Pharmacologically increased cortisol levels impair recall of associative background context memory in males, but not females

Laboratory studies have consistently shown that stress impairs memory retrieval of individual parts (items) of a memory. The stress-hormone cortisol has been particularly linked to this impairment. However, it is unclear whether cortisol similarly affects the binding of items to associative context information in memory, i.e. the constituents of episodic memory. Here, we examine memory retrieval of item and associative memory under pharmacologically elevated cortisol vs. normal levels. Given that previous studies have indicated potential sex differences in the stress- and cortisol-induced memory modulation, we additionally assessed whether there may be sex differences for the cortisol effect on memory retrieval. Eighty-four female and male participants were tested in a placebo controlled, double-blind between-subject design, assigned to either a cortisol (10 mg hydrocortisone) or a placebo group. Participants of both groups were presented foreground images of negative and neutral valence on different neutral background scenes. Twenty-four hours later, participants' memory for the images and their associated background scene was tested with a recognition task 20 min after substance administration. Among the 78 participants of both groups included in the final analysis, cortisol levels were higher in the cortisol group in comparison to the placebo group, and female participants had higher cortisol levels after hydrocortisone intake in comparison to male participants. Item memory did not differ between the placebo and cortisol group. In contrast, in males, but not females, associative memory for the background scene of emotional foreground images was lower in the cortisol vs. placebo group. Moreover, the individual cortisol increase during the recognition task was negatively correlated to memory for the background scenes of the emotional foreground images only in male participants of the cortisol group. This study shows that pharmacologically increased cortisol levels distinctly affect associative memory in female and male participants, but have no effect on item memory, indicating a complex interaction for the stress effects on memory.