Skip to main content
Top

Open Access 06-11-2024 | Schizophrenia | Original Paper

Polygenic risk for psychotic disorders in relation to cardiac autonomic dysfunction in unmedicated patients with schizophrenia

Authors: Alexander Refisch, Sergi Papiol, Andy Schumann, Berend Malchow, Karl-Jürgen Bär

Published in: European Archives of Psychiatry and Clinical Neuroscience

Login to get access

Abstract

Cardiac autonomic dysfunction (CADF), mainly characterized by increased heart rate, decreased heart rate variability, and loss of vagal modulation, has been extensively described in patients with schizophrenia (SCZ) and their healthy first-degree relatives. As such, it represents an apparent physiological link that contributes to the increased cardiovascular mortality in these patients. Common genetic variation is a putative underlying mechanism, along with lifestyle factors and antipsychotic medications. However, the extent to which CADF is associated with genetic factors for SCZ is unknown. A sample of 83 drug-naive SCZ patients and 96 healthy controls, all of European origin, underwent a 30-minute autonomic assessment under resting conditions. We incorporated parameters from several domains into our model, including time and frequency domains (mean heart rate, low/high frequency ratio) and compression entropy, each of which provides different insights into the dynamics of cardiac autonomic function. These parameters were used as outcome variables in linear regression models with polygenic risk scores (PRS) for SCZ as predictors and age, sex, BMI, smoking status, principal components of ancestry and diagnosis as covariates. Of the three CADF parameters, SCZ PRS was significantly associated with mean heart rate in the combined case/control sample. However, this association was was no longer significant after including diagnosis as a covariate (p = 0.29). In contrast, diagnostic status is statistically significant for all three CADF parameters, accounting for a significantly greater proportion of the variance in mean heart rate compared to SCZ PRS (approximately 16% vs. 4%). Despite evidence for a common genetic basis of CADF and SCZ, we were unable to provide further support for an association between the polygenic burden of SCZ and cardiac autonomic function beyond the diagnostic state. This suggests that there are other important characteristics associated with SCZ that lead to CADF that are not captured by SCZ PRS.
Appendix
Available only for authorised users
Literature
1.
go back to reference Tiihonen J, Lonnqvist J, Wahlbeck K, Klaukka T, Niskanen L, Tanskanen A, Haukka J (2009) <ArticleTitle Language=“En”>11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet Aug 22(9690):620–627CrossRef Tiihonen J, Lonnqvist J, Wahlbeck K, Klaukka T, Niskanen L, Tanskanen A, Haukka J (2009) <ArticleTitle Language=“En”>11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet Aug 22(9690):620–627CrossRef
2.
go back to reference Laursen TM, Nordentoft M, Mortensen PB (2014) Excess early mortality in schizophrenia. Annu Rev Clin Psychol 10:425–448PubMedCrossRef Laursen TM, Nordentoft M, Mortensen PB (2014) Excess early mortality in schizophrenia. Annu Rev Clin Psychol 10:425–448PubMedCrossRef
3.
go back to reference Olfson M, Gerhard T, Huang C, Crystal S, Stroup TS (2015) Premature Mortality Among Adults With Schizophrenia in the United States. JAMA Psychiatry Dec 72(12):1172–1181CrossRef Olfson M, Gerhard T, Huang C, Crystal S, Stroup TS (2015) Premature Mortality Among Adults With Schizophrenia in the United States. JAMA Psychiatry Dec 72(12):1172–1181CrossRef
4.
go back to reference Correll CU, Solmi M, Veronese N et al (2017) 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 Jun 16(2):163–180CrossRef Correll CU, Solmi M, Veronese N et al (2017) 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 Jun 16(2):163–180CrossRef
5.
go back to reference Chen Y, Zhang F, Yan Y, Wang S, Zhang L, Yan F (2022) Sudden Cardiac Death in Schizophrenia During Hospitalization: An Autopsy-Based Study. Front Psychiatry ;13 Chen Y, Zhang F, Yan Y, Wang S, Zhang L, Yan F (2022) Sudden Cardiac Death in Schizophrenia During Hospitalization: An Autopsy-Based Study. Front Psychiatry ;13
6.
