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Exploring the Association between Schizophrenia and Cardiovascular Diseases: Insights into the Role of Sigma 1 Receptor

. 2023 Jul 31 ; 72 (Suppl 2) : S113-S126.

Language English Country Czech Republic Media print

Document type Journal Article, Review

Contemporary society is characterized by rapid changes. Various epidemiological, political and economic crises represent a burden to mental health of nowadays population, which may at least partially explain the increasing incidence of mental disorders, including schizophrenia. Schizophrenia is associated with premature mortality by at least 13-15 years. The leading cause of premature mortality in schizophrenia patients is high incidence of cardiovascular diseases. The specific-cause mortality risk for cardiovascular diseases in schizophrenia patients is more than twice higher as compared to the general population. Several factors are discussed as the factor of cardiovascular diseases development. Intensive efforts to identify possible link between schizophrenia and cardiovascular diseases are made. It seems that sigma 1 receptor may represent such link. By modulation of the activity of several neurotransmitter systems, including dopamine, glutamate, and GABA, sigma 1 receptor might play a role in pathophysiology of schizophrenia. Moreover, significant roles of sigma 1 receptor in cardiovascular system have been repeatedly reported. The detailed role of sigma 1 receptor in both schizophrenia and cardiovascular disorders development however remains unclear. The article presents an overview of current knowledge about the association between schizophrenia and cardiovascular diseases and proposes possible explanations with special emphasis on the role of the sigma 1 receptor.

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Baker RE, Mahmud AS, Miller IF, Rajeev M, Rasambainarivo F, Rice BL, Takahashi S, Tatem AJ, Wagner CE, Wang LF, Wesolowski A, Metcalf CJE. Infectious disease in an era of global change. Nat Rev Microbiol. 2022;20:193–205. doi: 10.1038/s41579-021-00639-z. PubMed DOI PMC

Correll CU, Solmi M, Croatto G, Schneider LK, Rohani-Montez SC, Fairley L, Smith N, Bitter I, Gorwood P, Taipale H, Tiihonen J. Mortality in people with schizophrenia: a systematic review and meta-analysis of relative risk and aggravating or attenuating factors. World Psychiatry. 2022;21:248–271. doi: 10.1002/wps.20994. PubMed DOI PMC

Charlson FJ, Ferrari AJ, Santomauro DF, Diminic S, Stockings E, Scott JG, McGrath JJ, Whiteford HA. Global epidemiology and burden of schizophrenia: findings from the global burden of disease study 2016. Schizophr Bull. 2018;44:1195–1203. doi: 10.1093/schbul/sby058. PubMed DOI PMC

Pilon D, Patel C, Lafeuille MH, Zhdanava M, Lin D, Côté-Sergent A, Rossi C, Joshi K, Lefebvre P. Prevalence, incidence and economic burden of schizophrenia among Medicaid beneficiaries. Curr Med Res Opin. 2021;37:1811–1819. doi: 10.1080/03007995.2021.1954894. PubMed DOI

American Psychiatric Association, American Psychiatric Association, editor. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th ed. American Psychiatric Association; 2013. DOI

Bora E, Akdede BB, Alptekin K. Neurocognitive impairment in deficit and non-deficit schizophrenia: a meta-analysis. Psychol Med. 2017;47:2401–2413. doi: 10.1017/S0033291717000952. PubMed DOI

Janoutová J, Janácková P, Serý O, Zeman T, Ambroz P, Kovalová M, Varechová K, Hosák L, Jirík V, Janout V. Epidemiology and risk factors of schizophrenia. Neuro Endocrinol Lett. 2016;37:1–8. PubMed

Leucht S, Leucht C, Huhn M, Chaimani A, Mavridis D, Helfer B, Samara M, Rabaioli M, Bächer S, Cipriani A, Geddes JR, Salanti G, Davis JM. Sixty years of placebo-controlled antipsychotic drug trials in acute schizophrenia: systematic review, bayesian meta-analysis, and meta-regression of efficacy predictors. Am J Psychiatry. 2017;174:927–942. doi: 10.1176/appi.ajp.2017.16121358. PubMed DOI

Mailman RB, Murthy V. Third generation antipsychotic drugs: partial agonism or receptor functional selectivity? Curr Pharm Des. 2010;16:488–501. doi: 10.2174/138161210790361461. PubMed DOI PMC

tuplin ew, holahan mr. aripiprazole. a drug that displays partial agonism and functional selectivity. Curr Neuropharmacol. 2017;15:1192–1207. doi: 10.2174/1570159X15666170413115754. PubMed DOI PMC

Yang AC, Tsai SJ. New targets for schizophrenia treatment beyond the dopamine hypothesis. Int J Mol Sci. 2017;18:E1689. doi: 10.3390/ijms18081689. PubMed DOI PMC

