Diagnosis of major depressive disorder based on changes in multiple plasma neurotransmitters: a targeted metabolomics study

Sid · Sep 27, 2018

Small sample size but strengths of the study include using medication-free first-episode major depression and an illness control group (bipolar disorder).

Major depressive disorder (MDD) is a debilitating psychiatric illness. However, there is currently no objective laboratory-based diagnostic tests for this disorder. Although, perturbations in multiple neurotransmitter systems have been implicated in MDD, the biochemical changes underlying the disorder remain unclear, and a comprehensive global evaluation of neurotransmitters in MDD has not yet been performed.

Here, using a GC-MS coupled with LC-MS/MS-based targeted metabolomics approach, we simultaneously quantified the levels of 19 plasma metabolites involved in GABAergic, catecholaminergic, and serotonergic neurotransmitter systems in 50 first-episode, antidepressant drug-naïve MDD subjects and 50 healthy controls to identify potential metabolite biomarkers for MDD (training set). Moreover, an independent sample cohort comprising 49 MDD patients, 30 bipolar disorder (BD) patients and 40 healthy controls (testing set) was further used to validate diagnostic generalizability and specificity of these candidate biomarkers.

Among the 19 plasma neurotransmitter metabolites examined, nine were significantly changed in MDD subjects. These metabolites were mainly involved in GABAergic, catecholaminergic and serotonergic systems. The GABAergic and catecholaminergic had better diagnostic value than serotonergic pathway. A panel of four candidate plasma metabolite biomarkers (GABA, dopamine, tyramine, kynurenine) could distinguish MDD subjects from health controls with an AUC of 0.968 and 0.953 in the training and testing set, respectively. Furthermore, this panel distinguished MDD subjects from BD subjects with high accuracy.

This study is the first to globally evaluate multiple neurotransmitters in MDD plasma. The altered plasma neurotransmitter metabolite profile has potential differential diagnostic value for MDD.
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Full text at: https://www.nature.com/articles/s41398-018-0183-x

Hoopoe · Sep 27, 2018

The two biggest changes (both increases) were tyramine and dopamine levels.

Tyramine was 19.26±4.30 in patients and 1.98±0.33 in controls. Dopamine was 1.01±0.16 in patients and 0.28±0.04 in controls. Many of the other neurotransmitters had smaller changes.

How does this relate to monoamine oxidase inhibitors? Wouldn't they increase tyramine further?

Sid · Sep 27, 2018

strategist said: ↑

The two biggest changes (both increases) were tyramine and dopamine levels.

Tyramine was 19.26±4.30 in patients and 1.98±0.33 in controls. Dopamine was 1.01±0.16 in patients and 0.28±0.04 in controls. Many of the other neurotransmitters had smaller changes.

How does this relate to monoamine oxidase inhibitors? Wouldn't they increase tyramine further?
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This study measured plasma metabolites. What's going on in the brain is anyone's guess until we see some CSF data.

Hutan · Sep 27, 2018

This study is the first to globally evaluate multiple neurotransmitters in MDD plasma. The altered plasma neurotransmitter metabolite profile has potential differential diagnostic value for MDD.
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From the abstract, it looks like quite a nice study and pretty important: a potential biomarker holding up well when checked on a testing set.

It leaves me wondering why no one did this study before. Perhaps it's indicative of biomedicine becoming more important in what have been labelled psychiatric conditions?

Sid · Sep 28, 2018

Hutan said: ↑

From the abstract, it looks like quite a nice study and pretty important: a potential biomarker holding up well when checked on a testing set.

It leaves me wondering why no one did this study before. Perhaps it's indicative of biomedicine becoming more important in what have been labelled psychiatric conditions?
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There have been some previous metabolomic studies of MDD and other conditions labelled psychiatric but you know how it goes, everyone measures different things. There are a lot of metabolites.

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Diagnosis of major depressive disorder based on changes in multiple plasma neurotransmitters: a targeted metabolomics study

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Diagnosis of major depressive disorder based on changes in multiple plasma neurotransmitters: a targeted metabolomics study

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