• Hong Liang, Jørn Olsen, Wei Yuan, Sven Cnattingus, Mogens Vestergaard, Carsten Obel, Mika Gissler, and Jiong Li.
• From the Department of Reproductive Epidemiology and Social Science (HL, WY), National Population and Family Planning Key Laboratory of Contraceptive Drugs and Devices, Shanghai Institute of Planned Parenthood Research, Shanghai, China; Department of Clinical Epidemiology (JO, JL), Aarhus University Hospital, Aarhus, Denmark; Department of Epidemiology (JO), School of Public Health, University of California, Los Angeles, California, USA; Reproduction and Development Institute (WY), Fudan University, Shanghai, China; Department of Medicine (SC), Clinical Epidemiology Unit, Karolinska Institutet, Sweden; Section for General Practice (MV, CO), Department of Public Health, Aarhus University, Denmark; Research Unit of General Practice (MV, CO), Department of Public Health, Aarhus University, Denmark; and National Institute for Health and Welfare (MG), Finland and Nordic School of Public Health, Sweden.
• Medicine (Baltimore). 2016 Jan 1; 95 (3): e2434.

AbstractWe aimed to examine whether early life bereavement, as indicator of severe stress, was associated with an increased risk of schizophrenia later in life.Based on population registers, we established a cohort of all children born in Denmark (N = 1 686 416) and Sweden (N = 2 563 659) from 1973 to 1997. Children were categorized as exposed if they lost a first-degree relative during the first 18 years of life. Outcome is the first diagnosis of schizophrenia as either inpatient or outpatient. Log-linear Poisson regression models were used to estimate incidence rate ratios (IRRs).A total of 188,850 children (4.6%) experienced death of a first-degree relative from birth to 18 years of age. Compared with unexposed children, those exposed had overall a 39% higher risk of schizophrenia (= 1.39, 95% CI [confidence interval]: 1.32-1.47). The IRR was particularly high if the family member committed suicide (aIRR = 2.11, 95% CI: 1.90-2.34) or died due to an injury or accident (aIRR = 1.44, 95% CI: 1.27-1.63). The IRR of schizophrenia decreased with increasing child's age at bereavement (P < 0.0001). Children who experienced >1 death during the first 18 years of life (aIRR = 1.79, 95% CI: 1.46-2.19) had a higher risk than those with a single death (aIRR = 1.37, 95% CI: 1.30-1.45).The study suggested that exposure to death of a first-degree relative before 18 years was associated with an increased risk of schizophrenia in later life. The complex mechanisms behind these associations remain to be elucidated.

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