Skip to main content
PMC home page
Scientific Reports logoLink to Scientific Reports
. 2015 Jun 4;5:10793. doi: 10.1038/srep10793

Quality of life is associated with chronic inflammation in schizophrenia: a cross-sectional study

Faugere M 1,2, Micoulaud-Franchi JA 3,4, Alessandrini M 2, Richieri R 1,2, Faget-Agius C 1,2, Auquier P 2, Lançon C 1,2, Boyer L 2,a
PMCID: PMC4455112  PMID: 26041435

Abstract

Inflammation may play a crucial role in the pathogenesis of schizophrenia. However, the association between chronic inflammation and health outcomes in schizophrenia remains unclear, particularly for patient-reported outcomes. The aim of this study was to investigate the relationship between quality of life (QoL) and chronic inflammation assessed using C -Reactive Protein (CRP) in patients with schizophrenia. Two hundred and fifty six patients with schizophrenia were enrolled in this study. After adjusting for key socio-demographic and clinical confounding factors, patients with high levels of CRP (>3.0 mg/l) had a lower QoL than patients with normal CRP levels (OR = 0.97, 95% CI = 0.94–0.99). An investigation of the dimensions of QoL revealed that psychological well-being, physical well-being and sentimental life were the most salient features of QoL associated with CRP. Significant associations were found between lower educational level (OR = 4.15, 95% CI = 1.55–11.07), higher body mass index (OR = 1.16, 95% CI = 1.06–1.28), higher Fagerström score (OR = 1.22, 95% CI = 1.01–1.47) and high levels of CRP. After replications with longitudinal approaches, the association between QoL and chronic inflammation may offer interesting interventional prospects to act both on inflammation and QoL in patients with schizophrenia.

Schizophrenia occurs in approximately 1% of the population worldwide1. This disorder is a chronic disease characterised by psychotic symptoms2, cognitive impairment and functional decline3. All of these characteristics substantially impact the quality of life (QoL) of patients with schizophrenia4,5. Although there is strong evidence that multicomponent treatment involving medication, cognitive behavioural therapy, education, and exercise have beneficial effects on symptoms and functioning, most patients still have impaired QoL including affective, emotional, and social dimensions6,7. New approaches are therefore needed to act efficiently on QoL8.

Recent studies have explored questions about how non-biological factors, including affective, emotional, and social information, may be associated with chronic inflammation. In non-psychiatric populations, elevated C - Reactive Protein (CRP) has been reported to be associated with lower QoL level amongst the general population9, older individuals10 and in several chronic diseases (e.g., diabetes)11. The association between CRP and QoL may therefore offer interesting interventional prospects to act both on inflammation and QoL. These findings are of utmost importance in psychiatry, given that inflammatory responses and immune reactions may play a crucial role in the pathogenesis of schizophrenia12,13. Various studies have reported abnormalities of the immune reactions with the implication of blood lymphocyte abnormalities12, cytokine alterations13, oxidative stress anomalies14 and CRP elevations15 in schizophrenia. From a clinical perspective, elevated CRP levels are associated in schizophrenia with some pejorative psychiatric features16, high psychotic symptoms17,18 and high cognitive impairment19 . Moreover, elevated CRP levels are also associated with metabolic syndrome20 and high cardiovascular disease risk21. All of the clinical features that are associated with an elevated CRP level in schizophrenia are known to be associated with impaired QoL. Currently, however, no study has specifically investigated the relationship between impaired QoL and elevated CRP levels in patients with schizophrenia.

The aim of this study was to investigate the relationship between QoL and chronic inflammation assessed using CRP in patients with schizophrenia, in addition to considering key socio-demographic and clinical confounding factors.

