Hostname: page-component-745bb68f8f-b95js Total loading time: 0 Render date: 2025-01-12T12:51:54.582Z Has data issue: false hasContentIssue false
  • English
  • Français

Effect of polygenic risk score, family load of schizophrenia and exposome risk score, and their interactions, on the long-term outcome of first-episode psychosis

Published online by Cambridge University Press:  06 March 2023

M. J. Cuesta Open the ORCID record for M. J. Cuesta [Opens in a new window] ,
S. Papiol ,
B. Ibañez ,
E. García de Jalón ,
A. M. Sánchez-Torres ,
G. J. Gil-Berrozpe ,
L. Moreno-Izco ,
A. Zarzuela ,
L. Fañanás  and
V. Peralta
...Show all authors
M. J. Cuesta*
Affiliation:
Department of Psychiatry, Hospital Universitario de Navarra, Pamplona, Spain Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
S. Papiol
Affiliation:
Centro de Investigación Biomédica en Red de Salud Mental, Instituto de Salud Carlos III, Madrid, Spain Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, 80336, Germany Max Planck Institute of Psychiatry, Munich, Germany
B. Ibañez
Affiliation:
Navarra Institute for Health Research (IdiSNA), Pamplona, Spain Navarrabiomed – Hospital Universitario de Navarra – UPNA, Pamplona, Spain Red de Investigación en Atención Primaria, Servicios Sanitarios y Cronicidad (RICAPPS), Barcelona, Spain
E. García de Jalón
Affiliation:
Navarra Institute for Health Research (IdiSNA), Pamplona, Spain Mental Health Department, Servicio Navarro de Salud, Pamplona, Spain
A. M. Sánchez-Torres
Affiliation:
Department of Psychiatry, Hospital Universitario de Navarra, Pamplona, Spain Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
G. J. Gil-Berrozpe
Affiliation:
Department of Psychiatry, Hospital Universitario de Navarra, Pamplona, Spain Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
L. Moreno-Izco
Affiliation:
Department of Psychiatry, Hospital Universitario de Navarra, Pamplona, Spain Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
A. Zarzuela
Affiliation:
Navarra Institute for Health Research (IdiSNA), Pamplona, Spain Mental Health Department, Servicio Navarro de Salud, Pamplona, Spain
L. Fañanás
Affiliation:
Centro de Investigación Biomédica en Red de Salud Mental, Instituto de Salud Carlos III, Madrid, Spain Department of Evolutionary Biology, Ecology and Environmental Sciences, Faculty of Biology, University of Barcelona, Biomedicine Institute of the University of Barcelona (IBUB), Barcelona, Spain
V. Peralta
Affiliation:
Navarra Institute for Health Research (IdiSNA), Pamplona, Spain Mental Health Department, Servicio Navarro de Salud, Pamplona, Spain
SEGPEPs Group
Affiliation:
Red de Salud Mental de Álava, Vitoria-Gasteiz, Spain CSMIJ Ciutat Vella. Consorci Parc de Salut Mar, Barcelona, Spain
*
Author for correspondence: M. J. Cuesta, E-mail: mcuestaz@navarra.es
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Consistent evidence supports the involvement of genetic and environmental factors, and their interactions, in the etiology of psychosis. First-episode psychosis (FEP) comprises a group of disorders that show great clinical and long-term outcome heterogeneity, and the extent to which genetic, familial and environmental factors account for predicting the long-term outcome in FEP patients remains scarcely known.

Methods

The SEGPEPs is an inception cohort study of 243 first-admission patients with FEP who were followed-up for a mean of 20.9 years. FEP patients were thoroughly evaluated by standardized instruments, with 164 patients providing DNA. Aggregate scores estimated in large populations for polygenic risk score (PRS-Sz), exposome risk score (ERS-Sz) and familial load score for schizophrenia (FLS-Sz) were ascertained. Long-term functioning was assessed by means of the Social and Occupational Functioning Assessment Scale (SOFAS). The relative excess risk due to interaction (RERI) was used as a standard method to estimate the effect of interaction of risk factors.

