Schizophrenia - Single Genetic Changes In Two Genes Raise Risk

Editor's Choice
Academic Journal
Main Category: Schizophrenia
Also Included In: Psychology / Psychiatry;  Genetics
Article Date: 15 Dec 2011 - 8:00 PST

email to a friend   printer friendly   opinions  

According to a study by Johns Hopkins investigators published in the Nov. 16 issue of Neuron, the risk of developing schizophrenia may be increased by carrying single DNA letter changes from two different genes.

Researchers have found identifying the causes for psychiatric diseases like autism and schizophrenia difficult as they might be activated by several small genetic alterations. Individually these small genetic alterations may be insufficient to cause any change, but in the right combination may cause psychiatric disease.

Schizophrenia, as well as other major mental disorders, is known to be caused by extreme DNA alterations in the genetic letters of the DISC1 gene. These drastic alterations are rare and do not apply to most of individuals with schizophrenia. DISC1 is considered a starting point for investigating the cause of schizophrenia. Defects in DISC1 together with defects in other genes might contribute to disease.

Guo-li Ming, M.D., Ph.D., professor of neurology and neuroscience and member of the Johns Hopkins Institute for Cell Engineering, explained:

"We studied the function of two proteins known to interact, FEZ1 and DISC1, in cells and animal models, which suggested that these proteins work together in adult brain development. When we looked at the human genetic sequences of DISC1 and FEZ1, we found that a combination of small DNA changes raises risk for schizophrenia."

The team used molecular biology methods to lower the amount of FEZ1 in the new neurons in the adult mouse hippocampus, the researchers then analyzed the cells under a microscope in order to find out if DISC1 and FEZ1 collaborate in adult brain development. The neurons with less FEZ1 were bigger and had longer feelers and looked similar to cells with less DISC1. Neurons use feelers to find and communicate with other nearby neurons. According to the investigators these proteins may be collaborating in neurons in order to control feeler length and cell size. Disruption of this process may cause psychiatric diseases.

In order to see if combinations of single-letter DNA alterations in FEZ1 and DISC1 made individuals more susceptible to schizophrenia, the researchers examined existing cases of the disease and analyzed a large patient database, the Genetic Association Information Network, produced by the National Institutes of Health to identify genome associated diseases. They used statistical methods to analyze 4 different single-letter DNA alterations in the FEZ1 sequence from 1,378 healthy individuals and 1,351 individuals with schizophrenia.

Individually, single-letter DNA alterations in FEZ1 did not contribute to the risk of developing the disease. Although, when they examined these 4 different FEZ1 DNA letter alterations together with a DISC1 single DNA letter alteration already known to slightly increase the risk of schizophrenia, they discovered that one particular FEZ1 DNA alteration combined with the DISC1 alteration dramatically increased the risk of developing the disease by two and half times.

Hongjun Song, Ph.D., professor of neurology and director of the Stem Cell Program at the Institute for Cell Engineering, explained:

"By continuing to examine interactions of key genes involved with disease in cells and correlating the results with patient databases, we can begin to unravel the genetic contributions of psychiatric disorders that previously were a mystery to us,Finding sets of proteins, like FEZ1 and DISC1, that synergistically work together to cause disease will also give us new drug targets to develop new therapies."

Written by Grace Rattue
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

Visit our schizophrenia section for the latest news on this subject. Please use one of the following formats to cite this article in your essay, paper or report:

MLA

Grace Rattue. "Schizophrenia - Single Genetic Changes In Two Genes Raise Risk." Medical News Today. MediLexicon, Intl., 15 Dec. 2011. Web.
15 Dec. 2011. APA

Please note: If no author information is provided, the source is cited instead.

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam)

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.

View the original article here

ADHD Drugs Do Not Raise Stroke, Heart Attack Or Sudden Cardiac Death Risk

Editor's Choice
Academic Journal
Main Category: ADHD
Also Included In: Cardiovascular / Cardiology;  Psychology / Psychiatry
Article Date: 12 Dec 2011 - 11:00 PST

email to a friend   printer friendly   opinions  

Young and middle-aged adults who are prescribed ADHD (attention deficit/hyperactivity disorder) drugs do not have a higher chance of developing serious cardiovascular events, such as sudden cardiac death, heart attack or stroke, researchers from Kaiser Permanente Northern California, Oakland, reported in JAMA (Journal of the American Medical Association).

The authors explained that there had been concerns regarding the cardiovascular consequences of taking ADHD medications. This is because they can raise the patient's heart rate and blood pressure.