go back to reference Correll CU, Detraux J, De Lepeleire J, De Hert M (2015) Effects of antipsychotics, antidepressants and mood stabilizers on risk for physical diseases in people with schizophrenia, depression and bipolar disorder. World Psychiatry 2015/06/01(2):119–136CrossRef Correll CU, Detraux J, De Lepeleire J, De Hert M (2015) Effects of antipsychotics, antidepressants and mood stabilizers on risk for physical diseases in people with schizophrenia, depression and bipolar disorder. World Psychiatry 2015/06/01(2):119–136CrossRef
7.
go back to reference Sutterland AL, Blom MT, Ladee K, Lubbers JJM, Cohen D, de Haan L, Tan HL (2019) Increased prevalence of ECG suspicious for Brugada Syndrome in recent onset schizophrenia spectrum disorders. Schizophrenia Res 2019/08/01/ 210:59–65CrossRef Sutterland AL, Blom MT, Ladee K, Lubbers JJM, Cohen D, de Haan L, Tan HL (2019) Increased prevalence of ECG suspicious for Brugada Syndrome in recent onset schizophrenia spectrum disorders. Schizophrenia Res 2019/08/01/ 210:59–65CrossRef
8.
go back to reference Vohra J (2020) Sudden Cardiac Death in Schizophrenia: A Review. Heart Lung Circulation 2020/10/01(10):1427–1432CrossRef Vohra J (2020) Sudden Cardiac Death in Schizophrenia: A Review. Heart Lung Circulation 2020/10/01(10):1427–1432CrossRef
9.
go back to reference Sweeting J, Duflou J, Semsarian C (2013) Postmortem analysis of cardiovascular deaths in schizophrenia: A 10-year review. Schizophrenia Res 2013/11/01/ 150(2):398–403CrossRef Sweeting J, Duflou J, Semsarian C (2013) Postmortem analysis of cardiovascular deaths in schizophrenia: A 10-year review. Schizophrenia Res 2013/11/01/ 150(2):398–403CrossRef
10.
go back to reference Sessa F, Anna V, Messina G et al (2018) Heart rate variability as predictive factor for sudden cardiac death. Aging (Albany NY) Feb 23(2):166–177 Sessa F, Anna V, Messina G et al (2018) Heart rate variability as predictive factor for sudden cardiac death. Aging (Albany NY) Feb 23(2):166–177
11.
go back to reference Jensen MT, Marott JL, Lange P, Vestbo J, Schnohr P, Nielsen OW, Jensen JS, Jensen GB (2013) Resting heart rate is a predictor of mortality in COPD. Eur Respir J Aug 42(2):341–349CrossRef Jensen MT, Marott JL, Lange P, Vestbo J, Schnohr P, Nielsen OW, Jensen JS, Jensen GB (2013) Resting heart rate is a predictor of mortality in COPD. Eur Respir J Aug 42(2):341–349CrossRef
12.
go back to reference Huikuri HV, Stein PK (2013) Heart Rate Variability in Risk Stratification of Cardiac Patients. Prog Cardiovasc Dis 2013/09/01(2):153–159CrossRef Huikuri HV, Stein PK (2013) Heart Rate Variability in Risk Stratification of Cardiac Patients. Prog Cardiovasc Dis 2013/09/01(2):153–159CrossRef
13.
go back to reference Bär KJ, Letzsch A, Jochum T, Wagner G, Greiner W, Sauer H (2005) Loss of efferent vagal activity in acute schizophrenia. J Psychiatr Res Sep 39(5):519–527CrossRef Bär KJ, Letzsch A, Jochum T, Wagner G, Greiner W, Sauer H (2005) Loss of efferent vagal activity in acute schizophrenia. J Psychiatr Res Sep 39(5):519–527CrossRef
14.
go back to reference Correll CU, Robinson DG, Schooler NR et al (2014) Cardiometabolic risk in patients with first-episode schizophrenia spectrum disorders: baseline results from the RAISE-ETP study. JAMA Psychiatry Dec 1(12):1350–1363CrossRef Correll CU, Robinson DG, Schooler NR et al (2014) Cardiometabolic risk in patients with first-episode schizophrenia spectrum disorders: baseline results from the RAISE-ETP study. JAMA Psychiatry Dec 1(12):1350–1363CrossRef
15.