Results

Our results showed that a high FLS-Sz gave greater explanatory capacity for long-term outcome, followed by the ERS-Sz and then the PRS-Sz. The PRS-Sz did not discriminate significantly between recovered and non-recovered FEP patients in the long term. No significant interaction between the PRS-Sz, ERS-Sz or FLS-Sz regarding the long-term functioning of FEP patients was found.

Conclusions

Our results support an additive model of familial antecedents of schizophrenia, environmental risk factors and polygenic risk factors as contributors to a poor long-term functional outcome for FEP patients.

Keywords

Exposome risk score (ERS)first episode psychosisgene-environment interactionoutcomepolygenic risk score (PRS)schizophrenia
Type
Original Article
Information
Psychological Medicine , Volume 53 , Issue 14 , October 2023 , pp. 6838 - 6847
Check for updates
Copyright
Copyright © The Author(s), 2023. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

*

SEGPEPs Group: A. Ballesteros10, R. Hernández11, L. Janda2,8, R. Lorente2, D. Peralta2,8, M. Ribeiro1,2 and A. Rosero8

References

Aas, I. H. M. (2014). Collecting information for rating Global Assessment of Functioning (GAF): Sources of information and methods for information collection. Current Psychiatry Reviews, 10, 330–347. https://doi.org/10.2174/1573400509666140102000243.Google Scholar
Agerbo, E., Sullivan, P. F., Vilhjalmsson, B. J., Pedersen, C. B., Mors, O., Borglum, A. D., … Mortensen, P. B. (2015). Polygenic risk score, parental socioeconomic status, family history of psychiatric disorders, and the risk for schizophrenia: A Danish population-based study and meta-analysis. JAMA Psychiatry, 72, 635–641. https://doi.org/10.1001/jamapsychiatry.2015.0346.CrossRefGoogle ScholarPubMed
Alvarez-Jimenez, M., Gleeson, J. F., Henry, L. P., Harrigan, S. M., Harris, M. G., Killackey, E., … McGorry, P. D. (2012). Road to full recovery: Longitudinal relationship between symptomatic remission and psychosocial recovery in first-episode psychosis over 7.5 years. Psychological Medicine, 42, 595–606. https://doi.org/10.1017/S0033291711001504.CrossRefGoogle ScholarPubMed
Andreasen, N. C., Endicott, J., Spitzer, R. L., & Winokur, G. (1977). The family history method using diagnostic criteria. Reliability and validity. Archives of General Psychiatry, 34, 1229–1235.CrossRefGoogle ScholarPubMed
Andreasen, N. C., Flaum, M., & Arndt, S. (1992). The Comprehensive Assessment of Symptoms and History (CASH). An instrument for assessing diagnosis and psychopathology. Archives of General Psychiatry, 49, 615–623.CrossRefGoogle ScholarPubMed
APA (2013). Diagnostic and statistical manual of mental disorders (DSM-5). Arlington, VA: American Psychiatric Publishing.Google Scholar
Binder, E. B. (2019). Polygenic risk scores in schizophrenia: Ready for the real world? American Journal of Psychiatry, 176, 783–784. https://doi.org/10.1176/appi.ajp.2019.19080825.CrossRefGoogle ScholarPubMed
Bromet, E. J., Naz, B., Fochtmann, L. J., Carlson, G. A., & Tanenberg-Karant, M. (2005). Long-term diagnostic stability and outcome in recent first-episode cohort studies of schizophrenia. Schizophrenia Bulletin, 31, 639–649. https://doi.org/10.1093/schbul/sbi030.CrossRefGoogle ScholarPubMed
