Abnormal protein and mRNA expression of inflammatory cytokines in the prefrontal cortex of depressed individuals who died by suicide

Abnormal protein and mRNA expression of inflammatory cytokines in the prefrontal cortex of depressed individuals who died by suicide

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J Psychiatry Neurosci 2018;43(6):376-385

Ghanshyam N. Pandey, PhD; Hooriyah S. Rizavi, MS; Hui Zhang, PhD; Runa Bhaumik, PhD; Xinguo Ren, MD

Abstract

Background: Depression and stress are major risk factors for suicidal behaviour, and some studies show abnormalities of proinflammatory cytokines in the serum and cerebrospinal fluid (CSF) of depressed and suicidal patients. However, it is not clear if similar abnormalities of cytokines are present in the brain of suicidal and depressed patients.

Methods: We therefore determined the mRNA (using realtime polymerase chain reaction) and protein (using enzyme-linked immunosorbent assay and Western Blot) expression levels of interleukin (IL)-1β, IL-6, tumour necrosis factor (TNF)-α, lymphotoxin A, lymphotoxin B, IL-8, IL-10 and IL-13 in the prefrontal cortex (PFC) obtained from 24 depressed individuals who died by suicide and 24 nonpsychiatric controls.

Results: We observed that the mRNA and protein levels of IL-1β, IL-6, TNF-α, and lymphotoxin A were significantly increased, and levels of anti-inflammatory cytokine IL-10, and of IL-1 receptor antagonist (IL-1RA) were significantly decreased in the PFC of depressed individuals who died by suicide compared with controls. There were no significant differences in the protein and mRNA levels of IL-8 and IL-13 in the PFC.

Limitations: The main limitation of this study is that some of the suicide group had been taking antidepressant medication at the time of death.

Conclusion: Our results suggest that alterations of cytokines may be associated with the pathophysiology of depressed suicide and there may be an imbalance between pro- and anti-inflammatory cytokines in people who die by suicide. The causes of these increases in the brain of people who die by suicide, therefore, need to be investigated further.


Submitted Sept. 24, 2017; Revised Jan. 10, 2018; Accepted Jan. 22, 2018; Published online June 11, 2018

Affiliation: From the Department of Psychiatry, University of Illinois at Chicago, Chicago, Ill., USA.

Funding: This research was supported by grants RO1MH098554 and RO1MH106565 (Dr. Pandey) from the National Institute of Mental Health, Rockville, MD. The funding source had no role in the study design; collection, analysis and interpretation of data; or writing of the manuscript.

Competing interests: None declared.

Contributors: G. Pandey designed the study. H. Rizavi, H. Zhang and X. Ren acquired the data, which G. Pandey and R. Bhaumik analyzed. G. Pandey wrote the article, which all authors reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.

DOI: 10.1503/jpn.170192

Correspondence to: G.N. Pandey, University of Illinois at Chicago, 1601 West Taylor St, Chicago, IL 60612; Gpandey@psych.uic.edu