Scientists come up with new biomarkers for depression

New research shows that blood serum levels of anthranilic acid, a protein tryptophan metabolite, can aid in predicting clinical depression onset and progression.

High levels of anthranilic acid in blood serums may predict major depression.
High levels of anthranilic acid in blood serums may predict major depression.

Throughout 2017, more than 300 million people worldwide were struggling with depression and since then the number has increased year after year.

17.3 million people in the United States, or more than 7 percent of the adult population, reported at least one major depressive episode in 2017.

In recent years, numerous studies have pointed to a correlation between depression and chronic inflammation, leading to an overarching theory that the root cause of clinical depression could be inflammation.

Researchers have investigated multiple biological pathways leading to inflammation in an attempt to untangle the physiological mechanisms which may explain depression.

Of these, some interest has arisen in the so-called kynurenine (KYN) pathway. KYN is one of several pathways for metabolizing tryptophan — an essential amino acid that is also a precursor to serotonin, the “happiness hormone.”

Previous studies have suggested that low levels of tryptophan in the body may account for depression and sleep disorders.

Professor Kuniaki Saito and associate professor Yasuko Yamamoto of Fujita Health University in Japan now proposed that the KYN pathway’s metabolites— or the products resulting from metabolizing tryptophan — may serve as biomarkers that can help identify the risk of depression.

Tryptophan metabolites and depression

“Different lines of scientific evidence indicate that the signs of[ major depressive disorder] include tryptophane metabolism,” Yamamoto notes.

The researchers tested the blood serum levels of 61 participants whose clinical depression results suggested a high risk of the disorder to check whether certain tryptophan metabolites in the blood could signify depression in some at-risk individuals.

They compared these results with those of 51 control participants who did not have such a risk and published the findings in the Nature journal Scientific Reports.

Prof. Saito and team used high-performance liquid chromatography to accurately measure metabolite concentrations in the KYN pathway.

They found that people at risk of depression had higher anthranilic acid serum levels, and that women who were more likely to develop depression had lower tryptophan levels.

The KYN pathway absorbs and metabolizes tryptophan into anthranilic acid and thus raises its levels — a fact that enhances the results.

‘A strong, direct correlation’

The researchers then wanted to test whether metabolites would predict the development of depression in humans. To do so, they used data from 33 individuals whose ratings of clinical depression showed a strong progression toward the disease at different times.

The analysis revealed a clear correlation over time between ever higher levels of anthranilic acid and increasingly severe depression symptoms.

Professor Saito says, “This result confirms that there is indeed a clear, direct correlation between blood levels of anthranilic acid and the intensity of depression on the scale of clinical depression.”

Eventually, the researchers tested levels of tryptophan metabolite in 48 individuals with chronic pain and 42 individuals who were pain free.

Here too, the analysis revealed high anthranilic acid levels and low tryptophan levels in people with chronic pain. Such results may indicate a correlation between, on the one side, chronic pain and inflammation and, on the other, depression.

“In general,” the authors conclude, “such findings suggest that[ anthranilic acid] may be a sensitive biomarker used to identify[ people at high risk of developing depression].”

“Monitoring[ tryptophan] metabolites may be useful in determining the progression of disease in depression,” and, as Prof. Saito says, “for the development of preventive medicine for depressive symptoms.”

Findings may also help to create tailored depression therapies, authors write in their paper.

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