Table 1.
Description of studies showing associations between inflammatory markers and negative symptoms of schizophrenia.
| Markers studied | Serum/plasma | Assay | Population studied | N | Factors controlled for/included in statistical models | Comments | |
|---|---|---|---|---|---|---|---|
| Fan et al. (81) | CRP | Serum | Particle enhanced immunonephelometry | Inpatients with schizophrenia/schizoaffective disorder; no control group | 26 | None | High CRP group (>0.5 mg/dl; n=5) had higher PANSS scores on all subscales, including negative symptoms |
| Boozalis et al. (82) | CRP | Plasma | ELISA | Inpatients with schizophrenia; no control group | 39 | Age, sex, race, BMI | Positive correlation between CRP and PANSS negative symptoms both unadjusted and after adjusting for age, sex, race, and BMI |
| Liemburg et al. (83) | CRP | Plasma and Serum collected from different sites | Varied by sites; specific assays not disclosed | Outpatients from four different sites in the northern Netherlands; no control group | 2123 | Age, sex, smoking, use of anti-histaminergic antipsychotics, statins, fibrates, corticosteroids, antibiotics, chlorpromazine equivalents, BMI, metabolic syndrome, metabolic effects of antipsychotics (high, medium, low) | Association between CRP and PANSS negative symptom subscale in linear regression models |
| Garcia-Rizo e al. (75) | CRP and IL-6 | Not described | IL-6: ELISA CRP: not described |
Antipsychotic naïve patients with first episode nonaffective psychosis; no control group | 20 patients with deficit psychosis and 42 patients with non-deficit psychosis | Groups matched for age, sex, BMI, smoking | Higher concentrations of CRP and IL-6 in the deficit group compared to the non-deficit group |
| Goldsmith et al. (84) | IFN-γ, IL-1β, IL-6, sIL-2R, TNF | Plasma | Multiplex immunoassay | Outpatients with schizophrenia and healthy controls | 17 with deficit schizophrenia, 39 with non-deficit schizophrenia, 28 controls | Smoking, BMI, education | Higher concentrations of IL-6 and TNF in deficit patients compared to non-deficit and controls. TNF associated with PANSS negative symptoms in linear regression models |
| Stojanovic et al. (77) | IL-6, CRP, fibrinogen | Serum | CRP by immunoturbidimetry assay; IL-6 by ELISA | Outpatients with psychotic disorder (PD), ARMS subjects, healthy controls | 77 with psychotic disorder, 17 ARMS subjects, 25 controls | Sex, BMI, substance use, antipsychotic treatment, IL-6 rs1800795 genotype | Higher concentrations of IL-6 in ARMS compared to control group and in PD compared to control that becomes trend-level after Bonferroni correction. CRP differences between groups do not meet significance after Bonferroni correction. IL-6 associated with negative symptoms in linear regression models for both PD and ARMS subjects |
| Goldsmith et al. (85) | IFN-γ, IL-1β, IL-1RA, IL-4, IL-6, IL-8, IL-10, TNF | Plasma | Multiplex Immunoassay | CHR subjects; no control group | 37 | Age, sex, race, weight, baseline negative symptoms, baseline CDSS scores | Higher concentrations of TNF and lower concentrations of IL-6 predicted worse negative symptom trajectories at one year follow up |
| Xiu et al. (78) | IL-10 | Serum | ELISA | First episode drug naïve inpatients with schizophrenia; heathy controls | 128 patients with schizophrenia; 62 controls | Sex, age, education, smoking, BMI | Decreased IL-10 concentrations in the patients compared to controls. IL-10 was inversely correlated with negative symptoms severity on the PANSS. |
| Zhu et al. (86) | TNF and IL-1β | Serum | ELISA | First episode drug naïve patients with schizophrenia (both in and outpatients), chronic patients with schizophrenia (both in and outpatients), and healthy controls | 69 first episode patients, 87 patients with chronic schizophrenia, 61 healthy controls | Age, sex, course of illness | TNF and IL-1β concentrations were lower in first episode patients compared to healthy controls and higher in chronic patients compared to controls. Concentrations of both were correlated with the PANSS negative subscale in chronic, but not first episode patients. |
| Asevedo et al. (76) | IL-2 | Plasma | Cytometric bead array | Outpatients with chronic schizophrenia and healthy controls | 29 patients with schizophrenia; 26 controls | Differences between clozapine and other atypical antipsychotics was assessed | IL-2 concentrations were lower in patients compared to controls. IL-2 concentrations were negatively correlated with PANSS negative subscale score |
| Bresee et al. (87) | sIL-2R | Serum | ELISA | Outpatients with schizophrenia and healthy controls | 59 patients with schizophrenia; 57 controls | Sex, age, smoking, BMI, type of pharmacotherapy | sIL-2R concentrations were elevated in patients compared to controls. sIL-2R concentrations were correlated with PANSS negative subscale score |
| El Kissi et al. (79) | IFN-γ,IL-4, TGF-β, IL-17, BAFF | Serum | ELISA | Antipsychotic free acute inpatients with schizophrenia and healthy controls | 60 patients with schizophrenia; 28 controls | None | Positive correlation between IFN-γ and SANS total score; Negative correlation between IL-17 and SANS total score |
| Noto et al. (80) | CCL11, CCL24, MCP-1, MIP-1α, IL-8, IP-10, sTNF-R1, sTNF-R2, TNF, IL-2, IL-4, IL-6, IL-10, IFNγ, IL-17 | Serum | ELISA | Outpatients with schizophrenia and healthy controls | 54 patients with schizophrenia, 118 healthy controls | Sex, age, BMI, smoking, drug/alcohol use, ethnicity, monthly income (but not controlled for in all analyses) | Negative correlation between IL-2 and PANSS negative subscale score; Positive correlation between CCL11 and PANSS negative score |
CRP, C-Reactive Protein; PANSS, Positive and Negative Syndrome Scale; BMI, body mass index; ELISA, enzyme-linked immunosorbent assay; CDSS, Calgary Depression Scale for Schizophrenia; IL-6, interleukin 6; IFN-γ, interferon gamma; IL-1β, interleukin 1 beta; sIL-2R, soluble interleukin 2 receptor; TNF, tumor necrosis factor; ARMS, at risk mental state; IL-1RA, interleukin 1 receptor antagonist; IL-4, interleukin 4; IL-8, interleukin 8; IL-10, interleukin 10; CHR, clinical high risk; IL-2, interleukin 2; TGF-β, transforming growth factor beta; IL-17, interleukin 17; BAFF, B cell activating factor of the tumor necrosis factor family; SANS, Scale for the Assessment of Negative Symptoms; CCL11, eotaxin-1; CCL24, eotaxin-2; MCP-1, monocyte chemoattractant protein-1; MIP-1α, macrophage inflammatory protein 1α; IP-10, interferon-γ-inducible protein 10; sTNF-R1, soluble tumor necrosis factor receptor 1; sTNF-R2, soluble tumor necrosis factor receptor 2.