Table 1.
Summary of included studies evaluating the association between CRP and schizophrenia.
| Study | Study Design | Primary and Secondary Outcomes | Characteristics of Participants | Assessments | Main Findings | Correlation CRP and Schizophrenia? | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| [62] | Cross-sectional study | Association between CRP levels and severity of clinical psychopathology | 26 inpatients schizophrenia or schizoaffective disorder (DSM-IV-TR criteria) 18-65 yy stable on antipsychotic medications |
•Serum CRP levels (cut-off value =5 mg/L) •PANSS total score |
Subjects with CRP levels above the normal range (n=5) scored significantly higher than those with CRP levels in the normal range (n=21) at the PANSS total score, negative symptom subscale score and general psychopathology subscale score. | •Positive correlation with severity of psychopathology | |||||||||||||||||||||||||||||
| [57] | Cross-sectional study | Association between CRP levels and severity of clinical psychopathology and cognitive impairment | 413 outpatients schizophrenia or schizoaffective disorder (DSM-IV criteria) 13-65 yy ongoing antipsychotic, anticholinergic, non-lithium mood stabilizer, antidepressant medications. |
•Serum CRP levels •(cut-off value =5 mg/L) •PANSS total score •RBANS total score •PDS |
Individuals with CRP ≥5.0 mg/μl had significantly lower RBANS cognitive scores than those with CRP <5.0 mg/μl (F=8.07, pb.005). CRP groups did not differ in the severity of positive, negative, or general PANSS symptoms. |
•Positive correlation with severity of cognitive impairment •No correlation with severity of psychopathology |
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| [63] | Case-control study | Association between hsCRP levels and clinical psychopathology | 165 HC vs 207 in/outpatients schizophrenia (DSM-IV criteria) Arabic population 15-76 yy stable on antipsychotic medications |
•Serum CRP levels •(cut-off value =5 mg/L) •PANSS total score •SANS (Andreasen's Scale for Assessment of Negative Symptoms) total score •SCAN (WHO Schedule for Clinical Assessment in Neuropsychiatry – schizophrenia section) •CGI (Clinical Global Impression) •AIMS (Abnormal involuntary movement scale for tardive dyskinesia) |
Amongst schizophrenics, hsCRP levels were: (a) marginally higher in women with later age of disease onset; (b) highest with remission and with catatonic features; (c) lower with family history of psychosis. |
•Positive correlation with some psychopathological features | |||||||||||||||||||||||||||||
| [64] | Case-control study | Differences between CRP levels amongst bipolar disorder vs schizophrenia disorder Association between CRP levels and the presence of metabolic syndrome amongst these groups |
60 BD vs 63 inpatients schizophrenia (DSM-IV criteria) stable on antipsychotic medications |
•Serum CRP levels •(cut-off value =5 mg/L) •NCEP ATP III criteria for metabolic syndrome |
The prevalence of the metabolic syndrome was 31% in bipolar group compared to the 37% in schizophrenia group. Amongst bipolar disorder patients significantly higher CRP levels compared to schizophrenia group. |
•No significant correlation with psychopathology | |||||||||||||||||||||||||||||
| Study | Study Design | Primary and Secondary Outcomes | Characteristics of Participants | Assessments | Main Findings | Correlation CRP and Schizophrenia? | |||||||||||||||||||||||||||||
| [65] | Case-control study | Association between the CRP rs1417938, rs1800947, rs1205 variants with susceptibility to Schizophrenia |
105 HC vs 103 schizophrenia (DSM-IV criteria) Armenian population |
•Serum CRP levels (cut-off value =5 mg/L) •Genomic DNA extraction and gentotyping analysis |
•No significant differences found when the proportions of CRP variants were compared between the patients and HC (p>0.05). •Nevertheless, the rs1417938 AA homozygotes and rs1205*T carriers tended to be overrepresented in the patients by comparison with the HC (p=0.1 in both cases). |
•No significant correlation with psychopathology | |||||||||||||||||||||||||||||
| [55] | A cross-sectional case–control study | Association between hsCRP levels and clinical features of schizophrenia | 200 antipsychotic-free outpatients male schizophrenia (DSM-IV criteria) vs 200 HC Egyptian population |
•Serum CRP levels (cut-off value =5 mg/L) •PANSS total score |
