The Role of Stress and Mineralocorticoid Receptor Haplotypes in the Development of Symptoms of Depression and Anxiety During Adolescence

Abstract

Adolescence is a critical developmental period characterized by heightened levels of depressive and anxiety symptoms. Experiencing chronic or environmental stress, for example, as a result of traumatic events or insensitive parenting, increases the risk for depression and anxiety. However, not all adolescents develop depressive or anxiety symptoms following environmental stressors, due to differences in stress resilience. One of the factors involved in stress resilience is enhanced functionality of the mineralocorticoid receptor (MR), one of the two brain receptors for the stress hormone cortisol. High levels of MR functionality result in relatively lower rates of depression, particularly in women that experienced stress. However, much less is known about MR functionality in relation to the development of adolescent depression and to other internalizing behavior problems such as anxiety. We therefore examined whether the effects of a functional MR haplotype (i.e., the MR CA haplotype) on the development of depressive and anxiety symptoms are sexdependent, as well as interact with environmental stressors. In a community sample of adolescents (N = 343, 9 waves between age 13 and 24), environmental stressors were operationalized as parental psychological control and childhood trauma. Results showed a sex-dependent effect of MR CA haplotype on the development of depressive symptoms but not for anxiety symptoms. MR CA haplotypes were protective for girls but not for boys. This study sheds more light on the sex-dependent effects of MR functionality related to the development of depressive and anxiety symptoms during adolescence.

Stable Anxiety and Depression Trajectories in Late Adolescence for Oral Contraceptive Users

“…Both our raw and modeled data show an overall increase for depressive symptoms in late adolescence, which is in line with previous studies using the same dataset that have shown an increase in internalizing symptoms in late adolescence for boys and girls ( 56 – 58 ). In the study by Nelemans et al ( 57 ), the results for girls showed a larger intercept and less steep incline in depressive symptoms in late adolescence compared to boys.…”

Large-scale genomic data-mining implicates dysregulated nuclear receptor-mediated signaling in mental illness

“…MR is a high-affinity corticosteroid receptor that acts in synergy with the glucocorticoid receptor (GR) to mediate the molecular stress response. Both GR and MR belong to a gene co-expression cluster with peak expression in puberty and adulthood; however, whereas GR is widely expressed in the brain and peak in cerebellar tissue, MR expression peaks in limbic tissues, in accordance with previously published reports [147] . MR plays a well-documented and sex-biased role in stress resilience and depression [148] , where a functional MR haplotype protects against depression following early life trauma [149] .…”

Potential Biomarkers for Diagnosing Major Depressive Disorder Patients with Suicidal Ideation

“…Previous studies reported that the anxiety symptoms are frequently found to coexist with depression symptoms. 39 , 40 An epidemiologic study found that in patients with lifetime MDD, 59% of patients experienced at least one lifetime anxiety disorder. 41 Therefore, considering the high prevalence of comorbid anxiety disorder and MDD, we did not exclude the MDD patients with anxiety disorder in this study, which might enhance the generalizability of our conclusion.…”