Comorbilidad depresión-epilepsia: de la clínica a los modelos experimentales
Resumen
La depresión es un desorden psiquiátrico que está altamente asociado a la epilepsia, las personas con un incidente depresivo tienen mayor riesgo de sufrir epilepsia, del mismo modo que existe un mayor riesgo de padecer depresión después de presentar una crisis epiléptica. No obstante, los mecanismos neurobiológicos de esta comorbilidad no han sido descritos del todo, lo que en la clínica compromete el diagnóstico y tratamiento de estos pacientes. Por ejemplo, el uso de Inhibidores Selectivos de la Recaptura de Serotonina que son fármacos seguros y de uso común en pacientes con depresión, son motivo de controversia en pacientes con la comorbilidad con epilepsia. Para abordar algunos aspectos neurobiológicos de esta comorbilidad se han utilizado modelos experimentales que, a su vez, tienen sus alcances y limitaciones. Así, el objetivo de la presente revisión es describir la relación recíproca entre la depresión y la epilepsia cuando se presentan como trastornos comórbidos, además de discutir acerca de los efectos positivos y negativos de los inhibidores selectivos de la recaptación de serotonina como medicación contra la depresión, sobre ambas patologías. Así como los aportes y retos de los modelos experimentales de la comorbilidad depresión-epilepsia.
Abstract
Depression is a psychiatric disorder that is highly associated with epilepsy. People with depressive incidents have a higher risk of suffering epilepsy, in the same way that there is a higher risk of suffering depression after presenting an epileptic seizure. However, the neurobiological mechanisms of this comorbidity have not been described, which compromises the diagnosis and treatment of patients in clinical practice. For example, the use of Selective Serotonin Reuptake Inhibitors, which are safe and commonly used in patients with depression. However, use in patients with depression-epilepsy comorbidity causes controversy. Experimental models have been used to address some neurobiological aspects of this comorbidity, which also have their scopes and limitations. Therefore, the present review aims to analyze the reciprocal relationship between depression and epilepsy when presented as comorbid disorders and the positive and negative effects that antidepressant medication with selective serotonin reuptake inhibitors have on the course of both pathologies. As well as the contributions and challenges of experimental models of depression-epilepsy comorbidity.
Keywords: Comorbidity depression-epilepsy; depression; epilepsy; selective serotonin reuptake inhibitors; experimental models depression-epilepsy.
Palabras clave
Texto completo:
PDFReferencias
Tedrus GMAS, Souza DCM, Crepaldi CR, Petrarca YM. Suicide risk in epilepsy: Clinical variables, psychiatric disorders, and social support. Rev Neurol (Paris) 2023;179:183-187.
Organización Mundial de la Salud. Depresión. https://www.who.int/es/news-room/fact-sheets/detail/depression. Available at: Published December 2023.
Kanner AM. Can neurobiological pathogenic mechanisms of depression facilitate the development of seizure disorders? Lancet Neurol 2012;11:1093-1102.
Alhashimi R, Thoota S, Ashok T, Palyam V, Azam AT, Odeyinka O, Sange I. Comorbidity of Epilepsy and Depression: Associated Pathophysiology and Management. Cureus 2022;14.
Peng W, Fan F, Li X, Zhang QQ, Ding J, Wang X. Different behavioral and pathological changes between epilepsy-associated depression and primary depression models. Epilepsy and Behavior 2018;83:212-218.
Shen S, Dong Z, Zhang Q, Xiao J, Zhou D, Li J. The overlapping relationship among depression, anxiety, and somatic symptom disorder and its impact on the quality of life of people with epilepsy. Ther Adv Neurol Disord 2022;15.
Weiß M, Gründahl M, Deckert J, Eichner FA, Kohls M, Störk S, Heuschmann PU, Hein G. Differential network interactions between psychosocial factors, mental health, and health-related quality of life in women and men. Sci Rep 2023;13:11642.
João RB, Nogueira MH, Morita-Sherman ME, Alvim MKM, Johnny S, Pereira H, Pinheiro HP, Cendes F, Yasuda CL. The Relationship Between Depression and Anxiety Symptoms of Adult PWE and Caregivers in a Tertiary Center. Front Neurol 2022;13.
