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Suicide prevention drug steps closer with enzyme discovery

October 5th, 2016
Suicide is the cause of more than 42,000 deaths in the United States every year, making it the 10th leading cause of death in the country. Now, a new study paves the way for a drug to avert suicidal behavior, after identifying an enzyme related to brain inflammation that has the potential to predict and prevent suicide.
[A depressed man]
“Researchers say their findings may being us closer to a drug that can prevent suicidal behavior.”

In the journal Translational Psychiatry, researchers reveal how a certain variant of the enzyme ACMSD leads to abnormal levels of two acids in the brain, which may encourage suicidal behavior.

The research team – including senior author Dr. Lena Brundin of the Center for Neurodegenerative Science at Van Andel Research Institute in Grand Rapids, MI – say their findings could bring us closer to a blood test that can identify patients at high risk of suicide.

What is more, the study suggests ACMSD could be a promising drug target for suicide prevention.

According to Dr. Brundin and colleagues, previous research has suggested the immune system plays a role in depression and suicidal behavior, primarily by responding to stress with inflammation.

However, the underlying mechanisms of this association have been unclear, which has hampered the discovery of clinical strategies to prevent suicide. The new study aimed to shed some light.

Past studies have shown patients with suicidal behavior experience persistent inflammation in their blood and cerebrospinal fluid (CSF).

With this in mind, the researchers assessed the blood and CSF samples of more than 300 individuals from Sweden, some of whom had attempted suicide.

ACMSD enzyme variant more prevalent in people with suicidal behavior

On comparing samples, the team found that individuals who had attempted suicide had abnormal levels of both picolinic acid and quinolinic acid. These irregular acid levels were identifiable in samples taken straight after a suicidal attempt and at various points over the subsequent 2 years.

Among subjects with suicidal behavior, levels of picolinic acid – known to have neuroprotective effects – were too low, while their levels of quinolinic acid – a known neurotoxin – were too high.

These abnormal levels were most prominent in CSF, the team reports, though they could still be identified in blood samples.

Since previous research had shown that both picolinic and quinolinic acid are regulated by the enzyme ACMSD – known to regulate brain inflammation – the researchers conducted a genetic analysis of individuals with suicidal behavior, as well as healthy controls.

From this, they found that individuals who had attempted suicide were more likely to possess a specific variant of ACMSD, and this variant was associated with increased levels of quinolinic acid.

While the study is unable to demonstrate that ACMSD activity is directly linked to suicide risk, the researchers say their findings suggest the enzyme could be a potential drug target for suicide prevention.

“We now want to find out if these changes are only seen in individuals with suicidal thoughts or if patients with severe depression also exhibit this. We also want to develop drugs that might activate the enzyme ACMSD and thus restore balance between quinolinic and picolinic acid.”

Co-study leader Dr. Sophie Erhardt, Karolinska Institutet, Sweden

 

Additionally, since the results show that abnormal levels of picolinic and quinolinic acid can be identified in the blood, the team says they may bring us closer to a blood test that can identify patients at high risk of suicidal behavior.

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http://www.medicalnewstoday.com/articles/313287.php

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