•CRP levels for patients was significantly higher than that for controls (P=0.000). •PANSS scores and patients' data, which significantly correlated with serum hs-CRP levels •PANSS negative symptom score was second only to the waist circumference, with which they explained 54.7 % of the variation in serum hs-CRP. |
•Positive correlation with severity of psychopathology •Positive correlation with negative symptomatology |
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| [66] | Case-control study | Association between hsCRP levels and schizophrenia, bipolar disorder and non-psychiatric subjects | 295 schizophrenia vs 192 bipolar disorder (DSM-IV criteria) vs 228 non-psychiatric subjects | •Serum CRP levels (cut-off value =5 mg/L) •PANSS total score •SCID |
•The individuals with schizophrenia had significantly increased odds of having elevated levels of CRP relative to both the 75th and 90th percentile •CRP levels of the controls adjusting for the same covariates (OR 1.79, 95% CI 1.14, 2.82; p=.012; OR 2.76, 95% CI 1.58, 4.83, p=b.001). |
•Positive correlation with psychopathology •Positive correlation with negative symptomatology |
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| [67] | Case-control study | Association between hsCRP and three antipsychotic groups of schizophrenia subjects (clozapine, olanzapine and risperidone) | 36 HC vs 36 schizophrenia inpatients (DSM-IV criteria) Taiwanese population Stable on antipsychotic mediations (clozapine, olanzapine or risperidone) |
•Serum CRP levels (cut-off value =5 mg/L) •PANSS total score |
•An increase in the hsCRP levels in the schizophrenic group was observed in comparison with the HC (P = 0.013) | •Positive correlation with psychopathology •Positive correlation with negative symptomatology and illness duration |
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| [68] | A longitudinal birth cohort study | Association between early-life atopic disorder, inflammatory markers at age 9 and the risk of onset of psychotic episodes at age 13 years | 6785 13-year adolescents with atopic disorders (asthma and eczema) | •Serum CRP levels (cut-off value =N/A) •Serum IL-6 levels |
•Risk of psychotic episodes at age 13 years was increased for both groups (asthma and eczema) •Atopy was associated with increased serum IL-6 and CRP levels •Inflammatory markers were not associated with later psychotic episodes |
•Positive association between atopy and CRP levels •No association between CRP levels and risk of psychotic episodes |
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| Study | Study Design | Primary and Secondary Outcomes | Characteristics of Participants | Assessments | Main Findings | Correlation CRP and Schizophrenia? | |||||||||||||||||||||||||||||
| [69] | Prospective and cross-sectional study |
Association between hsCRP and risk of late and very-late onset schizophrenia | 78810 individuals from 2 large independent general population studies outpatients and inpatients |
•Serum CRP levels (cut-off value =5 mg/L) |
Age- and gender-adjusted hazard ratios vs individuals in the first quartile of CRP were 1.7 (95% CI: 0.3–8.9) for second quartile, 2.1 (0.4–10) for third quartile, and 11 (2.8–40) for fourth quartile individuals. The corresponding hazard ratio for fourth quartile individuals after multifactorial adjustment was 5.9 (1.4–24). Individuals with vs without schizophrenia had 63% increased plasma levels of CRP (P = 1 ×10−4). When CRP was on a continuous scale, a doubling in CRP yielded an age- and gender-adjusted observational OR of 1.5 (1.3–1.8) and a corresponding causal OR of 1.4 (0.5–4.3) (observed vs causal: P = .89). |
•Positive correlation with psychopathology •Positive correlation with the risk of late or very-late onset schizophrenia |
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| [70] | Retrospective, cross-sectional, naturalistic study |
Association between CRP levels and schizophrenia, major depression and bipolar disorder | 485 schizophrenia vs 319 major depression vs 260 bipolar disorder (DSM-IV criteria) inpatients | •Serum CRP levels (cut-off value =3 mg/L) | •Mean concentration of CRP levels in study groups was 5.30 mg/l amongst schizophrenics •There was no difference for CRP levels between patients with schizophrenia, unipolar depression, bipolar depression and bipolar mania (P=0.58). •No significant differences in the risk of having high level of CRP between the clinical groups •The rate of patients being above high level was higher in women. •Patients with CRP level in the low range were significantly younger (48.2 _ 20.1 vs. 51.1 _ 20.6 years, t _ 2.22, P _ 0.001) •Patients with CRP levels in the high range were significantly older (53.1 _ 20.4 vs. 47.9 _ 20.2 years, t _ _ 3.83, P _ 0.001) |
