Citations 2
The Role of Glutamate and Blood–Brain Barrier Disruption as a Mechanistic Link between Epilepsy and Depression
Gruenbaum, Benjamin F. , Schonwald, Antonia, Boyko, Matthew , Gruenbaum, Benjamin Fredrick , Boyko, Matthew , Zlotnik, Alexander Anatolievich
Cells | July 22, 2024 | Volume: 13 | Issue: 14 | Pages: 1228
Epilepsy is associated with substantial neuropsychiatric impairments that persist long after the onset of the condition, significantly impacting quality of life. The goal of this review was to uncover how the pathological consequences of epilepsy, such as excessive glutamate release and a disrupted blood–brain barrier (BBB), contribute to the emergence of neuropsychiatric disorders. We hypothesize that epilepsy induces a dysfunctional BBB through hyperexcitation, which then further amplifies post-ictal glutamate levels and, thus, triggers neurodegenerative and neuropsychiatric processes. This review identifies the determinants of glutamate concentration levels in the brain and explores potential therapeutic interventions that restore BBB integrity. Our focus on therapeutic BBB restoration is guided by the premise that it may improve glutamate regulation, consequently mitigating the neurotoxicity that contributes to the onset of neuropsychiatric symptoms.
Absence seizures and their relationship to depression and anxiety: Evidence for bidirectionality
Gruenbaum, Benjamin F. , Sandhu, Mani Ratnesh S. , Bertasi, Raphael A.O. , Bertasi, Tais G.O. , Schonwald, Antonia, Kurup, Anirudh, Gruenbaum, Shaun E. , Freedman, Isaac G. , Funaro, Melissa , Blumenfeld, Hal , Sanacora, Gerard , Freedman, Isaac , Bertasi, Tais Garcia de Oliveira , Gruenbaum, Benjamin Fredrick
Epilepsia | March 10, 2021 | Volume: 62 | Issue: 5 | Pages: 1041-1056
AbstractAbsence seizures (AS), presenting as short losses of consciousness with staring spells, are a common manifestation of childhood epilepsy that is associated with behavioral, emotional, and social impairments. It has also been suggested that patients with AS are more likely to suffer from mood disorders such as depression and anxiety. This systematic review and meta‐analysis synthesizes human and animal models that investigated mood disorders and AS. Of the 1019 scientific publications identified, 35 articles met the inclusion criteria for this review. We found that patients with AS had greater odds of developing depression and anxiety when compared to controls (odds ratio = 4.93, 95% confidence interval = 2.91–8.35, p < .01). The included studies further suggest a strong correlation between AS and depression and anxiety in the form of a bidirectional relationship. The current literature emphasizes that these conditions likely share underlying mechanisms, such as genetic predisposition, neurophysiology, and anatomical pathways. Further research will clarify this relationship and ensure more effective treatment for AS and mood disorders.