Mongan D, Ramesar M, Föcking M, Cannon M, Cotter D. Role of inflammation in the pathogenesis of schizophrenia: A review of the evidence, proposed mechanisms and implications for treatment. Early Interv Psychiatry. 2020;14:385–397. doi: 10.1111/eip.12859. PubMed DOI

Murray AJ, Rogers JC, Katshu MZUH, Liddle PF, Upthegrove R. Oxidative stress and the pathophysiology and symptom profile of schizophrenia spectrum disorders. Front Psychiatry. 2021. p. 12. https://www.frontiersin.org/articles/10.3389/fpsyt.2021.703452 https://doi.org/10.3389/fpsyt.2021.703452 . PubMed DOI PMC

Hjorthøj C, Stürup AE, McGrath JJ, Nordentoft M. Years of potential life lost and life expectancy in schizophrenia: a systematic review and meta-analysis. Lancet Psychiatry. 2017;4:295–301. doi: 10.1016/S2215-0366(17)30078-0. PubMed DOI

Gatov E, Rosella L, Chiu M, Kurdyak PA. Trends in standardized mortality among individuals with schizophrenia, 1993–2012: a population-based, repeated cross-sectional study. CMAJ. 2017;189(37):E1177–E1187. doi: 10.1503/cmaj.161351. PubMed DOI PMC

Westman J, Eriksson SV, Gissler M, Hällgren J, Prieto ML, Bobo WV, Frye MA, Erlinge D, Alfredsson L, Ösby U. Increased cardiovascular mortality in people with schizophrenia: a 24-year national register study. Epidemiol Psychiatr Sci. 2018;27:519–527. doi: 10.1017/S2045796017000166. PubMed DOI PMC

Yung NCL, Wong CSM, Chan JKN, Chen EYH, Chang WC. Excess mortality and life-years lost in people with schizophrenia and other non-affective psychoses: an 11-year population-based cohort study. Schizophr Bull. 2021;47(2):474–484. doi: 10.1093/schbul/sbaa137. PubMed DOI PMC

Girardi P, Schievano E, Fedeli U, Braggion M, Nuti M, Amaddeo F. Causes of mortality in a large population-based cohort of psychiatric patients in Southern Europe. J Psychiatr Res. 2021;136:167–172. doi: 10.1016/j.jpsychires.2021.01.050. PubMed DOI

Correll CU, Solmi M, Veronese N, Bortolato B, Rosson S, Santonastaso P, Thapa-Chhetri N, et al. Prevalence, incidence and mortality from cardiovascular disease in patients with pooled and specific severe mental illness: a large-scale meta-analysis of 3,211,768 patients and 113,383,368 controls. World Psychiatry. 2017;16:163–180. doi: 10.1002/wps.20420. PubMed DOI PMC

Li M, Fan YL, Tang ZY, Cheng XS. Schizophrenia and risk of stroke: A meta-analysis of cohort studies. Int J Cardiol. 2014;173:588–590. doi: 10.1016/j.ijcard.2014.03.101. PubMed DOI

Yung NCL, Wong CSM, Chan JKN, Or PCF, Chen EYH, Chang WC. Mortality in patients with schizophrenia admitted for incident ischemic stroke: A population-based cohort study. Eur Neuropsychopharmacol. 2020;31:152–157. doi: 10.1016/j.euroneuro.2019.12.107. PubMed DOI

Bongiorno DM, Daumit GL, Gottesman RF, Faigle R. Patients with stroke and psychiatric comorbidities have lower carotid revascularization rates. Neurology. 2019;92:e2514–e2521. doi: 10.1212/WNL.0000000000007565. PubMed DOI PMC

Willers C, Sunnerhagen KS, Lekander I, von Euler M. The association of pre-stroke psychosis and post-stroke levels of health, resource utilization, and care process: a register-based study. Front Neurol. 2018;9:1042. doi: 10.3389/fneur.2018.01042. PubMed DOI PMC

Kapral MK, Kurdyak P, Casaubon LK, Fang J, Porter J, Sheehan KA. Stroke care and case fatality in people with and without schizophrenia: a retrospective cohort study. BMJ Open. 2021;11:e044766. doi: 10.1136/bmjopen-2020-044766. PubMed DOI PMC

Lee E, Choi EK, Han KD, Lee H, Choe WS, Lee SR, Cha MJ, Lim WH, Kim YJ, Oh S. Mortality and causes of death in patients with atrial fibrillation: A nationwide population-based study. Plos One. 2018;13:e0209687. doi: 10.1371/journal.pone.0209687. PubMed DOI PMC

Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146:857. doi: 10.7326/0003-4819-146-12-200706190-00007. PubMed DOI

