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. 2022 Mar 31;11(7):1183.
doi: 10.3390/cells11071183.

The Immune Profile of Major Dysmood Disorder: Proof of Concept and Mechanism Using the Precision Nomothetic Psychiatry Approach

Michael Maes  1   2   3 , Muanpetch Rachayon  1 , Ketsupar Jirakran  1   4 , Pimpayao Sodsai  5   6 , Siriwan Klinchanhom  5   6 , Piotr Gałecki  7 , Atapol Sughondhabirom  1 , Agnieszka Basta-Kaim  8
Affiliations

The Immune Profile of Major Dysmood Disorder: Proof of Concept and Mechanism Using the Precision Nomothetic Psychiatry Approach

Michael Maes et al. Cells. .

Abstract

Major depressive disorder and a major depressive episode (MDD/MDE) are characterized by activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS). In MDD/MDE, recent precision nomothetic psychiatry studies discovered a new endophenotype class, namely major dysmood disorder (MDMD), a new pathway phenotype, namely reoccurrence of illness (ROI), and a new model of the phenome of depression. The aim of the present study is to examine the association between ROI, the phenome of depression, and MDMD's features and IRS, CIRS, macrophages (M1), T helper (Th)1, Th2, Th17, T regulatory, and growth factor (GF) profiles. Culture supernatants of unstimulated and stimulated (5 μg/mL of PHA and 25 μg/mL of LPS) diluted whole blood of 30 MDD/MDE patients and 20 controls were assayed for cytokines/GF using the LUMINEX assay. MDMD was characterized by increased M1, Th1, Th2, Th17, Treg, IRS, CIRS, neurotoxicity, and GF profiles. Factor analysis shows that ROI features and immune-GF profiles may be combined into a new pathway phenotype (an extracted latent vector). ROI, lifetime and recent suicidal behaviors, and severity of depression are significantly associated with immunotoxicity and GF profiles. Around 80.0% of the variance in the phenome is predicted by ROI and neurotoxicity or the IRS/CIRS ratio. The molecular pathways underpinning ROI-associated sensitization of immune/growth networks are transmembrane receptor protein kinase-triggered STAT protein phosphorylation, TLR/NF-κB, JAK-STAT, and the main proliferation/survival PI3K/Akt/RAS/MAPK pathway. In conclusion, MDMD's heightened immune responses are the consequence of ROI-associated sensitization combined with immunostimulatory triggers.

Keywords: cytokines; depression; inflammation; mood disorders; neuroimmunomodulation; psychiatry.

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Conflict of interest statement

The authors have no conflict of interest with any commercial or other association in connection with the submitted article.

Figures

Figure 1
Figure 1
Partial regression of the phenome score on the recurrence of illness (ROI).
Figure 2
Figure 2
Partial regression of the phenome score on the immune-neurotoxicity index.
Figure 3
Figure 3
Partial regression of the phenome score on an index of the compensatory immune-regulatory system.
Figure 4
Figure 4
Partial regression plot of the phenome score on the immune-inflammatory response system (IRS)/compensatory immune-regulatory system (CIRS) ratio.
Figure 5
Figure 5
(A) The protein–protein interaction network (PPIN) of the 14 differentially expressed immune/growth factors of major dysmood disorder (MDMD). (B) The first order PPIN of the growth factor cluster of MDMD.
Figure 6
Figure 6
Bar chart with the top ten Elsevier Pathways that are over-represented in the first-order protein–protein interaction network of major dysmood disorder. *: the term has a significant adjusted p-value (<0.05).
Figure 7
Figure 7
Results of GOnet enrichment analysis showing the 14 seed differentially expressed proteins of major dysmood disorder and their significant GO annotations.
See this image and copyright information in PMC

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