Jhaveri DJ, McGonigal A, Becker C, Benoliel J-J, Nandam LS, Soncin L, Kotwas I, Bernard C, Bartolomei F. Stress and Epilepsy: Towards Understanding of Neurobiological Mechanisms for Better Management. eNeuro 2023;10:ENEURO.0200-23.2023.
Kanner AM. Most antidepressant drugs are safe for patients with epilepsy at therapeutic doses: A review of the evidence. Epilepsy and Behavior 2016;61:282-286.
Singh T, Goel RK. Epilepsy Associated Depression: An Update on Current Scenario, Suggested Mechanisms, and Opportunities. Neurochem Res 2021;46:1305-1321.
Górska N, Słupski J, Cubała WJ, Wiglusz MS, Gałuszko-Węgielnik M. Antidepressants in epilepsy. Neurol Neurochir Pol 2018;52:657-661.
Favale E, Rubino V, Mainardi P, Lunardi G, Albano C. Anticonvulsant effect of fluoxetine in humans. Neurology 1995;45:1926-1927.
Thomé-Souza MS, Kuczynski E, Valente KD. Sertraline and fluoxetine: Safe treatments for children and adolescents with epilepsy and depression. Epilepsy and Behavior 2007;10:417-425.
Gigli GL, Diomedi M, Troisi A, Baldinetti F, Marciani MG, Girolami E, Pasini A. Lack of potentiation of anticonvulsant effect by fluoxetine in drug-resistant epilepsy. Seizure 1994;3:221-224.
Kühn KU, Quednow BB, Thiel M, Falkai P, Maier W, Elger CE. Antidepressive treatment in patients with temporal lobe epilepsy and major depression: A prospective study with three different antidepressants. Epilepsy and Behavior 2003;4:674-679.
Specchio LM, Iudice A, Specchio N, La Neve A, Spinelli A, Galli R, Rocchi R, Ulivelli M, de Tommaso M, Pizzanelli C, Murri L. Citalopram as treatment of depression in patients with epilepsy. Clin Neuropharmacol 2004;27:133-136.
Hovorka J, Herman E, Nemcová I. Treatment of interictal depression with citalopram in patients with epilepsy. Epilepsy and Behavior 2000;1:444-447.
Kanner AM, Kozak AM, Frey M. The use of sertraline in patients with epilepsy: Is it safe? Epilepsy and Behavior 2000;1:100-105.
Gilliam FG, Black KJ, Carter J, Freedland KE, Sheline YI, Tsai WY, Lustman PJ. A Trial of Sertraline or Cognitive Behavior Therapy for Depression in Epilepsy. Ann Neurol 2019;86:552-560.
Epps SA, Weinshenker D. Rhythm and blues: Animal models of epilepsy and depression comorbidity. Biochem Pharmacol 2013;85:135-146.
Gulbech Ording A, Toft Sørensen H. Concepts of comorbidities, multiple morbidities, complications, and their clinical epidemiologic analogs. Clin Epidemiol 2013;5:199-203.
Kanner AM. Psychiatric comorbidities in new onset epilepsy: Should they be always investigated? Seizure 2017;49:79-82.
Josephson CB, Jetté N. Psychiatric comorbidities in epilepsy. International Review of Psychiatry 2017;29:409-424.
Falco-Walter JJ, Scheffer IE, Fisher RS. The new definition and classification of seizures and epilepsy. Epilepsy Res 2018;139:73-79.
Noriega-Morales G, Shkurovich-Bialik P. Situación de la epilepsia en México y América Latina. Anales Médicos de la Asociación Médica del Centro Médico ABC 2020;65:224-232.
Falco-Walter JJ, Scheffer IE, Fisher RS. The new definition and classification of seizures and epilepsy. Epilepsy Res 2018;139.
Kanner AM. Depression and epilepsy: A bidirectional relation? Epilepsia 2011;52:21-27.