Højen AA, Nielsen PB, Riahi S, Jensen M, Lip GYH, Larsen TB, Søgaard M. Disparities in oral anticoagulation initiation in patients with schizophrenia and atrial fibrillation: A nationwide cohort study. Br J Clin Pharmacol. 2022;88:3847–3855. doi: 10.1111/bcp.15337. PubMed DOI PMC

Jaakkola J, Teppo K, Biancari F, Halminen O, Putaala J, Mustonen P, Haukka J, Linna M, Kinnunen J, Tiili P, Aro AL, Hartikainen J, Airaksinen KEJ, Lehto M. The effect of mental health conditions on the use of oral anticoagulation therapy in patients with atrial fibrillation: the FinACAF study. Eur Heart J - Qual Care Clin Outcomes. 2022;8:269–276. doi: 10.1093/ehjqcco/qcab077. PubMed DOI PMC

Fenger-Grøn M, Vestergaard CH, Ribe AR, Johnsen SP, Frost L, Sandbæk A, Davydow DS. Association between bipolar disorder or schizophrenia and oral anticoagulation use in Danish adults with incident or prevalent atrial fibrillation. JAMA Netw Open. 2021;4(5):e2110096. doi: 10.1001/jamanetworkopen.2021.10096. PubMed DOI PMC

Teppo K, Jaakkola J, Biancari F, et al. Mental health conditions and bleeding events in patients with incident atrial fibrillation: A Finnish nationwide cohort study. Gen Hosp Psychiatry. 2022;78:117–122. doi: 10.1016/j.genhosppsych.2022.08.003. PubMed DOI

Søgaard M, Skjøth F, Kjældgaard JN, Larsen TB, Hjortshøj SP, Riahi S. Atrial fibrillation in patients with severe mental disorders and the risk of stroke, fatal thromboembolic events and bleeding: a nationwide cohort study. BMJ Open. 2017;7:e018209. doi: 10.1136/bmjopen-2017-018209. PubMed DOI PMC

Teppo K, Jaakkola J, Lehto M, Biancari F, Airaksinen KEJ. The impact of mental health conditions on oral anticoagulation therapy and outcomes in patients with atrial fibrillation: A systematic review and meta-analysis. Am J Prev Cardiol. 2021;7:100221. doi: 10.1016/j.ajpc.2021.100221. PubMed DOI PMC

Shao M, Zhuo C, Gao X, Chen C, Xu Y, Tian H, Li G, Jiang D, Wang W. Reduced rate of revascularization in schizophrenic patients with acute myocardial infarction: A systematic review and meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2020;99:109870. doi: 10.1016/j.pnpbp.2020.109870. PubMed DOI

Shao M, Tian H, Wang L, Jiang D, Ji F, Zhuo C. Mortality risk following acute coronary syndrome among patients with schizophrenia: A meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2020;96:109737. doi: 10.1016/j.pnpbp.2019.109737. PubMed DOI

Fleetwood K, Wild SH, Smith DJ, Mercer SW, Licence K, Sudlow CLM, Jackson CA. Severe mental illness and mortality and coronary revascularisation following a myocardial infarction: a retrospective cohort study. BMC Med. 2021;19:67. doi: 10.1186/s12916-021-01937-2. PubMed DOI PMC

Kugathasan P, Laursen TM, Grøntved S, Jensen SE, Aagaard J, Nielsen RE. Increased long-term mortality after myocardial infarction in patients with schizophrenia. Schizophr Res. 2018;199:103–108. doi: 10.1016/j.schres.2018.03.015. PubMed DOI

Attar R, Wester A, Koul S, et al. Higher risk of major adverse cardiac events after acute myocardial infarction in patients with schizophrenia. Open Heart. 2020;7(2):e001286. doi: 10.1136/openhrt-2020-001286. PubMed DOI PMC

Attar R, Johansen MB, Valentin JB, Aagaard J, Jensen SE. Treatment following myocardial infarction in patients with schizophrenia. PLOS ONE. 2017;12(12):e0189289. doi: 10.1371/journal.pone.0189289. PubMed DOI PMC

Ayerbe L, Forgnone I, Addo J, Siguero A, Gelati S, Ayis S. Hypertension risk and clinical care in patients with bipolar disorder or schizophrenia; a systematic review and meta-analysis. J Affect Disord. 2018;225:665–670. doi: 10.1016/j.jad.2017.09.002. PubMed DOI

Chiu M, Rahman F, Vigod S, Wilton AS, Kurdyak P. Temporal trends in cardiovascular disease risk factor profiles in a population-based schizophrenia sample: a repeat cross-sectional study. J Epidemiol Community Health. 2018;72(1):71–77. doi: 10.1136/jech-2017-209565. PubMed DOI

Lurie I, Shoval G, Hoshen M, Balicer R, Weiser M, Weizman A, Krivoy A. The association of medical resource utilization with physical morbidity and premature mortality among patients with schizophrenia: An historical prospective population cohort study. Schizophr Res. 2021;237:62–68. doi: 10.1016/j.schres.2021.08.019. PubMed DOI