go back to reference Vancampfort D, Wampers M, Mitchell AJ, Correll CU, De Herdt A, Probst M, De Hert M (2013) A meta-analysis of cardio-metabolic abnormalities in drug naïve, first-episode and multi-episode patients with schizophrenia versus general population controls. World Psychiatry Oct 12(3):240–250CrossRef Vancampfort D, Wampers M, Mitchell AJ, Correll CU, De Herdt A, Probst M, De Hert M (2013) A meta-analysis of cardio-metabolic abnormalities in drug naïve, first-episode and multi-episode patients with schizophrenia versus general population controls. World Psychiatry Oct 12(3):240–250CrossRef
16.
go back to reference Ringen PA, Engh JA, Birkenaes AB, Dieset I, Andreassen OA (2014) Increased mortality in schizophrenia due to cardiovascular disease - a non-systematic review of epidemiology, possible causes, and interventions. Front Psychiatry 5:137PubMedPubMedCentralCrossRef Ringen PA, Engh JA, Birkenaes AB, Dieset I, Andreassen OA (2014) Increased mortality in schizophrenia due to cardiovascular disease - a non-systematic review of epidemiology, possible causes, and interventions. Front Psychiatry 5:137PubMedPubMedCentralCrossRef
17.
go back to reference He Q, Bennett AN, Liu J et al (2022) Exploring Lead loci shared between schizophrenia and Cardiometabolic traits. BMC Genomics Aug 25(1):617CrossRef He Q, Bennett AN, Liu J et al (2022) Exploring Lead loci shared between schizophrenia and Cardiometabolic traits. BMC Genomics Aug 25(1):617CrossRef
18.
go back to reference Strawbridge RJ, Johnston KJA, Bailey MES et al (2021) The overlap of genetic susceptibility to schizophrenia and cardiometabolic disease can be used to identify metabolically different groups of individuals. Sci Rep 2021/01/ 11(12):632CrossRef Strawbridge RJ, Johnston KJA, Bailey MES et al (2021) The overlap of genetic susceptibility to schizophrenia and cardiometabolic disease can be used to identify metabolically different groups of individuals. Sci Rep 2021/01/ 11(12):632CrossRef
19.
go back to reference Perry BI, Bowker N, Burgess S, Wareham NJ, Upthegrove R, Jones PB, Langenberg C, Khandaker GM (2022) Evidence for Shared Genetic Aetiology Between Schizophrenia, Cardiometabolic, and Inflammation-Related Traits: Genetic Correlation and Colocalization Analyses. Schizophr Bull Open Jan 3(1):sgac001CrossRef Perry BI, Bowker N, Burgess S, Wareham NJ, Upthegrove R, Jones PB, Langenberg C, Khandaker GM (2022) Evidence for Shared Genetic Aetiology Between Schizophrenia, Cardiometabolic, and Inflammation-Related Traits: Genetic Correlation and Colocalization Analyses. Schizophr Bull Open Jan 3(1):sgac001CrossRef
20.
21.
go back to reference Fukuda K, Kanazawa H, Aizawa Y, Ardell JL, Shivkumar K (2015) Cardiac innervation and sudden cardiac death. Circ Res Jun 5(12):2005–2019CrossRef Fukuda K, Kanazawa H, Aizawa Y, Ardell JL, Shivkumar K (2015) Cardiac innervation and sudden cardiac death. Circ Res Jun 5(12):2005–2019CrossRef
22.
go back to reference Ardell JL, Andresen MC, Armour JA et al (2016) Translational neurocardiology: preclinical models and cardioneural integrative aspects. J Physiol Jul 15(14):3877–3909CrossRef Ardell JL, Andresen MC, Armour JA et al (2016) Translational neurocardiology: preclinical models and cardioneural integrative aspects. J Physiol Jul 15(14):3877–3909CrossRef
23.
go back to reference Shivkumar K, Ardell JL (2016) Cardiac autonomic control in health and disease. J Physiol Jul 15(14):3851–3852CrossRef Shivkumar K, Ardell JL (2016) Cardiac autonomic control in health and disease. J Physiol Jul 15(14):3851–3852CrossRef
24.
go back to reference Hadaya J, Ardell JL (2020) Autonomic Modulation for Cardiovascular Disease. Front Physiol ;11 Hadaya J, Ardell JL (2020) Autonomic Modulation for Cardiovascular Disease. Front Physiol ;11
25.
