@article{99494255d45c4d8c8dbf3506b08362e9,
title = "Reduced expression of the glucocorticoid receptor in the hippocampus of patients with drug-resistant temporal lobe epilepsy and comorbid depression",
abstract = "OBJECTIVE: Depressive disorders are common among about 50% of the patients with drug-resistant temporal lobe epilepsy (TLE). The underlying etiology remains elusive, but hypothalamus-pituitary-adrenal (HPA) axis activation due to changes in glucocorticoid receptor (GR) protein expression could play an important role. Therefore, we set out to investigate expression of the GR in the hippocampus, an important brain region for HPA axis feedback, of patients with drug-resistant TLE, with and without comorbid depression.METHODS: GR expression was studied using immunohistochemistry on hippocampal sections from well-characterized TLE patients with depression (TLE + D, n = 14) and without depression (TLE - D, n = 12) who underwent surgery for drug-resistant epilepsy, as well as on hippocampal sections from autopsy control cases (n = 9). Video-electroencephalography (EEG), magnetic resonance imaging (MRI), and psychiatric and memory assessments were performed prior to surgery.RESULTS: Abundant GR immunoreactivity was present in dentate gyrus granule cells and CA1 pyramidal cells of controls. In contrast, neuronal GR expression was lower in patients with TLE, particularly in the TLE + D group. Quantitative analysis showed a smaller GR+ area in TLE + D as compared to TLE - D patients and controls. Furthermore, the ratio between the number of GR+/NeuN+ cells was lower in patients with TLE + D as compared to TLE - D and correlated negatively with the depression severity based on psychiatric history. The expression of the GR was also lower in glial cells of TLE + D compared to TLE - D patients and correlated negatively to the severity of depression.SIGNIFICANCE: Reduced hippocampal GR expression may be involved in the etiology of depression in patients with TLE and could constitute a biological marker of depression in these patients.",
keywords = "chronic stress, dysthymia, hypothalamus-pituitary-adrenal axis, major depression",
author = "Luciana D'Alessio and Lucia Mesarosova and Anink, {Jasper J} and Silvia Kochen and Patricia Sol{\'i}s and Silvia Oddo and Hector Konopka and Iyer, {Anand M} and Angelika M{\"u}hlebner and Lucassen, {Paul J} and Eleonora Aronica and {van Vliet}, {Erwin A}",
note = "Funding Information: We thank all the participants and collaborators of this study, all the team of the Epilepsy Center of Ramos Mej{\'i}a Hospital and El Cruce Hospital. We also thank Professor Ron de Kloet (Leiden) and Professor Marian Jo{\"e}ls (UMC Groningen) for their help in the collaboration between the Epilepsy Center of Buenos Aires and the Amsterdam UMC, location Academic Medical Center, in Amsterdam. The research leading to these results has received funding from the European Union's Seventh Framework Program (FP7/2007‐2013) under grant agreement 602102 (EPITARGET; EAvV, EA), the Dutch Epilepsy Foundation, project 16‐05 (EAvV), Hersenstichting Nederland (PJL), Alzheimer Nederland (PJL), the UvA research priority area Urban Mental Health (PJL) and the KNAW China Exchange program, grant 05CDP030 (PJL). The authors have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Funding Information: We thank all the participants and collaborators of this study, all the team of the Epilepsy Center of Ramos Mej?a Hospital and El Cruce Hospital. We also thank Professor Ron de Kloet (Leiden) and Professor Marian Jo?ls (UMC Groningen) for their help in the collaboration between the Epilepsy Center of Buenos Aires and the Amsterdam UMC, location Academic Medical Center, in Amsterdam. The research leading to these results has received funding from the European Union's Seventh Framework Program (FP7/2007-2013) under grant agreement 602102 (EPITARGET; EAvV, EA), the Dutch Epilepsy Foundation, project 16-05 (EAvV), Hersenstichting Nederland (PJL), Alzheimer Nederland (PJL), the UvA research priority area Urban Mental Health (PJL) and the KNAW China Exchange program, grant 05CDP030 (PJL). The authors have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Publisher Copyright: {\textcopyright} 2020 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy",
year = "2020",
month = aug,
doi = "10.1111/epi.16598",
language = "English",
volume = "61",
pages = "1595--1605",
journal = "Epilepsia",
issn = "0013-9580",
publisher = "Wiley-Blackwell",
number = "8",
}