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New study uncovers biological differences between psychiatric disorders

Tristan Manalac
23 Dec 2020
In psychiatric disorders, rather than producing serotonin, tryptophan is instead sequestered through and metabolized along the kynurenine pathway, yielding metabolic by-products such as kynurenic acid, quinolinic acid, and 3-hydroxykynurenine, according to a recent study.

Moreover, different psychiatric conditions have different level profiles of these metabolites. The neurotoxic quinolinic acid, for example, seems to be preferentially synthesized in mood disorders, such as major depressive (MDD) and bipolar (BD) disorder, but not in schizophrenia (SZ).

“Tryptophan, the main precursor of the kynurenine pathway, is decreased across all mental disorders considered. This likely reflects its relative importance in these disorders, particularly in the context of serotonin bioavailability,” the researchers said. “Decreased bioavailability of tryptophan is at least partially responsible for the depleted levels of serotonin found in MDD.”

A systematic search of three online databases returned 101 studies eligible for meta-analysis, comprising 10,912 participants (median age, 25 years). More than half (n=5,856) had psychiatric disorders, while 5,056 were controls. Most of the studies measured metabolites in plasma, as opposed to serum. [Mol Psychiatry 2020;doi:10.1038/s41380-020-00951-9]

In patients with MDD, tryptophan (g, –0.51; p<0.001), kynurenine (g, –0.26; p<0.001), and kynurenic acid (g, –0.37; p=0.001) were all significantly suppressed, while levels of quinolinic acid and 3-hydroxykynurenine were unaltered. The ratios of kynurenic acid to quinolinic acid (p<0.001), kynurenine (p=0.003), and 3-hydroxykynurenine (p<0.001) were all also significantly reduced in MDD.

In BD, levels of only tryptophan (g, –0.56; p<0.001) and kynurenic acid (g, –0.44; p<0.001) were significantly attenuated; the resulting ratio between kynurenic acid and quinolinic acid was likewise lowered (p<0.0001). No such impacts were observed for the other metabolites and ratios.

“In mood disorders, kynurenic acid is lower, and the ratios of kynurenic acid to kynurenine, and of kynurenic acid to 3-hydroxykynurenine are decreased compared to healthy subjects, suggesting an imbalance between the putatively neuroprotective kynurenic acid and the neurotoxic quinolinic acid, with a preponderance of quinolinic acid,” the researchers explained.

“Quinolinic acid, however, is not increased in mood disorders, thus it is not possible to say if this imbalance is due to a decrease in kynurenic acid … [solely or] in tandem with an increase in quinolinic acid,” they added.

In SZ, on the other hand, while bioavailable tryptophan was also lowered (g, –0.24; p=0.04) and its metabolism likewise shifted away from serotonin toward kynurenine, there was no strong evidence supporting an imbalance between the kynurenic and quinolinic acids.

Taken together, these findings suggest that “a differential pattern exists between mood disorders and SZ, with a preferential metabolism of kynurenine to the potentially neurotoxic quinolinic acid instead of the neuroprotective kynurenic acid in mood disorders but not in SZ,” the researchers said.

“Further studies are required to examine the individual characteristics that modulate kynurenine metabolism in these disorders and to investigate potential treatment options,” they added.

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Most Read Articles
01 Dec 2020
Tetanus toxoid 5 Lf, diphtheria toxoid 2 Lf, pertussis toxoid 2.5 mcg, filamentous haemagglutinin 5 mcg, fimbriae types 2 and 3 5 mcg, pertactin 3 mcg
Dr. Hsu Li Yang, Dr. Tan Thuan Tong, Dr. Andrea Kwa, 08 Jan 2021
Antimicrobial resistance has become increasingly dire as the rapid emergence of drug resistance, especially gram-negative pathogens, has outpaced the development of new antibiotics. At a recent virtual symposium, Dr Hsu Li Yang, Vice Dean (Global Health) and Programme Leader (Infectious Diseases), NUS Saw Swee Hock School of Public Health, presented epidemiological data on multidrug-resistant (MDR) gram-negative bacteria (GNB) in Asia, while Dr Tan Thuan Tong, Head and Senior Consultant, Department of Infectious Diseases, Singapore General Hospital (SGH), focused on the role of ceftazidime-avibactam in MDR GNB infections. Dr Andrea Kwa, Assistant Director of Research, Department of Pharmacy, SGH, joined the panel in an interactive fireside chat, to discuss challenges, practical considerations, and solutions in MDR gram-negative infections. This Pfizer-sponsored symposium was chaired by Dr Ng Shin Yi, Head and Senior Consultant of Surgical Intensive Care, SGH.
Tristan Manalac, Yesterday
While antibody titres against SARS-CoV-2 wane with time, the immune system is capable of producing memory B-cells that can last for at least 6 months after infection, suggesting that the body will be able to protect itself in the case of re-exposure, according to a new study.
Jairia Dela Cruz, 5 days ago
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