Treiman DM. GABAergic mechanisms in epilepsy. Epilepsia 2001;42:8-12.
Lupien SJ, McEwen BS, Gunnar MR, Heim C. Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci 2009;10:434-445.
Ryan-Coats SK, Hughes SD, Holz FM, Kreger RB, Koulibali CI, Khan HA, Harris KC, Kelly AE, Epps SA. Something new and something blue: Responses to novelty in a rodent model of depression and epilepsy comorbidity. Physiol Behav 2022;249.
Mazarati AM, Pineda E, Shin D, Tio D, Taylor AN, Sankar R. Comorbidity between epilepsy and depression: Role of hippocampal interleukin-1β. Neurobiol Dis 2010;37:461-467.
Hooper A, Paracha R, Maguire J. Seizure-induced activation of the HPA axis increases seizure frequency and comorbid depression-like behaviors. Epilepsy & Behavior 2018;78:124-133.
Josephson CB, Lowerison M, Vallerand I, Sajobi TT, Patten S, Jette N, Wiebe S. Association of depression and treated depression with epilepsy and seizure outcomes a multicohort analysis. JAMA Neurol 2017;74:533-539.
Koe AS, Salzberg MR, Morris MJ, O’Brien TJ, Jones NC. Early life maternal separation stress augmentation of limbic epileptogenesis: The role of corticosterone and HPA axis programming. Psychoneuroendocrinology 2014;42:124-133.
Ferlisi M, Shorvon S. Seizure precipitants (triggering factors) in patients with epilepsy. Epilepsy & Behavior 2014;33:101-105.
Rupasinghe R, Dezsi G, Ozturk E, Carron S, Hudson MR, Casillas-Espinosa PM, Jones NC. Early life adversity accelerates epileptogenesis and enhances depression-like behaviors in rats. Exp Neurol 2022;354.
Kapfhammer HP. Acute and Long-Term Mental and Physical Sequelae in the Aftermath of Traumatic Exposure – Some Remarks on “The Body Keeps the Score”. Psychiatr Danub 2018;30:254-272.
Olivier JDA, Blom T, Arentsen T, Homberg JR. The age-dependent effects of selective serotonin reuptake inhibitors in humans and rodents: A review. Prog Neuropsychopharmacol Biol Psychiatry 2011;35:1400-1408.
Ruiz-Santiago C, Rodríguez-Pinacho CV, Pérez-Sánchez G, Acosta-Cruz E. Effects of selective serotonin reuptake inhibitors on endocrine system (Review). Biomed Rep 2024;21.
Aguilar BL, Malkova L, N’Gouemo P, Forcelli PA. Genetically Epilepsy-Prone Rats Display Anxiety-Like Behaviors and Neuropsychiatric Comorbidities of Epilepsy. Front Neurol 2018;9.
Pineda E, Shin D, Sankar R, Mazarati AM. Comorbidity between epilepsy and depression: Experimental evidence for the involvement of serotonergic, glucocorticoid, and neuroinflammatory mechanisms. Epilepsia 2010;51:110-114.
De Lima TC, Rae GA. Effects of Cold-Restraint and Swim Stress on Convulsions Induced by Pentylenetetrazol and Electroshock: Influence of Naloxone Pretreatment. Pharmacol Biochem Behav 1991;40:297-300.
Abel EL, Berman RF, Abel EL, Berman RF. Effects of Water Immersion Stress on Convulsions Induced by Pentylenetetrazol. Vol 45.; 1993.
MacKenzie G, Maguire J. Chronic stress shifts the GABA reversal potential in the hippocampus and increases seizure susceptibility. Epilepsy Res 2015;109:13-27.
Zhu X, Dong J, Xia Z, Zhang A, Chao J, Yao H. Repeated restraint stress increases seizure susceptibility by activation of hippocampal endoplasmic reticulum stress. Neurochem Int 2017;110:25-37.
Jones NC, Lee HE, Yang M, Rees SM, Morris MJ, O’Brien TJ, Salzberg MR. Repeatedly stressed rats have enhanced vulnerability to amygdala kindling epileptogenesis. Psychoneuroendocrinology 2013;38:263-270.