•No correlation with psychopathology | |||||||||||||||||||||||||||||
| [71] | Case-control study | Association between CRP levels and different phases of schizophrenia | 79 with recent onset psychosis (inpatients); 249 with chronic schizophrenia (outpatients); 260 HC 18-65 yy |
•Serum CRP levels (cut-off value =5 mg/L) •PANSS total score •RBANS total score •FORM-A |
•The correlations were generally weak to moderate, ranging from r = 0.023 (antibodies to gliadin and CRP) to r = 0.27 (antibodies to gliadin and casein). •Generally, CRP was the most weakly correlated with the other measures, while the correlation between the level of casein antibodies and other measures was the strongest. •The chronic schizophrenia group differed from the control group for antibodies to gliadin (coefficient = .333, P = .007); CRP (coefficient = .469, P=<.001); ASCA (coefficient = .382, P=.005); pentraxin 3 (coefficient = .118, P = .023); and the composite inflammation score (coefficient = .453, P = <.001). The level of these markers was higher in the chronic schizophrenia group than in the control group. |
•Positive correlation with psychopathology •Positive correlation with chronic phase of schizophrenia |
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| Study | Study Design | Primary and Secondary Outcomes | Characteristics of Participants | Assessments | Main Findings | Correlation CRP and Schizophrenia? | |||||||||||||||||||||||||||||
| [72] | Cross-sectional study | Association between quality of life and CRP levels amongst schizophrenia subjects | 256 schizophrenia (DSM-IV criteria) stable on antipsychotic medications |
•Serum CRP levels (cut-off value =3 mg/L) •SQoL score and dimensions •BMI •PANSS total score •FTND •AUDIT |
•Compared to patients with normal CRP levels, those with high CRP levels were significantly older (p= 0.027), with a lower education level (p= 0.021), a longer duration of disorder (p= 0.018), a higher BMI (p= 0.000) and a higher Fagerström score (p= 0.041). Concerning QoL, patients with high CRP levels reported lower QoL scores for the SQoL 18 index. the PhW and the SL dimensions (p= 0.016, p= 0.005 and p= 0.003, respectively). •An educational level ≤12 years, a higher BMI and a higher Fagerström score remained significantly associated with high CRP level. An investigation of the various dimensions of the SQoL 18 revealed that PsW, PhW and SL were the most salient features of QoL associated with CRP. A trend was observed for the SE dimension |
•Positive correlation with psychopathology •Positive correlation with quality of life |
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| [40] | Post-hoc analysis on baseline data from a longitudinal study | Association between hsCRP levels and psychopathology amongst schizophrenia subjects | 65 outpatients schizophrenia or 23 schizoaffective disorder (DSM-IV criteria) vs 71 HC | •Serum CRP levels (cut-off value =N/A) •SAPS and SANS •D-KEFS •CIRS |
•hs-CRP levels were significantly higher in individuals with schizophrenia than in comparison subjects. •Higher hs-CRP levels in schizophrenia group were associated with female gender, more severe negative symptoms, greater medical comorbidity, and worse metabolic risk factors including BMI, fasting glucose, and haemoglobin A1c levels. Hs-CRP was not related to age, race, education, smoking status, antipsychotic dosage, or cognitive impairment. |
•Positive correlation with psychopathology •Positive correlation with severity of schizophrenia •No correlation with cognitive pattern |
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| [73] | Observational study | Association between CRP levels in childhood and the risk for the onset of depression and/or psychosis in adulthood | 4585 individuals at age 9 were assessed for CRP levels and then evaluated at age 18 with clinical assessments | •Serum CRP levels (cut-off value =N/A) •CIS-R (Clinical Interview Schedule-Revised) •MFQ (Mood and Feelings Questionnaire) Participants were assessed at age 9 and the at age 18 years |
