Posts tagged glutamate
Articles and news from the latest research reports.
Researchers focus on a brain protein and an antibiotic to block cocaine craving
A new study conducted by a team of Indiana University neuroscientists demonstrates that GLT1, a protein that clears glutamate from the brain, plays a critical role in the craving for cocaine that develops after only several days of cocaine use.
The study, appearing in The Journal of Neuroscience, showed that when rats taking large doses of cocaine are withdrawn from the drug, the production of GLT1 in the nucleus accumbens, a region of the brain implicated in motivation, begins to decrease. But if the rats receive ceftriaxone, an antibiotic used to treat meningitis, GLT1 production increases during the withdrawal period and decreases cocaine craving.
George Rebec, professor in the Department of Psychological and Brain Sciences, said drug craving depends on the release of glutamate, a neurotransmitter involved in motivated behavior. Glutamate is released in response to the cues associated with drug taking, so when addicts are exposed to these cues, their drug craving increases even if they have been away from the drug for some time.
The same behavior can be modeled in rats. When rats, who self-administer cocaine by pressing a lever that delivers the cocaine into their bodies, are withdrawn from the drug for several weeks, their craving returns if they are exposed to the cues that accompanied drug delivery in the past; in this case, a tone and light. But if the rats are treated with ceftriaxone during withdrawal, they no longer seek cocaine when the cues are presented.
Ceftriaxone appears to block craving by reversing the decrease in GLT1 caused by repeated exposure to cocaine. In fact, ceftriaxone increases GLT1, which allows glutamate to be cleared quickly from the brain. The Rebec research group localized this effect to the nucleus accumbens by showing that if GLT1 was blocked in this brain region even after ceftriaxone treatment, the rats would relapse.
While an earlier paper of Rebec’s group showed the effects of ceftriaxone on cocaine craving, the new paper was the first to localize the effects of ceftriaxone to the nucleus accumbens and was the first to show that ceftriaxone works after long withdrawal periods.
"The idea is that increasing GLT1 will prevent relapse. If we block GLT1, the ceftriaxone should not work," Rebec said. "We now have good evidence that ceftriaxone is acting on GLT1 and that the nucleus accumbens is the critical site."
Rebec said prior work on Huntington’s disease, a neurodegenerative disorder, alerted him and his team to the way ceftriaxone acts on the expression of GLT1, a protein that removes glutamate from the brain. Glutamate removal is a problem in Huntington’s disease, and Rebec’s team found that ceftriaxone increases GLT1 and improves neurological signs of the disease in mouse models.
It now is important to determine why cocaine decreases GLT1 and to see whether other drugs of abuse have the same effect. Rebec and colleagues have shown that ceftriaxone also can decrease the craving for alcohol in rats selectively bred to prefer alcohol.
Drug cues are one factor that can trigger relapse. Future work also will examine whether ceftriaxone can block drug craving induced by stress or by re-exposure to the drug. If so, it would mean that GLT1 could become an important target in the search for treatments to prevent drug relapse. Now, Rebec said, there are a number of factors to study. “We don’t yet know how long the effects of ceftriaxone last. Does an addict have to be on it for a month or will it lose its effectiveness? We don’t yet know what will happen.”
In the cocaine study, the rats self-administer cocaine for six hours a day for up to 11 days. Their behavior is much like that of a human addict.
"You might think that because they’re in there, they just take more, but they don’t just take more," Rebec said. "Like human addicts, they take the drug more and more rapidly and they want to get to it more and more quickly."
Withdrawal serves as an incubation period during which craving increases if it is activated by cues or other factors. “Something changes in the brain during that time to trigger the craving or make it more likely that you want the drug,” Rebec said. “That’s what ceftriaxone seems to be interfering with.”
Ceftriaxone is now in clinical trials on people with ALS, also known as Lou Gehrig’s disease, which has many mechanisms in common with other neurodegenerative diseases such as Huntington’s disease and Alzheimer’s.
Lead Acts to Trigger Schizophrenia
Study in Mice Points to a Synergistic Relationship Between Lead Exposure and Schizophrenia Gene
Mice engineered with a human gene for schizophrenia and exposed to lead during early life exhibited behaviors and structural changes in their brains consistent with schizophrenia. Scientists at Columbia University’s Mailman School of Public Health and the Johns Hopkins University School of Medicine say their findings suggest a synergistic effect between lead exposure and a genetic risk factor, and open an avenue to better understanding the complex gene-environment interactions that put people at risk for schizophrenia and other mental disorders.
