Family, twin, and epidemiologic studies have suggested that both genes and environment are important risk factors for the development of major depressive disorder (MDD). In the absence of consistent and strong main genetic effects, numerous studies have supported gene-environment interactions in this disorder. While the impact of negative environmental factors, such as early life stress, traumatic experiences, and negative life events have been established as risk factors, they are not sufficient to predict MDD. This article will review evidence suggesting that genetic variants moderate the effects of adversities on the development of MDD, with a focus on the importance of careful characterization of the stressful life events as well as systemic and molecular mechanisms that potentially mediate these gene-environment interactions.
"schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD) are largely unknown. These disorders are heterogeneous in nature, with genetic and environmental factors contributing to pathogenesis and aetiology (Levinson, 2006; van Os and Kapur, 2009; Kim et al., 2011; Craddock and Sklar, 2013; Klengel and Binder, 2013). Symptom profiles greatly overlap with regards to clinical psychopathology as well as putative pathophysiology (Smoller et al., 2013). "
"The gene Â environment interaction framework postulates that environmental factors cause disorders to occur and that genetic variants influence vulnerability as well as resilience to these factors, leading to psychopathology in some individuals only. It is well established that the experience of life adversity is an important environmental factor in the etiology of MDD (Klengel and Binder, 2013). For example, a study by Kendler and colleagues demonstrated a causal relationship between stressful life events and the onset of MDD (Kendler et al., 1999). "
[Show abstract][Hide abstract] ABSTRACT: Substantial research has been conducted investigating the association between life adversity and genetic vulnerability for depression, but clear mechanistic links are rarely identified and investigation often focused on single genetic variants. Complex phenotypes like depression, however, are likely determined by multiple variants in interaction with environmental factors. As variations in the mineralocorticoid receptor gene (NR3C2) have been related to a higher risk for depression, we investigated whether NR3C2 variance is related to negative memory bias, an established endophenotype for depression, in healthy participants. Furthermore, we explored the influence of life adversity on this association.
We used a set-based analysis to simultaneously test all measured variation in NR3C2 for an association with negative memory bias in 483 participants and an interaction with life adversity. To further specify this interaction, we split the sample into low and high live adversity groups and repeated the analyses in both groups separately.
NR3C2 variance was associated with negative memory bias, especially in the high life adversity group. Additionally, we identified a functional polymorphism (rs5534) related to negative memory bias and demonstrating a gene × life adversity interaction.
Variations in NR3C2 are associated with negative memory bias and this relationship appears to be influenced by life adversity. As negative memory bias is implicated in the susceptibility to depression, our findings provide mechanistic support for the notion that variations in NR3C2 – which could compromise the proper function of this receptor – are a risk factor for the development of mood disorders.
[Show abstract][Hide abstract] ABSTRACT: To study the effect of moderate stress on corticotrophin-releasing factor (CRF) components in the serotonergic midbrain region in a monkey model of functional hypothalamic amenorrhea.
After characterization of stress sensitivity, monkeys were moved to a novel room and given 20% less chow for 5 days before euthanasia.
Primate research center.
Female cynomolgus macaques (Macaca fascicularis) characterized as highly stress resilient (HSR, n = 5), medium stress resilient (n = 4), or stress sensitive (SS, n = 4).
Five days of diet in a novel room with unfamiliar conspecifics.
Density of CRF axons in the serotonergic dorsal raphe nucleus; the number of urocortin 1 (UCN1) cells; the density of UCN1 axons; the expression of CRF receptor 1 (CRF-R1) and CRF-R2 in the dorsal raphe nucleus.
The CRF innervation was higher in HSR than in SS animals; UCN1 cell number was higher in HSR than in SS animals and UCN1 axon bouton density was not different; all opposite of nonstressed animals. The CRF-R1 was not different between the sensitivity groups, but CRF-R2 was higher in HSR than in SS animals. The relative expression of CRF-R1 and CRF-R2 was similar to nonstressed animals.
The HSR animals respond to stress with an increase in CRF delivery to serotonin neurons. With stress, UCN1 transport decreases in HSR animals. The CRF receptor expression was similar with or without stress. These changes may contribute to resilience in HSR animals.
Fertility and sterility 07/2013; 100(4). DOI:10.1016/j.fertnstert.2013.05.052 · 4.59 Impact Factor
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