Buffered Cortisol Response to Stress in Patients With Epilepsy and Its Association With Memory and Quality of Life

Epilepsy is a chronic stress condition associated with dysregulation in the hypothalamic-pituitary-adrenal axis and cognitive and emotional comorbidities. Therefore, we aimed to examine the acute stress response integrity in adults with epilepsy and its relationship with affectivity, memory, and quality of life (QOL).

This hybrid single-blind controlled study involved 3 groups: an experimental group (EG) of patients with epilepsy exposed to the Trier Social Stress Test (TSST) during a neuropsychological assessment; a control group of patients with epilepsy who underwent neuropsychological testing without stress exposure; and a healthy group (HG) also exposed to the TSST. Patients were recruited from the Refractory Epilepsy Unit and randomly assigned to the experimental or control group. Six saliva samples were collected from all groups at consistent intervals to measure cortisol levels. Repeated measures analyses of covariance and Spearman correlations were performed.

The sample consisted of 147 participants: 38 patients in the EG (50% women; 38.50 ± 10.92 years), 50 patients in the control group (48% women; 40.82 ± 8.55 years), and 59 individuals in the HG (58% women; 40.82 ± 8.55 years). The EG showed an abolition of the stress response and no differences with those not exposed to the TSST. The HG exhibited the expected cortisol response to stress with a rise in the area under the curve with respect to increase, which contrasts with the decreases observed in both groups of patients (F_(2,146) = 9.15, η² = 0.11) with and without stress (mean difference [MD] = -107.90, 95% CI -176.75 to -39.05, and MD = -89.19, 95% CI -152.81 to -25.56, respectively). Cortisol production in the EG was related to lower seizure frequency (ρ = -0.40, 95% CI -0.66 to -0.08), and better memory retrieval (ρ = 0.43, 95% CI 0.15-0.68) and QOL (ρ = 0.40, 95% CI 0.10-0.65).

Patients with epilepsy may exhibit a buffered cortisol response to acute stress. Preservation of this response is associated with better clinical, cognitive, and QOL outcomes. Despite limitations such as the cross-sectional design and sample specificity, these findings could help clarify the underlying mechanisms of stress-epilepsy interaction.