deCode Genetics of Reykjavik, Iceland, and an author of one of the studies.

Schizophrenia is currently diagnosed by its symptoms. The human DNA can be thought of as a very long string of letters — about 3 billion of them — that sometimes form words (genes). Each newly identified deletion removes a section of about half a million to 2 million letters.

Major impact

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Low grades in school could indicate latent schizophrenia...

Low marks linked to schizophrenia
Saturday, 9 August 2008 - Poor performance at school could indicate an increased risk of developing schizophrenia, a study says.

UK and Swedish researchers followed more than 900,000 children born between 1973 and 1983. The Psychological Medicine paper found getting an E grade in any GCSE-stage exam was linked to a doubling of the small risk of developing schizophrenia. But a mental health charity said the illness was often linked with high, rather than low, intelligence. Schizophrenia, which commonly causes people to hear voices and experience paranoid delusions, often becomes evident in the late teens or early 20s.

Repeating years

The researchers, from the Institute of Psychiatry at King's College London, and the Karolinska Institute in Stockholm, looked at Swedish data on exam results taken at the age of 15 or 16. They then looked at hospital data on admissions for psychotic disorders including schizophrenia after the age of 17. "The people in the study might have had normal intelligence but started having low-level symptoms that disrupted their schooling" - Hilary Caprani, Rethink

Sweden has comprehensive national registers, with every individual having their own identification code, so the data could be compared. The general risk for an adult to be diagnosed with schizophrenia in any given year is seven in 100,000. Getting an E grade in any of the 16 subjects looked at by the researchers was linked to a doubling of that risk. The researchers found those with the poorest school performance overall had four times that risk of developing schizophrenia when they were adults. Other studies have shown that there is a link between schizophrenia and earlier problems with learning or understanding. However, the researchers said other factors were probably involved.

'Low-level symptoms'

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Bipolar genetic link...

Genetic traits linked to bipolar disorder
Sun., Aug. 17, 2008 WASHINGTON - Discovery of two influential genes could lead to better treatment

Two genes that influence the activity of nerve cells in the brain may play a key role in a person's risk for bipolar disorder, marked by dramatic swings from depression to manic behavior, researchers said on Sunday. The findings are not expected to lead to a genetic test for the risk of the condition but could help unravel the mystery of how it arises and lead to better treatments, they reported in the journal Nature Genetics. An international team of scientists examined the genomes of 10,596 people mainly from Britain and the United States, including 4,387 with bipolar disorder, also sometimes known as manic-depression.

The researchers found those with bipolar disorder more likely to have certain variants of the ANK3 and CACNA1C genes. Proteins made by the two genes help govern the flow of sodium and calcium ions into and out of neurons in the brain, influencing the activity of these nerve cells. "The key importance of this is that it gives us a clear idea of the sorts of chemicals and mechanisms in the brain that are involved in bipolar disorder," Nick Craddock of Britain's Cardiff University, who helped lead the study, said in a telephone interview.

"Over a number of years, that will help researchers to develop better approaches to diagnosis and treatment." Because it tends to run in families, scientists have been trying to pinpoint genes involved in bipolar disorder. This was the largest genetic analysis of its kind on the disease, which affects an estimated 1 percent to 3 percent of adults worldwide, Craddock said. The brain disorder causes extreme shifts in mood, energy and ability to function. It is marked by high periods of elation or irritability and low periods of sadness and hopelessness that can last months.

EQUILIBRIUM

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Anti-psychotic stroke risk...

Antipsychotic drug 'stroke risk'
Thursday, 28 August 2008 - More people than previously thought could be at higher risk of a stroke from antipsychotic drugs, a study claims.

Previous research suggested only some types of the drug increased the risk, particularly for people with dementia. However a study published in the British Medical Journal says all forms of antipsychotics boost the risk, in all patients. A mental health charity said patients on the drugs must be closely monitored. "This is another warning that all antipsychotics should be prescribed with great thought and care " - Marjorie Wallace, Sane

Antipsychotic drugs are generally used to control psychotic symptoms in patients with disorders such as schizophrenia, and some severe forms of depression. They are also thought to be widely used to control symptoms of dementia such as aggression, leading to accusations they were being used unnecessarily as a "chemical cosh" in some circumstances. They fall into two types - newer "atypical" and older "typical" antipsychotics. When the first concerns were raised in 2002, these focused on the "atypical" drugs.

These worries led to a recommendation from drug safety watchdogs in the UK that they not be given to people with dementia, and the government has been urged to strengthen this in England in its forthcoming dementia strategy. The latest findings, from researchers at the London School of Hygiene and Tropical Medicine, confirm the fears over dementia patients, but raise wider concerns.

They identified 6,700 patients from a GP database, all with an average age of 80, and concluded that there was more than a tripling of risk for dementia patients taking any sort of anti-psychotic drug. Patients without dementia taking any sort of antipsychotic had a 40% increase in risk. The researchers repeated the recommendation that patients with dementia should not be prescribed these drugs.