Results appear online in Schizophrenia Bulletin.
Going back to 2004, work by scientists at the Mailman School suggested a connection between prenatal lead exposure in humans and increased risk for schizophrenia later in life. But a big question remained: How could lead trigger the disease? Based on his own research, Tomás R. Guilarte, PhD, senior author of the new study, believed the answer was in the direct inhibitory effect of lead on the N-methyl-D-aspartate receptor (NMDAR), a synaptic connection point important to brain development, learning, and memory. His research in rodents found that exposure to lead blunted the function of the NMDAR. The glutamate hypothesis of schizophrenia postulates that a deficit in glutamate neurotransmission and specifically hypoactivity of the NMDAR can explain a significant portion of the dysfunction in schizophrenia.
In the new study, Dr. Guilarte, professor and chair of the department of Environmental Health Sciences at the Mailman School, and his co-investigators focused on mice engineered to carry the mutant form of Disrupted-in-Schizophrenia-1 (DISC1), a gene that is a risk factor for the disease in humans. Beginning before birth, half of the mutant DISC1 mice were fed a diet with lead, and half were given a normal diet. A second group of normal mice not expressing the mutant DISC1 gene were also split into the two feeding groups. All mice were put through a battery of behavioral tests and their brains were examined using MRI.
Mutant mice exposed to lead and given a psychostimulant exhibited elevated levels of hyperactivity and were less able to suppress a startle in response to a loud noise after being given an acoustic warning. Their brains also had markedly larger lateral ventricles—empty spaces containing cerebrospinal fluid—compared with other mice. These results mirror what is known about schizophrenia in humans.
While the role of genes in schizophrenia and mental disorders is well established, the effect of toxic chemicals in the environment is only just beginning to emerge. The study’s results focus on schizophrenia, but implications could be broader.
“We’re just scratching the surface,” says Dr. Guilarte. “We used lead in this study, but there are other environmental toxins that disrupt the function of the NMDAR.” One of these is a family of chemicals in air pollution called polycyclic aromatic hydrocarbons or PAHs. “Similarly, any number of genes could be in play,” adds Dr. Guilarte, noting that DISC1 is among many implicated in schizophrenia.
Future research may reveal to what extent schizophrenia is determined by environmental versus genetic factors or their interactions, and what other mental problems might be in the mix. One ongoing study by Dr. Guilarte is looking at whether lead exposure alone can contribute to deficits of one specialized type of neuron called parvalbumin-positive GABAergic interneuron that is known to be affected in the brain of schizophrenia patients. Scientists are also interested to establish the critical window for exposure—whether in utero or postnatal, or both.
“The animal model provides a way forward to answer important questions about the physiological processes underlying schizophrenia,” says Dr. Guilarte.
(Image: Flickr)
Restless Legs Syndrome, Insomnia And Brain Chemistry: A Tangled Mystery Solved?
Johns Hopkins researchers believe they may have discovered an explanation for the sleepless nights associated with restless legs syndrome (RLS), a symptom that persists even when the disruptive, overwhelming nocturnal urge to move the legs is treated successfully with medication.
Neurologists have long believed RLS is related to a dysfunction in the way the brain uses the neurotransmitter dopamine, a chemical used by brain cells to communicate and produce smooth, purposeful muscle activity and movement. Disruption of these neurochemical signals, characteristic of Parkinson’s disease, frequently results in involuntary movements. Drugs that increase dopamine levels are mainstay treatments for RLS, but studies have shown they don’t significantly improve sleep. An estimated 5 percent of the U.S. population has RLS.
The small new study, headed by Richard P. Allen, Ph.D., an associate professor of neurology at the Johns Hopkins University School of Medicine, used MRI to image the brain and found glutamate — a neurotransmitter involved in arousal — in abnormally high levels in people with RLS. The more glutamate the researchers found in the brains of those with RLS, the worse their sleep.
The findings are published in the May issue of the journal Neurology.
“We may have solved the mystery of why getting rid of patients’ urge to move their legs doesn’t improve their sleep,” Allen says. “We may have been looking at the wrong thing all along, or we may find that both dopamine and glutamate pathways play a role in RLS.”
