(Press-News.org) ANN ARBOR, Mich. — Numerous studies have shown that the brain molecule neuropeptide Y (NPY) helps to restore calm after stressful events. A team of University of Michigan-led researchers has now found that people whose genes predispose them to produce lower levels of NPY are more responsive to negative stimuli in key brain circuits related to emotion – and are therefore less resilient in the face of stress and may be at higher risk for developing a major depressive disorder.
The scientists hope the research will eventually help with early diagnosis and intervention for depression and other psychiatric illnesses, and in the development of therapies that can be tailored to individuals based on their genetic profiles. The findings were published Feb. 7 in the Archives of General Psychiatry.
"This is what we mean when we talk about 'personalized medicine,' " says the study's lead author, Brian Mickey, M.D., Ph.D., an assistant professor in the Department of Psychiatry at the University of Michigan Medical School and researcher at the U-M Molecular and Behavioral Neurosciences Institute. "These are genetic features that can be measured in any person. We hope they can guide us toward assessing an individual's risk for developing depression and anxiety."
The findings also help fill in new areas on the genetic "map" of depression, says the study's senior author Jon-Kar Zubieta, M.D., Ph.D., a professor of psychiatry and radiology and research professor at the Molecular and Behavioral Neurosciences Institute.
"We've identified a biomarker – in this case genetic variation – that is linked with increased risk of major depression," Zubieta says. "This appears to be another mechanism, independent of previous targets in depression research, such as serotonin, dopamine and norepinephrine."
Using three separate approaches, researchers found that individuals with the genotype that produces lower amounts of NPY had measurably stronger brain responses to negative stimuli and psychological responses to physical pain. They were also overrepresented in a population diagnosed with a major depressive disorder.
Three approaches
Using three separate approaches, each with a varying number of research subjects ranging from 58 to 152, U-M researchers and their partners studied the link between NPY gene expression and emotional processing.
U-M researchers recruited and characterized participants, performed neuroimaging, and conducted the pain challenge. Their partners at the Laboratory of Neurogenetics at the National Institute on Alcohol Abuse and Alcoholism in Bethesda, Md. performed the genotyping.
The research subjects were classified according to whether they had low, medium or high NPY gene expression.
Using functional magnetic resonance imaging (fMRI), the scientists observed the brain activity of each subject as he or she viewed neutral words (such as "material") negatively charged words (like "murderer"), and positively charge words (like "hopeful").
In response to negative words, subjects in the low NPY group showed strong activation in the prefrontal cortex, which is involved with processing emotion, while subjects with high NPY demonstrated a much smaller response.
"This tells us that individuals with the risk-associated NPY gene variant tend to activate this key brain region more than other people, even in the absence of stress and before psychiatric symptoms are present," says Mickey.
In a second test, healthy subjects reported their emotional experiences during a stress challenge. Saline solution was injected into the jaw muscle, which produces moderate pain for 20 minutes, but no lasting harm. The level of pain was adjusted for each person to until it was, for them, a 4 on a scale of 1 to 10.
These subjects rated the positivity or negativity of their feelings both before and after the pain challenge. Those in the low NPY group were more negative both before and after the pain – meaning they were more emotionally affected while anticipating the pain and while reflecting on their experience immediately afterward.
Lastly, scientists compared the NPY genotypes of subjects with major depressive disorder with control subjects to see if there was an association between the condition and low expression of NPY.
Subjects with low-expression NPY genotypes were overrepresented in the group with depression.
"We're not just associating a particular gene with a particular illness," Zubieta says. "We're expanding the understanding of the physiology of depression."
INFORMATION:
Funding: The research was supported by grants from the National Institutes of Mental Health, National Institute on Drug Abuse, the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism, and the Phil F. Jenkins Research Fund.
Disclosures: Zubieta has acted as consultant for Eli Lilly and Co, Merck and Johnson & Johnson over the last year.
Additional U-M authors: Mary M. Heitzeg, Ph.D.; David T. Hsu, Ph.D.; Scott A. Langenecker, Ph.D.; Tiffany M. Love, Ph.D., Marta Peciña, M.D., Ph.D.; Tal Shafir, Ph.D.
Other authors:
Laboratory of Neurogenetics at the National Institute on Alcohol Abuse and Alcoholism, Bethesda, Md.: Zhifeng Zhou, Ph.D.; Colin A. Hodgkinson, Ph.D.; David Goldman, M.D.; Elizabeth Heinz
University of Maryland Dental School: Christian S. Stohler, D.M.D.