'Last resort'

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Prob'ly `cause older fathers are more likely to be further along in their drinking...

Older fathers linked with bipolar
Monday, 1 September 2008 - Older fathers are more likely to have children with bipolar disorder than younger men, research suggests.

The risk goes up when men are older than 29 before they start their family, and is highest if they are over 55. Increasing paternal age has already been linked with schizophrenia and autism, but not bipolar disorder, formerly known as manic depression. The Swedish study, in Archives of Psychiatry, suggests the risk may, in part, be explained by ageing sperm.

DNA errors

Unlike women who are born with all their eggs, men make new sperm throughout their adult life. The process of making sperm involves copying DNA, and this is prone to error, particularly as men age, say the Karolinska Institute researchers.

Bipolar disorder

* People with bipolar disorder fluctuate between intense depression and mania, interspersed by periods of relative calm
* The exact causes of bipolar disorder aren't known, but it appears to run in families
* About 1 in every 100 people develop bipolar disorder in their lifetime

Lead researcher Emma Frans explained: "Women are born with their full supply of eggs. Therefore, DNA copy errors should not increase in number with maternal age." Consistent with this notion, they found smaller effects of increased maternal age on the risk of bipolar disorder in the families they studied. For the study, they identified 13,428 patients in Swedish registers with a diagnosis of bipolar disorder. For each one they randomly selected from the registers five controls who were the same sex and age but did not have bipolar disorder.

Older dads

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Antidepressants help reduce teen suicides...

Teen Suicide Rate "Very Disturbing"
Sept. 2, 2008 - Experts Say There Is A Connection Between A Reduction In The Use Of Antidepressants And Suicide

The number of teen suicides has fallen slightly, but the rate remains disturbingly high, possibly fueled by drug warnings that have scared many from using antidepressants. The suicide rate was about 4.5 per 100,000 in 2005, the most recent data available. That follows an 18 percent spike the previous year that alarmed experts when first reported. That's because until then, suicides among 10- to 19-year-olds had been on a steady decline since 1996. Dr. David Fassler, a psychiatry professor at the University of Vermont, said the report suggests a "very disturbing" upward trend that correlates with a decline in teen use of antidepressants.

That decline stems from the Food and Drug Administration's 2004 black-box warning label because of reports that the drugs can increase risks for suicidal tendencies. Fassler, who wasn't involved in the new study, is among psychiatrists who believe the drugs' benefits, including treating depression that can lead to suicide, outweigh their risks. He said he has no financial ties to makers of antidepressants. The new report shows the rate dropped by about 5 percent from 4.7 in 2004 - or from 1,983 suicides in 2004 to 1,883 in 2005.

That's still 600 more suicides than would have been expected had the earlier trend continued, said lead author Jeffrey Bridge, a researcher at Nationwide Children's Hospital in Columbus, Ohio. Patrick Tolan, director of the University of Illinois-Chicago's juvenile research institute, said it will be important to continue tracking teen suicides to see if the rate continues to decline or hovers at a higher than expected level. Regardless, suicide remains a leading cause of teen deaths and "a major public health issue," he said.

Teen Suicide Rate "Very Disturbing", Experts Say There Is A Connection Between A Reduction In The Use Of Antidepressants And Suicide - CBS News

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New meds not more effective than old ones...

Newer Drugs No Better Than Older Ones for Childhood Schizophrenia
MONDAY, Sept. 15,`08 -- Newer antipsychotic medications are no better at relieving symptoms of schizophrenia in children and adolescents than older antipsychotic medications are, a new study finds.

The assumption has been that the newer drugs are safer and more effective; however, earlier trials found they are no more effective than the first-generation drugs, and they have different side effects than the older drugs, said Dr. Thomas R. Insel, director of the National Institute of Mental Health, which funded the study. "This new trial looks at children where these new antipsychotics have been more widely used in the last five to eight years. The question was: Are these new drugs a better choice for children?" Insel said.

In the trial, researchers did not find any significant difference between older and newer antipsychotics, except for the side effects. "All three of the antipsychotics we tested seemed to significantly reduce symptoms of schizophrenia in children and adolescents," said study author Dr. Linmarie Sikich, an assistant professor of psychiatry at the University of North Carolina at Chapel Hill. "But they have very different side effects. And none of them look any better than the others in terms of how much they reduce symptoms or how quickly they reduce symptoms."

Current guidelines for treating early-onset schizophrenia recommend using the newer drugs first, Sikich said. "We think this study says you should seriously consider using the older drug first," she said. "Physicians really need to make an individual decision based on what side effects are likely to be most concerning -- what is problematic for their particular patient. Many people are going to have to try a few drugs to find which is best for them." In addition, Sikich noted there was no difference between the older and newer drugs in how long people continue to take them. The report was published in the Sept. 15 online edition ofThe American Journal of Psychiatry.

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