Epilepsy is a neurological disorder that affects almost 1% of the general population. It is characterized by the predisposition and recurrence of epileptic seizures, with neurobiological, cognitive, psychological, and social consequences. Furthermore, epilepsy is associated with an increased risk of comorbidities, which can affect the prognosis of the disease and impact other areas of the individual, such as social life, in which patients with epilepsy face challenges. All these factors interact with each other, directly or indirectly affecting quality of life. Therefore, the correct management and treatment of epilepsy should include aspects beyond seizure control, promoting early detection of those patients especially vulnerable to its consequences. Stress is defined as the process triggered by a stimulus perceived as harmful to homeostasis, which elicits a response to restore equilibrium. Thus, stress can be conceptualized within the Stimulus-Organism-Response model. The maintenance or recurrence of stressors can lead to a situation of chronic stress, which has been identified as a factor related to pathological processes. Due to their unpredictability, uncontrollability, and the threat they pose to health, epileptic seizures have been considered acute stressors. Therefore, seizure repeatability leads to the conceptualization of epilepsy within a chronic stress model. The close relationship between stress and epilepsy supports this framework, such as the role of stress as a seizure trigger, the higher levels of perceived stress, or the dysregulation of the hypothalamic-pituitary-adrenal axis in this population. This approach in epilepsy could help to achieve more appropriate disease management as well as a more comprehensive perspective. Therefore, this Thesis, which is divided into eleven chapters, aims to explore the stress process in epilepsy. The first chapter is a general introduction organized in two sections. The first one describes the impact of epilepsy on the individual, focusing on two of the most common comorbidities (i.e., mood disorders and cognitive impairment) and the impact of epilepsy on the social area and quality of life. The second section conceptualizes epilepsy within a chronic stress model, describing the stress process and the relationship between stress and epilepsy. Due to the scarcity of studies addressing epilepsy within this theoretical framework, and considering the importance of subjective appraisal in the stress process, the second chapter contains a systematic review of perceived stress and epilepsy. This study aims to offer a more homogeneous view of its impact and facilitate understanding its particularities in this population. The third chapter describes the theoretical model that follows the present Thesis, detailing the proposed aims and the enunciated hypotheses. The fourth chapter attempts to determine the impact of a social stressor. This chapter includes Study 1, which aims to explore the effect of academic and/or employment insertion on cognitive performance, perceived social support, negative affectivity, and quality of life, as well as the relationship between these variables. The fifth and sixth chapters are focused on exploring individual modulator factors of stress in epilepsy. The fifth chapter comprises Study 2, which examines the effect of a new antiseizure medication on cognitive performance, negative affectivity, and quality of life after three and six months of adjunctive treatment. The sixth chapter contains Study 3, aimed at identifying stress profiles in epilepsy, and studying the differences in cognitive performance and quality of life according to these phenotypes. The seventh chapter addresses the cortisol response to acute psychosocial laboratory stressor exposure. In this chapter, Study 4 explores the differences in the cortisol response to the Trier Social Stress Test between patients with epilepsy and healthy people. In addition, it compares cortisol levels between patients with epilepsy who were subjected to the stressor and patients with epilepsy who were not. Finally, it examines the relationship between cortisol response and memory functioning, mood, and quality of life. These chapters emphasize the importance of the consideration of stress in epilepsy. Nevertheless, there is a need for appropriate instruments to assess perceived stress in drug-resistant epilepsy. Therefore, the eighth chapter, through Study 5, discusses the development and validation of a new scale to measure perceived stress in this population. The ninth chapter provides a general discussion of the results obtained. Moreover, the clinical implications, limitations and future directions are provided. The tenth chapter summarizes the main conclusions of the present Thesis. Finally, the eleventh chapter provides a comprehensive summary of this Thesis in Spanish, encompassing the objectives through to the conclusions reached.
2024-09-25
