Hypothalamic-pituitary-adrenal axis targets for the treatment of epilepsy

• Published in: Neuroscience letters 2021-02, Vol.746, p.135618-135618, Article 135618
• Main Authors: Basu, Trina, Maguire, Jamie, Salpekar, Jay A.
• Format: Article
• Language: English
• Subjects: Adrenocorticotropic Hormone - antagonists & inhibitors; Adrenocorticotropic Hormone - metabolism; Animals; Anticonvulsants - administration & dosage; Corticosterone - antagonists & inhibitors; Corticosterone - metabolism; Cortisol; Desoxycorticosterone - antagonists & inhibitors; Desoxycorticosterone - metabolism; Epilepsy; Epilepsy - drug therapy; Epilepsy - epidemiology; Epilepsy - metabolism; HPA axis; Humans; Hypothalamo-Hypophyseal System - drug effects; Hypothalamo-Hypophyseal System - metabolism; Mental Disorders - drug therapy; Mental Disorders - epidemiology; Mental Disorders - metabolism; Pituitary-Adrenal System - drug effects; Pituitary-Adrenal System - metabolism; Psychiatry; Stress; Treatment; Treatment Outcome
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2020.135618

•Neurophysiologic responses to stress link the hypothalamic pituitary adrenal (HPA) axis function and seizure activity.•A positive correlation exists between seizure frequency and cortisol levels.•Increased circulating stress hormones cause temporal lobe damage, which worsens the susceptibility to seizures as well as anxiety or depression.•Treatment that targets the HPA axis may yield improvement in both epilepsy and psychiatric comorbidities. Stress is a common seizure trigger in persons with epilepsy. The body’s physiological response to stress is mediated by the hypothalamic-pituitary-adrenal (HPA) axis and involves a hormonal cascade that includes corticotropin releasing hormone (CRH), adrenocorticotropin releasing hormone (ACTH) and the release of cortisol (in humans and primates) or corticosterone (in rodents). The prolonged exposure to stress hormones may not only exacerbate pre-existing medical conditions including epilepsy, but may also increase the predisposition to psychiatric comorbidities. Hyperactivity of the HPA axis negatively impacts the structure and function of the temporal lobe of the brain, a region that is heavily involved in epilepsy and mood disorders like anxiety and depression. Seizures themselves damage temporal lobe structures, further disinhibiting the HPA axis, setting off a vicious cycle of neuronal damage and increasing susceptibility for subsequent seizures and psychiatric comorbidity. Treatments targeting the HPA axis may be beneficial both for epilepsy and for associated stress-related comorbidities such as anxiety or depression. This paper will highlight the evidence demonstrating dysfunction in the HPA axis associated with epilepsy which may contribute to the comorbidity of psychiatric disorders and epilepsy, and propose treatment strategies that may dually improve seizure control as well as alleviate stress related psychiatric comorbidities.