Activation of the immune-inflammatory response system and the compensatory immune-regulatory system in antipsychotic naive first episode psychosis

Increased Levels of Plasma Tumor Necrosis Factor-α Mediate Schizophrenia Symptom Dimensions and Neurocognitive Impairments and Are Inversely Associated with Natural IgM and Paraoxonase 1 Activity

“…Previously, increased IL-4 levels were detected in first-episode psychosis and in acute schizophrenic episodes [3,15,45]. Our findings may indicate that deficit schizophrenia is accompanied by the simultaneous upregulation of M1 and Th-2 cytokines which is in accordance with the IRS-CIRS theory of schizophrenia [3].…”

“…Furthermore, deficits in the CIRS also appear to contribute to OSOS as well as to different symptom domains of schizophrenia and the deficit syndrome [15][16][17][18]. Firstly, while M1, Th-1 and Th-17 cytokines are significantly increased in first-episode psychosis, the levels of the immuneregulatory soluble cytokine receptors including sTNFR2, sIL-1 receptor antagonist (sIL-1RA) and sIL-2R are not increased indicating that lowered CIRS effects are associated with activated immune pathways [15].…”

“…Furthermore, deficits in the CIRS also appear to contribute to OSOS as well as to different symptom domains of schizophrenia and the deficit syndrome [15][16][17][18]. Firstly, while M1, Th-1 and Th-17 cytokines are significantly increased in first-episode psychosis, the levels of the immuneregulatory soluble cytokine receptors including sTNFR2, sIL-1 receptor antagonist (sIL-1RA) and sIL-2R are not increased indicating that lowered CIRS effects are associated with activated immune pathways [15]. Secondly, deficit schizophrenia is characterized by impairments in innate immune resilience as indicated by lowered natural IgM directed against oxidative specific epitopes (OSEs) and lowered levels of paraoxonase 1 (PON1) which both protect against immune activation, nitro-oxidative stress, and increased bacterial translocation [16,18].…”

Immunoendocrine Peripheral Effects Induced by Atypical Antipsychotics

“…In the blood of schizophrenic patients, the treatment with risperidone (2-6 mg/day) for 4 weeks showed a decrease in the number of Th17 cells (183). In vitro, differentiated human adipocytes incubated with risperidone (100 ng/ml, 11 days) induced transcription factor NF-κB target genes of IL-1β and IL-8 molecules (184).…”

High Mobility Group Protein 1 and Dickkopf-Related Protein 1 in Schizophrenia and Treatment-Resistant Schizophrenia: Associations with Interleukin-6, Symptom Domains, and Neurocognitive Impairments

“…4,6 Our results further extend the findings that TRS is accompanied by IRS activation as indicated by increased levels of sIL-6R, IL-8, CCL2 and CCL3, and by CIRS activation as indicated by elevated levels of sIL-1RA, sTNFR1, and sTNFR2. 4-6, 13,14 Noto et al 45 reported that drug naïve first-episode psychosis is characterized by significant IRS (M1 + Th-1 + Th-17) and CIRS (Th-2 and Treg) responses and that treatment with risperidone attenuates both IRS and CIRS responses while increased baseline levels of some CIRS biomarkers may predict clinical improvement. All in all, the above results and the current study indicate that antipsychotic agents may attenuate the immune response in some SCZ patients, namely in PRTT, thereby improving symptoms and neurocognitive deficits.…”