•Risks of psychotic episodes and psychotic disorder at age 18 years were increased with higher IL-6 levels but not with CRP levels, at baseline (adjusted OR, 1.81; 95% CI, 1.01-3.28; and adjusted OR, 2.40; 95% CI, 0.88-6.22, respectively). •Higher IL-6 levels (not CRP levels) in childhood were associated with subsequent risks of depression and Pes (Psychotic episodes) in a dose-dependent manner. |
•No correlation with psychopathology | |||||||||||||||||||||||||||||
| Study | Study Design | Primary and Secondary Outcomes | Characteristics of Participants | Assessments | Main Findings | Correlation CRP and Schizophrenia? | |||||||||||||||||||||||||||||
| [74] | Cross-sectional study | Association between vitamin D, CRP levels and risk of schizophrenia | 93 outpatients schizophrenia or schizoaffective disorder (DSM-IV criteria) vs 93 family-matched HC 18-65 yy |
•Serum CRP levels (cut-off value =N/A) •25(OH)D concentrations |
•Mean levels of CRP and 25(OH)D were 43.3% higher and 26.7% lower for patients compared to controls, respectively. •25(OH)D were inversely associated with CRP in the patients, but not in the controls. •The proportions of patients significantly increased with increasing quartiles of CRP, while significantly decreased with increasing quartiles of 25(OH)D. •Among individuals with high CRP, participants with high 25(OH)D have significantly lower proportion (adjusted OR = 0.217, 95% CI 0.063, 0.751) of schizophrenia compared to those with low 25(OH)D. •High levels of vitamin D may be linked to reduced risk of schizophrenia with elevated CRP |
•Inverse correlation between CRP and vitamin D levels | |||||||||||||||||||||||||||||
| [75] | Cross-sectional study | Association between aggressive behavior and inflammatory markers in schizophrenia | 213 schizophrenia (DSM-IV-TR) inpatients 19-89 yy |
•Serum CRP levels (cut-off value =N/A) •PANSS total score and subscales |
•CRP levels significantly correlated with other laboratory markers indicating increased inflammation including leukocyte count and neutrophil to lymphocyte ratio (r = 0.387, P< 0.0001 and r = 0.356, P < 0.0001) respectively. •Inpatients with elevated CRP levels displayed increased aggressive behaviour compared to patients with normal CRP levels (<1 mg/dL). This was manifested by higher rates of restraint during hospitalization (x 2= 5.22, P=0.031) and increased PANSS-EC score (U=5410.5, P=0.012). •Elevated CRP levels were not associated with suicidal behaviour. •Multivariate analysis revealed that higher PANSS-EC score was associated with elevated CRP after controlling for the covariates age, sex, BMI and smoking. |
•Positive correlation with psychopathology •Positive correlation with aggressive behavior •Negative correlation with suicidal behavior |
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| [76] | Case-control study | Association between hsCRP levels and lipid profile amongst schizophrenia subjects | 40 male outpatients schizophrenia (DSM-IV criteria) Indian population 18-45 yy |
•Serum CRP levels (cut-off value =N/A) •PANSS total score •Lipid profile |
•Copper, ceruloplasmin, total cholesterol, LDL-Cholesterol and hs-CRP were significantly increased and HDL Cholesterol was significantly reduced in schizophrenia cases when compared with controls •In a subtest, when drug naïve cases (n = 22) were compared with controls, we found that cases showed significantly increased serum copper (21.80±6.27 vs 18.19±5.78, p = 0.026), ceruloplasmin (518.6±137.18 vs 214.9±58.8, p=0.001) and significantly reduced HDL-Cholesterol(0.87±0.14 vs ±1.01 ±0.22, p = 0.009) reflecting the main results. •Total cholesterol significantly correlated with both negative symptom score and general psycho pathology score, while triacylglycerol correlated only with general psycho pathology score in schizophrenia cases. Serum copper and hs-CRP levels did not show any significant correlation with the PANSS scores. In cases, serum copper correlated significantly with hs-CRP (r = 0.338, p = 0.003). |
•No correlation with psychopathology | |||||||||||||||||||||||||||||
| Study | Study Design | Primary and Secondary Outcomes | Characteristics of Participants | Assessments | Main Findings | Correlation CRP and Schizophrenia? | |||||||||||||||||||||||||||||
| [77] | Genetic cross-sectional study | Association between activated immune/inflammation response-related genes and schizophrenia via CRP levels | 19 schizophrenia (DSM-IV criteria) vs 19 HC | •Serum CRP levels (cut-off value =N/A) •RNA extraction from post-mortem at the level of the posterior lateral ventricle from subjects with schizophrenia and HC |