Gur S, Weizman S, Stubbs B, Matalon A, Meyerovitch J, Hermesh H, Krivoy A. Mortality, morbidity and medical resources utilization of patients with schizophrenia: A case-control community-based study. Psychiatry Res. 2018;260:177–181. doi: 10.1016/j.psychres.2017.11.042. PubMed DOI

Attar R, Valentin JB, Freeman P, Andell P, Aagaard J, Jensen SE. The effect of schizophrenia on major adverse cardiac events, length of hospital stay, and prevalence of somatic comorbidities following acute coronary syndrome. Eur Heart J - Qual Care Clin Outcomes. 2019;5:121–126. doi: 10.1093/ehjqcco/qcy055. PubMed DOI

Lang X, Liu Q, Fang H, Zhou Y, Forster MT, Li Z, Zhang X. The prevalence and clinical correlates of metabolic syndrome and cardiometabolic alterations in 430 drug-naive patients in their first episode of schizophrenia. Psychopharmacology (Berl) 2021;238:3643–3652. doi: 10.1007/s00213-021-05983-9. PubMed DOI

Gabilondo A, Alonso-Moran E, Nuño-Solinis R, Orueta JF, Iruin A. Comorbidities with chronic physical conditions and gender profiles of illness in schizophrenia. Results from PREST, a new health dataset. J Psychosom Res. 2017;93:102–109. doi: 10.1016/j.jpsychores.2016.12.011. PubMed DOI

Chen YL, Pan CH, Chang CK, Chen PH, Chang HM, Tai MH, Su SS, Tsai SY, Chen CC, Kuo CJ. Physical illnesses before diagnosed as schizophrenia: a nationwide case-control study. Schizophr Bull. 2020;46:785–794. doi: 10.1093/schbul/sbaa009. PubMed DOI PMC

Hagi K, Nosaka T, Dickinson D, Lindenmayer JP, Lee J, Friedman J, Boyer L, Han M, Abdul-Rashid NA, Correll CU. Association between cardiovascular risk factors and cognitive impairment in people with schizophrenia: a systematic review and meta-analysis. JAMA Psychiatry. 2021;78(5):510–518. doi: 10.1001/jamapsychiatry.2021.0015. PubMed DOI PMC

Chen PH, Tsai SY, Pan CH, Chang HM, Chen YL, Su SS, Chen CC, Kuo CJ. Age effect on incidence, physical, and psychiatric comorbidity for sudden cardiac death in schizophrenia (in French) Can J Psychiatry. 2021;66:367–375. doi: 10.1177/0706743720948429. PubMed DOI PMC

Nasrallah HA, Meyer JM, Goff DC, McEvoy JP, Davis SM, Stroup TS, Lieberman JA. Low rates of treatment for hypertension, dyslipidemia and diabetes in schizophrenia: Data from the CATIE schizophrenia trial sample at baseline. Schizophr Res. 2006;86:15–22. doi: 10.1016/j.schres.2006.06.026. PubMed DOI

Launders N, Kirsh L, Osborn DPJ, Hayes JF. The temporal relationship between severe mental illness diagnosis and chronic physical comorbidity: a UK primary care cohort study of disease burden over 10 years. Lancet Psychiatry. 2022;9:725–735. doi: 10.1016/S2215-0366(22)00225-5. PubMed DOI PMC

Lambert AM, Parretti HM, Pearce E, et al. Temporal trends in associations between severe mental illness and risk of cardiovascular disease: A systematic review and meta-analysis. PLOS Med. 2022;19(4):e1003960. doi: 10.1371/journal.pmed.1003960. PubMed DOI PMC

Jørgensen M, Mainz J, Egstrup K, Johnsen SP. Quality of care and outcomes of heart failure among patients with schizophrenia in Denmark. Am J Cardiol. 2017;120:980–985. doi: 10.1016/j.amjcard.2017.06.027. PubMed DOI

Heiberg IH, Jacobsen BK, Balteskard L, Bramness JG, Naess Ø, Ystrom E, Reichborn-Kjennerud T, Hultman CM, Nesvåg R, Høye A. Undiagnosed cardiovascular disease prior to cardiovascular death in individuals with severe mental illness. Acta Psychiatr Scand. 2019;139:558–571. doi: 10.1111/acps.13017. PubMed DOI PMC

Perez-Pinar M, Mathur R, Foguet Q, Ayis S, Robson J, Ayerbe L. Cardiovascular risk factors among patients with schizophrenia, bipolar, depressive, anxiety, and personality disorders. Eur Psychiatry. 2016;35:8–15. doi: 10.1016/j.eurpsy.2016.02.004. PubMed DOI