Calafato, M. S., Thygesen, J. H., Ranlund, S., Zartaloudi, E., Cahn, W., Crespo-Facorro, B., … Bramon, E. (2018). Use of schizophrenia and bipolar disorder polygenic risk scores to identify psychotic disorders. British Journal of Psychiatry, 213, 535–541. https://doi.org/10.1192/bjp.2018.89.CrossRefGoogle ScholarPubMed
Cannon, M., Jones, P. B., & Murray, R. M. (2002). Obstetric complications and schizophrenia: Historical and meta-analytic review. American Journal of Psychiatry, 159, 1080–1092. https://doi.org/10.1176/appi.ajp.159.7.1080.CrossRefGoogle ScholarPubMed
Chang, C. C., Chow, C. C., Tellier, L. C., Vattikuti, S., Purcell, S. M., & Lee, J. J. (2015). Second-generation PLINK: Rising to the challenge of larger and richer datasets. Gigascience, 4, 7. https://doi.org/10.1186/s13742-015-0047-8.CrossRefGoogle Scholar
Cuesta, M. J., Zarzuela, A., Sanchez-Torres, A. M., Lorente-Omenaca, R., Moreno-Izco, L., Sanjuan, J., … Peralta, V. (2015). Familial liability to schizophrenia and mood disorders and cognitive impairment in psychosis. Psychiatry Research, 227, 258–264. https://doi.org/10.1016/j.psychres.2015.03.024.CrossRefGoogle ScholarPubMed
Das, S., Forer, L., Schonherr, S., Sidore, C., Locke, A. E., Kwong, A., … Fuchsberger, C. (2016). Next-generation genotype imputation service and methods. Nature Genetics, 48, 1284–1287. https://doi.org/10.1038/ng.3656.CrossRefGoogle ScholarPubMed
Davies, C., Segre, G., Estradé, A., Radua, J., De Micheli, A., Provenzani, U., … Fusar-Poli, P. (2020). Prenatal and perinatal risk and protective factors for psychosis: A systematic review and meta-analysis. The Lancet. Psychiatry, 7, 399–410. https://doi.org/10.1016/s2215-0366(20)30057-2.CrossRefGoogle ScholarPubMed
Durbin, R. (2014). Efficient haplotype matching and storage using the positional burrows-wheeler transform (PBWT). Bioinformatics (Oxford, England), 30, 1266–1272. https://doi.org/10.1093/bioinformatics/btu014.Google ScholarPubMed
Erzin, G., Pries, L. K., Dimitrakopoulos, S., Ralli, I., Xenaki, L. A., Soldatos, R. F., … Stefanis, N. (2021a). Association between exposome score for schizophrenia and functioning in first-episode psychosis: Results from the Athens first-episode psychosis research study. Psychological Medicine, 1–10. https://doi.org/10.1017/s0033291721004542.Google ScholarPubMed
Erzin, G., Pries, L. K., van Os, J., Fusar-Poli, L., Delespaul, P., Kenis, G., … Guloksuz, S. (2021b). Examining the association between exposome score for schizophrenia and functioning in schizophrenia, siblings, and healthy controls: Results from the EUGEI study. European Psychiatry, 64, e25. https://doi.org/10.1192/j.eurpsy.2021.19.CrossRefGoogle ScholarPubMed
Esterberg, M. L., Trotman, H. D., Holtzman, C., Compton, M. T., & Walker, E. F. (2010). The impact of a family history of psychosis on age-at-onset and positive and negative symptoms of schizophrenia: A meta-analysis. Schizophrenia Research, 120, 121–130. https://doi.org/10.1016/j.schres.2010.01.011.CrossRefGoogle ScholarPubMed
Etchecopar-Etchart, D., Mignon, R., Boyer, L., & Fond, G. (2022). Schizophrenia pregnancies should be given greater health priority in the global health agenda: Results from a large-scale meta-analysis of 43,611 deliveries of women with schizophrenia and 40,948,272 controls. Molecular Psychiatry, 27, 3294–3305. https://doi.org/10.1038/s41380-022-01593-9.CrossRefGoogle Scholar
Fusar-Poli, P., McGorry, P. D., & Kane, J. M. (2017). Improving outcomes of first-episode psychosis: An overview. World Psychiatry, 16, 251–265. https://doi.org/10.1002/wps.20446.CrossRefGoogle ScholarPubMed
