Immune dysfunction in bipolar disorder and suicide risk: is there an association between peripheral corticotropin‐releasing hormone and interleukin‐1β?

Monfrim, Xênia; Gazal, Marta; Leon, Pâmela B. de; Quevedo, Luciana; Souza, Luciano D.M.; Jansen, Karen; Oses, Jean Pierre; Pinheiro, Ricardo Tavares; Silva, Ricardo A.; Lara, Diogo R.; Ghisleni, Gabriele; Spessato, Bárbara Coiro; Kaster, Manuella P.

doi:10.1111/bdi.12214

Cited by 55 publications

(30 citation statements)

References 47 publications

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“…Consistent with the previous studies, it was revealed that in BD, the immune system is chronically activated by microglia, which in turn produces cytokines that render the brain to a vulnerable and unstable state, precipitating mood disturbances [45][46][47]. In fact, higher levels of IL-1β were associated with dysfunction and increased suicide risk in patients with BD [48].…”

Section: Mechanisms Of Neuroinflammationsupporting

confidence: 83%

Reducing Neuroinflammation in Psychiatric Disorders: Novel Target of Phosphodiesterase 4 (PDE4) and Developing of the PDE4 Inhibitors

Wang¹,

Wang²,

Li³

et al. 2017

Mechanisms of Neuroinflammation

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Multiple lines of evidence support the pathogenic role of neuroinflammation in psychiatric illness. Cyclic adenosine monophosphate (cAMP) is a critical regulator of microglia homeostasis; as the predominant negative modulator of cyclic AMP signaling within microglia, and phosphodiesterase 4 (PDE4) represents a promising target for modulating immune function. The approach for pharmacological manipulation of cAMP levels using specifc PDE4 inhibitors provokes an ant-iinflammatory response. Specifcally, PDE4 inhibitors have recently emerged as a potential therapeutic strategy for neuroinflammatory, neurodegenerative, and psychiatric diseases. Mechanistically, PDE4 inhibitors produce an anti-inflammatory and neuroprotection efect by increasing the accumulation of cAMP and activating protein kinase A (PKA), the signaling pathway of which is thought to play an important role in the development of psychiatric disorders. This chapter reviews present knowledge of the relationship between neuroinflammation and classical psychiatric disorders (major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia) and demonstrates the signaling pathways that underlie the use of PDE4 inhibitors in neuroinflammation. In addition, among the four subtypes (A-D) of PDE4, it remains unclear which one exerts suppressive efects on neuroinflammation. Understanding how PDE4 and neuroinflammation interact can reveal pathogenic clues and help target new preventive and symptomatic therapies for psychiatric illness.

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Section: Mechanisms Of Neuroinflammationsupporting

confidence: 83%

Reducing Neuroinflammation in Psychiatric Disorders: Novel Target of Phosphodiesterase 4 (PDE4) and Developing of the PDE4 Inhibitors

Wang¹,

Wang²,

Li³

et al. 2017

Mechanisms of Neuroinflammation

View full text Add to dashboard Cite

show abstract

“…Three out of nine studies found higher levels of IL-1β, but seven found no association with suicidal ideation and behavior in samples of CSF (Martinez et al, 2012) and serum (Monfrim et al, 2014), or with suicide, in postmortem tissue (Pandey et al, 2012). …”

Section: Resultsmentioning

confidence: 98%

“…Two prospective studies (Isung et al, 2012b; Lindqvist et al, 2011) concerned the ability of baseline cytokine levels, among 182 individuals with a history of suicide attempt, to predict 16 subsequent suicides. Seven articles concerned suicidal ideation (Gabbay et al, 2009; Juengst et al, 2014; Karlović et al, 2012; Martinez et al, 2012; Mendlovic et al, 1999; Monfrim et al, 2014; O'Donovan et al, 2013) in 499 research participants: 156 patients with suicidal ideation, 188 patients with no suicidal ideation, and 176 normal controls. See Tables 1-3 for a description of the included studies.…”

Section: Resultsmentioning

confidence: 99%

The role of cytokines in the pathophysiology of suicidal behavior

Ganança

Oquendo

Tyrka

et al. 2016

Psychoneuroendocrinology

186

128

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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.

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“…In vivo blood levels for IL-1β were significantly increased in patients with suicidality, without significant between-study heterogeneity, despite inclusion of subjects with different primary psychiatric diagnoses. One study investigated patients with bipolar disorder with versus without suicidality (28), and two studies investigated patients with MDD with versus without suicidality (14,16). These findings raise the possibility that associations between cytokines and suicidality may be independent of psychiatric diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Meta-Analysis of Cytokines and Chemokines in Suicidality: Distinguishing Suicidal Versus Nonsuicidal Patients

Parker

Miller

2015

Biological Psychiatry

299

212

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Immune dysfunction in bipolar disorder and suicide risk: is there an association between peripheral corticotropin‐releasing hormone and interleukin‐1β?

Abstract: These results suggest that peripheral mechanisms linking stress hormones and the immune system might be critical patterns involved in suicidal behavior associated with BD.

Cited by 55 publications

References 47 publications

Reducing Neuroinflammation in Psychiatric Disorders: Novel Target of Phosphodiesterase 4 (PDE4) and Developing of the PDE4 Inhibitors

Reducing Neuroinflammation in Psychiatric Disorders: Novel Target of Phosphodiesterase 4 (PDE4) and Developing of the PDE4 Inhibitors

The role of cytokines in the pathophysiology of suicidal behavior

Meta-Analysis of Cytokines and Chemokines in Suicidality: Distinguishing Suicidal Versus Nonsuicidal Patients

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