J.M. Geleijnse

A common and functional mineralocorticoid receptor haplotype enhances optimism and protects against depression in females

Mineralocorticoid (MR) and glucocorticoid receptors (GR) are abundantly expressed in the limbic brain and mediate cortisol effects on the stress-response and behavioral adaptation. Dysregulation of the stress response impairs adaptation and is a risk factor for depression, which is twice as abundant in women than in men. Because of the importance of MR for appraisal processes underlying the initial phase of the stress response we investigated whether specific MR haplotypes were associated with personality traits that predict the risk of depression. We discovered a common gene variant (haplotype 2, frequency ∼0.38) resulting in enhanced MR activity. Haplotype 2 was associated with heightened dispositional optimism in study 1 and with less hopelessness and rumination in study 2. Using data from a large genome-wide association study we then established that haplotype 2 was associated with a lower risk of depression. Interestingly, all effects were restricted to women. We propose that common functional MR haplotypes are important determinants of inter-individual variability in resilience to depression in women by differentially mediating cortisol effects on the stress system.

Effects of n−3 fatty acids on depressive symptoms and dispositional optimism after myocardial infarction

BACKGROUNDnIn patients who have experienced a myocardial infarction (MI), n-3 (omega-3) PUFA status is low, whereas the risk of depression is increased.nnnOBJECTIVEnThe objective was to assess whether the plant-derived α-linolenic acid (ALA) and the fish fatty acids EPA and DHA would improve affective states.nnnDESIGNnIn a secondary analysis of the randomized, double-blind, placebo-controlled Alpha Omega Trial, 4116 of 4837 (85.1%) patients (aged 60-80 y; 79.2% men) who had experienced an MI were included. Margarine spreads were used to deliver 400 mg EPA-DHA/d, 2 g ALA/d, both EPA-DHA and ALA, or a placebo for 40 mo. At 40 mo, the endpoints of depressive symptoms (15-item Geriatric Depression Scale) and dispositional optimism (a 4-item questionnaire and the Life Orientation Test-Revised) were analyzed by using a posttest-only design.nnnRESULTSnThe 4 randomly assigned groups did not differ in baseline characteristics. ALA supplementation significantly increased plasma cholesteryl ester concentrations of ALA by 69%, and EPA-DHA supplementation increased plasma cholesteryl ester concentrations of EPA and DHA by 61% and 30%, respectively. Depressive symptoms or dispositional optimism did not differ between groups with the use of n-3 fatty acids compared with placebo at the 40-mo follow-up. The standardized mean (±SE) differences in depressive symptoms were as follows: for EPA-DHA plus ALA (n = 1009) compared with placebo (n = 1030), -0.025 ± 0.044 (P = 0.57); for EPA-DHA (n = 1007) compared with placebo, -0.048 ± 0.044 (P = 0.28); and for ALA (n = 1022) compared with placebo, -0.047 ± 0.044 (P = 0.29).nnnCONCLUSIONSnIn patients who had experienced an MI, low-dose EPA-DHA supplementation, ALA supplementation, or a combination of both did not affect depressive symptoms and dispositional optimism. These findings are in accord with those from previous trials in individuals without psychopathology or without severe depressive symptoms. This trial was registered at clinicaltrials.gov as NCT00127452.