Aggression as an independent entity even in psychosis- the role of inflammatory cytokines

Das, Sourav Kumar; Deuri, Sailendra Kumar; Sarmah, Anil; Pathak, Kangkan; Baruah, Aparajeeta; Sengupta, Soumik; Mehta, Sumit; Avinash, Priya Ranjan; Kalita, Kamal Narayan; Hazarika, Jyoti

doi:10.1016/j.jneuroim.2016.01.012

Cited by 37 publications

(20 citation statements)

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“…As aggression and agitation are two overlapping clinical signs with several symptoms in common, these findings are also relevant to our study. Previously, levels of IFN-γ, IL-10 and TGF-β have been reported to be associated with aggression in schizophrenia patients [13, 14]. In line with this, we found a trend towards an association between IFN-γ and agitation in the sub-group non-affective psychoses.…”

Section: Discussionsupporting

confidence: 90%

“…There are also some studies on the association between aggression and cytokines. A study on inpatients diagnosed with schizophrenia, demonstrated a possible association between interferon (IFN) -γ and interleukin (IL) -10 and aggression [14]. However, the results are conflicting and another study found aggression to be associated with IL-17, IL-3, and transforming growth factor (TGF) -β [13].…”

Section: Introductionmentioning

confidence: 99%

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Cytokines in agitated and non-agitated patients admitted to an acute psychiatric department: A cross-sectional study

Larsen¹,

Stunes²,

Vaaler³

et al. 2019

PLoS ONE

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BackgroundDifferent psychiatric diagnostic groups have been reported to have cytokine levels deviating from healthy controls. In acute clinical settings however, the specific challenging symptoms and signs are more important than a diagnostic group. Thus, exploration of cytokines and immune activity and their role in specific symptoms is important. Reports in this field so far are sparse.ObjectiveIn the present study, we aimed to examine the association between immune activity measured as levels of cytokines and agitation (independent of diagnostic group) in patients admitted to an acute psychiatric inpatient department.MethodsA total of 316 patients admitted to an acute psychiatric inpatient department were included. Thirty-nine patients with psychosis were subject to subgroup analyses. Agitation was assessed by the Positive and Negative Syndrome Scale, Excitement Component (PANSS-EC). Based on PANNS-EC patients were stratified into two groups: 67 agitated patients and 249 non-agitated patients. Serum concentrations of the following immune markers were measured: interleukin (IL) -1β, IL-4, IL-6, IL-10, tumor necrosis factor (TNF) -α, interferon (IFN) -γ and transforming growth factor (TGF) -β.ResultsSerum levels of TNF-α were significantly higher in patients with agitation compared to those without, both when all patients were included in the analyses (p = 0.004) and in the psychosis group (p = 0.027). After correcting for multiple testing, only the findings in the total population remained significant.ConclusionsOur findings suggest an association between TNF-α and agitation in an acute psychiatric population. A similar trend was reproduced to the psychosis subgroup. This suggests that agitation might be an independent entity associated with cytokines across different diagnostic groups.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Cytokines in agitated and non-agitated patients admitted to an acute psychiatric department: A cross-sectional study

Larsen¹,

Stunes²,

Vaaler³

et al. 2019

PLoS ONE

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“…Decreased levels of IFN-γ were also reported in patients with acute psychotic symptoms who were drug-naive for at least 6 months (52) and in chronic patients. The details of the medications that were used were not reported in these studies (53, 54).…”

