Hypothalamic-Pituitary-Adrenal Axis Dysfunction Elevates SUDEP Risk in a Sex-Specific Manner

被引:4
作者
Basu, Trina [1 ]
Antonoudiou, Pantelis [1 ]
Weiss, Grant L. [1 ]
Coleman, Emanuel M. [1 ]
David, Julian [2 ]
Friedman, Daniel [3 ]
Laze, Juliana [3 ]
Strain, Misty M. [2 ]
Devinsky, Orrin [3 ]
Boychuk, Carie R. [2 ]
Maguire, Jamie [1 ]
机构
[1] Tufts Univ, Sch Med, Boston, MA 02111 USA
[2] Univ Missouri, Columbia, MO 65211 USA
[3] NYU, Langone Med Ctr, Comprehens Epilepsy Ctr, New York, NY 10016 USA
基金
美国国家卫生研究院; 美国国家科学基金会;
关键词
comorbidities; epilepsy; HPA axis; neuroendocrine; SUDEP; TEMPORAL-LOBE EPILEPSY; HPA AXIS; BEHAVIORAL ALTERATIONS; INDUCED ACTIVATION; STRESS; DEPRESSION; EPIDEMIOLOGY; MECHANISMS; DEATH; MODEL;
D O I
10.1523/ENEURO.0162-24.2024
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Epilepsy is often comorbid with psychiatric illnesses, including anxiety and depression. Despite the high incidence of psychiatric comorbidities in people with epilepsy, few studies address the underlying mechanisms. Stress can trigger epilepsy and depression. Evidence from human and animal studies supports that hypothalamic-pituitary-adrenal (HPA) axis dysfunction may contribute to both disorders and their comorbidity (Kanner, 2003). Here, we investigate if HPA axis dysfunction may influence epilepsy outcomes and psychiatric comorbidities. We generated a novel mouse model ( Kcc2 / Crh KO mice) lacking the K+/Cl- + /Cl - cotransporter, KCC2, in corticotropin-releasing hormone (CRH) neurons, which exhibit stress- and seizure-induced HPA axis hyperactivation (Melon et al., 2018). We used the Kcc2/Crh / Crh KO mice to examine the impact on epilepsy outcomes, including seizure frequency/ burden, comorbid behavioral deficits, and sudden unexpected death in epilepsy (SUDEP) risk. We found sex differences in HPA axis dysfunction's effect on chronically epileptic KCC2/Crh KO mice seizure burden, vulnerability to comorbid behavioral deficits, and SUDEP. Suppressing HPA axis hyperexcitability in this model using pharmacological or chemogenetic approaches decreased SUDEP incidence, suggesting that HPA axis dysfunction may contribute to SUDEP. Altered neuroendocrine markers were present in SUDEP cases compared with people with epilepsy or individuals without epilepsy. Together, these findings implicate HPA axis dysfunction in the pathophysiological mechanisms contributing to psychiatric comorbidities in epilepsy and SUDEP.
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页数:13
相关论文
共 43 条
[31]   The HPA axis in major depression: classical theories and new developments [J].
Pariante, Carmine M. ;
Lightman, Stafford L. .
TRENDS IN NEUROSCIENCES, 2008, 31 (09) :464-468
[32]   Adverse Cardiovascular Outcomes of Corticosteroid Excess [J].
Pimenta, Eduardo ;
Wolley, Martin ;
Stowasser, Michael .
ENDOCRINOLOGY, 2012, 153 (11) :5137-5142
[33]   Psychiatric comorbidity in relation to clinical characteristics of epilepsy: A retrospective observational study [J].
Revdal, Eline ;
Kolstad, Bjorn Patrick ;
Winsvold, Bendik Slagsvold ;
Selmer, Kaja Kristine ;
Morken, Gunnar ;
Brodtkorb, Eylert .
SEIZURE-EUROPEAN JOURNAL OF EPILEPSY, 2023, 110 :136-143
[34]   Stress and Epilepsy: Multiple Models, Multiple Outcomes [J].
Sawyer, Nikki T. ;
Escayg, Andrew .
JOURNAL OF CLINICAL NEUROPHYSIOLOGY, 2010, 27 (06) :445-452
[35]   The incidence of SUDEP A nationwide population-based cohort study [J].
Sveinsson, Olafur ;
Andersson, Tomas ;
Carlsson, Sofia ;
Tomson, Torbjorn .
NEUROLOGY, 2017, 89 (02) :170-177
[36]   Association Between Psychiatric Comorbidities and Mortality in Epilepsy [J].
Tao, Gerard ;
Auvrez, Clarissa ;
Nightscales, Russell ;
Barnard, Sarah ;
McCartney, Lara ;
Malpas, Charles B. ;
Perucca, Piero ;
Chen, Zhibin ;
Adams, Sophia ;
McIntosh, Anne ;
Ignatiadis, Sophia ;
O'Brien, Patrick ;
Cook, Mark J. ;
Kwan, Patrick ;
Berkovic, Samuel F. ;
D'Souza, Wendyl ;
Velakoulis, Dennis ;
O'Brien, Terence J. .
NEUROLOGY-CLINICAL PRACTICE, 2021, 11 (05) :429-437
[37]   Cardiac Sudden Death in Psychiatric Patients [J].
Uchida, Hiroyuki ;
Suzuki, Takefumi .
CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE, 2015, 60 (05) :203-205
[38]   Neural regulation of endocrine and autonomic stress responses [J].
Ulrich-Lai, Yvonne M. ;
Herman, James P. .
NATURE REVIEWS NEUROSCIENCE, 2009, 10 (06) :397-409
[39]  
Vlastelica M, 2008, PSYCHIAT DANUB, V20, P411
[40]   The glucocorticoid receptor specific modulator CORT108297 reduces brain pathology following status epilepticus [J].
Wulsin, Aynara C. ;
Kraus, Kimberly L. ;
Gaitonde, Kevin D. ;
Suru, Venkat ;
Arafa, Salwa R. ;
Packard, Benjamin A. ;
Herman, James P. ;
Danzer, Steve C. .
EXPERIMENTAL NEUROLOGY, 2021, 341