Ge, T., Chen, C. Y., Ni, Y., Feng, Y. A., & Smoller, J. W. (2019). Polygenic prediction via Bayesian regression and continuous shrinkage priors. Nature Communications, 10, 1776. https://doi.org/10.1038/s41467-019-09718-5.CrossRefGoogle ScholarPubMed
Goldman, H. H., Skodol, A. E., & Lave, T. R. (1992). Revising axis V for DSM-IV: A review of measures of social functioning. American Journal of Psychiatry, 149, 1148–1156. https://doi.org/10.1176/ajp.149.9.1148.Google ScholarPubMed
Guloksuz, S., Pries, L. K., Delespaul, P., Kenis, G., Luykx, J. J., Lin, B. D., … van Os, J. (2019). Examining the independent and joint effects of molecular genetic liability and environmental exposures in schizophrenia: Results from the EUGEI study. World Psychiatry, 18, 173–182. https://doi.org/10.1002/wps.20629.CrossRefGoogle ScholarPubMed
Heilbronner, U., Samara, M., Leucht, S., Falkai, P., & Schulze, T. G. (2016). The longitudinal course of schizophrenia across the lifespan: Clinical, cognitive, and neurobiological aspects. Harvard Review of Psychiatry, 24, 118–128. https://doi.org/10.1097/HRP.0000000000000092.CrossRefGoogle ScholarPubMed
Hosmer, D. W., & Lemeshow, S. (1992). Confidence interval estimation of interaction. Epidemiology (Cambridge, Mass.), 3, 452–456. https://doi.org/10.1097/00001648-199209000-00012.CrossRefGoogle ScholarPubMed
Iyegbe, C. O., & O'Reilly, P. F. (2022). Genetic origins of schizophrenia find common ground. Nature, 604, 433–435. https://doi.org/10.1038/d41586-022-00773-5.CrossRefGoogle ScholarPubMed
Jaaskelainen, E., Juola, P., Hirvonen, N., McGrath, J. J., Saha, S., Isohanni, M., … Miettunen, J. (2013). A systematic review and meta-analysis of recovery in schizophrenia. Schizophrenia Bulletin, 39, 1296–1306. https://doi.org/10.1093/schbul/sbs130.CrossRefGoogle ScholarPubMed
Johnstone, E. C., Frith, C. D., Lang, F. H., & Owens, D. G. (1995). Determinants of the extremes of outcome in schizophrenia. British Journal of Psychiatry, 167, 604–609.CrossRefGoogle ScholarPubMed
Jonas, K. G., Lencz, T., Li, K., Malhotra, A. K., Perlman, G., Fochtmann, L. J., … Kotov, R. (2019). Schizophrenia polygenic risk score and 20-year course of illness in psychotic disorders. Translational Psychiatry, 9, 300. https://doi.org/10.1038/s41398-019-0612-5.CrossRefGoogle ScholarPubMed
Kakela, J., Panula, J., Oinas, E., Hirvonen, N., Jaaskelainen, E., & Miettunen, J. (2014). Family history of psychosis and social, occupational and global outcome in schizophrenia: A meta-analysis. Acta Psychiatrica Scandinavica, 130, 269–278. https://doi.org/10.1111/acps.12317.CrossRefGoogle ScholarPubMed
Kendler, K. S., & Gardner, C. O. (2010). Interpretation of interactions: Guide for the perplexed. British Journal of Psychiatry, 197, 170–171. https://doi.org/10.1192/bjp.bp.110.081331.CrossRefGoogle ScholarPubMed
Kendler, K. S., & Neale, M. C. (2009). “Familiality” or heritability. Archives of General Psychiatry, 66, 452–453. https://doi.org/10.1001/archgenpsychiatry.2009.14.CrossRefGoogle ScholarPubMed
Knol, M. J., van der Tweel, I., Grobbee, D. E., Numans, M. E., & Geerlings, M. I. (2007). Estimating interaction on an additive scale between continuous determinants in a logistic regression model. International Journal of Epidemiology, 36, 1111–1118. https://doi.org/10.1093/ije/dym157.CrossRefGoogle Scholar
