Psychopathology after cardiac surgery and intensive care treatment

Abstract

In this thesis, the occurrence of stress-related psychopathology after cardiac surgery and intensive care treatment is assessed. We primarily focused on post-traumatic stress disorder (PTSD) and depression symptomatology, but the effects of benzodiazepine administration, delirium, anxiety, and cognitive impairment were discussed as well. Psychopathology might hamper full recovery after cardiac surgery and intensive care treatment. Therefore, factors that are potentially associated with the development of psychopathology were explored. The possible association between benzodiazepine use in the intensive care unit (ICU) and the occurrence of various forms of psychopathology - both during ICU admission and after discharge - was investigated. Most evidence was found for an association between benzodiazepines and delirium. The effect of benzodiazepines on long-term types of psychopathology was less clear. Moreover, it remains uncertain how benzodiazepines exert their effects for a considerable period of time after discharge. The extent to which dosage, duration, and administration of other GABAergic medication is of influence, is still unknown as well. Furthermore, we focused on the development of PTSD and depression in cardiac surgery patients who were subsequently admitted to the ICU, examining various potentially associated factors. First, the long-term effects of dexamethasone administration during cardiac surgery versus placebo on the occurrence of PTSD and depression were assessed. Overall, dexamethasone did not have beneficial, nor detrimental effects on psychopathology up to four years after surgery. Second, the role of high trait anxiety, a common personality trait reflecting high neuroticism, was investigated in these patients. We evaluated the possible relation between stress exposure during life and vulnerability to stress-related psychopathology. Trait anxiety was found to be an important mediator of this relationship, and therefore a candidate screening measure in this setting. Third, investigation of common genetic variation in main hypothalamic-pituitary-adrenal axis receptors showed that the protective effect of dexamethasone on symptoms of PTSD was dependent on polymorphisms (i.e., rs41423247, rs10052957, and rs6189) of its main target, the glucocorticoid receptor. Further, no effect on symptoms of depression, nor involvement of genetic variation of the mineralocorticoid receptor or FK506 binding protein was found. Combined, our data supports partial involvement fo trait anxiety in the development of stress-related psychopathology, and a potential beneficial effect of dexamethasone in female patients after cardiac surgery and ICU admission.