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J Clin Med. 2019 Jul 23;8(7). pii: E1081. doi: 10.3390/jcm8071081.

Early Parental Death and Risk of Psychosis in Offspring: A Six-Country Case-Control Study.

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Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Department of Psychiatry, Boston Medical Center, Boston University School of Medicine, Boston, MA 02118, USA.
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AE, UK.
Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, 90129 Palermo, Italy.
Department of Medical and Surgical Science, Psychiatry Unit, Alma Mater Studiorum Università di Bologna, 40126 Bologna, Italy.
INSERM U955, Equipe 15, Institut National de la Santé et de la Recherche Médicale, 94010 Créteil, France.
Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM (CIBERSAM), 28007 Madrid, Spain.
Etablissement Public de Santé Maison Blanche, 75020 Paris, France.
Department of Psychiatry, Early Psychosis Section, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Department of Medicine, Psychiatry Area, School of Medicine, Universidad de Oviedo, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), 33006 Oviedo, Spain.
Barcelona Clinic Schizophrenia Unit, Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS, CIBERSAM, 08036 Barcelona, Spain.
Department of Psychiatry, School of Medicine, Universidad de Valencia, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), 46010 Valencia, Spain.
Department of Psychiatry, Servicio de Psiquiatría Hospital "Virgen de la Luz," 16002 Cuenca, Spain.
Department of Psychiatry, Psychiatry Genetic Group, Instituto de Investigación Sanitaria de Santiago de Compostela, Complejo Hospitalario Universitario de Santiago de Compostela, 15706 Santiago de Compostela, Spain.
Division of Psychiatry, Department of Neuroscience and Behaviour, Ribeirão Preto Medical School, University of São Paulo, São Paulo 14049-900, Brazil.
Department of Preventative Medicine, Faculdade de Medicina FMUSP, University of São Paulo, São Paulo 01246-903, Brazil.
Rivierduinen Institute for Mental Health Care, 2333 ZZ Leiden, The Netherlands.
Department of Psychiatry, University of Cambridge, Cambridge CB2 0SZ, UK.
Psylife Group, Division of Psychiatry, University College London, London W1T 7NF, UK.
Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, South Limburg Mental Health Research and Teaching Network, Maastricht University Medical Centre, 6200 MD Maastricht, The Netherlands.
Department of Psychosis Studies, Institute of Psychiatry, King's College London, London SE5 8AF, UK.
Department of Health Service and Population Research, Institute of Psychiatry, King's College London, London SE5 8AF, UK.


Evidence for early parental death as a risk factor for psychosis in offspring is inconclusive. We analyzed data from a six-country, case-control study to examine the associations of early parental death, type of death (maternal, paternal, both), and child's age at death with psychosis, both overall and by ethnic group. In fully adjusted multivariable mixed-effects logistic regression models, experiencing early parental death was associated with 1.54-fold greater odds of psychosis (95% confidence interval (CI): 1.23, 1.92). Experiencing maternal death had 2.27-fold greater odds (95% CI: 1.18, 4.37), paternal death had 1.14-fold greater odds (95% CI: 0.79, 1.64), and both deaths had 4.42-fold greater odds (95% CI: 2.57, 7.60) of psychosis compared with no early parental death. Experiencing parental death between 11 and 16 years of age had 2.03-fold greater odds of psychosis than experiencing it before five years of age (95% CI: 1.02, 4.04). In stratified analyses, experiencing the death of both parents had 9.22-fold greater odds of psychosis among minority ethnic groups (95% CI: 2.02-28.02) and no elevated odds among the ethnic majority (odds ratio (OR): 0.96; 95% CI: 0.10-8.97), which could be due in part to the higher prevalence of early parental death among minority ethnic groups but should be interpreted cautiously given the wide confidence intervals.


case-control; childhood adversities; early bereavement; early parental death; ethnic minorities; multi-country; population-based; psychosis; schizophrenia

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