Peritogiannis V, Ninou A, Samakouri M. Mortality in schizophrenia-spectrum disorders: recent advances in understanding and management. Healthc Basel Switz. 2022;10:2366. doi: 10.3390/healthcare10122366. PubMed DOI PMC

Milian MJ, Fone K, Steckler T, Horan WP. Negative symptoms of schizophrenia: Clinical characteristics, pathophysiological substrates, experimental models and prospects for improved treatment. Eur Neuropsychopharmacol. 2014;24:645–692. doi: 10.1016/j.euroneuro.2014.03.008. PubMed DOI

Manu P, Dima L, Shulman M, Vancampfort D, De Hert M, Correll CU. Weight gain and obesity in schizophrenia: epidemiology, pathobiology, and management. Acta Psychiatr Scand. 2015;132:97–108. doi: 10.1111/acps.12445. PubMed DOI

Batel P. Addiction and schizophrenia. Eur Psychiatry J Assoc Eur Psychiatr. 2000;15:115–122. doi: 10.1016/S0924-9338(00)00203-0. PubMed DOI

Onyeka IN, Collier Høegh M, Nåheim Eien EM, Nwaru BI, Melle I. Comorbidity of physical disorders among patients with severe mental illness with and without substance use disorders: a systematic review and meta-analysis. J Dual Diagn. 2019;15:192–206. doi: 10.1080/15504263.2019.1619007. PubMed DOI

Li Z, Wang S, Chen Y, Wu X, Gu Y, Lang X, Wu F, Zhang XY. Smoking affects the patterns of metabolic disorders and metabolic syndrome in patients with first-episode drug-naive schizophrenia: a large sample study based on the chinese han population. Int J Neuropsychopharmacol. 2021;24:798–807. doi: 10.1093/ijnp/pyab038. PubMed DOI PMC

Bradford DW, Kim MM, Braxton LE, Marx CE, Butterfield M, Elbogen EB. Access to medical care among persons with psychotic and major affective disorders. Psychiatr Serv. 2008;59:847–852. doi: 10.1176/ps.2008.59.8.847. PubMed DOI

Roberts L, Roalfe A, Wilson S, Lester H. Physical health care of patients with schizophrenia in primary care: a comparative study. Fam Pract. 2007;24:34–40. doi: 10.1093/fampra/cml054. PubMed DOI

Tek C, Kucukgoncu S, Guloksuz S, Woods SW, Srihari VH, Annamalai A. Antipsychotic-induced weight gain in first-episode psychosis patients: a meta-analysis of differential effects of antipsychotic medications. Early Interv Psychiatry. 2016;10:193–202. doi: 10.1111/eip.12251. PubMed DOI PMC

Castillo-Sánchez M, Fàbregas-Escurriola M, Bergè-Baquero D, Foguet-Boreu Q, Fernández-San Martín MI, Goday-Arno A. Schizophrenia, antipsychotic drugs and cardiovascular risk: Descriptive study in primary care. Eur Psychiatry J Assoc Eur Psychiatr. 2015;30:535–541. doi: 10.1016/j.eurpsy.2014.12.010. PubMed DOI

Abosi O, Lopes S, Schmitz S, Fiedorowicz JG. Cardiometabolic effects of psychotropic medications. Horm Mol Biol Clin Investig. 2018;36 doi: 10.1515/hmbci-2017-0065. /j/hmbci.2018.36.issue-1/hmbci-2017-0065/hmbci-2017-0065.xml . PubMed DOI PMC

Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. The Lancet. 2009;373:31–41. doi: 10.1016/S0140-6736(08)61764-X. PubMed DOI

Hirsch L, Yang J, Bresee L, Jette N, Patten S, Pringsheim T. Second-generation antipsychotics and metabolic side effects: a systematic review of population-based studies. Drug Saf. 2017;40:771–781. doi: 10.1007/s40264-017-0543-0. PubMed DOI

Hammoudeh S, Al Lawati H, Ghuloum S, Iram H, Yehya A, Becetti I, Al-Fakhri N, Ghabrash H, Shehata M, Ajmal N, Amro I, Safdar H, Eltorki Y, Al-Amin H. Risk factors of metabolic syndrome among patients receiving antipsychotics: a retrospective study. Community Ment Health J. 2020;56:760–770. doi: 10.1007/s10597-019-00537-y. PubMed DOI PMC

Straus SMJM, Bleumink GS, Dieleman JP, et al. Antipsychotics and the risk of sudden cardiac death. Arch Intern Med. 2004;164(12):1293–1297. doi: 10.1001/archinte.164.12.1293. PubMed DOI

Taub S, Hoshen M, Balicer R, Kamhi-Nesher S, Weizman A, Krivoy A. Metabolic predictors for mortality among patients treated with long-term clozapine - A longitudinal study. Eur Neuropsychopharmacol. 2020;41:63–69. doi: 10.1016/j.euroneuro.2020.09.002. PubMed DOI