Methods

Study participants

The study evaluated all prospective patients attending daytime hospital hours in our university and psychiatric hospital during a period of 4 years, from June 2010 to September 2014. The inclusion criteria were as follows: (1) age range 18–85 years old, (2) diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV-TR) criteria22, (3) antipsychotic medication stable for a minimum of 3 months, and (4) French as a native language. The exclusion criteria were as follows: (1) diagnoses other than schizophrenia on Axis I of the DSM-IV-TR, except for nicotine dependence, (2) major non-psychiatric disease, (3) mental retardation and (4) any identifiable acute, intermittent or chronic infections or being on routine anti-inflammatory or immunosuppressive therapy: a clinical examination was performed, based on interrogatory about infectious signs and history, physical examination (including the following examination: temperature, weight, mouth, lymph nodes, abdomen, skin and cardiopulmonary auscultation) and serology (HIV, HBV and HCV). The data collection was approved by the Commission Nationale de l’Informatique et des Libertés (CNIL number 1223715). This study was constructed in accordance with the Declaration of Helsinki and French good clinical practices23. All of the patients were informed of the study and gave written, informed consent after a standardised and structured clinical interview.

Data collection

The following data were collected:

  1. Socio-demographic information: gender, age, educational level, professional activity.

  2. Clinical characteristics: duration of disorder; body mass index (BMI); smoking status assessed by the Fagerström Test for Nicotine Dependence (FTND)24; alcohol consumption assessed by the Alcohol Use Disorders Identification Test (AUDIT)25; psychotic symptoms based on the Positive and Negative Syndrome Scale (PANSS), which consists of three subscales (positive, negative, and general psychopathology)26,27.

  3. Drug information: antipsychotic medications (presence of atypical antipsychotic), presence of clozapine, presence of olanzapine, and chlorpromazine equivalent dose (in milligrams per day). Among atypical antipsychotics, clozapine and olanzapine are of specific interest for our study because of their potential link to metabolic syndrome and chronic inflammation28,29,30.

  4. QoL measurement: QoL was assessed using the SQoL 18 questionnaire, which is a self-administered, multidimensional instrument developed and validated for the specific assessment of QoL in patients with schizophrenia31,32,33,34. The SQoL 18 consists of 18 items describing the following eight dimensions: Psychological Well-being (PsW), Self-Esteem (SE), Family Relationships (RFa), Relationships with Friends (RFr), Resilience (RE), Physical Well-being (PhW), Autonomy (AU), and Sentimental Life (SL) as well as a global score (the index)33. Dimensions and index scores range from 0, indicating the lowest QoL, to 100, the highest QoL.

  5. Chronic inflammatory marker: serum levels of CRP were determined using sensitive regular immunoassays (ELISA). The results are expressed as milligram per litre. The detection limit was 0.08 μg/ml. Patients were classified into 2 groups: normal CRP level (≤3.0 mg/l) and High CRP (>3.0 mg/l)21,35,36.

Statistical analysis

The characteristics of the entire group of patients with schizophrenia are expressed in proportions or as means and standard deviations. The socio-demographic and clinical characteristics, drug information, and QoL were compared between the two groups (normal CRP level vs. High CRP) using Student t test for continuous variables and Chi-square test for categorical variables.

A multivariate logistic regression was then performed to estimate the adjusted Odds Ratio (OR) and its corresponding 95% confidence interval (CI) for an association between the SQoL 18 index (independent variable) and CRP (dependent variable), with adjustment for confounding factors selected from the univariate based on a threshold p-value ≤0.20 (age, educational level, duration of disorder, BMI, Fagerström test and SQoL 18 index were selected). A set of additional variables was included in the models because of their clinical and socio-demographic interest (gender, presence of atypical antipsychotics, AUDIT, PANSS total score)17,18,29,37,38. This analysis was repeated replacing the SQoL 18 index with each dimension of the SQoL 18 to determine the most salient features of QoL associated with CRP.

All of the tests were two-sided. Statistical significance was defined as p < 0.05. Statistical analysis was performed using the SPSS version 18.0 software package (SPSS Inc., Chicago, IL, USA).