go back to reference Bär K-J, Berger S, Metzner M et al (2010) Autonomic dysfunction in unaffected first-degree relatives of patients suffering from schizophrenia. Schizophr Bull 36(5):1050–1058PubMedCrossRef Bär K-J, Berger S, Metzner M et al (2010) Autonomic dysfunction in unaffected first-degree relatives of patients suffering from schizophrenia. Schizophr Bull 36(5):1050–1058PubMedCrossRef
26.
go back to reference Singh JP, Larson MG, O’Donnell CJ, Tsuji H, Evans JC, Levy D (1999) Heritability of Heart Rate Variability. Circulation 1999/05/04 99(17):2251–2254CrossRef Singh JP, Larson MG, O’Donnell CJ, Tsuji H, Evans JC, Levy D (1999) Heritability of Heart Rate Variability. Circulation 1999/05/04 99(17):2251–2254CrossRef
27.
go back to reference Su S, Lampert R, Lee F et al (2010) Common genes contribute to depressive symptoms and heart rate variability: the Twins Heart Study. Twin Res Hum Genet Feb 13(1):1–9CrossRef Su S, Lampert R, Lee F et al (2010) Common genes contribute to depressive symptoms and heart rate variability: the Twins Heart Study. Twin Res Hum Genet Feb 13(1):1–9CrossRef
28.
go back to reference Golosheykin S, Grant JD, Novak OV, Heath AC, Anokhin AP (2017) Genetic influences on heart rate variability. Int J Psychophysiol May 115:65–73CrossRef Golosheykin S, Grant JD, Novak OV, Heath AC, Anokhin AP (2017) Genetic influences on heart rate variability. Int J Psychophysiol May 115:65–73CrossRef
29.
go back to reference de Geus E, van Lien R, Neijts M, Willemsen G (2015) 17 Genetics of Autonomic Nervous System Activity. The Oxford handbook of molecular psychology :357 de Geus E, van Lien R, Neijts M, Willemsen G (2015) 17 Genetics of Autonomic Nervous System Activity. The Oxford handbook of molecular psychology :357
30.
go back to reference Muñoz ML, Jaju D, Voruganti S et al (2018) Heritability and genetic correlations of heart rate variability at rest and during stress in the Oman Family Study. J Hypertens Jul 36(7):1477–1485CrossRef Muñoz ML, Jaju D, Voruganti S et al (2018) Heritability and genetic correlations of heart rate variability at rest and during stress in the Oman Family Study. J Hypertens Jul 36(7):1477–1485CrossRef
31.
go back to reference Jensen MT, Wod M, Galatius S, Hjelmborg JB, Jensen GB, Christensen K (2018) Heritability of resting heart rate and association with mortality in middle-aged and elderly twins. Heart Jan 104(1):30–36CrossRef Jensen MT, Wod M, Galatius S, Hjelmborg JB, Jensen GB, Christensen K (2018) Heritability of resting heart rate and association with mortality in middle-aged and elderly twins. Heart Jan 104(1):30–36CrossRef
32.
go back to reference Hilker R, Helenius D, Fagerlund B, Skytthe A, Christensen K, Werge TM, Nordentoft M, Glenthøj B (2018) Heritability of Schizophrenia and Schizophrenia Spectrum Based on the Nationwide Danish Twin Register. Biol Psychiatry Mar 15(6):492–498CrossRef Hilker R, Helenius D, Fagerlund B, Skytthe A, Christensen K, Werge TM, Nordentoft M, Glenthøj B (2018) Heritability of Schizophrenia and Schizophrenia Spectrum Based on the Nationwide Danish Twin Register. Biol Psychiatry Mar 15(6):492–498CrossRef
33.
go back to reference Counotte J, Pot-Kolder R, van Roon AM, Hoskam O, van der Gaag M, Veling W (2017) High psychosis liability is associated with altered autonomic balance during exposure to Virtual Reality social stressors. Schizophr Res Jun 184:14–20CrossRef Counotte J, Pot-Kolder R, van Roon AM, Hoskam O, van der Gaag M, Veling W (2017) High psychosis liability is associated with altered autonomic balance during exposure to Virtual Reality social stressors. Schizophr Res Jun 184:14–20CrossRef
34.