Strømme MF, Mellesdal LS, Bartz-Johannesen C, Kroken RA, Krogenes M, Mehlum L, Johnsen E. Mortality and non-use of antipsychotic drugs after acute admission in schizophrenia: A prospective total-cohort study. Schizophr Res. 2021;235:29–35. doi: 10.1016/j.schres.2021.07.009. PubMed DOI

Laursen TM, Nordentoft M, Mortensen PB. Excess Early Mortality in Schizophrenia. Annu Rev Clin Psychol. 2014;10:425–448. doi: 10.1146/annurev-clinpsy-032813-153657. PubMed DOI

Smith SB, Su TP, editors. Sigma Receptors: Their Role in Disease and as Therapeutic Targets. Vol. 964. Springer International Publishing; 2017. PubMed DOI

Stracina T, Novakova M. Cardiac Sigma Receptors - An Update. Physiol Res. :S561–S576. doi: 10.33549/physiolres.934052. Published online December 28, 2018. PubMed DOI

Aydar E, Cobos EJ, Maurice T, Murell-Lagnado RD, Safrany ST. Editorial: Sigma Receptors. Front Pharmacol. 2020. p. 11. https://www.frontiersin.org/articles/10.3389/fphar.2020.590519, https://doi.org/10.3389/fphar.2020.590519. PubMed DOI PMC

Aishwarya R, Abdullah CS, Morshed M, Remex NS, Bhuiyan MdS. Sigmar1’s Molecular, Cellular, and Biological Functions in Regulating Cellular Pathophysiology. Front Physiol. 2021. [Accessed January 14, 2023]. p. 12. https://www.frontiersin.org/articles/10.3389/fphys.2021.705575, https://doi.org/10.3389/fphys.2021.705575. PubMed DOI PMC

Sałaciak K, Pytka K. Revisiting the sigma-1 receptor as a biological target to treat affective and cognitive disorders. Neurosci Biobehav Rev. 2022;132:1114–1136. doi: 10.1016/j.neubiorev.2021.10.037. PubMed DOI PMC

Fontanilla D, Johannessen M, Hajipour AR, Cozzi NV, Jackson MB, Ruoho AE. The hallucinogen N,N-Dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator. Science. 2009;323(5916):934–937. doi: 10.1126/science.1166127. PubMed DOI PMC

Nichols DE. N,N-dimethyltryptamine and the pineal gland: Separating fact from myth. J Psychopharmacol (Oxf) 2018;32:30–36. doi: 10.1177/0269881117736919. PubMed DOI

Quirion R, Bowen WD, Itzhak Y, Junien JL, Musacchio JM, Rothman RB, Su TP, Tam SW, Taylor DP. A proposal for the classification of sigma binding sites. Trends Pharmacol Sci. 1992;13:85–86. doi: 10.1016/0165-6147(92)90030-A. PubMed DOI

Hayashi T, Su TP. Regulating ankyrin dynamics: Roles of sigma-1 receptors. Proc Natl Acad Sci. 2001;98(2):491–496. doi: 10.1073/pnas.98.2.491. PubMed DOI PMC

Hayashi T, Su TP. Sigma-1 receptor chaperones at the ER- mitochondrion interface regulate Ca2+ signaling and cell survival. Cell. 2007;131:596–610. doi: 10.1016/j.cell.2007.08.036. PubMed DOI

Mori T, Hayashi T, Hayashi E, Su TP. Sigma-1 Receptor Chaperone at the ER-Mitochondrion Interface Mediates the Mitochondrion-ER-Nucleus Signaling for Cellular Survival. PLOS ONE. 2013;8(10):e76941. doi: 10.1371/journal.pone.0076941. PubMed DOI PMC

Alonso G, Phan V, Guillemain I, Saunier M, Legrand A, Anoal M, Maurice T. Immunocytochemical localization of the sigma1 receptor in the adult rat central nervous system. Neuroscience. 2000;97:155–170. doi: 10.1016/S0306-4522(00)00014-2. PubMed DOI

Hellewell SB, Bruce A, Feinstein G, Orringer J, Williams W, Bowen WD. Rat liver and kidney contain high densities of σ1 and σ2 receptors: characterization by ligand binding and photoaffinity labeling. Eur J Pharmacol Mol Pharmacol. 1994;268:9–18. doi: 10.1016/0922-4106(94)90115-5. PubMed DOI

Ela C, Barg J, Vogel Z, Hasin Y, Eilam Y. Sigma receptor ligands modulate contractility, Ca++ influx and beating rate in cultured cardiac myocytes. J Pharmacol Exp Ther. 1994;269(3):1300–1309. PubMed

Novakova M, Ela C, Barg J, Vogel Z, Hasin Y, Eilam Y. Inotropic action of σ receptor ligands in isolated cardiac myocytes from adult rats. Eur J Pharmacol. 1995;286:19–30. doi: 10.1016/0014-2999(95)00424-J. PubMed DOI

