Glutamate neurotransmission system may be involved with depression risk

November 13, 2012

Researchers using a new approach to identifying genes associated with depression have found that variants in a group of genes involved in transmission of signals by the neurotransmitter glutamate appear to increase the risk of depression. The report published in the journal Translational Psychiatry suggests that drugs targeting the glutamate system may help improve the limited success of treatment with current antidepressant drugs.

"Instead of looking at DNA variations one at a time, we looked at grouping of genes in the same biological pathways and found that a set of genes involved in glutamatergic transmisson was associated with the risk of depression," says Jordan Smoller, MD, ScD, director of the Psychiatric and Neurodevelopmental Genetics Unit in the Massachusetts General Hospital (MGH) Department of Psychiatry, senior author of the study. "Our findings are particularly interesting in light of recent studies showing that drugs affecting glutamate transmission can have rapid antidepressant effects."

While the risk of depression clearly runs in families, the genome-wide association studies typically used to identify gene variants that increase disease risk have been unable to find strongly associated genes. The research team - which includes investigators from the Broad Institute of MIT and Harvard and other research centers in the U.S., Australia and the Netherlands - adopted a strategy called gene set pathway analysis.

Starting with a set of genes that previous studies had implicated in depression, they used an analysis process called text mining to scan the medical literature for information on the biological function of these genes. Based on those findings, they identified 178 biological pathways that included these genes. Only one of those pathways - the one involved in transmission of neural signals carried by glutamate - was significantly associated with the risk for depression.

"Glutamate is the excitatory transmitter most widely used by the central nervous system, and several studies in animals and humans have suggested that it may play a role in depression," explains Smoller, an associate professor of Psychiatry at Harvard Medical School. "Most intriguingly, recent studies have found that ketamine - a drug known to block one glutamate receptor - appears to have antidepressant effects that are much faster than those of traditional antidepressants, which can take several weeks to become effective. Now additional research needs to confirm these findings and investigate exactly how variation in glutamate function affects brain systems involved in depression."
-end-
Phil Hyoun Lee, PhD, of the MGH Psychiatric and Neurodevelopmental Genetics Unit (PNGU) is lead author of the Translational Psychiatry report. Additional co-authors are Roy Perlis, MD, Richie Siburian, Stephen Haddad, MS, Catherine Mayerfeld, and Shaun Purcell, PhD, MGH PNGU; Erroll Rueckert, PhD, MGH Center for Human Genetic Research; Jae-Yoon Jung, PhD, Harvard Medical School; Enda Byrne, PhD, Naomi Wray, PhD, and Nicholas Martin, PhD, Queensland Institute of Medical Research, Australia; Andrew Heath, DPhil, Michele Pergadia, PhD, and Pamela Madden, PhD, Washington University, St. Louis; Dorret Boomsma, PhD, and B.W. Penninx, PhD, VU University, Amsterdam, The Netherlands; and Pamela Sklar, MD, PhD, Mount Sinai School of Medicine, New York. Lee, Perlis, Rueckert, Purcell and Smoller are also affiliated with the Broad Institute. The study was supported by grants from the National Institute of Mental Health.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $750 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine. In July 2012, MGH moved into the number one spot on the 2012-13 U.S. News & World Report list of "America's Best Hospitals."

Massachusetts General Hospital

Related Depression Articles from Brightsurf:

Children with social anxiety, maternal history of depression more likely to develop depression
Although researchers have known for decades that depression runs in families, new research from Binghamton University, State University of New York, suggests that children suffering from social anxiety may be at particular risk for depression in the future.

Depression and use of marijuana among US adults
This study examined the association of depression with cannabis use among US adults and the trends for this association from 2005 to 2016.

Maternal depression increases odds of depression in offspring, study shows
Depression in mothers during and after pregnancy increased the odds of depression in offspring during adolescence and adulthood by 70%.

Targeting depression: Researchers ID symptom-specific targets for treatment of depression
For the first time, physician-scientists at Beth Israel Deaconess Medical Center have identified two clusters of depressive symptoms that responded to two distinct neuroanatomical treatment targets in patients who underwent transcranial magnetic brain stimulation (TMS) for treatment of depression.

A biological mechanism for depression
Researchers report that in depressed individuals there are increased amounts of an unmodified structural protein, called tubulin, in lipid rafts compared with non-depressed individuals.

Depression in adults who are overweight or obese
In an analysis of primary care records of 519,513 UK adults who were overweight or obese between 2000-2016 and followed up until 2019, the incidence of new cases of depression was 92 per 10,000 people per year.

Why stress doesn't always cause depression
Rats susceptible to anhedonia, a core symptom of depression, possess more serotonin neurons after being exposed to chronic stress, but the effect can be reversed through amygdala activation, according to new research in JNeurosci.

Which comes first: Smartphone dependency or depression?
New research suggests a person's reliance on his or her smartphone predicts greater loneliness and depressive symptoms, as opposed to the other way around.

Depression breakthrough
Major depressive disorder -- referred to colloquially as the 'black dog' -- has been identified as a genetic cause for 20 distinct diseases, providing vital information to help detect and manage high rates of physical illnesses in people diagnosed with depression.

CPAP provides relief from depression
Researchers have found that continuous positive airway pressure (CPAP) treatment of obstructive sleep apnea (OSA) can improve depression symptoms in patients suffering from cardiovascular diseases.

Read More: Depression News and Depression Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.