go back to reference Clamor A, Lincoln TM, Thayer JF, Koenig J (2016) Resting vagal activity in schizophrenia: meta-analysis of heart rate variability as a potential endophenotype. Br J psychiatry: J mental Sci Jan 208(1):9–16CrossRef Clamor A, Lincoln TM, Thayer JF, Koenig J (2016) Resting vagal activity in schizophrenia: meta-analysis of heart rate variability as a potential endophenotype. Br J psychiatry: J mental Sci Jan 208(1):9–16CrossRef
35.
go back to reference Tegegne BS, Said MA, Ani A et al (2023) Phenotypic but not genetically predicted heart rate variability associated with all-cause mortality. Commun Biol Oct 6(1):1013CrossRef Tegegne BS, Said MA, Ani A et al (2023) Phenotypic but not genetically predicted heart rate variability associated with all-cause mortality. Commun Biol Oct 6(1):1013CrossRef
36.
go back to reference Nolte IM, Munoz ML, Tragante V et al (2017) Genetic loci associated with heart rate variability and their effects on cardiac disease risk. Nat Commun Jun 14:8:15805CrossRef Nolte IM, Munoz ML, Tragante V et al (2017) Genetic loci associated with heart rate variability and their effects on cardiac disease risk. Nat Commun Jun 14:8:15805CrossRef
37.
go back to reference Newton-Cheh C, Guo CY, Wang TJ, O’Donnell CJ, Levy D, Larson MG (2007) Genome-wide association study of electrocardiographic and heart rate variability traits: the Framingham Heart Study. BMC Med Genet Sep 19(Suppl 1):S7CrossRef Newton-Cheh C, Guo CY, Wang TJ, O’Donnell CJ, Levy D, Larson MG (2007) Genome-wide association study of electrocardiographic and heart rate variability traits: the Framingham Heart Study. BMC Med Genet Sep 19(Suppl 1):S7CrossRef
38.
go back to reference Eppinga RN, Hagemeijer Y, Burgess S et al (2016) Identification of genomic loci associated with resting heart rate and shared genetic predictors with all-cause mortality. Nat Genet Dec 48(12):1557–1563CrossRef Eppinga RN, Hagemeijer Y, Burgess S et al (2016) Identification of genomic loci associated with resting heart rate and shared genetic predictors with all-cause mortality. Nat Genet Dec 48(12):1557–1563CrossRef
39.
go back to reference van de Vegte YJ, Eppinga RN, van der Ende MY et al (2023) Genetic insights into resting heart rate and its role in cardiovascular disease. Nat Commun 2023/08/02(1):4646CrossRef van de Vegte YJ, Eppinga RN, van der Ende MY et al (2023) Genetic insights into resting heart rate and its role in cardiovascular disease. Nat Commun 2023/08/02(1):4646CrossRef
40.
go back to reference Trubetskoy V, Pardiñas AF, Qi T et al (2022) Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Nat Apr 604(7906):502–508 Trubetskoy V, Pardiñas AF, Qi T et al (2022) Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Nat Apr 604(7906):502–508
41.
go back to reference Refisch A, Chung HY, Komatsuzaki S, Schumann A, Mühleisen TW, Nöthen MM, Hübner CA, Bär KJ (2020) A common variation in HCN1 is associated with heart rate variability in schizophrenia. Schizophr Res Nov 18 Refisch A, Chung HY, Komatsuzaki S, Schumann A, Mühleisen TW, Nöthen MM, Hübner CA, Bär KJ (2020) A common variation in HCN1 is associated with heart rate variability in schizophrenia. Schizophr Res Nov 18
42.
go back to reference Refisch A, Komatsuzaki S, Ungelenk M et al (2022) Associations of common genetic risk variants of the muscarinic acetylcholine receptor M2 with cardiac autonomic dysfunction in patients with schizophrenia. World J Biol Psychiatry Mar 9:1–11 Refisch A, Komatsuzaki S, Ungelenk M et al (2022) Associations of common genetic risk variants of the muscarinic acetylcholine receptor M2 with cardiac autonomic dysfunction in patients with schizophrenia. World J Biol Psychiatry Mar 9:1–11
43.