However, this latest study, involving 150,359 adults with ADHD, found no higher risk of having a cardiovascular event in people taking ADHD medications compared to those who don't. All the adults were young to middle-aged.

The findings of this study are being published ahead of schedule because of their public health importance.

The authors explained:

"Between 2001 and 2010, use of medications labeled for treatment of ADHD increased even more rapidly in adults than in children. According to a 2006 U.S. Food and Drug Administration (FDA) advisory committee briefing on the safety of ADHD medications, more than 1.5 million U.S. adults were taking stimulants in 2005, and adults received approximately 32 percent of all issued prescriptions.

Placebo-controlled studies in children and adults indicate that stimulants and atomoxetine [a medication used to treat ADHD] elevate systolic blood pressure levels by approximately 2 to 5 mm Hg and diastolic blood pressure levels by 1 to 3 mm Hg and also lead to increases in heart rate. Although these effects would be expected to slightly increase risk for myocardial infarction [MI; heart attack], sudden cardiac death (SCD), and stroke, clinical trials have not been large enough to assess risk of these events."

Laurel A. Habel, Ph.D., and team set out to determine whether taking ADHD medications during adulthood might be linked to a higher risk of stroke, heart attack or sudden cardiac death (SCD). They gathered data from four computerized health records at four different sites - the earliest site started in 1986, they all ended in 2005. They also used data from a 2007 survey.

All the study participants were aged from 25 to 64 years, who had been taking various ADHD medications which included amphetamine, atomoxetine, or methylphenidate. They matched each ADHD medication user to two non-users in each study site, by sex, birth date, and calendar year. In total, including users and non-users, the study looked at 443,198 individuals.

They reported a total of 1,357 heart attacks, 296 sudden cardiac deaths, and 575 strokes during follow-up.

After examining the data and analyzing them, they found no statistically significant difference in risk between the users and non-users of ADHD medications for the three serious cardiovascular events.

The researchers wrote:

"We also found little support for an increased risk for any specific medication or with longer duration of current use. Results were similar when users were restricted to new users. Rate ratios did not appear to be influenced by prior cardiovascular disease or by prior non-ADHD psychiatric conditions. They also were similar across age groups.

As expected, event rates were substantially higher in the Medicaid population; however, the rate ratio for current use was similar to that in other sites."

Risk of cardiovascular events were no different for one-off, medium and short term users, during their period of taking their medications and for periods over 12 months after discontinuing. There was a similar or very slightly increased risk in new users compared to non-users.

The authors emphasized that they could not rule out a modest rise in serious cardiovascular events, because of some limitations in the study, which did not have full information on a number of factors which could have influenced the results, as well as other factors associated with ADHD drug usage.

Philip Shaw, M.D., Ph.D., who used to work at the NIMH (National Institute of Mental Health) and is now with the Human Genome Research Institute, said the study's findings have raised a number of clinically important issues:

"First, the findings support the final decision by the FDA in 2006 not to place a black box warning of serious cardiovascular events on ADHD medications for all children and adults but to pursue further research. The findings, however, do not directly inform the current black box warning for psychostimulants, which is confined to patients with structural heart lesions.

The study focused on very rare events, which prevented examination of specific subgroups such as individuals with cardiac disease. Joint care by cardiologists and other physicians remains necessary for these individuals.

In addition, the study provides no evidence to support routine obtaining of electrocardiograms before starting treatment, certainly insofar as this recommendation was driven by concerns about serious cardiovascular events."

Written by Christian Nordqvist
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

Visit our adhd section for the latest news on this subject. "ADHD Medications and Risk of Serious Cardiovascular Events in Young and Middle-aged Adults"
Laurel A. Habel et al
JAMA. Published online December 12, 2011. doi: 10.1001/jama.2011.1830 Please use one of the following formats to cite this article in your essay, paper or report:

MLA

Christian Nordqvist. "ADHD Drugs Do Not Raise Stroke, Heart Attack Or Sudden Cardiac Death Risk." Medical News Today. MediLexicon, Intl., 12 Dec. 2011. Web.
12 Dec. 2011. APA

Please note: If no author information is provided, the source is cited instead.

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam)

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.

View the original article here

Prostate Cancer - Androgen Deprivation Therapy Does Not Raise Cardiovascular Death Risk

Editor's Choice
Academic Journal
Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Cancer / Oncology
Article Date: 08 Dec 2011 - 7:00 PST

email to a friend   printer friendly   opinions  

A study published in the December issue of JAMA shows that even though earlier investigations suggested that androgen deprivation therapy designed to inhibit the production of male sex hormones for the treatment of prostate cancer may increase mortality risk from cardiovascular causes, researchers of a meta-analysis of previous randomized trials did not find any links to men with unfavorable risk, nonmetastatic prostate cancer. They did however find a link of a lower risk of prostate cancer specific death and all-cause death with androgen deprivation therapy.

