Associations between cognitive performance and cortisol reaction to the DEX/CRH test in patients recovered from depression

Background: Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in major depression (MDD) is one of the most reliably reported neurobiological characteristics of affective disorders. Whether these alterations in HPA axis regulation are limited to the acute stage of MDD or whether they persist after recovery, remains ambiguous. A relationship between hypercortisolemia and cognitive dysfunction in acutely depressed patients has been repeatedly observed and it was also demonstrated in a number of studies that a discrete cognitive impairment often persists in the remitted state of depression. In the present study we were interested, whether these subtle impairments in cognitive functioning observed in patients recovered from depression compared to healthy control subjects are associated with HPA axis feedback sensitivity.

Methods: In 20 recovered patients and 20 matched healthy controls we assessed HPA axis feedback sensitivity with the combined dexamethasone suppression/corticotropin-releasing-hormone (DEX/CRH) challenge test. Furthermore cognitive performance was investigated with respect to the following domains: verbal memory (Auditory Verbal Learning Test, VLMT), attention and executive control (Trail Making Test, TMT-A/B) as well as verbal fluency (Controlled Oral Word Association Test, COWAT).

Results: Recovered patients showed a significantly poorer cognitive performance compared to healthy controls (all p<.05). With regard to HPA-axis activity, no overall difference was observed in the DEX/CRH test between recovered patients and controls. In recovered patients however, a significant association was observed between cortisol response and verbal memory (main effect VLMT trial 1-5: p=.046), attention (main effect TMT-A: p=.015) and executive functioning in terms of set shifting (interaction samples*TMT-B: p=.018). Poorer test performance was related to increased cortisol levels in response to challenge.

Conclusions: The present findings suggest that patients recovered from MDD are especially vulnerable toward detrimental effects of subtle HPA axis disturbances on cognitive performance.