Section: Alterations In the Levels Of Cytokines In Schizophrenic Patimentioning

confidence: 99%

Cytokine Alterations in Schizophrenia: An Updated Review

2019

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Schizophrenia, a multisystem disorder with an unknown etiology, is associated with several immune dysfunctions, including abnormal levels of circulating cytokines. In this review, we investigated the changes of cytokines in schizophrenic patients, their connection with behavioral symptoms severity and their potential clinical implications. We also assessed the possible causative role of abnormal cytokine levels in schizophrenia pathogenesis. Based on meta-analyses, we categorized cytokines according to their changes in schizophrenic patients into four groups: (1) increased cytokines, including interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1β, IL-12, and transforming growth factor (TGF)-β, (2) non-altered cytokines, including IL-2, IL-4, and IL-17, (3) increased or non-altered cytokines, including IL-8 and interferon (IFN)-γ, and (4) IL-10 with increased, decreased, and non-altered levels. Notably, alterations in cytokines may be variable in four different categories of SP, including first-episode and drug-naïve, first-episode and non-drug-naïve, stable chronic, and chronic in acute relapse. Furthermore, disease duration, symptoms severity, incidence of aggression, and cognitive abilities are correlated with levels of certain cytokines. Clinical implications of investigating the levels of cytokine in schizophrenic patients include early diagnosis, novel therapeutic targets development, patient stratification for choosing the best therapeutic protocol, and predicting the prognosis and treatment response. The levels of IL-6, IL-8, IFN-γ, IL-2 are related to the treatment response. The available evidence shows a potential causative role for cytokines in schizophrenia development. There is a substantial need for studies investigating the levels of cytokines before disease development and delineating the therapeutic implications of the disrupted cytokine levels in schizophrenia.

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“…Aggressive behavior in humans is complex in its expression (i.e., physical and verbal) as well as its causes (i.e., provoked emotion) and consequences on victims (i.e., trauma induced psychopathology) (Box 2 ). Several mental disorders, such as schizophrenia, psychosis, antisocial personality disorder, impulse control disorder, depression, attention deficit disorder, and autism spectrum disorders accompany escalated forms of aggression toward others (violence) or one's self (self-mutilation) (Connor et al, 2002 ; Raine et al, 2002 ; Volavka et al, 2005 ; Comai et al, 2012 ; Matson and Jang, 2014 ; Das et al, 2016 ).…”

Section: Aggression and The Immune System In Humansmentioning

confidence: 99%

“…Also, hostile marital relationships are associated with slower wound healing and dysregulated cytokine production at wound sites (Kiecolt-Glaser et al, 2005 ). Pathological levels of aggression in intermittent explosive disorder (IED) or psychosis appear to be linked to heightened proinflammatory cytokines (Coccaro et al, 2014 ; Das et al, 2016 ). A similar relationship is observed in healthy individuals with high aggression as a personality trait.…”

Section: Aggression and The Immune System In Humansmentioning

confidence: 99%

Aggression, Social Stress, and the Immune System in Humans and Animal Models

Takahashi

Flanigan

McEwen

et al. 2018

Front. Behav. Neurosci.

191

107

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Social stress can lead to the development of psychological problems ranging from exaggerated anxiety and depression to antisocial and violence-related behaviors. Increasing evidence suggests that the immune system is involved in responses to social stress in adulthood. For example, human studies show that individuals with high aggression traits display heightened inflammatory cytokine levels and dysregulated immune responses such as slower wound healing. Similar findings have been observed in patients with depression, and comorbidity of depression and aggression was correlated with stronger immune dysregulation. Therefore, dysregulation of the immune system may be one of the mediators of social stress that produces aggression and/or depression. Similar to humans, aggressive animals also show increased levels of several proinflammatory cytokines, however, unlike humans these animals are more protected from infectious organisms and have faster wound healing than animals with low aggression. On the other hand, subordinate animals that receive repeated social defeat stress have been shown to develop escalated and dysregulated immune responses such as glucocorticoid insensitivity in monocytes. In this review we synthesize the current evidence in humans, non-human primates, and rodents to show a role for the immune system in responses to social stress leading to psychiatric problems such as aggression or depression. We argue that while depression and aggression represent two fundamentally different behavioral and physiological responses to social stress, it is possible that some overlapped, as well as distinct, pattern of immune signaling may underlie both of them. We also argue the necessity of studying animal models of maladaptive aggression induced by social stress (i.e., social isolation) for understanding neuro-immune mechanism of aggression, which may be relevant to human aggression.

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Aggression as an independent entity even in psychosis- the role of inflammatory cytokines

Cited by 37 publications

References 50 publications

Cytokines in agitated and non-agitated patients admitted to an acute psychiatric department: A cross-sectional study

Cytokines in agitated and non-agitated patients admitted to an acute psychiatric department: A cross-sectional study

Cytokine Alterations in Schizophrenia: An Updated Review

Aggression, Social Stress, and the Immune System in Humans and Animal Models

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