For the study, Allen and his colleagues examined MRI images and recorded glutamate activity in the thalamus, the part of the brain involved with the regulation of consciousness, sleep and alertness. They looked at images of 28 people with RLS and 20 people without. The RLS patients included in the study had symptoms six to seven nights a week persisting for at least six months, with an average of 20 involuntary movements a night or more.
The researchers then conducted two-day sleep studies in the same individuals to measure how much rest each person was getting. In those with RLS, they found that the higher the glutamate level in the thalamus, the less sleep the subject got. They found no such association in the control group without RLS.
Previous studies have shown that even though RLS patients average less than 5.5 hours of sleep per night, they rarely report problems with excessive daytime sleepiness. Allen says the lack of daytime sleepiness is likely related to the role of glutamate, too much of which can put the brain in a state of hyperarousal — day or night.
If confirmed, the study’s results may change the way RLS is treated, Allen says, potentially erasing the sleepless nights that are the worst side effect of the condition. Dopamine-related drugs currently used in RLS do work, but many patients eventually lose the drug benefit and require ever higher doses. When the doses get too high, the medication actually can make the symptoms much worse than before treatment. Scientists don’t fully understand why drugs that increase the amount of dopamine in the brain would work to calm the uncontrollable leg movement of RLS.
Allen says there are already drugs on the market, such as the anticonvulsive gabapentin enacarbil, that can reduce glutamate levels in the brain, but they have not been given as a first-line treatment for RLS patients.
RLS wreaks havoc on sleep because lying down and trying to relax activates the symptoms. Most people with RLS have difficulty falling asleep and staying asleep. Only getting up and moving around typically relieves the discomfort. The sensations range in severity from uncomfortable to irritating to painful.
“It’s exciting to see something totally new in the field — something that really makes sense for the biology of arousal and sleep,” Allen says.
As more is understood about this neurobiology, the findings may not only apply to RLS, he says, but also to some forms of insomnia.
(Source: hopkinsmedicine.org)
High Levels of Glutamate in Brain May Kick-Start Schizophrenia
An excess of the brain neurotransmitter glutamate may cause a transition to psychosis in people who are at risk for schizophrenia, reports a study from investigators at Columbia University Medical Center (CUMC) published in the current issue of Neuron.
The findings suggest 1) a potential diagnostic tool for identifying those at risk for schizophrenia and 2) a possible glutamate-limiting treatment strategy to prevent or slow progression of schizophrenia and related psychotic disorders.
“Previous studies of schizophrenia have shown that hypermetabolism and atrophy of the hippocampus are among the most prominent changes in the patient’s brain,” said senior author Scott Small, MD, Boris and Rose Katz Professor of Neurology at CUMC. “The most recent findings had suggested that these changes occur very early in the disease, which may point to a brain process that could be detected even before the disease begins.”
To locate that process, the Columbia researchers used neuroimaging tools in both patients and a mouse model. First they followed a group of 25 young people at risk for schizophrenia to determine what happens to the brain as patients develop the disorder. In patients who progressed to schizophrenia, they found the following pattern: First, glutamate activity increased in the hippocampus, then hippocampus metabolism increased, and then the hippocampus began to atrophy.
To see if the increase in glutamate led to the other hippocampus changes, the researchers turned to a mouse model of schizophrenia. When the researchers increased glutamate activity in the mouse, they saw the same pattern as in the patients: The hippocampus became hypermetabolic and, if glutamate was raised repeatedly, the hippocampus began to atrophy.
Theoretically, this dysregulation of glutamate and hypermetabolism could be identified through imaging individuals who are either at risk for or in the early stage of disease. For these patients, treatment to control glutamate release might protect the hippocampus and prevent or slow the progression of psychosis.
Strategies to treat schizophrenia by reducing glutamate have been tried before, but with patients in whom the disease is more advanced. “Targeting glutamate may be more useful in high-risk people or in those with early signs of the disorder,” said Jeffrey A. Lieberman, MD, a renowned expert in the field of schizophrenia, Chair of the Department of Psychiatry at CUMC, and president-elect of the American Psychiatric Association. “Early intervention may prevent the debilitating effects of schizophrenia, increasing recovery in one of humankind’s most costly mental disorders.”
In an accompanying commentary, Bita Moghaddam, PhD, professor of neuroscience and of psychiatry, University of Pittsburgh, suggests that if excess glutamate is driving schizophrenia in high-risk individuals, it may also explain why a patient’s first psychotic episodes are often caused by periods of stress, since stress increases glutamate levels in the brain.