go back to reference Refisch A, Komatsuzaki S, Ungelenk M et al (2022) Analysis of CACNA1C and KCNH2 Risk Variants on Cardiac Autonomic Function in Patients with Schizophrenia. Genes (Basel) Nov 16 ;13(11) Refisch A, Komatsuzaki S, Ungelenk M et al (2022) Analysis of CACNA1C and KCNH2 Risk Variants on Cardiac Autonomic Function in Patients with Schizophrenia. Genes (Basel) Nov 16 ;13(11)
44.
go back to reference Diagnostic and statistical manual of mental disorders: DSM-IV: Fourth edition. Washington, DC: American Psychiatric Association, [1994] ©1994; (1994) Diagnostic and statistical manual of mental disorders: DSM-IV: Fourth edition. Washington, DC: American Psychiatric Association, [1994] ©1994; (1994)
45.
go back to reference Kübler U (2013) Structured Clinical Interview for DSM-IV (SCID). In: Gellman MD, Turner JR (eds) Encyclopedia of Behavioral Medicine. Springer New York, New York, NY, pp 1919–1920CrossRef Kübler U (2013) Structured Clinical Interview for DSM-IV (SCID). In: Gellman MD, Turner JR (eds) Encyclopedia of Behavioral Medicine. Springer New York, New York, NY, pp 1919–1920CrossRef
46.
go back to reference Kay SR, Fiszbein A, Opler LA (1987) The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 13(2):261–276PubMedCrossRef Kay SR, Fiszbein A, Opler LA (1987) The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 13(2):261–276PubMedCrossRef
47.
go back to reference Wessel N, Voss A, Malberg H, Ziehmann C, Voss HU, Schirdewan A, Meyerfeldt U, Kurths J (2000) Nonlinear analysis of complex phenomena in cardiological data. Herzschrittmachertherapie und Elektrophysiologie 2000/10/01(3):159–173CrossRef Wessel N, Voss A, Malberg H, Ziehmann C, Voss HU, Schirdewan A, Meyerfeldt U, Kurths J (2000) Nonlinear analysis of complex phenomena in cardiological data. Herzschrittmachertherapie und Elektrophysiologie 2000/10/01(3):159–173CrossRef
48.
go back to reference Fortin J, Haitchi G, Bojic A et al (2001) Validation verification task force® Monit 510 Fortin J, Haitchi G, Bojic A et al (2001) Validation verification task force® Monit 510
49.
go back to reference Bär KJ, Boettger MK, Koschke M, Schulz S, Chokka P, Yeragani VK, Voss A (2007) Non-linear complexity measures of heart rate variability in acute schizophrenia. Clin Neurophysiol Sep 118(9):2009–2015CrossRef Bär KJ, Boettger MK, Koschke M, Schulz S, Chokka P, Yeragani VK, Voss A (2007) Non-linear complexity measures of heart rate variability in acute schizophrenia. Clin Neurophysiol Sep 118(9):2009–2015CrossRef
50.
go back to reference Heart rate variability (1996) : standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation Mar 1(5):1043–1065 Heart rate variability (1996) : standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation Mar 1(5):1043–1065
51.
go back to reference Baumert M, Baier V, Haueisen J, Wessel N, Meyerfeldt U, Schirdewan A, Voss A (2004) Forecasting of life threatening arrhythmias using the compression entropy of heart rate. Methods Inf Med 43(2):202–206PubMedCrossRef Baumert M, Baier V, Haueisen J, Wessel N, Meyerfeldt U, Schirdewan A, Voss A (2004) Forecasting of life threatening arrhythmias using the compression entropy of heart rate. Methods Inf Med 43(2):202–206PubMedCrossRef
52.
go back to reference Chang CC, Chow CC, Tellier LCAM, Vattikuti S, Purcell SM, Lee JJ (2015) Second-generation PLINK: rising to the challenge of larger and richer datasets. GigaScience ;4(1):s13742-13015-10047-13748 Chang CC, Chow CC, Tellier LCAM, Vattikuti S, Purcell SM, Lee JJ (2015) Second-generation PLINK: rising to the challenge of larger and richer datasets. GigaScience ;4(1):s13742-13015-10047-13748
53.
go back to reference Delaneau O, Zagury JF, Marchini J (2013) Improved whole-chromosome phasing for disease and population genetic studies. Nat Methods Jan 10(1):5–6CrossRef Delaneau O, Zagury JF, Marchini J (2013) Improved whole-chromosome phasing for disease and population genetic studies. Nat Methods Jan 10(1):5–6CrossRef
54.
