An update on the efficacy of anti-inflammatory agents for patients with schizophrenia: a meta-analysis

Çakici, Nuray; Beveren, Nico J.M. van; Judge-Hundal, G.; Koola, Maju Mathew; Sommer, Iris

doi:10.1017/s0033291719001995

Cited by 145 publications

(94 citation statements)

References 146 publications

(161 reference statements)

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“…A recent meta-analysis showed that a variety of medications can reduce the severity of symptoms of schizophrenia. These medications are aspirin (by reducing inflammation by modifying cyclooxygenase-2 enzyme), estrogens (through immunomodulatory effects), minocycline (by inhibiting microglia), and N-acetylcysteine (as an anti-inflammatory agent) (130).…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

Cytokine Alterations in Schizophrenia: An Updated Review

2019

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“…There is a growing literature on the role of anti-inflammatory treatments in individuals with schizophrenia (97)(98)(99). Given the heterogeneity of inflammatory markers in the studies demonstrating relationships with negative symptom severity, blocking inflammation in treatment trials represents a complementary approach to understanding these relationships.…”

Section: Negative Symptoms and Anti-inflammatory Treatment Trialsmentioning

confidence: 99%

Inflammation and Negative Symptoms of Schizophrenia: Implications for Reward Processing and Motivational Deficits

Goldsmith

Rapaport

2020

Front. Psychiatry

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Negative symptoms of schizophrenia are debilitating and chronic in nature, are difficult to treat, and contribute to poor functional outcomes. Motivational deficits are a core negative symptom and may involve alterations in reward processing, which involve subcortical regions such as the basal ganglia. More specifically, dopamine-rich regions like the ventral striatum, have been implicated in these reward-processing deficits. Inflammation is one mechanism that may underlie negative symptoms, and specifically motivational deficits, via the effects of inflammatory cytokines on the basal ganglia. Previous work has demonstrated that inflammatory stimuli decrease neural activity in the ventral striatum and decrease connectivity in reward-relevant neural circuitry. The immune system has been shown to be involved in the pathophysiology of schizophrenia, and inflammatory cytokines have been shown to be altered in patients with the disorder. This paper reviews the literature on associations between inflammatory markers and negative symptoms of schizophrenia as well as the role of anti-inflammatory drugs to target negative symptoms. We also review the literature on the role of inflammation and reward processing deficits in both healthy controls and individuals with depression. We use the literature on inflammation and depression as a basis for a model that explores potential mechanisms responsible for inflammation modulating certain aspects of negative symptoms in patients with schizophrenia. This approach may offer novel targets to treat these symptoms of the disorder that are significant barriers to functional recovery and do not respond well to available antipsychotic medications.

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“…To add more, investigations revealed, in animal models of psychiatric disorders and in patients, that estrogen and estrogen signaling are disturbed and that they are associated with not only the cognitive deficits but, also, the manifestations of the symptoms, which could also be reversed with estrogen administration or treatments targeting estrogen-signaling pathways [ 11 , 12 , 13 ]. Thus, together with much evidence on estrogen signaling disruptions in psychiatric disorders, recently, their effects have been taken under examination in multiple clinical trials for the critical assessment and evaluation of their efficacy as a new treatment for psychiatric patients [ 14 , 15 , 16 , 17 , 18 ]. Altogether, accumulating evidence suggests that estrogen and estrogen signaling may be highly implicated in the pathophysiology of psychiatric disorders, warranting a comprehensive and integrated understanding of estrogen and estrogen signaling across multiple levels of the brain system architecture from cellular and molecular to systemic to elucidate the mechanisms involved in its therapeutic effects in psychiatric disorders.…”

Section: Introductionmentioning

confidence: 99%

The Role of Estrogen Receptors and Their Signaling across Psychiatric Disorders

Hwang

Lee

Kim

et al. 2020

IJMS

112

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Increasing evidence suggests estrogen and estrogen signaling pathway disturbances across psychiatric disorders. Estrogens are not only crucial in sexual maturation and reproduction but are also highly involved in a wide range of brain functions, such as cognition, memory, neurodevelopment, and neuroplasticity. To add more, the recent findings of its neuroprotective and anti-inflammatory effects have grown interested in investigating its potential therapeutic use to psychiatric disorders. In this review, we analyze the emerging literature on estrogen receptors and psychiatric disorders in cellular, preclinical, and clinical studies. Specifically, we discuss the contribution of estrogen receptor and estrogen signaling to cognition and neuroprotection via mediating multiple neural systems, such as dopaminergic, serotonergic, and glutamatergic systems. Then, we assess their disruptions and their potential implications for pathophysiologies in psychiatric disorders. Further, in this review, current treatment strategies involving estrogen and estrogen signaling are evaluated to suggest a future direction in identifying novel treatment strategies in psychiatric disorders.

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An update on the efficacy of anti-inflammatory agents for patients with schizophrenia: a meta-analysis

Cited by 145 publications

References 146 publications

Cytokine Alterations in Schizophrenia: An Updated Review

Cytokine Alterations in Schizophrenia: An Updated Review

Inflammation and Negative Symptoms of Schizophrenia: Implications for Reward Processing and Motivational Deficits

The Role of Estrogen Receptors and Their Signaling across Psychiatric Disorders

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