•CRP levels can be increased by infection and/or inflammation •Peripheral stimulus (e.g., viral and/or bacterial) may activate the co-expression module related to immune/inflammation responses in schizophrenics |
•Positive correlation with schizophrenia | |||||||||||||||||||||||||||||
| [78] | Case-control study and meta-analysis of case-control studies | Association between CRP levels and risk of schizophrenia onset | 418 inpatients schizophrenia (DSM-IV criteria) vs 1365 HC Japanese population |
•Serum CRP levels (cut-off value =N/A) •SNP selection and genotyping |
•The presence of higher serum CRP levels in patients with schizophrenia compared to controls in the Japanese population by conducting an ANCOVA with separate genotypes of the 2 SNPs (rs2794520 and rs1183910) identified in the meta-analyses of genome-wide association studies of CRP although the difference between 2 groups in the stratum of rs2794520 CC genotype did not reach statistical significance after the Bonferroni adjustment. | •Positive correlation with psychopathology | |||||||||||||||||||||||||||||
| [79] | Case-control study | Association between oxidative stress and immune dysregulation, CRP levels and schizophrenia and depression | 22 drug-naïve first episode patients with schizophrenia vs 18 drug-naïve first episode patients with major depression vs 43 HC |
• Serum CRP levels (cut-off value =N/A) •EEG •PANSS total score •HAM-D (21-items) •creatinine, glucose, lipids, liver enzymes and a urine drug screen |
•At baseline, 8-iso-PGF2α levels were higher in patients with schizophrenia (p = 0.004) and major depression (p = 0.037), with a trend toward higher SOD concentrations in schizophrenia (p = 0.053). •After treatment, schizophrenia patients showed a further increase in 8-iso-PGF2α (p = 0.016). These results were not related to age, sex, disease severity, medication or adipose tissue mass. •8-iso-PGF2α was associated with smoking, endocrine stress axis activation, CRP levels and low plasma concentrations of brain-derived neurotrophic factor. •Serum hsCRP levels tended to be higher in depressed patients at baseline compared to controls (p = 0.062) and increased in both patient groups following treatment to reach significance only in schizophrenia patients (p= 0.012). |
•Positive correlation with psychopathology | |||||||||||||||||||||||||||||
| [80] | Neuroimaging case-control study | Association with neuroimaging, inflammatory markers and schizophrenia | 28 early-course schizophrenia (DSM-IV criteria) vs 21 HC | •Serum CRP levels (cut-off value =N/A) •MRI data BPRS, SAPS, SANS, Go-No-Go test, WCST, WLMT, 3T Siemens Tim Trio system, peripheral blood sample |
•CRP levels did not correlate with psychopathology or neurocognitive measures •CRP levels did not correlate with positive symptomatology and WCST performance scale |
•No correlation with psychopathology •No correlation with cognitive pattern •No correlation with severity of illness |
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| Study | Study Design | Primary and Secondary Outcomes | Characteristics of Participants | Assessments | Main Findings | Correlation CRP and Schizophrenia? | |||||||||||||||||||||||||||||
| [81] | Case-control study | Association between CRP levels and clinical manifestation, psychopathology and demographic characteristics in clinically acutely agitated schizophrenia subjects | 32 newly admitted schizophrenia subjects (DSM-IV criteria) vs 42 HC 20-65 yy Chinese population |
•Serum CRP levels (cut-off value =N/A) •PANSS total score |
•Serum hsCRP levels are significantly higher in acutely agitated patients with schizophrenia than in comparison subjects (P<0.001, Z=-5.828). •After medical treatment for 2 weeks, serum hsCRP levels were statistically decreased (P<0.001, Z=-3.935). •The reduction of serum hsCRP levels after treatment is consistent with the decrease of PANSS-EC scores of the patients. |
•Positive association with psychopathology •Positive correlation with antipsychotic medication |
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| [82] | Cross-sectional study | Association between physical functional capacity and inflammatory markers in schizophrenia | 40 schizophrenia (DSM-IV criteria) outpatients Brazilian population stable on antipsychotic medications 16-60 yy |