Crawford KW, Bowen WD. Sigma-2 Receptor Agonists Activate a Novel Apoptotic Pathway and Potentiate Antineoplastic Drugs in Breast Tumor Cell Lines1. Cancer Res. 2002;62:313–322. PubMed

Megalizzi V, Le Mercier M, Decaestecker C. Sigma receptors and their ligands in cancer biology: overview and new perspectives for cancer therapy. Med Res Rev. 2012;32:410–427. doi: 10.1002/med.20218. PubMed DOI

Novakova M. Sigma receptors: With special reference to cardiac muscle. Exp Clin Cardiol. 1998;3(3):113–120.

Su TP. σ receptors. Eur J Biochem. 1991;200:633–642. doi: 10.1111/j.1432-1033.1991.tb16226.x. PubMed DOI

Wolfe SA, De Souza EB. Sigma and phencyclidine receptors in the brain-endocrine-immune axis. NIDA Res Monogr. 1993;133:95–123. doi: 10.1037/e495962006-007. PubMed DOI

Brune S, Pricl S, Wünsch B. Structure of the σ 1 Receptor and its ligand binding site: miniperspective. J Med Chem. 2013;56:9809–9819. doi: 10.1021/jm400660u. PubMed DOI

Hayashi T, Su TP, Kagaya A, Nishida A, Shimizu M, Yamawaki S. Neuroleptics with differential affinities at dopamine D2 receptors and sigma receptors affect differently the N-methyl-D-aspartate-induced increase in intracellular calcium concentration: Involvement of protein kinase. Synapse. 1999;31(1):20–28. doi: 10.1002/(SICI)1098-2396(199901)31:1<20::AID-SYN4>3.0.CO;2-2. PubMed DOI

Bowen WD. Interaction of sigma receptors with signal transduction pathways and effects on second messengers. London: Academic Press; 1994. pp. 139–165.

Weatherspoon JK, Gonzalez-Alvear GM, Frank AR, Werling LL. Regulation of [3H]dopamine release from mesolimbic and mesocortical areas of guinea pig brain by sigma receptors. Schizophr Res. 1996;21:51–62. doi: 10.1016/0920-9964(96)00030-8. PubMed DOI

Nuwayhid SJ, Werling LL. ς 1 Receptor agonist-mediated regulation of N-Methyl-d-aspartate-stimulated [3H] dopamine release is dependent upon protein kinase C. J Pharmacol Exp Ther. 2003;304:364–369. doi: 10.1124/jpet.102.043398. PubMed DOI

Lencesova L, Szadvari I, Babula P, Kubickova J, Chovancova B, Lopusna K, Rezuchova I, Novakova Z, Krizanova O, Novakova M. Disruption of dopamine D1/D2 receptor complex is involved in the function of haloperidol in cardiac H9c2 cells. Life Sci. 2017;191:186–194. doi: 10.1016/j.lfs.2017.10.026. PubMed DOI

Gursoy M, Gul Z, Buyukuysal RL. Sigma receptor ligands haloperidol and ifenprodil attenuate hypoxia induced dopamine release in rat striatum. Neurol Res. 2022;44:927–936. doi: 10.1080/01616412.2022.2072100. PubMed DOI

Sambo DO, Lebowitz JJ, Khoshbouei H. The sigma-1 receptor as a regulator of dopamine neurotransmission: A potential therapeutic target for methamphetamine addiction. Pharmacol Ther. 2018;186:152–167. doi: 10.1016/j.pharmthera.2018.01.009. PubMed DOI PMC

Hong J, Sha S, Zhou L, Wang C, Yin J, Chen L. Sigma-1 receptor deficiency reduces MPTP-induced parkinsonism and death of dopaminergic neurons. Cell Death Dis. 2015;6:e1832. doi: 10.1038/cddis.2015.194. PubMed DOI PMC

Hayashi T, Su TP. An update on the development of drugs for neuropsychiatric disorders: focusing on the σ1 receptor ligand. Expert Opin Ther Targets. 2008;12:45–58. doi: 10.1517/14728222.12.1.45. PubMed DOI

Chen J, Li G, Qin P, et al. Allosteric Modulation of the Sigma-1 Receptor Elicits Antipsychotic-like Effects. Schizophr Bull. 2022;48:474–484. https://doi.org/10.1093/schbul/sby054, https://doi.org/10.1093/schbul/sbab137. PubMed DOI PMC

Munguia-Galaviz FJ, Miranda-Diaz AG, Cardenas-Sosa MA, Echavarria R. Sigma-1 receptor signaling: in search of new therapeutic alternatives for cardiovascular and renal diseases. Int J Mol Sci. 2023;24:1997. doi: 10.3390/ijms24031997. PubMed DOI PMC