Results

Patient characteristics

Two hundred fifty six outpatients with schizophrenia participated in our study (Table 1). The mean age of the patients was 35.96 years (±12.01), and 71.9% of the patients were male. The patients showed moderate severity of symptoms, with a total PANSS score corresponding to 71.09 (±24.40) and sub-scores of 15.20 (±6.88), 20.00 (±7.95) and 35.89 (±12.09), respectively, for positive, negative, and general psychopathology factors. Of the total number of patients, the mean chlorpromazine equivalent dose was 856.69 (±791.44) milligrams per day; 88.3% were treated by atypical antipsychotics, 24.2% were treated by clozapine, and 15.7% were treated by olanzapine.

Table 1. Socio-demographic and clinical characteristics of the study sample (n = 256).

  Entire Group (N = 256)
 Normal CRP level ≤3.0 mg (N = 156)
 High CRP >3.0 mg (N = 100)
 Normal CRP level vs. High CRP p-value
  Mean or % SD Mean or % SD Mean or % SD p
Gender (Male) 184 (71.9%) — 116 (74.4%) — 68 (68.0%) — 0.270a
Age (years) 35.96 12.01 34.62 11.60 38.03 12.38 0.027
Education level (>12 years) 144 (56.3%) — 97 (62.2%) — 47 (47.5%) — 0.021a
Professional activity (yes) 39 (15.2%) — 24 (16.1%) — 15 (15.3%) — 0.866a
Duration of disorder (years) 13.04 9.72 11.86 9.31 14.82 10.11 0.018
Body mass index 26.63 5.35 25.33 4.93 28.68 5.35 0.000
Presence of atypical antipsychotic 226 (88.3%) — 136 (87.2%) — 90 (90.0%) — 0.494a
Presence of Clozapine 62 (24.2%) — 36 (23.1%) — 26 (26.0%) — 0.594a
Presence of Olanzapine 40 (15.6%) — 27 (17.3%) — 13 (13.0%) — 0.354a
Chlorpromazine equivalent dose (mg/day) 856.69 791.44 844.31 899.46 875.76 591.47 0.758
Fagerström test 5.36 2.724 4.98 2.80 5.88 2.55 0.041
AUDITb 6.33 7.76 6.60 8.09 5.99 7.34 0.627
PANSSc Total 71.09 24.40 70.33 25.16 72.27 23.24 0.535
PANSS Positive factor 15.20 6.88 14.82 7.07 15.79 6.56 0.272
PANSS Negative factor 20.00 7.95 19.95 8.14 20.08 7.69 0.898
PANSS General psychopathology factor 35.89 12.09 35.56 12.46 36.40 11.54 0.588
SQoL 18d index 54.87 19.14 57.22 19.35 51.27 18.32 0.016
Psychological Well-being 57.60 28.72 60.20 30.03 53.62 26.25 0.076
Self-Esteem 55.88 30.48 58.72 29.97 51.52 30.89 0.067
Family Relationships 62.55 27.58 64.14 26.40 60.10 29.27 0.257
Relationships with Friends 42.83 31.10 43.09 30.54 42.42 32.08 0.868
Resilience 58.93 27.09 61.40 27.99 55.13 25.33 0.073
Physical Well-being 56.82 26.37 60.77 23.20 50.76 29.71 0.005
Autonomy 62.05 28.20 62.66 28.26 61.11 28.23 0.671
Sentimental Life 42.33 29.74 46.79 30.40 35.48 27.47 0.003
Open in a new tab

aχ2 test for qualitative variables

bAlcohol Use Disorders Identification Test

cPositive And Negative Syndrome Scale

dSchizophrenia Quality of Life questionnaire 18: Scores range from 0 to 100; higher scores represent higher QoL.

Comparison of patients with normal CRP level and High CRP

Among the 256 patients with schizophrenia, 100 (39.06%) had a high CRP level. 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). A trend was observed for the SE, PsW and RE dimensions (p = 0.067, p = 0.076 and p = 0.073, respectively).

Factors associated with High CRP

In the multivariate analyses reported in Tables 2 and 3, the relationship between the SQoL 18 index score and CRP level remained significant after adjusting for socio-demographic, clinical and drug characteristics. 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.

Table 2. Factors associated with high CRP: multivariate analysis.