Reference: "Emotion Processing, Major Depression, and Functional Genetic Variation of Neuropeptide Y," Archives of General Psychiatry, Feb. 7, 2011
U-M Resources:
Department of Psychiatry, www.psych.med.umich.edu
Molecular and Behavioral Neurosciences Institute, mbni.med.umich.edu/mbni/index.html
END
ANN ARBOR, Mich. — As loved ones with dementia disappear into symptoms of aggression, agitation or delusions, families are left with few good medical solutions. A new generation of antipsychotic medications gained popularly in the 1990s because they avoided side effects such as Parkinson's syndrome associated with conventional antipsychotic medications used to treat dementia.
But a new study led by University of Michigan and VA Ann Arbor Healthcare System researchers shows the use of these second-generation medications began to decline significantly in 2003, years ahead ...
The bone marrow stem cells responsible for generating new blood cells are less fixed and more flexible than previously thought, according to a paper published online on February 7 in the Journal of Experimental Medicine (www.jem.org).
Some earlier studies suggested that these hematopoietic stem cells (HSCs) come in two distinct varieties: those that remain dormant during times of health but possess the ability to regenerate the whole blood system after trauma such as irradiation or chemotherapy, and those that divide frequently and contribute to new blood production during ...
Never before has a therapy proven more beneficial for women than men in preventing heart disease – until now.
A new study, published today in the Journal of the American College of Cardiology, found that women receive a significantly greater benefit – a 70 percent reduction in heart failure and a 72 percent reduction in death – from cardiac resynchronization therapy with defibrillator (CRT-D) than men.
"In prior cardiac studies, men and women generally received similar benefit from preventive medical therapy," said cardiologist Arthur J. Moss, M.D., professor of Medicine ...
In a finding of significant worldwide public-health consequence, researchers at the UC Davis School of Medicine and in the Academy of Sciences in the Czech Republic have found that emissions from the indoor use of coal for heating and cooking may impair early childhood growth and development.
The research, published online today in the Archives of Pediatrics & Adolescent Medicine, a JAMA Archives journal, found that children reared in homes where coal was the primary fuel source exhibited shorter stature at 36 months of age when compared with children reared in households ...
Berkeley – New experiments at the University of California, Berkeley, may one day lead to anti-viral treatments that involve swallowing Salmonella bacteria, effectively using one bug to stop another.
Researchers at UC Berkeley's School of Public Health have reprogrammed Salmonella, the same foodborne pathogen that can cause diarrhea, fever and abdominal cramps, to safely transport virus-stopping enzymes into cells without causing disease. Not only did this technique effectively treat mice infected with cytomegalovirus, it worked as an oral solution that was swallowed ...
Grenoble (France) – A novel X-ray imaging technology is helping scientists better understand how in the course of evolution snakes have lost their legs. The researchers hope the new data will help resolve a heated debate about the origin of snakes: whether they evolved from a terrestrial lizard or from one that lived in the oceans. New, detailed 3-D images reveal that the internal architecture of an ancient snake's leg bones strongly resembles that of modern terrestrial lizard legs. The results are published in the 8 February issue of the Journal of Vertebrate Paleontology.
The ...
A diet, high in fats, sugars, and processed foods in early childhood may lower IQ, while a diet packed full of vitamins and nutrients may do the opposite, suggests research published online in the Journal of Epidemiology and Community Health.
The authors base their findings on participants in the Avon Longitudinal Study of Parents and Children (ALSPAC), which is tracking the long term health and wellbeing of around 14,000 children born in 1991 and 1992.
Parents completed questionnaires, detailing the types and frequency of the food and drink their children consumed ...
Care home residents are more than four times as likely to get the wrong dose of medicine when it is in liquid form as they are when given pills/capsules provided in a dispenser, indicates research published online in BMJ Quality and Safety.
Dispensers, known as monitored dosage systems or MDS for short, comprise a tray or cassette with compartments for one or more doses for a particular day or a given time. They are intended to simplify drug rounds for care home staff and cut the risk of mistakes.
But swallowing difficulties mean that some elderly people need to take ...
Up to three quarters of hospital tests are not being followed up, suggests a systematic review of international evidence, published in BMJ Quality and Safety.
This failure can have serious implications for patients, including missed or delayed diagnoses and even death, the study shows.
The authors base their findings on a systematic review of evidence published in English between 1990 and 2010, and available on reputable research databases.
Analysis of the findings of the 12 studies which were suitable for inclusion indicated that between 20% and 61% of inpatient ...
San Diego, CA, February 8, 2011 – When the FDA proposed new rules restricting outdoor tobacco advertising near schools and playgrounds in 2009, the tobacco industry argued that such rules would lead to a near complete ban on tobacco advertising in urban areas. An article in the March 2011 issue of the American Journal of Preventive Medicine shows that the effect of these rules would be less severe than the industry contends.
"It is critical to point out one subtle, but important difference between the analysis that the tobacco industry conducted and the analysis presented ...
