title: Infections and exposure to anti-infective agents and the risk of severe mental disorders: a nationwide study.
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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.affiliation: Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark.|iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.
authors.forename: O
authors.initials: O
authors.lastname: Köhler
authors.affiliation: iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.|National Centre for Register-based Research, Aarhus University, Aarhus, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Petersen
authors.affiliation: Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark.|iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.|Centre for Integrated Register-based Research at Aarhus University (CIRRAU), Aarhus, Denmark.
authors.forename: O
authors.initials: O
authors.lastname: Mors
authors.affiliation: iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.|National Centre for Register-based Research, Aarhus University, Aarhus, Denmark.|Centre for Integrated Register-based Research at Aarhus University (CIRRAU), Aarhus, Denmark.
authors.forename: P B
authors.initials: PB
authors.lastname: Mortensen
authors.affiliation: Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Yolken
authors.affiliation: National Centre for Register-based Research, Aarhus University, Aarhus, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Gasse
authors.affiliation: National Centre for Register-based Research, Aarhus University, Aarhus, Denmark.|Mental Health Centre Copenhagen, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: M E
authors.initials: ME
authors.lastname: Benros
mesh_terms: D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000009:adverse effects* / Q000145:classification; D003141:Communicable Diseases / Q000150:complications / Q000188:drug therapy*; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000453:epidemiology*; D016016:Proportional Hazards Models; D012042:Registries; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology*; D055815:Young Adult
chemical_list: D000890:Anti-Infective Agents
keywords: affective disorders; epidemiology; neuroimmunology; pharmacoepidemiology; schizophrenia