Factors Adjusted odds ratio 95%CIa p-value
Gender (/Male) 0.50 0.17-1.49 0.216
Age (years) 1.03 0.97-1.09 0.291
Education level (/>12 years) 4.15 1.55-11.07 0.005
Presence of atypical antipsychotic (/Absence) 0.50 0.13-1.97 0.322
Duration of disorder (years) 1.01 0.94-1.09 0.794
Body mass index 1.16 1.06-1.28 0.002
Fagerström Test 1.22 1.01-1.47 0.043
AUDITb 1.01 0.95-1.07 0.721
PANSSc total 0.99 0.97-1.01 0.392
SQoL 18d index 0.97 0.94-0.99 0.021
Open in a new tab

aConfidence Interval

bAlcohol Use Disorders Identification Test

cPositive And Negative Syndrome Scale

dSchizophrenia Quality of Life questionnaire 18

Table 3. SQoL 18 dimensions scores associated with high CRP: multivariate analyses.

SQoL 18a dimensions Adjusted odds ratio 95%CIb p-value
Psychological Well-being 0.98 0.96-0.99 0.020
Self-Esteem 0.99 0.97-1.00 0.082
Family Relationships 1.00 0.98-1.02 0.995
Relationships with Friends 0.99 0.98-1.01 0.329
Resilience 0.99 0.97-1.00 0.110
Physical Well-being 0.97 0.95-0.99 0.005
Autonomy 0.99 0.98-1.01 0.534
Sentimental Life 0.98 0.97-0.99 0.015
Open in a new tab

aSchizophrenia Quality of Life questionnaire 18: scores range from 0 to 100; higher scores represent higher QoL.

bConfidence Interval.

Discussion

This study investigated the relationship between QoL and chronic inflammation in patients with schizophrenia. Our findings provide evidence for a moderate association between high CRP levels and low QoL levels, including psychological well-being, physical well-being and sentimental life dimensions of QoL. Additionally, low educational level, high BMI and high Fagerström score also showed a significant relationship with high CRP level, whereas the severity of psychotic symptoms was not associated with CRP.

The main finding of our study is the existence of the relationship between QoL and chronic inflammation in patients with schizophrenia, after adjusting for key socio-demographic and clinical confounding factors. These findings support previous studies that reported the association between low QoL levels and high CRP levels amongst non-psychiatric populations9,10,11. However, the cross-sectional design of our study precludes any conclusions about the directionality of the association between QoL and inflammation in schizophrenia.

We hypothesise that QoL through its psychological, physical and social features predicts chronic inflammation in schizophrenia. Several studies reported that psychosocial factors, including poor well-being, were predictors of chronic inflammation and poor health39. The influence of psychological well-being on CRP may be supported by studies that reported an association between psychological stress and the dysregulation of the hypothalamic-pituitary-adrenal axis involved in inflammation40. Physical well-being may result from the physical fitness of individuals, which is also involved in inflammatory processes. Physically fit individuals demonstrate lower inflammatory responses to mental stress41. Moreover, regular exercise has been consistently associated with anti-inflammatory effects, whereas sedentary behaviour is now considered an important risk factor for inflammation and many health conditions independent of physical activity levels42. Concerning the relationship between sentimental life and CRP, a growing body of literature has revealed the biophysiological mechanisms underlying the associations between social disconnectedness and chronic inflammation, which play an important role in health and longevity43,44. A recent study has also reported that the elevation of CRP could be limited by the marital status of individuals45,46. Interestingly, these findings may explain the mechanisms underlying the relationship between QoL and relapse in schizophrenia. QoL has been reported to be an independent predictor for relapse in schizophrenia, more than the severity of symptoms47. It may be that relapse is triggered by mechanisms associated with inflammatory processes associated with QoL changes. Taken together, these findings raise the possibility that patients with schizophrenia destined to develop chronic inflammation might be identifiable using QoL measures and might potentially benefit from adapted therapeutic strategies to prevent it. QoL could therefore be considered a reliable predictor of chronic inflammation by healthcare professionals. From this perspective, clinicians should be encouraged to think about chronic inflammation in patients reporting poor QoL.