•Serum CRP levels (cut-off value =5 mg/L) •Borg scale •6MWT |
•CRP levels were higher in clinical sample compared to general population •Impaired 6MWD and dyspnea on the Borg scale were correlated to CRP (r= −0.369, p = 0.019 and r = −0.376, p = 0.017 and r = 0.354, p = 0.025 and r = 0.535, p < 0.001, respectively). |
•Positive correlation with psychopathology | |||||||||||||||||||||||||||||
| [83] | Case-control study | Association between exposure to infectious agents, inflammatory markers and schizophrenia vs bipolar disorder vs HC | 28 schizophrenia or schizoaffective disorder (DSM-IV criteria) vs 32 Bipolar disorder (type I or II) outpatients (DSM-IV criteria) vs 60 HC | •Serum CRP levels (cut-off value =N/A) •Serum pentraxin-3 and sCD14 levels •Measurement of the antibody levels of infectious agents (T. Gondii, CMV, HSV-1 and HSV-2) •BACS •PANSS total score |
•No significant differences in the six antibody levels between schizophrenics vs HC •Schizophrenia patients showed a significant increase only in sCD14 (p=0.038) compared with controls. •No significant relationship between the PANSS/BACS scores and the antibody levels or inflammation markers, amongst schizophrenics |
•No correlation with psychopathology •No correlation with cognitive pattern |
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| [84] | Case-control study | Association between inflammatory markers and BDNF genetic variants and schizophrenic phenotype | 44 unrelated outpatients schizophrenia (DSM-IV criteria) vs 50 HC Egyptian population |
•Serum CRP levels (cut-off value =N/A) •PANSS total score |
•Significantly higher CRP levels amongst schizophrenics vs HC | •Positive correlation with psychopathology | |||||||||||||||||||||||||||||
| [85] | Case-control study | Association between classic risk markers of cardiovascular disease and inflammation amongst schizophrenics | 105 schizophrenia inpatients (DSM-IV criteria) vs 148 HC Estonian population Stable antipsychotic medication |
•Serum CRP levels (cut-off value =N/A) •Serum levels of the following elements: TG, LDL-c, HDL-c, HbA1c, CRP, TNF-a, IFN-g, IL-1a, IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, MCP-1, VEGF and EGF •PANSS total score |
•IL-4 was significantly (P < 0.002) lower among patients. Conversely, the levels of other markers (IL-2, IL-6, IL-8, IFN-g and MCP-1, IL-10, VEGF, EGF) levels were significantly (P < 0.000001 and P < 0.05, respectively) elevated in patients compared to controls. •Higher but not significant CRP levels amongst schizophrenics compared to HC |
•No correlation with psychopathology | |||||||||||||||||||||||||||||
| Study | Study Design | Primary and Secondary Outcomes | Characteristics of Participants | Assessments | Main Findings | Correlation CRP and Schizophrenia? | |||||||||||||||||||||||||||||
| [86] | Population-based cross-cohort study | Association between CRP levels and white blood cells across individuals with schizophrenia, bipolar disorder and depression | 2472 schizophrenia (DSM-IV criteria) outpatients Danish population |
•Serum CRP levels (cut-off value=N/A) •White blood cells count |
•At first diagnosis with severe mental disorder, the median CRP level was 3 mg/L across the mental disorders •Overall CRP levels were higher among inpatients (p=.006), females (p<.001), individuals who had redeemed prescription(s) for antipsychotic drugs (p<.001) and those with somatic comorbidity (p<.001) •CRP levels were higher in the first period of the study and lowest in most recent years (p=.04) •Individuals with elevated CRP levels at baseline had increased rates of all-cause mortality •CRP levels were not associated with subsequent admission at a psychiatric hospital |
•Positive correlation with psychopathology •Positive correlation with mortality |
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| [87] | Prospective birth cohort study | Association between CRP levels assessed at age 15/16 and subsequent hospitalization for schizophrenia and related psychosis until age 27 | 6362 schizophrenia or schizoaffective disorder (DSM-IV criteria) Finnish population 15-16 yy |
•Serum CRP levels (cut-off value =3 mg/L) | •Higher CRP levels at age 15/16 years were associated with female sex, increased BMI, lower maternal education, and increased smoking and alcohol use. •Serum CRP levels at age 15/16 years were associated with risk of schizophrenia by age 27 years. •Serum CRP levels were negatively correlated with age of onset (rs=-0.40; P=0.07), suggesting that higher CRP levels at age 15/16 years were associated with earlier illness onset. •There was no evidence of a sex difference in the association between CRP and schizophrenia. |