Coleman EM, White M, Antonoudiou P, Weiss GL, Scarpa G, Stone B, Maguire J. Early life stress influences epilepsy outcomes in mice. Epilepsy and Behavior 2025;163.
Kumar G, Jones NC, Morris MJ, Rees S, O’Brien TJ, Salzberg MR. Early Life Stress Enhancement of Limbic Epileptogenesis in Adult Rats: Mechanistic Insights. PLoS One 2011;6:e24033.
Rupasinghe R, Dezsi G, Ozturk E, Carron S, Hudson MR, Casillas-Espinosa PM, Jones NC. Early life adversity accelerates epileptogenesis and enhances depression-like behaviors in rats. Exp Neurol 2022;354.
Salzberg M, Kumar G, Supit L, Jones NC, Morris MJ, Rees S, O'Brien TJ. Early Postnatal Stress Confers Enduring Vulnerability to Limbic Epileptogenesis. Epilepsia 2007;48:2079-2085.
Rao U, Hammen C, Ortiz LR, Chen L-A, Poland RE. Effects of Early and Recent Adverse Experiences on Adrenal Response to Psychosocial Stress in Depressed Adolescents. Biol Psychiatry 2008;64:521-526.
Katz RJ, Hersh S, And SH. Amitriptyline and Scopolamine in an Animal Model of Depression. Vol 5.; 1981:265-271.
Du Preez A, Law T, Onorato D, Lim YM, Eiben P, Musaelyan K, Egeland M, Hye A, Zunszain PA, Thuret S, Pariante CM, Fernandes C. The type of stress matters: repeated injection and permanent social isolation stress in male mice have a differential effect on anxiety- and depressive-like behaviours, and associated biological alterations. Transl Psychiatry 2020;10.
da Silva RPB, Pinheiro IL, da Silva RKB, Moretti EC, de Oliveira Neto OB, Ferraz-Pereira K, Galindo LCM. Social isolation and post-weaning environmental enrichment effects on rat emotional behavior and serotonergic system. International Journal of Developmental Neuroscience 2024;84:265-280.
Chang CH, Hsiao YH, Chen YW, Yu YJ, Gean PW. Social isolation-induced increase in NMDA receptors in the hippocampus exacerbates emotional dysregulation in mice. Hippocampus 2015;25:474-485.
Kaneda Y, Kawata A, Suzuki K, Matsunaga D, Yasumatsu M, Ishiwata T. Comparison of neurotransmitter levels, physiological conditions, and emotional behavior between isolation-housed rats with group-housed rats. Dev Psychobiol 2021;63:452-460.
Walker RA, Suthard RL, Perison TN, Sheehan NM, Dwyer CC, Lee JK, Enabulele EK, Ray MH, McDannald MA. Dorsal Raphe 5-HT Neurons Utilize, But Do Not Generate, Negative Aversive Prediction Errors. eNeuro 2022;9.
Bondi CO, Rodriguez G, Gould GG, Frazer A, Morilak DA. Chronic unpredictable stress induces a cognitive deficit and anxiety-like behavior in rats that is prevented by chronic antidepressant drug treatment. Neuropsychopharmacology 2008;33:320-331.
Hill MN, Hellemans KGC, Verma P, Gorzalka BB, Weinberg J. Neurobiology of chronic mild stress: Parallels to major depression. Neurosci Biobehav Rev 2012;36:2085-2117.
Lupien SJ, Juster RP, Raymond C, Marin MF. The effects of chronic stress on the human brain: From neurotoxicity, to vulnerability, to opportunity. Front Neuroendocrinol 2018;49:91-105.
Dubé CM, Molet J, Singh-Taylor A, Ivy A, Maras PM, Baram TZ. Hyper-excitability and epilepsy generated by chronic early-life stress. Neurobiol Stress 2015;2:10-19.
Pitkänen A, Lukasiuk K, Edward Dudek F, Staley KJ. Epileptogenesis. Cold Spring Harb Perspect Med 2015;5.
