Biological correlates of early life stressful events in major depressive disorder. (March 2021)

• Record Type: Journal Article
• Authors: Silva, Rosana Carvalho; Maffioletti, Elisabetta; Gennarelli, Massimo; Baune, Bernhard T.; Minelli, Alessandra
• Is Part Of: Psychoneuroendocrinology. Volume 125(2021)
• Publication Date: 2021-03
• Subjects: Major depressive disorder (MDD) -- Childhood maltreatment -- Early life stress -- Biomarkers -- Gene expression -- Epigenetics; Psychoneuroendocrinology -- Periodicals; Endocrinology -- Periodicals; Neurology -- Periodicals; Psychiatry -- Periodicals; Neuropsychoendocrinologie -- Périodiques; 616.8
• DOI: 10.1016/j.psyneuen.2020.105103
• Languages: English
• ISSNs: 0306-4530

Abstract

Abstract: Major depressive disorder (MDD) is the most common psychiatric disorder and responds for important psychosocial consequences. Stressful life events, especially early life stress (ELS), contribute to an increased probability to develop MDD, leading in particular to severe and chronic manifestation and unfavorable treatment outcome. The association between ELS and MDD seems to have biological bases, consisting in dysregulations occurring at different levels. The aim of this narrative review is to propose an overview of the literature ranging from genetic, epigenetic, expression and protein to neuroimaging correlates underlying this relationship. A search on Pubmed of studies assessing biological correlates of ELS in MDD development, focusing on human studies conducted in both peripheral and brain tissues, was performed. Evidence indicated that the hypothalamic-pituitary-adrenal (HPA) axis and the serotonergic, dopaminergic, neurotrophin and oxytocin systems might play a role in the mediation between ELS and MDD. The most consistent results were found for genetic and epigenetic studies and indicated a joint involvement of the systems mentioned. Expression studies are less numerous and point to an involvement of stress-related systems. Concerning protein studies, the main mediators are markers related to the inflammatory and immune systems. Neuroimaging studies aiming at evaluating brain alterations connecting ELS and MDD in relation to biomarkers indicated the hippocampus, the amygdala and the frontal cortex as important anatomical mediators. These findings can build the bases for future research and clinical interventions; indeed, the clarification of biological mechanisms mediating the relationship between ELS and MDD can lead to new and individualized preventive and therapeutic possibilities. Highlights: ELS strongly contributes to the vulnerability to develop MDD. Several biomarkers underlie the relationship between ELS and MDD. Imbalances in various biological pathways may mediate the relation between ELS and MDD. Main mediators are markers related to the inflammatory and immune systems. ELS biomarkers can lead to individualized therapeutic strategies in MDD.