Cognitive impairment in major depression: Association with circadian salivary cortisol

Cognitive deficits and elevated cortisol are hallmarks of depression. Cortisol acts via mineralo- and glucocorticoid receptors, which have their highest density in the hippocampus, a brain area closely related to cognitive function. Several studies have separately investigated cortisol secretion and cognitive deficits in depression. However, only few studies have assessed their association and have come to inconclusive results. We examined 52 medication-free patients with major depression (37 women, 15 men, mean age 35 years±11, Hamilton Depression Scale mean score 27±5) and 50 healthy control subjects, matched for age, gender and years of education. We applied several neuropsychological tests. Salivary cortisol levels were measured on the same day at 8:00, 12:00, 16:00 and 22:00 hours. Compared to healthy subjects, patients had significantly higher cortisol levels and were impaired in verbal memory, visuospatial memory, working memory, and selective attention. In depressed patients, but not in healthy controls, we found a negative correlation between salivary cortisol levels (area under the curve) and hippocampus-related neuropsychological domains (verbal memory, visuospatial memory) and executive function. Cognitive deficits appear to be related to cortisol secretion in depressed patients. Elevated cortisol may downregulate minerolo- and glucocorticoid receptors in the hippocampus, which might in part be responsible for cognitive deficits in depressed patients.