Our research, which ranges from molecular biology and cell biology to human psychopathology, has focused on the effects of glucocorticoid hormones. These adrenal corticosteroid hormones support homeostasis and health by their actions in many organs, including the brain.
However, long term underexposure or overexposure to glucocorticoids can have detrimental effects, and may put people at risk of developing psychopathologies like depression, psychosis, and post traumatic stress disorder. Our group discovered that one corticosteroid receptor type in the brain [the mineralocorticoid receptor-MR] controls the onset of the stress response, while the other [glucocorticoid receptor- GR] manages later adaptations. These effects are brought about via coordinated rapid non-genomic effects, and slow persistent genomic effects, which both modulate neuronal excitability and communication. Adaptation to stress is then brought about by altered autonomic and behavioral functions, as reflected by changes in motivation, emotional arousal, and cognitive performance. We study molecular MR and GR targets in addition to mechanisms of receptor sensitivity and specific effector mechanisms, which may be targeted by novel selective ligands. The consequences of glucocorticoid signaling for the integration of cognition and emotion are studied in rodents and man, using newly developed methodologies for [functional] genomics, e.g. based on in vivo use of siRNA. Early life experience and genetic variability of the stress system in rodents and humans are investigated to understand individual differences in coping with stress. The effects of stress and stress hormones are assessed in models of vulnerability and resilience to neurodevelopmental and affective disorders.