We also hypothesise that chronic inflammation can cause changes in QoL. In accordance with this hypothesis, a recent study suggested that the progression of chronic inflammatory disease may exert a significant negative impact on QoL in both emotional and social domains10. This hypothesis may be supported by the sickness behavioural model48,49. CRP is a general marker of inflammatory processes and is associated with several interleukins (e.g., IL-6) functionally involved in the development of symptoms of sickness through direct effects on the central nervous system48. Symptoms of sickness (e.g., fatigue, reduced appetite, sleep disorders, altered mood and cognition) are well known to negatively impact QoL amongst non-psychiatric populations48. Our results suggest that symptoms of sickness may also be related to poor QoL in patients with schizophrenia. Future studies should confirm this hypothesis and then explore the beneficial value of various interventions including pharmaceutical and non-pharmaceutical strategies on chronic inflammation, the symptoms of sickness and QoL in patients with schizophrenia.

The association between educational level, BMI, smoking and CRP were expected, confirming the findings of most previous studies. A low socioeconomic standing including low education level has been found to be associated with chronic inflammation39,50,51. Smoking has been associated with many cardiovascular risk factors, including high CRP levels, which remains in former smokers52,53. By producing oxidative stress and stimulating hematopoietic cells, smoking activates pro-inflammatory cytokines (e.g., IL-6), which in turn stimulate the production of CRP52,54. Lastly, an increase in macrophage infiltration in fat tissues has been observed in excess of weight, which promotes the substantial production of inflammatory cytokines55. In contrast, the lack of an association between CRP and symptoms is more surprising. However, previous studies have reported discordant results on this issue17,19. The inconsistencies may be because possible confounding factors (e.g., BMI, smoking, alcohol consumption and antipsychotic medications) were rarely considered in previous studies56.

Limitations and perspectives

Several limitations should be considered in our study

First, an important methodological problem is the definition of our groups (normal CRP level and high CRP). Indeed, there are no generally accepted criteria for relapse. However, we have chosen the most consensual definition in the recent scientific literature, recognized as the cut-off point for high cardiovascular risk21,35,36.

Second, CRP was the sole marker of inflammation in this study. Although CRP is strongly associated with IL-6 activity, we did not directly assess any of the cytokines. Future studies with extensive assessment of inflammatory markers may be required.

Third, we have only collected CRP at one time point, and repeated testing has been recommended to confirm elevated plasma levels35 because concentrations can be affected by acute infection. However, patients with acute infections were removed and did not alter any of the results.

Last, although our work accounts for a large set of potentially confounding variables, additional factors might have been interesting to consider. Particularly, cognitive impairment, a core symptom of schizophrenia, is associated with metabolic syndrome57,58 and chronic inflammation19. However, as most studies revealed nonsignificant relationships between most neurocognitive measures and QoL59,60, our findings should not be modified.

Conclusion

Our study suggests that chronic inflammation is moderatly associated with lower QoL levels in patients with schizophrenia. After replications with longitudinal approaches, the association between QoL and chronic inflammation may offer interesting interventional prospects to act both on inflammation and QoL in patients with schizophrenia. Moreover, it would be important to include systematic measures of inflammation markers into future clinical trials or intervention studies in schizophrenia (including cognitive or social interventions) in order to get a broader insight on the effect of those interventions which may not only concern clinical symptoms and quality of life but also inflammation markers. Such intervention studies may also be relevant to examine the dynamics of the relationship between clinical symptoms, QoL and inflammation markers.

Additional Information

How to cite this article: Faugere, M. et al. Quality of life is associated with chronic inflammation in schizophrenia : a cross-sectional study. Sci. Rep. 5, 10793; doi: 10.1038/srep10793 (2015).

Acknowledgments

Our thanks to all the patients and staff who helped with the study.

Footnotes

Author Contributions M.F., J.A.M., M.A. and L.B. wrote the manuscript. All authors designed the study and wrote the protocol. M.F., J.A.M. and C.L. conducted the literature search. R.R. and C.F.A. recruited the patients. M.A., P.A. and L.B. conducted the statistical analyses. All authors contributed to and approved the final manuscript.

