O Köhler1,2, L Petersen2,3, O Mors1,2,4, P B Mortensen2,3,4, R H Yolken5, C Gasse3, M E Benros3,6. 1. Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark. 2. iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark. 3. National Centre for Register-based Research, Aarhus University, Aarhus, Denmark. 4. Centre for Integrated Register-based Research at Aarhus University (CIRRAU), Aarhus, Denmark. 5. Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, USA. 6. Mental Health Centre Copenhagen, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Abstract
OBJECTIVE: Severe infections are associated with increased risks of mental disorders; however, this is the first large-scale study investigating whether infections treated with anti-infective agents in the primary care setting increase the risks of schizophrenia and affective disorders. METHOD: We identified all individuals born in Denmark 1985-2002 (N = 1 015 447) and studied the association between infections treated with anti-infective agents and the subsequent risk of schizophrenia and affective disorders during 1995-2013. Cox regression analyses were adjusted for important confounders. RESULTS: Infections treated with anti-infective agents were associated with increased risks of schizophrenia by a hazard rate ratio (HRR) of 1.37 (95%-CI = 1.20-1.57) and affective disorders by a HRR of 1.64 (95%-CI = 1.48-1.82), fitting a dose-response and temporal relationship (P < 0.001). The excess risk was primarily driven by infections treated with antibiotics, whereas infections treated with antivirals, antimycotics, and antiparasitic agents were not significant after mutual adjustment. Individuals with infections requiring hospitalization had the highest risks for schizophrenia (HRR = 2.05; 95%-CI = 1.77-2.38) and affective disorders (HRR = 2.59; 95%-CI = 2.31-2.89). CONCLUSION: Infections treated with anti-infective agents and particularly infections requiring hospitalizations were associated with increased risks of schizophrenia and affective disorders, which may be mediated by effects of infections/inflammation on the brain, alterations of the microbiome, genetics, or other environmental factors.
OBJECTIVE: Severe infections are associated with increased risks of mental disorders; however, this is the first large-scale study investigating whether infections treated with anti-infective agents in the primary care setting increase the risks of schizophrenia and affective disorders. METHOD: We identified all individuals born in Denmark 1985-2002 (N = 1 015 447) and studied the association between infections treated with anti-infective agents and the subsequent risk of schizophrenia and affective disorders during 1995-2013. Cox regression analyses were adjusted for important confounders. RESULTS:Infections treated with anti-infective agents were associated with increased risks of schizophrenia by a hazard rate ratio (HRR) of 1.37 (95%-CI = 1.20-1.57) and affective disorders by a HRR of 1.64 (95%-CI = 1.48-1.82), fitting a dose-response and temporal relationship (P < 0.001). The excess risk was primarily driven by infections treated with antibiotics, whereas infections treated with antivirals, antimycotics, and antiparasitic agents were not significant after mutual adjustment. Individuals with infections requiring hospitalization had the highest risks for schizophrenia (HRR = 2.05; 95%-CI = 1.77-2.38) and affective disorders (HRR = 2.59; 95%-CI = 2.31-2.89). CONCLUSION:Infections treated with anti-infective agents and particularly infections requiring hospitalizations were associated with increased risks of schizophrenia and affective disorders, which may be mediated by effects of infections/inflammation on the brain, alterations of the microbiome, genetics, or other environmental factors.
Authors: Ole Köhler-Forsberg; Liselotte Petersen; Christiane Gasse; Preben B Mortensen; Soren Dalsgaard; Robert H Yolken; Ole Mors; Michael E Benros Journal: JAMA Psychiatry Date: 2019-03-01 Impact factor: 21.596
Authors: Lauren Breithaupt; Ole Köhler-Forsberg; Janne Tidselbak Larsen; Michael E Benros; Laura Marie Thornton; Cynthia M Bulik; Liselotte Petersen Journal: JAMA Psychiatry Date: 2019-08-01 Impact factor: 21.596
Authors: Younga H Lee; Sara Cherkerzian; Larry J Seidman; George D Papandonatos; David A Savitz; Ming T Tsuang; Jill M Goldstein; Stephen L Buka Journal: Am J Psychiatry Date: 2019-10-04 Impact factor: 18.112