Antibiotics or Infection Itself? The Possible Importance of Inflammatory Cytokines on Mental States

See reply by Lurie et al and article by Lurie et al

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Antibiotics or Infection Itself? The Possible Importance of Inflammatory Cytokines on Mental States

To the Editor: We read the recent report by Lurie and coauthors1 with great interest. We completely agree with the authors that recurrent antibiotic exposure can increase the risk of depression and anxiety via changes in intestinal microbiota. The authors obtained their results based on very large cohort studies carried out over many years.

However, we are afraid that they overlooked the importance of infections that require up to 5 courses of antibiotic administration. Though acute or chronic infections often affect the mental status of the host by inducing proinflammatory cytokines, change in the intestinal microbiota caused by antibiotic treatment is often reversed after short administration-free periods.2

Thus, we cannot exclude the possibility that depression and/or anxiety are associated with the severe infectious diseases and are mediated via the induction of various cytokines. Unfortunately, Lurie and colleagues’ report completely lacks the clinical diagnosis and/or pathogens that were targeted by the antibiotics.

Increased levels of proinflammatory cytokines and chemokines, as well as acute phase proteins and cellular adhesion molecules, have been reported in patients with depression.3 Local cytokine concentrations in the central nervous system (CNS) do not correlate with peripheral blood levels. However, under some conditions, cytokines can cross the blood-brain barrier, enter the CNS, and affect neural functions by altering neurotransmitter metabolism, neuroendocrine function, and synaptic plasticity. In addition, during CNS inflammation, such as encephalitis and meningitis, cytokines and chemokines produced in situ might cause permanent brain damage.

Another interpretation is that the serious bacterial infection, which required antibiotic treatment, might have caused the depression and anxiety. For example, Goodwin4 suggested an association between an increased risk of depression and anxiety during childhood and adolescence with previous severe infection events. In adults, an increased risk of depression and anxiety has also been associated with chronic infectious disorders, including tuberculosis.5,6 Further, patients admitted with major psychiatric disorders, including schizophrenia, bipolar disorder, depression, or anxiety, have been reported to have an increased risk for pneumococcal infections, even if they are under 60 years of age.7

Taken together, while we must avoid needless administration of antibiotics, we need not hesitate to use them in patients with bacterial infections, because infections can increase the risk of mental disorders by inducing proinflammatory responses at the systemic or CNS levels.

References

1. Lurie I, Yang YX, Haynes K, et al. Antibiotic exposure and the risk for depression, anxiety, or psychosis: a nested case-control study. J Clin Psychiatry. 2015;76(11):1522-1528. PubMed doi:10.4088/JCP.15m09961

2. Jakobsson HE, Jernberg C, Andersson AF, et al. Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome. PLoS One. 2010;5(3):e9836. PubMed doi:10.1371/journal.pone.0009836

3. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006;27(1):24-31. PubMed doi:10.1016/j.it.2005.11.006

4. Goodwin RD. Association between infection early in life and mental disorders among youth in the community: a cross-sectional study. BMC Public Health. 2011;11:878. PubMed doi:10.1186/1471-2458-11-878

5. Duko B, Gebeyehu A, Ayano G. Prevalence and correlates of depression and anxiety among patients with tuberculosis at WolaitaSodo University Hospital and Sodo Health Center, WolaitaSodo, South Ethiopia, cross sectional study. BMC Psychiatry. 2015;15:214. PubMed doi:10.1186/s12888-015-0598-3

6. Pan SW, Yen YF, Feng JY, et al. The risk of depressive disorder among contacts of Tuberculosis patients in a TB-endemic area: a population-based cohort study. Medicine (Baltimore). 2015;94(43):e1870. PubMed doi:10.1097/MD.0000000000001870

7. Seminog OO, Goldacre MJ. Risk of pneumonia and pneumococcal disease in people with severe mental illness: English record linkage studies. Thorax. 2013;68(2):171-176. PubMed doi:10.1136/thoraxjnl-2012-202480

Wakako Ishii, MDa,b

Shihoko Komine-Aizawa, MD, PhDb

aizawa.shihoko@nihon-u.ac.jp

Satoshi Hayakawa, MD, PhDb

aDepartment of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan.

bDivision of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan.

Potential conflicts of interest: None.

Funding/support: None.

J Clin Psychiatry 2016;77(12):e1653

dx.doi.org/10.4088/JCP.16lr11074

© Copyright 2016 Physicians Postgraduate Press, Inc.