References

  1. McGrath J., Saha S., Chant D. & Welham J. Schizophrenia: A Concise Overview of Incidence, Prevalence, and Mortality. Epidemiol. Rev. 30, 67–76 (2008). [DOI] [PubMed] [Google Scholar]
  2. Bruijnzeel D. & Tandon R. The Concept of Schizophrenia: From the 1850s to the DSM-5. Psychiatr. Ann. 41, 289–295 (2011). [Google Scholar]
  3. Dickinson D., Iannone V. N., Wilk C. M. & Gold J. M. General and specific cognitive deficits in schizophrenia. Biol. Psychiatry 55, 826–833 (2004). [DOI] [PubMed] [Google Scholar]
  4. Awad & Voruganti. Measuring quality of life in patients with schizophrenia: an update. PharmacoEconomics 30, 183–195 (2012). [DOI] [PubMed] [Google Scholar]
  5. Boyer L. et al. Measuring quality of life in patients with schizophrenia: an overview. Expert Rev. Pharmacoecon. Outcomes Res. 13, 343–349 (2013). [DOI] [PubMed] [Google Scholar]
  6. Adelufosi A. O., Ogunwale A., Abayomi O. & Mosanya J. T. Socio-demographic and clinical correlates of subjective quality of life among Nigerian outpatients with schizophrenia. Psychiatry Res. 209, 320–325 (2013). [DOI] [PubMed] [Google Scholar]
  7. Hsiao C.-Y., Hsieh M.-H., Tseng C.-J., Chien S.-H. & Chang C.-C. Quality of life of individuals with schizophrenia living in the community: relationship to socio-demographic, clinical and psychosocial characteristics: Quality of life of individuals with schizophrenia. J. Clin. Nurs. 21, 2367–2376 (2012). [DOI] [PubMed] [Google Scholar]
  8. Boyer L., Baumstarck K., Guedj E. & Auquier P. What’s wrong with quality-of-life measures? A philosophical reflection and insights from neuroimaging. Expert Rev. Pharmacoecon. Outcomes Res. 14, 767–769 (2014). [DOI] [PubMed] [Google Scholar]
  9. Hamer M. & Chida Y. Life satisfaction and inflammatory biomarkers: The 2008 Scottish Health Survey1: Life satisfaction and C-reactive protein. Jpn. Psychol. Res. 53, 133–139 (2011). [Google Scholar]
  10. Nowakowski A. C. Chronic inflammation and quality of life in older adults: a cross-sectional study using biomarkers to predict emotional and relational outcomes. Health Qual. Life Outcomes 12, 141 (2014). [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cummings D. M., King D. E. & Mainous A. G. C-Reactive Protein, Antiinflammatory Drugs, and Quality of Life in Diabetes. Ann. Pharmacother. 37, 1593 (2003). [DOI] [PubMed] [Google Scholar]
  12. Miller B. J., Gassama B., Sebastian D., Buckley P. & Mellor A. Meta-Analysis of Lymphocytes in Schizophrenia: Clinical Status and Antipsychotic Effects. Biol. Psychiatry 73, 993–999 (2013). [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Miller B. J., Buckley P., Seabolt W., Mellor A. & Kirkpatrick B. Meta-Analysis of Cytokine Alterations in Schizophrenia: Clinical Status and Antipsychotic Effects. Biol. Psychiatry 70, 663–671 (2011). [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Flatow J., Buckley P. & Miller B. J. Meta-Analysis of Oxidative Stress in Schizophrenia. Biol. Psychiatry 74, 400–409 (2013). [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Miller B. J., Culpepper N. & Rapaport M. H. C-reactive protein levels in schizophrenia: a review and meta-analysis. Clin. Schizophr. Relat. Psychoses 7, 223–230 (2014). [DOI] [PubMed] [Google Scholar]
  16. Akanji A. O., Ohaeri J. U., Al-Shammri S. & Fatania H. R. Association of blood levels of C-reactive protein with clinical phenotypes in Arab schizophrenic patients. Psychiatry Res. 169, 56–61 (2009). [DOI] [PubMed] [Google Scholar]
  17. Fan X. et al. Elevated serum levels of C-reactive protein are associated with more severe psychopathology in a subgroup of patients with schizophrenia. Psychiatry Res. 149, 267–271 (2007). [DOI] [PubMed] [Google Scholar]