Knol, M. J., & VanderWeele, T. J. (2012). Recommendations for presenting analyses of effect modification and interaction. International Journal of Epidemiology, 41, 514–520. https://doi.org/10.1093/ije/dyr218.CrossRefGoogle ScholarPubMed
Kokkevi, A., & Hartgers, C. (1995). EuropASI: European adaptation of a multidimensional assessment instrument for drug and alcohol dependence. European Addiction Research, 1, 208–210.CrossRefGoogle Scholar
Lally, J., Ajnakina, O., Stubbs, B., Cullinane, M., Murphy, K. C., Gaughran, F., & Murray, R. M. (2017). Remission and recovery from first-episode psychosis in adults: Systematic review and meta-analysis of long-term outcome studies. British Journal of Psychiatry, 211, 350–358. https://doi.org/10.1192/bjp.bp.117.201475.CrossRefGoogle ScholarPubMed
Lewis, S., Owen, R., & Murray, R. (1989). Obstetric complications and schizophrenia. In SC, S. and CA, T. (Eds.), Schizophrenia: Scientific progress (pp. 56–68). New York: Oxford University Press.Google Scholar
Lichtenstein, P., Yip, B. H., Bjork, C., Pawitan, Y., Cannon, T. D., Sullivan, P. F., & Hultman, C. M. (2009). Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: A population-based study. Lancet (London, England), 373, 234–239. https://doi.org/10.1016/S0140-6736(09)60072-6.CrossRefGoogle ScholarPubMed
Mas, S., Boloc, D., Rodriguez, N., Mezquida, G., Amoretti, S., Cuesta, M. J., … Group, P. E. (2020). Examining gene-environment interactions using aggregate scores in a first-episode psychosis cohort. Schizophrenia Bulletin, 46, 1019–1025. https://doi.org/10.1093/schbul/sbaa012.CrossRefGoogle Scholar
McCarthy, S., Das, S., Kretzschmar, W., Delaneau, O., Wood, A. R., Teumer, A., … Haplotype Reference, C. (2016). A reference panel of 64976 haplotypes for genotype imputation. Nature Genetics, 48, 1279–1283. https://doi.org/10.1038/ng.3643.Google Scholar
McLellan, A. T., Kushner, H., Metzger, D., Peters, R., Smith, I., Grissom, G., … Argeriou, M. (1992). The fifth edition of the addiction severity index. Journal of Substance Abuse Treatment, 9, 199–213. https://doi.org/10.1016/0740-5472(92)90062-s.CrossRefGoogle ScholarPubMed
Morgan, V. A., Waterreus, A., Ambrosi, T., Badcock, J. C., Cox, K., Watts, G. F., … Jablensky, A. (2021). Mental health recovery and physical health outcomes in psychotic illness: Longitudinal data from the Western Australian survey of high impact psychosis catchments. Australian and New Zealand Journal of Psychiatry, 55, 711–728. https://doi.org/10.1177/0004867420954268.CrossRefGoogle ScholarPubMed
Niemi, L. T., Suvisaari, J. M., Haukka, J. K., & Lonnqvist, J. K. (2005). Childhood growth and future development of psychotic disorder among Helsinki high-risk children. Schizophrenia Research, 76, 105–112. https://doi.org/10.1016/j.schres.2004.11.004.CrossRefGoogle ScholarPubMed
Oliver, D., Spada, G., Englund, A., Chesney, E., Radua, J., Reichenberg, A., … Fusar-Poli, P. (2020). Real-world digital implementation of the Psychosis Polyrisk Score (PPS): A pilot feasibility study. Schizophrenia Research, 226, 176–183. https://doi.org/10.1016/j.schres.2020.04.015.CrossRefGoogle ScholarPubMed
Padmanabhan, J. L., Shah, J. L., Tandon, N., & Keshavan, M. S. (2017). The “polyenviromic risk score”: Aggregating environmental risk factors predicts conversion to psychosis in familial high-risk subjects. Schizophrenia Research, 181, 17–22. https://doi.org/10.1016/j.schres.2016.10.014.CrossRefGoogle ScholarPubMed
