Overview of the Genetics of Major Depressive Disorder

Abstract

Major depressive disorder (MDD) is a common psychiatric illness with high levels of morbidity and mortality. Despite intensive research during the past several decades, the neurobiological basis and pathophysiology of depressive disorders remain unknown. Genetic factors play important roles in the development of MDD, as indicated by family, twin, and adoption studies, and may reveal important information about disease mechanisms. This article describes recent developments in the field of psychiatric genetics, with a focus on MDD. Early twin studies, linkage studies, and association studies are discussed. Recent findings from genome-wide association studies are reviewed and future directions discussed. Despite all efforts, thus far, no single genetic variation has been identified to increase the risk of depression substantially. Genetic variants are expected to have only small effects on overall disease risk, and multiple genetic factors in conjunction with environmental factors are likely necessary for the development of MDD. Future large-scale studies are needed to dissect this complex phenotype and to identify pathways involved in the etiology of MDD.

microRNA and mRNA profiles in nucleus accumbens underlying depression versus resilience in response to chronic stress

“…Major depression is presumably caused by chronic stress life plus genetic vulnerability, and is characterized by persistent negative mood, such as anhedonia, interest loss, and low self‐esteem (Camp & Cannon‐Albright, 2005; Hamilton, Chen, & Gotlib, 2013; Jabbi, Korf, Ormel, Kema, & den Boer, 2008; Keers & Uher, 2012; Klengel & Binder, 2013; Lohoff, 2010; Moylan, Maes, Wray, & Berk, 2013; Wilde, Mitchell, Meiser, & Schofield, 2013). Pathological changes in monoamine synapses, hypothalamus‐pituitary‐adrenal axis, and brain‐derived neurotrophic factor are believed to cause neuronal atrophy in the ventral tegmental area, nucleus accumbens, and prefrontal cortex from depressive patients and depression‐like animals (Banasr, Dwyer, & Duman, 2011; Bennett et al, 2008; Duman, 2010; Elizalde et al, 2008; Ma, Xu, et al, 2016; Pittenger & Duman, 2008; Sandi & Haller, 2015; Xu, Cui, & Wang, 2016).…”

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

“…Although many factors were considered as the cause of this disease, its etiology has not been ascertained yet. Studies with families, twins and fosterlings reveal that genetic factors play an important role in its etiology 1 . The prevalence of disease varies according to countries and age groups 2 .…”

“…The prevalence of disease varies according to countries and age groups 2 . 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 .…”

The ‘affect tagging and consolidation’ (ATaC) model of depression vulnerability

“…The importance of interactions between variants in clock genes and genes which modulate monoaminergic pathways such as the 5-HT system may go some way towards explaining the weak association between 'risk genes' and the prevalence of depression (Lohoff, 2010;Mitjans & Arias, 2012), whilst accounting for the comparatively high heritability of MDD (Agrawal, Jacobson, Gardner, Prescott, & Kendler, 2004;Kendler, Gardner, Neale, & Prescott, 2001;Sullivan, Neale, & Kendler, 2000). It should be noted however that in order to focus on core elements of the ATaC model we have discussed in this review only the fundamental mechanisms underlying negatively-biased emotional memory; notwithstanding, we acknowledge that the overarching cause of depression is likely to be much more complex.…”