Multidimensional Analysis of Major Depression: Association Between BDNF Methylation, Psychosocial and Cognitive Domains

Abstract

Major Depression is a complex disorder with a growing incidence worldwide and multiple variables have been associated with its etiology. Nonetheless, its diagnosis is continually changing and the need to understand it from a multidimensional perspective is clear. The purpose of this study was to identify risk factors for depression in a case-control study with 100 depressive inpatients and 87 healthy controls. A multivariate logistic regression analysis was performed including psychosocial factors, cognitive maladaptive schema domains, and specific epigenetic marks (BDNF methylation levels at five CpG sites in promoter IV). A family history of depression, the cognitive schemas of impaired autonomy/performance, impaired limits, other-directedness, and the methylation level of a specific CpG site were identified as predictors. Interestingly, we found a mediating effect of those cognitive schemas in the relationship between childhood maltreatment and depression. Also, we found that depressive patients exhibited hypomethylation in a CpG site of BDNF promoter IV, which adds to the current discussion about the role of methylation in depression. We highlight that determining the methylation of a specific region of a single gene offers the possibility of accessing a highly informative an easily measurable variable, which represents benefits for diagnosis. Following complete replication and validation on larger samples, models like ours could be applicable as additional diagnostic tools in the clinical context.

Keywords: BDNF; epigenetics; family history of depression; major depressive disorder; maladaptive cognitive schemas; methylation.

Figure 1

BDNF promoter IV region evaluated in this study (chr11: 27,701,519-27,701,826 UCSC Genome Browser Human GRCh38/hg38 Assembly).

Figure 2

Effect of childhood maltreatment on likelihood of MDD through cognitive schemas. Causal mediation analysis results. ACME stands for average causal mediation effects of childhood maltreatment on the likelihood of MDD through the cognitive schemas; ADE stands for average direct effects of childhood maltreatment on the likelihood of MDD; Total effect stands for the total effects (direct and indirect) of childhood maltreatment on the likelihood of MDD.