First steps of synapse building captured in live zebra fish embryos
Using spinning disk microscopy on barely day-old zebra fish embryos, University of Oregon scientists have gained a new window on how synapse-building components move to worksites in the central nervous system.
What researchers captured in these see-through embryos — in what may be one of the first views of early glutamate-driven synapse formation in a living vertebrate — were orderly movements of protein-carrying packets along axons to a specific site where a synapse would be formed.
Washbourne addresses:
► The basic importance of the findings
► The connection to diseases, including autism
The discovery, in research funded by the National Institutes of Health, is described in a paper placed online ahead of publication in the April 25 issue of the open-access journal Cell Reports. It is noteworthy because most synapses formed in vertebrates use glutamate as a neurotransmitter, and breakdowns in the process have been tied to conditions such as autism, schizophrenia and mental retardation.
The zebra fish has become one of the leading research models for studying early development, in general, and human-disease states.
In this case, researchers used immunofluorescence labeling to highlight the area they put under the microscopes. The embryos they studied were barely 24-hours old and a millimeter in length, but neurons in their spinal cord were already forming connections called synapses. Images were taken every 30 seconds over two hours.
"If we zoom out a bit and look at development in the human, the majority of synapse formation occurs in the cortex after birth and continues for the first two years in a baby’s life," said Philip Washbourne, a professor of biology and member of the UO’s Institute of Neuroscience.
Previous studies, done in vitro, contradicted each other, with one, in 2000, identifying a single packet of building blocks arriving at a pre-synaptic terminal. The other, in 2004, identified two protein packets. After watching the process unfold live, with imaging over long time spans, Washbourne said: “We now see at least three, and maybe more, such deliveries.”
"Axons are long processes — think of them as highways — of neurons. In humans, these can be a meter long, from spinal cord to your big toe," he said. It’s in the cell body where all the proteins are made, and they have to be transported out. Is it done by a single bus or by several cars? These results point to additional layers of complexity in the established mechanisms of synaptogenesis."
The new research also showed that sequence also is crucial. Two different pre-synaptic packages of molecules repeatedly arrived in the same order. A key building block — the protein synapsin — always arrived third. As these delivery vehicles traveled the axonal highway, another protein, a cyclin-dependent kinase known as Cdk5, acts as a stoplight at the synapse-construction site, where phosphorylation occurs. More research is needed on Cdk5, Washbourne said.
"Understanding how all this happens will inform us to what’s going wrong in neurodevelopment that leads to diseases," Washbourne said. "We have indications that the glue that gets all this going includes a gene that has been linked to autism, so knowing how these molecules start the process of synapse formation — and what goes wrong in people with mutations in these genes — might allow for a therapeutic targeting to correct the mutations and manipulate the stop signs."
Brain cell signal network genes linked to schizophrenia risk in families
New genetic factors that predispose to schizophrenia have been uncovered in five families with several affected relatives. The psychiatric disorder can disrupt thinking, feeling, and acting, and blur the border between reality and imagination.
Dr. Debby W. Tsuang, professor of psychiatry and behavioral sciences, and Dr. Marshall S. Horwitz, professor of pathology, both at the University of Washington in Seattle, led the multi-institutional study. Tsuang is also a staff physician at the Puget Sound Veterans Administration Health Care System.
The results are published in the April 3 online edition of the JAMA Psychiatry.
Loss of brain nerve cell integrity occurs in schizophrenia, but scientists have not worked out the details of when and how this happens. In all five families in the present study, the researchers found rare variants in genes tied to the networking of certain signal receptors on nerve cells distributed throughout the brain. These N-methyl-D-aspartate, or NMDA, receptors are widespread molecular control towers in the brain. They regulate the release of chemical messages that influence the strength of brain cell connections and the ongoing remodeling of the networks.
These receptors respond to glutamate, one of the most common nerve-signaling chemicals in the brain, and they are also found on brain circuits that manage dopamine release. Dopamine is a nerve signal associated with reward-seeking, movement and emotions. Deficits in glutamate and dopamine function have both been implicated in schizophrenia but most of the medications that have been developed to treat schizophrenia have targeted dopamine receptors.
Tsuang and her groups’ discovery of gene variations that disturb N-methyl-D-aspartate receptor networking functions supports the hypothesis that decreased NMDA receptor-mediated nerve-signal transmissions contributes to some cases of schizophrenia.
Tsuang pointed out that several hallucinogenic drugs, such as ketamine and phencyclidine (PCP, or angel dust), block N-methyl-D-aspartate receptors and can produce symptoms similar to schizophrenia. These are the strongest evidence implicating these receptors in schizophrenia. The drugs sometimes induce psychosis and terrifying sensory detachment. Reports of such effects in recreational drug users fingered faulty NMDA receptor networks as suspects in schizophrenia.
In all five of their study families, Tsuang’s team detected rare protein-altering variants in one of three genes involved with the N-methyl-D-aspartate receptor network. One of the genes, GRM5, is directly linked with glutamate signaling. In the other two genes, the links are indirect and connected through other proteins synthesized in brain cells. One of these proteins, PPEF2, appears to affect the levels of certain brain nerve-cell signaling mediators, and the other altered protein, LRP1B, may compete with a normal protein for a binding spot on a subunit of the NMDA receptor.
These discoveries provide additional clues to the molecular disarray that might occur in the brain nerve cells of some patients with schizophrenia, and suggest new targets for therapy for certain patients. In a disease occurring in about 1 percent of the population, the picture of how and why schizophrenia arises in all these people is far from complete.
“Disorders like schizophrenia are likely to have many underlying causes,” Tsuang noted. She added that it might eventually make sense to divide schizophrenia into categories based, for example, on which biochemical pathways in the brain are disrupted. Treatments might be developed to correct the exact malfunctioning mechanisms underlying various forms of the disease.
Tsuang gave an example: Agents that stimulate N-methyl-D-aspartate receptor-mediated nerve-signal transmissions include glycine-site blockers and glycine-transport inhibitors have shown some encouraging results in pre-clinical drug trials, but mostly in adjunctive treatment in addition to standard antipsychotic therapy.
“But perhaps the data we have generated will help pharmaceutical companies target specific subunits of the NMDA receptors and pathways,” Tsuang said. She added, however, that effective treatments may lag by many years after these kinds of discoveries. Someday it may make sense to initiate such treatments in people at high genetic risk when early symptoms, such as apathy and lack of motivation, appear, and before brain dysfunction is severe.
Also, possessing the newly discovered gene mutations does not always mean that a person will become schizophrenic. In the recent family study, three of the five families had relatives with the protein-altering variants who did not have schizophrenia.
“This isn’t surprising,” Tsuang observed, “Given that schizophrenia is such a complex disorder, we would expect that not everyone who carries the variants would develop the disease.” In the future, researchers will be seeking what triggers the gene variants into causing problems, other mutations within affected individuals’ genetic profile that might promote or protect against disease, as well as non-genetic factors in the onset of the illness in genetically susceptible people.
The researchers also utilized a strategy and selected more distant relatives of affected individuals for genetic sequencing. Distant kin share, a smaller proportion of genes compared to closely related family members. For example,siblings typically on the average share about 50 percent of their genes whereas cousins on the average share 12.5 percent of their genes. The researhers also hypothesized that the causative mutation within each family would be the same variant.
This strategy helped the researchers decrease the number of genetic variants that were detected by sequencing and thereby concentrate only on the remaining strongest candidates. The researchers also filtered their results against the many publicly available sequencing databases. This allowed them to pick out genetic variants not seen in individuals without psychiatric illness.
According to Tsuang, the research team was excited by recent advances in technology enabled them to uncover unknown, rare genetic variants not previously found in large populations without psychiatric condition. The ability to rapidly sequence only those portions of the genome that code for proteins made this experiment possible.
The next step for the researchers will be to screen for the newly discovered genetic variants in a large sample of unrelated cases of schizophrenia compared to controls. They want to determine if the variants are statistically associated with the disease.
The Mysterious GRIN3A and the Cause of Schizophrenia
Since the 1960s, psychiatrists have been hunting for substances made by the body that might accumulate in abnormally high levels to produce the symptoms associated with schizophrenia. In particular, there was a search for chemicals that might be related to the hallucinogens phencyclidine (PCP) or lysergic acid diethylamide (LSD), which could explain the emergence of psychotic symptoms in schizophrenia. This “auto-intoxication” hypothesis led investigators on a wild goose chase where substances, including the “Pink Spot” and the “Frohman Factor”, were isolated from people with schizophrenia and implicated in their illness, but these findings were later discredited.