go back to reference Ge T, Chen C-Y, Ni Y, Feng Y-CA, Smoller JW (2019) Polygenic prediction via Bayesian regression and continuous shrinkage priors. Nat Commun 2019/04/16(1):1776CrossRef Ge T, Chen C-Y, Ni Y, Feng Y-CA, Smoller JW (2019) Polygenic prediction via Bayesian regression and continuous shrinkage priors. Nat Commun 2019/04/16(1):1776CrossRef
55.
go back to reference So HC, Chau KL, Ao FK, Mo CH, Sham PC (2019) Exploring shared genetic bases and causal relationships of schizophrenia and bipolar disorder with 28 cardiovascular and metabolic traits. Psychol Med Jun 49(8):1286–1298CrossRef So HC, Chau KL, Ao FK, Mo CH, Sham PC (2019) Exploring shared genetic bases and causal relationships of schizophrenia and bipolar disorder with 28 cardiovascular and metabolic traits. Psychol Med Jun 49(8):1286–1298CrossRef
56.
go back to reference Momen NC, Plana-Ripoll O, Agerbo E et al (2020) Association between Mental Disorders and Subsequent Medical Conditions. N Engl J Med Apr 30(18):1721–1731CrossRef Momen NC, Plana-Ripoll O, Agerbo E et al (2020) Association between Mental Disorders and Subsequent Medical Conditions. N Engl J Med Apr 30(18):1721–1731CrossRef
57.
go back to reference Kim DR, Bale TL, Epperson CN (2015) Prenatal programming of mental illness: current understanding of relationship and mechanisms. Curr Psychiatry Rep Feb 17(2):5CrossRef Kim DR, Bale TL, Epperson CN (2015) Prenatal programming of mental illness: current understanding of relationship and mechanisms. Curr Psychiatry Rep Feb 17(2):5CrossRef
58.
go back to reference Koutsouleris N, Davatzikos C, Borgwardt S et al (2014) Accelerated brain aging in schizophrenia and beyond: a neuroanatomical marker of psychiatric disorders. Schizophr Bull Sep 40(5):1140–1153CrossRef Koutsouleris N, Davatzikos C, Borgwardt S et al (2014) Accelerated brain aging in schizophrenia and beyond: a neuroanatomical marker of psychiatric disorders. Schizophr Bull Sep 40(5):1140–1153CrossRef
59.
go back to reference Veeneman RR, Vermeulen JM, Abdellaoui A et al (2022) Exploring the Relationship Between Schizophrenia and Cardiovascular Disease: A Genetic Correlation and Multivariable Mendelian Randomization Study. Schizophr Bull 48(2):463–473PubMedCrossRef Veeneman RR, Vermeulen JM, Abdellaoui A et al (2022) Exploring the Relationship Between Schizophrenia and Cardiovascular Disease: A Genetic Correlation and Multivariable Mendelian Randomization Study. Schizophr Bull 48(2):463–473PubMedCrossRef
60.
go back to reference Andreassen OA, Djurovic S, Thompson WK et al (2013) Improved detection of common variants associated with schizophrenia by leveraging pleiotropy with cardiovascular-disease risk factors. Am J Hum Genet Feb 7(2):197–209CrossRef Andreassen OA, Djurovic S, Thompson WK et al (2013) Improved detection of common variants associated with schizophrenia by leveraging pleiotropy with cardiovascular-disease risk factors. Am J Hum Genet Feb 7(2):197–209CrossRef
61.
go back to reference Pouget JG, Han B, Wu Y et al (2019) Cross-disorder analysis of schizophrenia and 19 immune-mediated diseases identifies shared genetic risk. Hum Mol Genet Oct 15(20):3498–3513CrossRef Pouget JG, Han B, Wu Y et al (2019) Cross-disorder analysis of schizophrenia and 19 immune-mediated diseases identifies shared genetic risk. Hum Mol Genet Oct 15(20):3498–3513CrossRef
62.
go back to reference Renna ME, Hoyt MA, Ottaviani C, Mennin DS (2020) An experimental examination of worry and relaxation on cardiovascular, endocrine, and inflammatory processes. Psychoneuroendocrinology Dec 122:104870CrossRef Renna ME, Hoyt MA, Ottaviani C, Mennin DS (2020) An experimental examination of worry and relaxation on cardiovascular, endocrine, and inflammatory processes. Psychoneuroendocrinology Dec 122:104870CrossRef
63.