  18. Fawzi M. H., Fawzi M. M., Fawzi M. M. & Said N. S. C-reactive protein serum level in drug-free male Egyptian patients with schizophrenia. Psychiatry Res. 190, 91–97 (2011). [DOI] [PubMed] [Google Scholar]
  19. Dickerson F., Stallings C., Origoni A., Boronow J. & Yolken R. C-reactive protein is associated with the severity of cognitive impairment but not of psychiatric symptoms in individuals with schizophrenia. Schizophr. Res. 93, 261–265 (2007). [DOI] [PubMed] [Google Scholar]
  20. Lasić D. et al. Metabolic syndrome and inflammation markers in patients with schizophrenia and recurrent depressive disorder. Psychiatr. Danub. 26, 214–219 (2014). [PubMed] [Google Scholar]
  21. Sicras-Mainar A., Rejas-Gutiérrez J., Navarro-Artieda R. & Blanca-Tamayo M. C-reactive protein as a marker of cardiovascular disease in patients with a schizophrenia spectrum disorder treated in routine medical practice. Eur. Psychiatry 28, 161–167 (2013). [DOI] [PubMed] [Google Scholar]
  22. American Psychiatric Association. Diagnostic and statistical manual-text revision (DSM-IV-TRim, 2000). (American Psychiatric Association, 2000).
  23. WMA. [The Helsinki Declaration of the World Medical Association (WMA). Ethical principles of medical research involving human subjects]. Pol. Merkur. Lek. Organ Pol. Tow. Lek. 36, 298–301 (2014). [PubMed] [Google Scholar]
  24. Heatherton T. F., Kozlowski L. T., Frecker R. C. & Fagerström K. O. The Fagerström Test for Nicotine Dependence: a revision of the Fagerström Tolerance Questionnaire. Br. J. Addict. 86, 1119–1127 (1991). [DOI] [PubMed] [Google Scholar]
  25. Saunders J. B., Aasland O. G., Babor T. F., de la Fuente J. R. & Grant M. Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption--II. Addict. Abingdon Engl. 88, 791–804 (1993). [DOI] [PubMed] [Google Scholar]
  26. Kay S. R., Opler L. A. & Fiszbein A. Significance of positive and negative syndromes in chronic schizophrenia. Br. J. Psychiatry J. Ment. Sci. 149, 439–448 (1986). [DOI] [PubMed] [Google Scholar]
  27. Lançon C., Reine G., Llorca P. M. & Auquier P. Validity and reliability of the French-language version of the Positive and Negative Syndrome Scale (PANSS). Acta Psychiatr. Scand. 100, 237–243 (1999). [DOI] [PubMed] [Google Scholar]
  28. Lieberman J. A. et al. Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia. N. Engl. J. Med. 353, 1209–1223 (2005). [DOI] [PubMed] [Google Scholar]
  29. Meyer J. M. et al. Inflammatory Markers in Schizophrenia: Comparing Antipsychotic Effects in Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness Study. Biol. Psychiatry 66, 1013–1022 (2009). [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Gupta A., Dadheech G., Yadav D., Sharma P. & Gautam S. Metabolic Issues in Schizophrenic Patients Receiving Antipsychotic Treatment. Indian J. Clin. Biochem. 29, 196–201 (2014). [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Auquier P. et al. Toward Meeting the Needs of Homeless People with Schizophrenia: The Validity of Quality of Life Measurement. PLoS ONE 8, e79677 (2013). [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Baumstarck K. et al. Self-reported quality of life measure is reliable and valid in adult patients suffering from schizophrenia with executive impairment. Schizophr. Res. 147, 58–67 (2013). [DOI] [PubMed] [Google Scholar]
  33. Boyer L. et al. The development of the S-QoL 18: A shortened quality of life questionnaire for patients with schizophrenia. Schizophr. Res. 121, 241–250 (2010). [DOI] [PubMed] [Google Scholar]
  34. Caqueo-Urízar A., Boyer L., Boucekine M. & Auquier P. Spanish cross-cultural adaptation and psychometric properties of the Schizophrenia Quality of Life short-version questionnaire (SQoL18) in 3 middle-income countries: Bolivia, Chile and Peru. Schizophr. Res. 159, 136–143 (2014). [DOI] [PubMed] [Google Scholar]
