Importance of the brain corticosteroid receptor balance in metaplasticity, cognitive performance and neuro-inflammation.

Bruce McEwen's discovery of receptors for corticosterone in the rat hippocampus introduced higher brain circuits in the neuroendocrinology of stress. Subsequently, these receptors were identified as mineralocorticoid receptors (MRs) that are involved in appraisal processes, choice of coping style, encoding and retrieval. The MR-mediated actions on cognition are complemented by slower actions via glucocorticoid receptors (GRs) on contextualization, rationalization and memory storage of the experience. These sequential phases in cognitive performance depend on synaptic metaplasticity that is regulated by coordinate MR- and GR activation. The receptor activation includes recruitment of coregulators and transcription factors as determinants of context-dependent specificity in steroid action; they can be modulated by genetic variation and (early) experience. Interestingly, inflammatory responses to damage seem to be governed by a similarly balanced MR:GR-mediated action as the initiating, terminating and priming mechanisms involved in stress-adaptation. We conclude with five questions challenging the MR:GR balance hypothesis.

Mineralocorticoid receptor haplotype, oral contraceptives and emotional information processing.

BACKGROUND: Oral contraceptives (OCs) affect mood in some women and may have more subtle effects on emotional information processing in many more users. Female carriers of mineralocorticoid receptor (MR) haplotype 2 have been shown to be more optimistic and less vulnerable to depression. AIM: To investigate the effects of oral contraceptives on emotional information processing and a possible moderating effect of MR haplotype. METHODS: Cross-sectional study in 85 healthy premenopausal women of West-European descent. RESULTS: We found significant main effects of oral contraceptives on facial expression recognition, emotional memory and decision-making. Furthermore, carriers of MR haplotype 1 or 3 were sensitive to the impact of OCs on the recognition of sad and fearful faces and on emotional memory, whereas MR haplotype 2 carriers were not. LIMITATIONS: Different compounds of OCs were included. No hormonal measures were taken. Most naturally cycling participants were assessed in the luteal phase of their menstrual cycle. CONCLUSIONS: Carriers of MR haplotype 2 may be less sensitive to depressogenic side-effects of OCs.

Need for alternative ways of phenotyping of mood, anxiety, and somatoform disorders in biological research.

Variation in psychiatric symptomatology is continuous and does not coalesce into fairly well-defined categorical DSM-IV clusters. As a consequence, DSM-IV fails to meaningfully integrate information generated by neuroendocrine research. Continuous psychological dimensions selected for their predictiveness with respect to endophenotypes, as biological intermediate factors, are proposed to be the best ways in reaching an understanding of the causations in mood, anxiety, and somatoform disorders.