title: The role of cytokines in the pathophysiology of suicidal behavior.
abstract: OBJECTIVE
  Immune dysregulation has been implicated in depression and other psychiatric disorders. What is less clear is how immune dysregulation can affect risk of suicidal behavior. We reviewed the scientific literature concerning cytokines related to suicidal ideation, suicidal behavior and suicide, and surveyed clinical and neurobiological factors associated with cytokine levels that may modulate effects of inflammation on suicide risk.
  
  
  METHODS
  We searched PubMed, Embase, Scopus and PsycINFO for relevant studies published from 1980 through February, 2015. Papers were included if they were written in English and focused on cytokine measurements in patients with suicidal behaviors.
  
  
  RESULTS
  The literature search yielded 22 studies concerning cytokines and suicidal ideation, suicide attempts or suicide completion. The most consistent finding was elevated interleukin (IL)-6, found in 8 out of 14 studies, in CSF, blood, and postmortem brain. In one study, IL-6 in CSF was also found to be higher in violent than nonviolent attempters and to correlate with future suicide completion. Low plasma IL-2 was observed in 2 studies of suicide attempters, while divergent results were seen for tumor necrosis factor (TNF)-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, IL-4, and soluble Il-2 receptors.
  
  
  CONCLUSIONS
  Given the complexity suggested by the heterogenous cytokine findings, putative mediators and moderators of inflammation on suicidal behavior merit further study. Elevated IL-6 was the most robust cytokine finding, associated with suicidal ideation and both nonfatal suicide attempts and suicides. Future studies should evaluate the predictive value of high IL-6, consider how this may alter brain function to impact suicidal behavior, and explore the potential beneficial effects of reducing IL-6 on suicide risk.
authors.affiliation: Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, 10032 NY, USA; Department of Psychiatry, Columbia University, New York, 10032 NY, USA; Department of Psychiatry, School of Medicine, University of Lisbon, 1649-035 Lisbon, Portugal.
authors.forename: Licínia
authors.initials: L
authors.lastname: Ganança
authors.affiliation: Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, 10032 NY, USA; Department of Psychiatry, Columbia University, New York, 10032 NY, USA.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Oquendo
authors.affiliation: Laboratory for Clinical and Translational Neuroscience, Butler Hospital and Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, 02912 RI, USA.
authors.forename: Audrey R
authors.initials: AR
authors.lastname: Tyrka
authors.affiliation: Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, 10032 NY, USA; Department of Psychiatry, Columbia University, New York, 10032 NY, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Cisneros-Trujillo
authors.affiliation: Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, 10032 NY, USA; Department of Psychiatry, Columbia University, New York, 10032 NY, USA; Department of Radiology, Columbia University, New York, 10032 NY, USA.
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
authors.affiliation: Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, 10032 NY, USA; Department of Psychiatry, Columbia University, New York, 10032 NY, USA. Electronic address: es2316@cumc.columbia.edu.
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Sublette
mesh_terms: D016207:Cytokines / Q000097:blood*; D003863:Depression / Q000097:blood / Q000453:epidemiology / Q000523:psychology; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000453:epidemiology / Q000523:psychology; D018836:Inflammation Mediators / Q000097:blood; D016728:Self-Injurious Behavior / Q000097:blood* / Q000453:epidemiology / Q000523:psychology; D059020:Suicidal Ideation; D013405:Suicide / Q000523:psychology / Q000706:statistics & numerical data; D013406:Suicide, Attempted / Q000523:psychology / Q000706:statistics & numerical data
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators
keywords: Cytokines; Depression; Inflammation; Stress; Suicide