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The underlying etiology remains elusive, but hypothalamus\u2010pituitary\u2010adrenal (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\u2010resistant TLE, with and without comorbid depression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>GR expression was studied using immunohistochemistry on hippocampal sections from well\u2010characterized TLE patients with depression (TLE\u00a0+\u00a0D, n\u00a0=\u00a014) and without depression (TLE \u2212 D, n\u00a0=\u00a012) who underwent surgery for drug\u2010resistant epilepsy, as well as on hippocampal sections from autopsy control cases (n\u00a0=\u00a09). Video\u2013electroencephalography (EEG), magnetic resonance imaging (MRI), and psychiatric and memory assessments were performed prior to surgery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u00a0+\u00a0D group. Quantitative analysis showed a smaller GR+\u00a0area in TLE\u00a0+\u00a0D as compared to TLE \u2212 D patients and controls. Furthermore, the ratio between the number of GR+\/NeuN+\u00a0cells was lower in patients with TLE\u00a0+\u00a0D as compared to TLE \u2212 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\u00a0+\u00a0D compared to TLE \u2212 D patients and correlated negatively to the severity of depression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.16598","type":"journal-article","created":{"date-parts":[[2020,7,11]],"date-time":"2020-07-11T21:39:43Z","timestamp":1594503583000},"page":"1595-1605","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Reduced expression of the glucocorticoid receptor in the hippocampus of patients with drug\u2010resistant temporal lobe epilepsy and comorbid 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