Dissecting major depression: The role of blood biomarkers and adverse childhood experiences in distinguishing clinical subgroups

Luisa Lo Iacono; Silvia Bussone; Diego Andolina; Renata Tambelli; Alfonso Troisi; Valeria Carola

doi:10.1016/j.jad.2020.07.034

Dissecting major depression: The role of blood biomarkers and adverse childhood experiences in distinguishing clinical subgroups

J Affect Disord. 2020 Nov 1:276:351-360. doi: 10.1016/j.jad.2020.07.034. Epub 2020 Jul 16.

Authors

Luisa Lo Iacono¹, Silvia Bussone², Diego Andolina³, Renata Tambelli², Alfonso Troisi⁴, Valeria Carola⁵

Affiliations

¹ IRCCS Fondazione Santa Lucia, Rome, Italy.
² Department of Dynamic and Clinical Psychology, Sapienza University of Rome, Via degli Apuli, 1, 00185 Rome, Italy.
³ IRCCS Fondazione Santa Lucia, Rome, Italy; Department of Psychology, Sapienza University of Rome, Rome, Italy.
⁴ Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
⁵ IRCCS Fondazione Santa Lucia, Rome, Italy; Department of Dynamic and Clinical Psychology, Sapienza University of Rome, Via degli Apuli, 1, 00185 Rome, Italy. Electronic address: valeria.carola@uniroma1.it.

PMID: 32871665
DOI: 10.1016/j.jad.2020.07.034

Abstract

Background: The syndromic diagnosis of major depressive disorder (MDD) is associated with individual differences in prognosis, course, treatment response, and outcome. There is evidence that patients with a history to adverse childhood experiences (ACEs) may belong to a distinct clinical subgroup. The combination of data on ACEs and blood biomarkers could allow the identification of diagnostic MDD subgroups.

Methods: We selected several blood markers (global DNA methylation, and VEGF-a, TOLLIP, SIRT1, miR-34a genes) among factors that contribute to the pathogenetic mechanisms of MDD. We examined their level in 37 MDD patients and 30 healthy subjects. ACEs were measured by the Parental Bonding Instrument and the Childhood Trauma Questionnaire.

Results: We found significant differences between patients and healthy subjects in three biomarkers (TOLLIP, VEGF-a, and global DNA methylation), independently from the confounding effect of parental care received. By contrast, SIRT1 differences were modulated by quality of parental care. The lowest levels of SIRT1 were recorded in patients with active symptoms and low maternal/paternal care. miR-34a and SIRT1 levels were associated with MDD symptoms especially in early-life stressed patients.

Limitations: Small sample size, no information on personality comorbidity and suicidal history, cross-sectional definition of remission, and lack of follow-up.

Conclusions: Our findings suggest that the levels of global DNA methylation, TOLLIP, and VEGF-a reflect pathophysiological changes associated with MDD that are independent from the long-term effects of low parental care. This study also suggests that SIRT1 may be an additional variable distinguishing the ecophenotype that includes MDD patients with exposure to ACEs.

Keywords: Adverse childhood experiences; Childhood Trauma Questionnaire; Global DNA methylation; Major depressive disorder; MicroRNA-34a; Parental bonding instrument; SIRT1; TOLLIP; VEGF-a.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adverse Childhood Experiences*
Biomarkers
Child
Cross-Sectional Studies
Depression
Depressive Disorder, Major* / diagnosis
Humans
Intracellular Signaling Peptides and Proteins

Substances

Biomarkers
Intracellular Signaling Peptides and Proteins
TOLLIP protein, human