Pedersen, G., Urnes, Ø, Hummelen, B., Wilberg, T., & Kvarstein, E. H. (2018). Revised manual for the global assessment of functioning scale. European Psychiatry, 51, 16–19. https://doi.org/10.1016/j.eurpsy.2017.12.028.CrossRefGoogle ScholarPubMed
Peralta, V., Garcia de Jalon, E., Moreno-Izco, L., Peralta, D., Janda, L., Sanchez-Torres, A. M., … Group, S. E. (2022). Long-term outcomes of first-admission psychosis: A naturalistic 21-year follow-up study of symptomatic, functional and personal recovery and their baseline predictors. Schizophrenia Bulletin, 48, 631–642. https://doi.org/10.1093/schbul/sbab145.CrossRefGoogle ScholarPubMed
Peralta, V., Moreno-Izco, L., Garcia de Jalon, E., Sanchez-Torres, A. M., Janda, L., Peralta, D., … Group, S. E. (2021). Prospective long-term cohort study of subjects with first-episode psychosis examining eight major outcome domains and their predictors: Study protocol. Frontiers in Psychiatry, 12, 643112. https://doi.org/10.3389/fpsyt.2021.643112.CrossRefGoogle ScholarPubMed
Pries, L. K., Dal Ferro, G. A., van Os, J., Delespaul, P., Kenis, G., Lin, B. D., … Guloksuz, S. (2020). Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum. Epidemiology and Psychiatric Sciences, 29, e182. https://doi.org/10.1017/s2045796020000943.CrossRefGoogle ScholarPubMed
Pries, L. K., Erzin, G., van Os, J., Ten Have, M., de Graaf, R., van Dorsselaer, S., … Guloksuz, S. (2021). Predictive performance of exposome score for schizophrenia in the general population. Schizophrenia Bulletin, 47, 277–283. https://doi.org/10.1093/schbul/sbaa170.CrossRefGoogle ScholarPubMed
Pries, L. K., Lage-Castellanos, A., Delespaul, P., Kenis, G., Luykx, J. J., Lin, B. D., … Guloksuz, S. (2019). Estimating exposome score for schizophrenia using predictive modeling approach in two independent samples: The results from the EUGEI study. Schizophrenia Bulletin, 45, 960–965. https://doi.org/10.1093/schbul/sbz054.CrossRefGoogle ScholarPubMed
Radua, J., Ramella-Cravaro, V., Ioannidis, J. P. A., Reichenberg, A., Phiphopthatsanee, N., Amir, T., … Fusar-Poli, P. (2018). What causes psychosis? An umbrella review of risk and protective factors. World Psychiatry, 17, 49–66. https://doi.org/10.1002/wps.20490.CrossRefGoogle ScholarPubMed
Ran, M. S., Xiao, Y., Zhao, X., Zhang, T. M., Yu, Y. H., Mao, W. J., … Chan, C. L. (2018). Family history of psychosis and outcome of people with schizophrenia in rural China: 14-year follow-up study. Asian Journal of Psychiatry, 32, 14–19. https://doi.org/10.1016/j.ajp.2017.11.016.CrossRefGoogle ScholarPubMed
Rey, J. M., Singh, M., Hung, S. F., Dossetor, D. R., Newman, L., Plapp, J. M., & Bird, K. D. (1997). A global scale to measure the quality of the family environment. Archives of General Psychiatry, 54, 817–822. https://doi.org/10.1001/archpsyc.1997.01830210061006.CrossRefGoogle ScholarPubMed
Rey, J. M., Walter, G., Plapp, J. M., & Denshire, E. (2000). Family environment in attention deficit hyperactivity, oppositional defiant and conduct disorders. Australian and New Zealand Journal of Psychiatry, 34, 453–457. https://doi.org/10.1080/j.1440-1614.2000.00735.x.CrossRefGoogle ScholarPubMed
Rodriguez, V., Alameda, L., Quattrone, D., Tripoli, G., Gayer-Anderson, C., Spinazzola, E., … Vassos, E. (2022). Use of multiple polygenic risk scores for distinguishing schizophrenia-spectrum disorder and affective psychosis categories in a first-episode sample; the EU-GEI study. Psychological Medicine, 1–10. https://doi.org/10.1017/S0033291721005456.Google Scholar