•Positive correlation with psychopathology •Positive correlation with a earlier onset of schizophrenia |
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| [88] | Cross-sectional study | Association between brain damage, associated biomarkers, including inflammatory markers (e.g., PCR levels) and schizophrenia and mood disorder | 96 inpatients with schizophrenia (n=70) or mood disorder (n=26) (DSM-IV criteria) Japanese population |
•Serum CRP levels (cut-off value =N/A) |
•In both group of patients, the concentration of CRP (0.07 mg/dl for SZ and 0.14 mg/dl for mood disorders) was higher than that in control subjects (0.03 mg/dl). | •Positive correlation with psychopathology | |||||||||||||||||||||||||||||
| [89] | Case-control study | Association between CRP levels and clinical manifestation, psychopathology of schizophrenia. | 41 schizophrenia inpatients (DSM-IV criteria) vs 40 HC 18-65 yy Drug-free before enrollment |
•Serum CRP levels (cut-off value =N/A) •PANSS total score •MOAS |
•A significantly negative correlations between hsCRP levels and the thought disorder score of PANSS (r = -0.355, p = 0.023), and also between the plasma IL-10 levels and the total and general scores of PANSS (r =-0.325, p =0.038; r =-0.397, p =0.010). •A significantly positive correlation was found between hsCRP/IL-10 and the general score of PANSS (r = 0.393, p = 0.011). •No significant correlation between hsCRP, logIL-10, hsCRP/IL-10 and other variables about the PANSS scores. •Positive correlations were observed between hsCRP and total and verbal aggression score of MOAS (r =0.654, p =0.006; r =0.678, p = 0.015), and also between hsCRP/IL-10 and the total MOAS score (r =0.636, p =0.008). |
•Positive correlation with psychopathology •Positive correlation with aggressiveness |
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| Study | Study Design | Primary and Secondary Outcomes | Characteristics of Participants | Assessments | Main Findings | Correlation CRP and Schizophrenia? | |||||||||||||||||||||||||||||
| [90] | Prospective cohort study | Association between temporal change of cognitive functioning and predictors of cognitive performance with CRP levels in schizophrenia | 132 schizophrenia or schizoaffective disorder (DSM-IV criteria) | •Serum CRP levels (cut-off value =N/A) •RBANS •Selected genetic polymorphisms |
•Immediate Memory and Attention showed modest but statistically significant improvements (gains of 0.89 ± 0.33 and 0.76 ± 0.29 points per year, respectively) •Visuospatial/Constructional performance showed a modest but statistically significant decline (of 0.80±0.25 points per year). •A greater psychiatric symptom severity was associated with worse cognitive performance for most cognitive measures. |
•No correlation with cognitive pattern | |||||||||||||||||||||||||||||
| [91] | Case-control study | Association between a set of proinflammatory markers and general cognitive functioning amongst psychotic subjects | 121 Schizophrenia spectrum disorder vs 111 bipolar spectrum disorder (DSM-IV criteria) vs 241 HC | •Serum CRP levels (cut-off value =N/A) •WAIS •PANSS total score •GAF •YMRS •CDSS •Other serum factors: soluble tumor necrosis factor receptor 1 (sTNF-R1) interleukin 1 receptor antagonist (IL-1Ra), osteoprotegerin, von Willebrand factor, C-reactive protein, interleukin-6 and CD40 ligand |
•Significant negative associations with general cognitive function were found for sTNF-R1 (p=2 × 10−5), IL-1Ra (p=0.002) and sCD40 ligand (p=0.003). •A significant negative association between inflammatory markers and general cognitive abilities after adjusting for possible confounders. |
•No association with psychopathology •No association with cognitive pattern |
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| [92] | Cross-sectional study | Association between CRP levels and sensory gating deficit in schizophrenia | 55 schizophrenia (DSM-IV criteria) stable on antipsychotic medication |
•Serum CRP levels (cut-off value =5 mg/L) •sensory gating assessment with a conditioning-testing P50 procedure •PANSS total score |
