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Original Investigation |

A Nationwide Cohort Study of the Association Between Hospitalization With Infection and Risk of Death by Suicide

Helene Lund-Sørensen, BM1,2; Michael E. Benros, PhD1,2; Trine Madsen, PhD1,2; Holger J. Sørensen, MD1,2; William W. Eaton, PhD3; Teodor T. Postolache, MD4,5,6; Merete Nordentoft, DrMedSc1,2,7; Annette Erlangsen, PhD2,3
[+] Author Affiliations
1Faculty of Health Sciences, Copenhagen University Hospital, Copenhagen, Denmark
2Mental Health Centre Copenhagen, Capital Region of Denmark, Denmark
3Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
4Mood and Anxiety Disorders Program, Department of Psychiatry, School of Medicine, University of Maryland, Baltimore
5Rocky Mountain Mental Illness Research Education and Clinical Center, Veterans Integrated Service Network 19, Denver, Colorado
6Military and Veterans Microbiome Consortium on Research and Education, Denver, Colorado
7iPSYCH, The LundbeckFoundation Initiative for Integrated Psychiatric Research, Aarhus, Denmark
JAMA Psychiatry. 2016;73(9):912-919. doi:10.1001/jamapsychiatry.2016.1594.
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Importance  Findings suggest that infections might be linked to the development of psychiatric disorders and suicidal behavior. Large-scale studies are needed to investigate the effect of infection on the risk of suicide.

Objective  To estimate the association between hospitalization with infection and the risk of death by suicide.

Design, Setting, and Participants  Nationwide, population-based, prospective cohort study with more than 149 million person-years of follow-up. Data were analyzed with survival analysis techniques and were adjusted for sex, age, calendar period, cohabitation status, socioeconomic status, and the Charlson Comorbidity Index. Individual data were drawn from Danish longitudinal registers. A total of 7.22 million individuals 15 years or older living in Denmark between January 1, 1980, and December 31, 2011, were observed during a 32-year follow-up period.

Main Outcomes and Measures  The risk of death by suicide was identified in the Danish Cause of Death Register. Incidence rate ratios (IRRs) and accompanying 95% CIs were used as measures of relative risk.

Results  In 7 221 578 individuals (3 601 653 men and 3 619 925 women) observed for a total of 149 061 786 person-years, 32 683 suicides were observed during the follow-up period. Among the suicides, 7892 (24.1%) individuals had previously been diagnosed as having an infection during a hospitalization. Hospitalization with infection was linked to an elevated risk of suicide, with an IRR of 1.42 (95% CI, 1.38-1.46) compared with those without prior infection. Dose-response relationships were observed with respect to the number of hospital contacts for different infections. For example, having 7 or more infections was linked to an IRR of 2.90 (95% CI, 2.14-3.93). The number of days of treatment for infections was associated with an elevated risk of suicide in a dose-response relationship. More than 3 months of hospital treatment was linked to an IRR of 2.38 (95% CI, 2.05-2.76). The population-attributable risk associated with hospitalization with infection accounted for 10.1% of suicides.

Conclusions and Relevance  An increased risk of death by suicide was found among individuals hospitalized with infection in prospective and dose-response relationships. These findings indicate that infections may have a relevant role in the pathophysiological mechanisms of suicidal behavior.

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Figure.
Incidence Rate Ratios With 95% CIs (Error Bars) of Suicide in Denmark (1980-2011)

Adjusted for sex, age, calendar period, socioeconomic status, cohabitation status, and the Charlson Comorbidity Index. In panel C, the reference group was individuals with no infections.

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Hypnotics, Infection, Depression, and Suicide
Posted on August 11, 2016
Daniel F Kripke
Professor of Psychiatry Emeritus, University of California, San Diego
Conflict of Interest: None Declared
Lund-Sorensen et al. and the supportive report of Batty et al. give strong evidence that the presence of infection and inflammation predict suicide. These reports have overlooked hypnotic drugs (sleeping pills) as a probable causal element among the pathways leading to suicide.

First, controlled trials prove that hypnotic drugs cause increased rates of infection, as demonstrated by controlled trials and as supported by epidemiologic studies and animal and in vitro research. Likewise, controlled trials prove that hypnotics cause incident depressions, and depressions cause suicides. It has been repeatedly shown that suicide rates are remarkably elevated among patients who take hypnotics and that hypnotics are present in the blood of a substantial portion of suicides. Moreover, hypnotics play a synergistic role with opiates in the current overdose epidemic. Much detailed evidence is summarized in a recent publication, F1000Research 2016, 5:918 (doi: 10.12688/f1000research.8729.1).

Since depression may be treated with hypnotics and infections might also sometimes lead to hypnotic use, particularly when hospitalization is needed, the causal pathways appear complex and not unidirectional. Assessing the role of each causal element will be an important goal for future research.

Withholding and withdrawing hypnotic drugs may be a simple and powerful intervention for suicide prevention.
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