The role of pro-inflammatory cytokines in the neuroinflammation and neurogenesis of schizophrenia

Abstract

Schizophrenia is a serious mental illness with chronic symptoms and significant impairment in psychosocial functioning. Although novel antipsychotics have been developed, the negative and cognitive symptoms of schizophrenia are still unresponsive to pharmacotherapy. The high level of social impairment and a chronic deteriorating course suggest that schizophrenia likely has neurodegenerative characteristics. Inflammatory markers such as pro-inflammatory cytokines are well-known etiological factors for psychiatric disorders, including schizophrenia. Inflammation in the central nervous system is closely related to neurodegeneration. In addition to pro-inflammatory cytokines, microglia also play an important role in the inflammatory process in the CNS. Uncontrolled activity of pro-inflammatory cytokines and microglia can induce schizophrenia in tandem with genetic vulnerability and glutamatergic neurotransmitters. Several studies have investigated the possible effects of antipsychotics on inflammation and neurogenesis. Additionally, anti-inflammatory adjuvant therapy has been under investigation as a treatment option for schizophrenia. Further studies should consider the confounding effects of systemic factors such as metabolic syndrome and smoking. In addition, the unique mechanisms by which pro-inflammatory cytokines are involved in the etiopathology of schizophrenia should be investigated. In this article, we aimed to review (1) major findings regarding neuroinflammation and pro-inflammatory cytokine alterations in schizophrenia, (2) interactions between neuroinflammation and neurogenesis as possible neural substrates for schizophrenia, and (3) novel pharmacological approaches.

Keywords: AMPA; BBB; C-reactive protein; CATIE; CNS; COX-1; COX-2; CRP; CSF; Clinical Antipsychotic Trials of Intervention Effectiveness; Cytokine; DISC-1; Disrupted-in-schizophrenia 1; HPA; IDO; IFN-γ; IL-10; IL-12; IL-2; IL-3; IL-4; IL-6; IL-8; KYNA; LIF; LTP; MAPK; MDD; N-methyl-D-aspartate; NMDA; NRG-1; Neurodegeneration; Neurogenesis; Neuroinflammation; PolyI:C; RNA; Ribonucleic acid; SGZ; SNPs; SVZ; Schizophrenia; Single nucleotide polymorphisms; TGF-β; TNF-R1; TNF-R2; TNF-α; TNF-α receptor 1; TNF-α receptor 2; Th1; Th17; Th2; alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; blood–brain barrier; central nervous system; cerebrospinal fluid; cyclooxygenase-1; cyclooxygenase-2; glycoprotein 130; gp130; hypothalamus-pituitary-adrenal; indolamine 2,3-dioxygenase; interferon gamma; interleukin-10; interleukin-12; interleukin-2; interleukin-3; interleukin-4; interleukin-6; interleukin-8; kynurenic acid; leukemia inhibitory factor; long-term potentiation; mRNA; major depressive disorder; messenger RNA; mitogen-activated protein kinase; neurergulin-1; polyriboinosinic-polyribocytidilic acid; sIL-2R; soluble IL-2 receptor; subgranular zone; subventricular zone; transforming growth factor beta; tumor necrosis factor alpha; type 17T helper cell; type 1T helper cells; type 2T helper cells.