•Elevated CRP levels were associated with higher rate of sensory gating deficit (60% vs. 12.5%, p b 0.001) |
•Positive correlation with cognitive pattern •No association with psychopathology •No association with severity of illness |
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| Study | Study Design | Primary and Secondary Outcomes | Characteristics of Participants | Assessments | Main Findings | Correlation CRP and Schizophrenia? | |||||||||||||||||||||||||||||
| [93] | Prospective cohort study | Association between CRP levels and cognitive impairment | 369 schizophrenia or schizoaffective disorder (DSM-IV criteria) outpatients stable on antipsychotic medications |
•Serum CRP levels (cut-off value =3 mg/L) •PANSS total score •YMRS •National Adult Reading Test, Wechsler Adult Intelligence Scale, 3rd Ed., FSIQ, VIQ, PIQ, Letter Number Sequencing, Trail Making Test, California Verbal Learning Test, Doors Test, CPT-IP |
•Abnormal CRP levels, found in 104 patients (28.2%), were associated with impaired General Intellectual Ability and Abstract Reasoning (aOR = 0.56, 95% CI 0.35–0.90, P = .014), independently of age, sex, education level, psychotic symptomatology, treatments, and addiction comorbidities. •Abnormal CRP levels were associated with the decline of all components of working memory (respectively effect size [ES]= 0.25, P= .033; ES= 0.27, P= .04; ES= 0.33, P= .006; and ES= 0.38, P = .004) and a wide range of other impaired cognitive functions, including memory (ES= 0.26, P= .026), learning abilities (ES= 0.28, P= .035), semantic memory (ES= 0.26, P= .026), mental flexibility (ES= 0.26, P= .044), visual attention (ES= 0.23, P = .004) and speed of processing (ES= 0.23, P = .043). |
•Positive correlation with cognitive pattern | |||||||||||||||||||||||||||||
| [94] | RCT | Association between CRP levels and cognitive performance in schizophrenia | 124 schizophrenia (DSM-IV criteria) inpatients and 62 patients were retested at discharge or after 6 weeks at the latest 18-65 yy |
•Serum CRP levels (cut-off value =3 mg/L) •PANSS total score •CDSS •CGI-S •GAF-F •RBANS |
•There was an inverse relationship between overall cognitive performance and CRP level at admittance •The association increased in sub-analyses including only patients with schizophrenia. In cognitive subdomain analyses statistically significant inverse associations were found between the CRP level and Delayed memory and Attention, respectively. •No associations were found between CRP level and other measures of psychopathology including psychosis symptoms, depression, or functioning. •At follow-up the association between CRP level and cognition was no longer present. •There was a significant increase in cognitive performance between baseline and follow-up. •There was a stronger increase in overall cognition scores in patients with higher baseline CRP levels. |
•Positive correlation with cognitive pattern | |||||||||||||||||||||||||||||
HC: healthy controls; IL-10: Interleukin-10; PANSS: Positive and Negative Syndrome Scale; PANSS-EC: PANSS excitement component; CRP: C-reactive protein; hsCRP: high sensitive C-reactive protein; EEG: electroencephalography; HAMD-21: Hamilton Depression Scale (21 items); sCD14: soluble CD14; BACS: Brief Assessment of Cognition in Schizophrenia; MDD: major depression disorder; standard deviation; 6MWT: 6-min walk test; SNP: single-nucleotide polymorphisms; FSIQ: Full Scale IQ; VIQ: Verbal IQ; PIQ: Performance IQ; CPT-IP: The Continuous Performance Test—Identical Pairs; CGI-S: Clinical Global Impression—Severity of Illness scale; GAF-F: Global Assessment of Functioning—Split Version, Functions scale; SAPS: Scale for Assessment of Positive Symptoms; SANS: Scales for Assessment Of Negative Symptoms; D-KEFS: Delis-Kaplan Executive Function System; CIRS: Total Score from the Cumulative Illness Rating Scale; ASCA: Saccharomyces cerevisiae; SCID: Structured Clinical Interview for DSM-IV; BMI: body mass index; FTND 24: Fagerström Test for Nicotine Dependence; AUDIT: Alcohol Use Disorders Identification Test; SQoL: Quality of Life Screening; GAF: General Assessment of Functioning,; YMRS: Young Mania Rating Scale; CDSS Calgary Depression Scale for Schizophrenia; CPT-IP: Continuous Performance Test; WCST: Wisconsin Card Sorting Test; RBANS: Repeatable Battery for the Assessment of Neuropsychological Status classified as deficit or non-deficit; PDS: Proxy for the Deficit Syndrome derived from PANSS scores.