  35. Pearson T. A. Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: A Statement for Healthcare Professionals From the Centers for Disease Control and Prevention and the American Heart Association. Circulation 107, 499–511 (2003). [DOI] [PubMed] [Google Scholar]
  36. Wysokiński A., Margulska A., Strzelecki D. & Kłoszewska I. Levels of C-reactive protein (CRP) in patients with schizophrenia, unipolar depression and bipolar disorder. Nord. J. Psychiatry 1–8 (2014). 10.3109/08039488.2014.984755 [DOI] [PubMed] [Google Scholar]
  37. Dickerson F. et al. C-reactive protein is elevated in schizophrenia. Schizophr. Res. 143, 198–202 (2013). [DOI] [PubMed] [Google Scholar]
  38. Van Os J. & Kapur S. Schizophrenia. The Lancet 374, 635–645 (2009). [DOI] [PubMed] [Google Scholar]
  39. Morozink J. A., Friedman E. M., Coe C. L. & Ryff C. D. Socioeconomic and psychosocial predictors of interleukin-6 in the MIDUS national sample. Health Psychol. Off. J. Div. Health Psychol. Am. Psychol. Assoc. 29, 626–635 (2010). [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Brotman D. J., Golden S. H. & Wittstein I. S. The cardiovascular toll of stress. Lancet 370, 1089–1100 (2007). [DOI] [PubMed] [Google Scholar]
  41. Hamer M. & Steptoe A. Association between physical fitness, parasympathetic control, and proinflammatory responses to mental stress. Psychosom. Med. 69, 660–666 (2007). [DOI] [PubMed] [Google Scholar]
  42. Berk M. et al. So depression is an inflammatory disease, but where does the inflammation come from? BMC Med. 11, 200 (2013). [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Pantell M. et al. Social isolation: a predictor of mortality comparable to traditional clinical risk factors. Am. J. Public Health 103, 2056–2062 (2013). [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Yang Y. C., McClintock M. K., Kozloski M. & Li T. Social Isolation and Adult Mortality: The Role of Chronic Inflammation and Sex Differences. J. Health Soc. Behav. 54, 182–202 (2013). [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Donoho C. J., Crimmins E. M. & Seeman T. E. Marital Quality, Gender, and Markers of Inflammation in the MIDUS Cohort. J. Marriage Fam. 75, 127–141 (2013). [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Sbarra D. A. Marriage Protects Men from Clinically Meaningful Elevations in C-Reactive Protein: Results from the National Social Life, Health, and Aging Project (NSHAP): Psychosom. Med. 71, 828–835 (2009). [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Boyer L. et al. Quality of life is predictive of relapse in schizophrenia. BMC Psychiatry 13, (2013). [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Dantzer R., O’Connor J. C., Freund G. G., Johnson R. W. & Kelley K. W. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat. Rev. Neurosci. 9, 46–56 (2008). [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Dantzer R. & Kelley K. W. Twenty years of research on cytokine-induced sickness behavior. Brain. Behav. Immun. 21, 153–160 (2007). [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Gruenewald T. L., Cohen S., Matthews K. A., Tracy R. & Seeman T. E. Association of socioeconomic status with inflammation markers in black and white men and women in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Soc. Sci. Med. 69, 451–459 (2009). [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Pollitt R. A. et al. Cumulative life course and adult socioeconomic status and markers of inflammation in adulthood. J. Epidemiol. Community Health 62, 484–491 (2008). [DOI] [PubMed] [Google Scholar]
  52. