Quinolinic Acid: Suicide Attempts Linked To Chemical's Presence In Spinal Fluid, Study Says



The glutamate pathways in the ‘normal’ brain
In the normal brain the prominent glutamatergic pathways are: the cortico-cortical pathways; the pathways between the thalamus and the cortex; and the extrapyramidal pathway (the projections between the cortex and striatum). Other glutamate projections exist between the cortex, substantia nigra, subthalmic nucleus and pallidum. Glutamate-containing neuronal terminals are ubiquitous in the central nervous system and their importance in mental activity and neurotransmission is considerable.


by: Stephanie Pappas, LiveScience

Published: 12/18/2012

A chemical in the brain may explain why some people become suicidal — and it may link inflammation of the body to disorders of the mind.

According to new research, suicidal individuals have elevated levels of quinolinic acid in the fluid surrounding the central nervous system. The discovery could explain a missing link between inflammation and mental illness, said study researcher Lena Brundin, a professor of translational science and molecular medicine at Michigan State University. Previously, scientists had linked suicidal feelings to the kind of bodily inflammation that occurs during illness or stress, but they weren't able to explain how inflammation could translate to depression, hopelessness and a desire to kill oneself.

The new study of 100 Swedish patients finds that the higher the level of quinolinic acid in the spinal fluid, the stronger their desire to commit suicide.

"The sicker the patient, the higher the quinolinic acid," Brundin told LiveScience.

The roots of suicide

There were nearly 37,000 suicide deaths in 2009 in the United States and 633,000 emergency room visits for self-inflicted injury, according to the Centers for Disease Control and Prevention (CDC). Between 2000 and 2009, suicide surpassed car accidents as the No. 1 cause of injury-related deaths in the United States, according to research released in September.

But risk factors for suicide can be tricky to pin down. Brundin and her colleagues previously found that suicidal patients had higher levels of cytokines, protein molecules associated with inflammation. Inflammation is an immune response; in the short term, it's crucial for moving immune cells to the source of a wound or infection. But when inflammatory responses become chronic, they can damage the body.

Studies in mice have also found that an overactive immune system appears to be linked to depression. However, researchers didn't understand how the process of inflammation might influence mental health.

"We still were missing the link between inflammation and what was actually happening to the brain cells," Brundin said.

To find out, Brundin and her colleagues tested 100 Swedish adults for quinolinic acid, a compound known to be generated by inflammation and to have an effect in the brain due to its similarities to the neurotransmitter glutamate. This is a tough compound to test for, requiring not a simple blood draw but the extraction of cerebrospinal fluid, the clear, yellowish liquid that cushions the brain and spinal cord.

About two-thirds of the Swedish participants were tested right after hospitalization for a suicide attempt. The rest were healthy. The results revealed that the stronger the urge to commit suicide, the higher the levels of quinolinic acid in the spinal fluid.

Hope for treatments

The researchers did not compare the suicidal patients with severely depressed but not suicidal individuals, so it's not clear whether quinolinic acid is linked only to suicide or to difficult-to-treat depression more broadly. Either way, Brundin said, the research suggests a need to widen depression treatments beyond those used today, which are usually based around the neurotransmitter serotonin.

Specifically, the neurotransmitter glutamate might offer new avenues for treatment. Glutamate is the neurotransmitter that quinolinic acid mimics. In a healthy brain, it plays an important role in exciting nerve cells. However, the discovery that quinolinic acid contributes to suicide or depression by playing copycat to glutamate suggests that targeting this neurotransmitter could provide relief.

Already, small studies have suggested the anesthetic ketamine, when injected into the bloodstream, can banish suicidal symptoms within hours, Brundin said. Ketamine has anti-glutamate effects.

"If the pharmaceutical industry can continue developing anti-glutamate medication, I think that might be a great hope for suicidal and depressive patients," Brundin said.

Brundin and her colleagues will report their findings in a forthcoming issue of the journal
Neuropsychopharmacology.