The mysterious GRIN3A is a new version of the hunt for an intrinsic mechanism that produces schizophrenia-like symptoms. GRIN3A is a gene that codes for the GluN3A subunit of the N-methyl-D-aspartate-type (NMDA) receptor, a target for the neurotransmitter glutamate in the brain. Functional NMDA receptors usually have two GluN1 subunits and two GluN2 subunits. The ability of glutamate to activate these receptors is blocked by PCP and the anesthetic/hallucinogen, ketamine. When the GluN3A subunit is incorporated, it prevents the NMDA receptor from being activated by glutamate, almost as if the receptor had been blocked by PCP.
It is unclear why the brain needs this mechanism for normal brain development and function, hence the mystery surrounding GRIN3A. One piece of evidence supporting a link between GluN3A and schizophrenia is the finding that GluN3A levels are elevated in the post-mortem brain tissue from people who had been diagnosed with schizophrenia.
In this issue of Biological Psychiatry, Japanese researchers led by Dr. Takeo Yoshikawa provide new support for this hypothesis by implicating variation in GRIN3A in the heritable risk for schizophrenia.
Schizophrenia is thought to have a substantial genetic background which is, to some extent, population-specific. Genome-wide searches have revealed many common genomic variants with weak effects, but the remaining “missing heritability” is largely unknown. Scientists theorize that it may be partly explained by rare variants with large effect.
To identify genetic variants with larger effect sizes, Yoshikawa and his colleagues examined genetic data from several Asian populations. They identified a rare variant in GRIN3A with study-wide significance.
"This discovery is important, because the ‘NMDA receptor hypothesis’ for schizophrenia is a common disease model," said Yoshikawa. "We propose a novel point of therapeutic intervention in the NMDA receptor signaling system for schizophrenia."
Dr. John Krystal, Editor of Biological Psychiatry, commented, “The notion that a genetic trait that acts like PCP in the brain produces schizophrenia is a very attractive but over-simplistic hypothesis. It is that the biology of schizophrenia is much more complicated than this single factor. Nonetheless, perhaps this study of GRIN3A brings us another step closer to understanding glutamate abnormalities in schizophrenia.”
(Source: alphagalileo.org)
Countering brain chemical could prevent suicides
Researchers have found the first proof that a chemical in the brain called glutamate is linked to suicidal behavior, offering new hope for efforts to prevent people from taking their own lives.
Writing in the journal Neuropsychopharmacology, Michigan State University’s Lena Brundin and an international team of co-investigators present the first evidence that glutamate is more active in the brains of people who attempt suicide. Glutamate is an amino acid that sends signals between nerve cells and has long been a suspect in the search for chemical causes of depression.
“The findings are important because they show a mechanism of disease in patients,” said Brundin, associate professor of translational science and molecular medicine in MSU’s College of Human Medicine. “There’s been a lot of focus on another neurotransmitter called serotonin for about 40 years now. The conclusion from our paper is that we need to turn some of that focus to glutamate.”
Brundin and colleagues examined glutamate activity by measuring quinolinic acid – which flips a chemical switch that makes glutamate send more signals to nearby cells – in the spinal fluid of 100 patients in Sweden. About two-thirds of the participants were admitted to a hospital after attempting suicide and the rest were healthy.
They found that suicide attempters had more than twice as much quinolinic acid in their spinal fluid as the healthy people, which indicated increased glutamate signaling between nerve cells. Those who reported the strongest desire to kill themselves also had the highest levels of the acid.
The results also showed decreased quinolinic acid levels among a subset of patients who came back six months later, when their suicidal behavior had ended.
The findings explain why earlier research has pointed to inflammation in the brain as a risk factor for suicide. The body produces quinolinic acid as part of the immune response that creates inflammation.
Brundin said anti-glutamate drugs are still in development, but could soon offer a promising tool for preventing suicide. In fact, recent clinical studies have shown the anesthetic ketamine – which inhibits glutamate signaling – to be extremely effective in fighting depression, though its side effects prevent it from being used widely today.
In the meantime, Brundin said physicians should be aware of inflammation as a likely trigger for suicidal behavior. She is partnering with doctors in Grand Rapids, Mich., to design clinical trials using anti-inflammatory drugs.
“In the future, it’s likely that blood samples from suicidal and depressive patients will be screened for inflammation,” Brundin said. “It is important that primary health care physicians and psychiatrists work closely together on this.”