Gene–Environment Interaction in Major Depression: Focus on Experience-Dependent Biological Systems

Abstract

Major depressive disorder (MDD) is a multifactorial and polygenic disorder, where multiple and partially overlapping sets of susceptibility genes interact each other and with the environment, predisposing individuals to the development of the illness. Thus, MDD results from a complex interplay of vulnerability genes and environmental factors that act cumulatively throughout individual’s lifetime. Among these environmental factors, stressful life experiences, especially those occurring early in life, have been suggested to exert a crucial impact on brain development, leading to permanent functional changes that may contribute to lifelong risk for mental health outcomes. In this review, we will discuss how genetic variants (polymorphisms, SNPs) within genes operating in neurobiological systems that mediate stress response and synaptic plasticity, can impact, by themselves, the vulnerability risk for MDD; we will also consider how this MDD risk can be further modulated when gene × environment interaction is taken into account. Finally, we will discuss the role of epigenetic mechanisms, and in particular of DNA methylation and miRNAs expression changes, in mediating the effect of the stress on the vulnerability risk to develop MDD. Taken together, we aim to underlie the role of genetic and epigenetic processes involved in stress- and neuroplasticity-related biological systems on the development of MDD after exposure to early life stress, thereby building the basis for future research and clinical interventions.

Neuronal correlates of depression

“…Recent groundbreaking studies showing rapid alleviation of depression with deep brain stimulation (DBS) strongly suggests that depression is a neural circuit disorder [8–11]. Advances in molecular studies have highlighted the role of specific molecular signaling and epigenetic changes and the associated modifications in neuronal development of depression [12–17]. It is likely that these differential molecular and functional responses in various brain regions may be responsible for the wide spectrum of symptoms observed in depressive patients.…”

Relationship between major depressive disorder and ACE gene I/D polymorphism in a Turkish population

“…Studies suggest that 10% to 15% of the general population will be exposed to clinical depression during their life 1 . Although the etiopathogenesis of the disease is not fully understood yet, it has been estimated that a genetic susceptibility could be effective in the onset of MDD 3 . Also, MDD is because of a complex genetic heterogeneity.…”

The BDNF Val66Met Polymorphism Interacts with Maternal Parenting Influencing Adolescent Depressive Symptoms: Evidence of Differential Susceptibility Model

“…A large number of studies have examined G 9 E interactions using a candidate-gene approach when investigating adult depression (Lopizzo et al 2015), but less research on gene-environment interaction has targeted youth. Extant G 9 E work on youth depression has mostly focused on the interaction between the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and childhood maltreatment or stressful life events, yielding mixed findings concerning the putative risk allele (Dunn et al 2011).…”