go back to reference Pillinger T, Osimo EF, de Marvao A et al (2023) Effect of polygenic risk for schizophrenia on cardiac structure and function: a UK Biobank observational study. Lancet Psychiatry 10(2):98–107PubMedCrossRef Pillinger T, Osimo EF, de Marvao A et al (2023) Effect of polygenic risk for schizophrenia on cardiac structure and function: a UK Biobank observational study. Lancet Psychiatry 10(2):98–107PubMedCrossRef
64.
go back to reference Pillinger T, D’Ambrosio E, McCutcheon R, Howes OD (2019) Is psychosis a multisystem disorder? A meta-review of central nervous system, immune, cardiometabolic, and endocrine alterations in first-episode psychosis and perspective on potential models. Mol Psychiatry Jun 24(6):776–794CrossRef Pillinger T, D’Ambrosio E, McCutcheon R, Howes OD (2019) Is psychosis a multisystem disorder? A meta-review of central nervous system, immune, cardiometabolic, and endocrine alterations in first-episode psychosis and perspective on potential models. Mol Psychiatry Jun 24(6):776–794CrossRef
65.
go back to reference Zhang R, Sjölander A, Ploner A, Lu D, Bulik CM, Bergen SE (2022) Novel disease associations with schizophrenia genetic risk revealed in ~ 400,000 UK Biobank participants. Mol Psychiatry Mar 27(3):1448–1454CrossRef Zhang R, Sjölander A, Ploner A, Lu D, Bulik CM, Bergen SE (2022) Novel disease associations with schizophrenia genetic risk revealed in ~ 400,000 UK Biobank participants. Mol Psychiatry Mar 27(3):1448–1454CrossRef
66.
go back to reference Garrett L, Trümbach D, Spielmann N, Wurst W, Fuchs H, Gailus-Durner V, Hrabě de Angelis M, Hölter SM (2022) A rationale for considering heart/brain axis control in neuropsychiatric disease. Mamm Genome /12/20 2022. Garrett L, Trümbach D, Spielmann N, Wurst W, Fuchs H, Gailus-Durner V, Hrabě de Angelis M, Hölter SM (2022) A rationale for considering heart/brain axis control in neuropsychiatric disease. Mamm Genome /12/20 2022.
67.
go back to reference Zheutlin AB, Chekroud AM, Polimanti R et al (2018) Multivariate Pattern Analysis of Genotype-Phenotype Relationships in Schizophrenia. Schizophr Bull Aug 20(5):1045–1052CrossRef Zheutlin AB, Chekroud AM, Polimanti R et al (2018) Multivariate Pattern Analysis of Genotype-Phenotype Relationships in Schizophrenia. Schizophr Bull Aug 20(5):1045–1052CrossRef
68.
go back to reference Dron JS, Hegele RA (2019) The evolution of genetic-based risk scores for lipids and cardiovascular disease. Curr Opin Lipidol Apr 30(2):71–81CrossRef Dron JS, Hegele RA (2019) The evolution of genetic-based risk scores for lipids and cardiovascular disease. Curr Opin Lipidol Apr 30(2):71–81CrossRef
69.
go back to reference Trifu SC, Kohn B, Vlasie A, Patrichi BE (2020) Genetics of schizophrenia (Review). Exp Ther Med Oct 20(4):3462–3468 Trifu SC, Kohn B, Vlasie A, Patrichi BE (2020) Genetics of schizophrenia (Review). Exp Ther Med Oct 20(4):3462–3468
Metadata
Title
Polygenic risk for psychotic disorders in relation to cardiac autonomic dysfunction in unmedicated patients with schizophrenia
Authors
Alexander Refisch
Sergi Papiol
Andy Schumann
Berend Malchow
Karl-Jürgen Bär
Publication date
06-11-2024
Publisher
Springer Berlin Heidelberg
Keyword
Schizophrenia
Published in
European Archives of Psychiatry and Clinical Neuroscience
Print ISSN: 0940-1334
Electronic ISSN: 1433-8491
DOI
https://doi.org/10.1007/s00406-024-01933-6