Androgen deprivation therapy (ADT) in the form of a gonadotropin-releasing hormone (GnRH) agonist is a mainstay of prostate cancer treatment. The U.S. Food and Drug Administration were prompted to issue a safety warning as well as a joint statement by several medical societies in order to raise awareness of a possible association between ADT and cardiovascular events after several studies indicated that ADT may increase the risk of cardiovascular death. However, these findings have not been confirmed in other studies.

Paul L. Nguyen, M.D., of the Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, and his team conducted a meta-analysis of randomized controlled trials in order to find out if ADT is connected with cardiovascular mortality in men with unfavorable-risk, nonmetastatic prostate cancer, all-cause mortality, and prostate cancer-specific mortality (PCSM).

The researchers reviewed medical literature and found eight randomized trials (n = 4,141 patients) that met inclusion criteria for the meta-analysis. In these trials the median (midpoint) follow-up ranged between 7.6 and 13.2 years.

They reported that: There were 255 cardiovascular deaths among the 2,200 individuals who were treated with ADT, equivalent to an overall incidence of cardiovascular death of 11%.For the control group, they found there were 252 cardiovascular deaths among the 1,941 patients, for an overall incidence of 11.2%.Among participants in short-course ADT trials (6 months or less), the percentage of cardiovascular death was 10.5% compared to 10.3% for the control group.For patients who participated in long-course ADT trials (3+ years), the percentage of cardiovascular deaths was 11.5% vs. 11.5% for the control group.Furthermore, the team discovered that patients' age did not alter their findings, as there was no connection between cardiovascular mortality and ADT whether the median age of the patient was younger or older than 70 years.

443 PCSM deaths occurred among the 2,527 men in the ADT group and 552 PCSM deaths occurred among the 2,278 participants in the control group. The relative risk of PCSM was 31% lower for men who received ADT, with an incidence of 13.5 percent compared to 22.1% for the control group. In total there were 1,140 deaths among men in the ADT group and 1,213 total deaths among men in the control group, with examination suggesting that the relative risk of all-cause mortality was 14% lower for those who received ADT compared to men in the control group (incidence, 37.7% vs. 44.4% respectively).

The researchers explain:

"Overall, the results of our study should be generally reassuring to most men with unfavorable-risk prostate cancer considering ADT, because it was associated with improved survival without measure excess in cardiovascular mortality, but a few important points need to be raised. First, none of the trials were stratified by preexisting cardiovascular comorbidity; therefore, our study cannot exclude the possibility that a small subgroup of men with underlying cardiac disease (even if controlled) could experience excess cardiovascular mortality due to ADT.

A second issue is that although our study assessed total cardiovascular deaths, it could not exclude the possibility that cardiovascular deaths happen earlier in men receiving ADT. In conclusion, our meta-analysis of more than 4,000 patients could not find any evidence that ADT increases the risk of cardiovascular death among men with unfavorable-risk, nonmetastatic prostate cancer, but did find a significant association between ADT and improved prostate cancer-specific survival and overall survival."

William K. Kelly, D.O., and Leonard G. Gomella, M.D., of Thomas Jefferson University, Kimmel Cancer Center, Philadelphia, write that with over 600,000 individuals in the U.S., with prostate cancer receiving ADT treatment, the benefits and short- and long-term risk of ADT must be clearly outlined.

"...men with cardiac disease who have the highest risks from complications from ADT should follow the appropriate secondary preventive measures from the American Heart Association (lipid-lowering therapy, antihypertensive therapy, glucose-lowering therapy, and antiplatelet therapy). Although ADT has been part of the treatment regimen for several decades, clinicians treating patients with prostate cancer are still understanding the short-term and long-term biological effects of biochemical castration but now have better appreciation of these complications."

Written by Grace Rattue
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

Visit our prostate / prostate cancer section for the latest news on this subject. Article - JAMA. 2011;306[21]:2359-2366.
Editorial - JAMA. 2011;306[21]:2382-2383 Please use one of the following formats to cite this article in your essay, paper or report:

MLA

Grace Rattue. "Prostate Cancer - Androgen Deprivation Therapy Does Not Raise Cardiovascular Death Risk." Medical News Today. MediLexicon, Intl., 8 Dec. 2011. Web.
8 Dec. 2011. APA

Please note: If no author information is provided, the source is cited instead.

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam)

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.

View the original article here