Santesteban-Echarri, O., Paino, M., Rice, S., Gonzalez-Blanch, C., McGorry, P., Gleeson, J., & Alvarez-Jimenez, M. (2017). Predictors of functional recovery in first-episode psychosis: A systematic review and meta-analysis of longitudinal studies. Clinical Psychology Review, 58, 59–75. https://doi.org/10.1016/j.cpr.2017.09.007.CrossRefGoogle ScholarPubMed
Stepniak, B., Papiol, S., Hammer, C., Ramin, A., Everts, S., Hennig, L., … Ehrenreich, H. (2014). Accumulated environmental risk determining age at schizophrenia onset: A deep phenotyping-based study. The Lancet. Psychiatry, 1, 444–453. https://doi.org/10.1016/S2215-0366(14)70379-7.CrossRefGoogle ScholarPubMed
Stilo, S. A., & Murray, R. M. (2019). Non-genetic factors in schizophrenia. Current Psychiatry Reports, 21, 100. https://doi.org/10.1007/s11920-019-1091-3.CrossRefGoogle ScholarPubMed
Trubetskoy, V., Pardinas, A. F., Qi, T., Panagiotaropoulou, G., Awasthi, S., Bigdeli, T. B., … Schizophrenia Working Group of the Psychiatric Genomics, C. (2022). Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Nature, 604, 502–508. https://doi.org/10.1038/s41586-022-04434-5.CrossRefGoogle ScholarPubMed
van Os, J., Kenis, G., & Rutten, B. P. (2010). The environment and schizophrenia. Nature, 468, 203–212. https://doi.org/10.1038/nature09563.CrossRefGoogle ScholarPubMed
van Os, J., Pries, L. K., Ten Have, M., de Graaf, R., van Dorsselaer, S., Delespaul, P., … Guloksuz, S. (2022). Evidence, and replication thereof, that molecular-genetic and environmental risks for psychosis impact through an affective pathway. Psychological Medicine, 52, 1910–1922. https://doi.org/10.1017/S0033291720003748.CrossRefGoogle ScholarPubMed
Vassos, E., Di Forti, M., Coleman, J., Iyegbe, C., Prata, D., Euesden, J., … Breen, G. (2017). An examination of polygenic score risk prediction in individuals with first-episode psychosis. Biological Psychiatry, 81, 470–477. https://doi.org/10.1016/j.biopsych.2016.06.028.CrossRefGoogle ScholarPubMed
Vassos, E., Kou, J., Tosato, S., Maxwell, J., Dennison, C. A., Legge, S. E., … Murray, R. M. (2022). Lack of support for the genes by early environment interaction hypothesis in the pathogenesis of schizophrenia. Schizophrenia Bulletin, 48, 20–26. https://doi.org/10.1093/schbul/sbab052.CrossRefGoogle ScholarPubMed
Vassos, E., Sham, P., Kempton, M., Trotta, A., Stilo, S. A., Gayer-Anderson, C., … Morgan, C. (2020). The Maudsley environmental risk score for psychosis. Psychological Medicine, 50, 2213–2220. https://doi.org/10.1017/S0033291719002319.CrossRefGoogle ScholarPubMed
Verdoux, H., van Os, J., Sham, P., Jones, P., Gilvarry, K., & Murray, R. (1996). Does familiality predispose to both emergence and persistence of psychosis? A follow-up study. British Journal of Psychiatry, 168, 620–626.CrossRefGoogle ScholarPubMed
Zheutlin, A. B., Dennis, J., Karlsson Linner, R., Moscati, A., Restrepo, N., Straub, P., … Smoller, J. W. (2019). Penetrance and pleiotropy of polygenic risk scores for schizophrenia in 106,160 patients across four health care systems. American Journal of Psychiatry, 176, 846–855. https://doi.org/10.1176/appi.ajp.2019.18091085.CrossRefGoogle Scholar
Supplementary material: File

Cuesta et al. supplementary material

Tables S1-S4

Download Cuesta et al. supplementary material(File)
File 39.3 KB