Löscher W, Brandt C. Prevention or modification of epileptogenesis after brain insults: Experimental approaches and translational research. Pharmacol Rev 2010;62:668-700.
Blumenfeld H, Rivera M, Vasquez JG, Shah A, Ismail D, Enev M, Zaveri HP. Neocortical and thalamic spread of amygdala kindled seizures. Epilepsia 2007;48:254-262.
Racine RJ. Modification of seizure activity by electrical stimulation: I. After-discharge threshold. Electroencephalogr Clin Neurophysiol 1972;32:269-279.
Hewapathirane DS, Burnham WMI. Propagation of amygdala-kindled seizures to the hippocampus in the rat: Electroencephalographic features and behavioural correlates. Neurosci Res 2005;53:369-375.
Rice AC, DeLorenzo RJ. NMDA receptor activation during status epilepticus is required. Brain Res 1998;782:240-247.
Nehlig A, Pereira de Vasconcelos A. The model of pentylenetetrazol-induced status epilepticus in the immature rat: short- and long-term effects. Epilepsy Res 1996;26:93-103.
Bazyan AS, Mel’nik VI, Bikbulatova LS, Karpova MN. The Pentylenetetrazole Allosteric Component of the GABA A Receptor Plasticity. Translated from Doklady Akademii Nauk 2002;386:407-410.
Jeong HG, Ko YH, Han C, Kim YK, Joe SH. Distinguishing Quantitative Electroencephalogram Findings between Adjustment Disorder and Major Depressive Disorder. Psychiatry Investig 2013;10:62.
Decker SL, Fillmore PT, Roberts AM. Coherence: The measurement and application of brain connectivity. NeuroRegulation 2017;4:3-13.
Bowyer SM. Coherence a measure of the brain networks: past and present. Neuropsychiatr Electrophysiol 2016;2.
Ren Y, Pan L, Du X, Li X, Hou Y, Bao J, Song Y. Theta oscillation and functional connectivity alterations related to executive control in temporal lobe epilepsy with comorbid depression. Clinical Neurophysiology 2020;131:1599-1609.
Peng W, Mao L, Yin D, Sun W, Wang H, Zhang Q, Wang J, Chen C, Zeng M, Ding J, Wang X. Functional network changes in the hippocampus contribute to depressive symptoms in epilepsy. Seizure 2018;60:16-22.
Medvedeva TM, Sysoeva MV, Sysoev IV, Vinogradova LV. Intracortical functional connectivity dynamics induced by reflex seizures. Exp Neurol 2023;368.
Magdaleno-Madrigal VM, Contreras-Murillo G, Valdés-Cruz A, Martínez-Vargas D, Martínez A, Villasana-Salazar B, Almazán-Alvarado S. Effects of High- and Low-Frequency Stimulation of the Thalamic Reticular Nucleus on Pentylentetrazole-Induced Seizures in Rats. Neuromodulation 2019;22:425-434.
Santos-Valencia F, Almazán-Alvarado S, Rubio-Luviano A, Valdés-Cruz A, Magdaleno-Madrigal VM, Martínez-Vargas D. Temporally irregular electrical stimulation to the epileptogenic focus delays epileptogenesis in rats. Brain Stimul 2019;12:1429-1438.
DOI: https://doi.org/10.25009/eb.v16i41.2644
Enlaces refback
- No hay ningún enlace refback.
eNeurobiología es una revista de publicación continua editada por el Instituto de Investigaciones Cerebrales de la Universidad Veracruzana. Estamos ubicados en Av. Dr. Luis Castelazo Ayala, s/n, colonia Industrial Ánimas, C.P. 91190, Xalapa-Enríquez, Veracruz, México. Teléfono: 8418900 ext. 13062, www.iice.uv.mx; eneurobiologia@uv.mx. Reserva de Derechos al Uso Exclusivo 04-2023-061314100600-102, otorgada por el Instituto Nacional de Derechos de Autor. ISSN: 2007-3054. Esta obra está bajo una Licencia Creative Commons Attribution 4.0 International.