Mitchell AJ, Vancampfort D, Sweers K, van Winkel R, Yu W, De Hert M. Prevalence of metabolic syndrome and metabolic abnormalities in schizophrenia and related disorders - a systematic review and meta-analysis. Schizophr Bull. 2013;39:306–318. https://doi.org/10.1093/schbul/sbs082, https://doi.org/10.1093/schbul/sbr148. PubMed DOI PMC

Ke M, He G, Wang H, Cheng S, Xu Y. Sigma receptor knockdown augments dysfunction and apoptosis of beta cells induced by palmitate. Exp Biol Med Maywood NJ. 2021;246:1491–1499. doi: 10.1177/1535370221997780. PubMed DOI PMC

Abdullah CS, Alam S, Aishwarya R, et al. Molecular function of Sigma-1 receptor in obesity-induced metabolic dysfunction. J Mol Cell Cardiol. 2017;112:149. doi: 10.1016/j.yjmcc.2017.07.058. DOI

Kaar SJ, Natesan S, McCutcheon R, Howes OD. Antipsychotics: Mechanisms underlying clinical response and side-effects and novel treatment approaches based on pathophysiology. Neuropharmacology. 2020;172:107704. doi: 10.1016/j.neuropharm.2019.107704. PubMed DOI

Grimm O, Kaiser S, Plichta MM, Tobler PN. Altered reward anticipation: Potential explanation for weight gain in schizophrenia? Neurosci Biobehav Rev. 2017;75:91–103. doi: 10.1016/j.neubiorev.2017.01.029. PubMed DOI

Su TP, Su TC, Nakamura Y, Tsai SY. The sigma-1 receptor as a pluripotent modulator in living systems. Trends Pharmacol Sci. 2016;37:262–278. doi: 10.1016/j.tips.2016.01.003. PubMed DOI PMC

Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, Samara M, Barbui C, Engel RR, Geddes JR, Kissling W, Stapf MP, Lässig B, Salanti G, Davis JM. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet Lond Engl. 2013;382:951–962. doi: 10.1016/S0140-6736(13)60733-3. PubMed DOI

Wu C, Tsai Y, Tsai H. Antipsychotic drugs and the risk of ventricular arrhythmia and/or sudden cardiac death: a nation-wide case-crossover study. J Am Heart Assoc. 4:e001568. PubMed PMC

Stracina T, Slaninova I, Polanska H, Axmanova M, Olejnickova V, Konecny P, Masarik M, Krizanova O, Novakova M. Long-term haloperidol treatment prolongs qt interval and increases expression of sigma 1 and IP3 receptors in guinea pig hearts. Tohoku J Exp Med. 2015;236:199–207. doi: 10.1620/tjem.236.199. PubMed DOI

Vesely P, Stracina T, Hlavacova M, Halamek J, Kolarova J, Olejnickova V, Mrkvicova V, Paulova H, Novakova M. Haloperidol affects coupling between QT and RR intervals in guinea pig isolated heart. J Pharmacol Sci. 2019;139:23–28. doi: 10.1016/j.jphs.2018.11.004. PubMed DOI

Tarabová B, Nováková M, Lacinová L. Haloperidol moderately inhibits cardiovascular L-type calcium current. Gen Physiol Biophys. 2009;28:249–259. doi: 10.4149/gpb_2009_03_249. PubMed DOI

Bébarová M, Matejovic P, Pásek M, Nováková M. Effect of haloperidol on transient outward potassium current in rat ventricular myocytes. Eur J Pharmacol. 2006;550:15–23. doi: 10.1016/j.ejphar.2006.08.046. PubMed DOI

Novakova M, Sedlakova B, Sirova M, Fialova K, Krizanova O. Haloperidol increases expression of the inositol 1,4,5-trisphosphate receptors in rat cardiac atria, but not in ventricles. Gen Physiol Biophys. 2010;29:381–389. doi: 10.4149/gpb_2010_04_381. PubMed DOI

Nguyen EC, McCracken KA, Liu Y, Pouw B, Matsumoto RR. Involvement of sigma (sigma) receptors in the acute actions of methamphetamine: receptor binding and behavioral studies. Neuropharmacology. 2005;49:638–645. doi: 10.1016/j.neuropharm.2005.04.016. PubMed DOI

Chen Y, Hajipour AR, Sievert MK, Arbabian M, Ruoho AE. Characterization of the cocaine binding site on the sigma-1 receptor. Biochemistry. 2007;46:3532–3542. doi: 10.1021/bi061727o. PubMed DOI

Quadir SG, Cottone P, Sabino V. Role of sigma receptors in alcohol addiction. [Accessed March 15, 2023];Front Pharmacol. 2019 :10. doi: 10.3389/fphar.2019.00687. PubMed DOI PMC

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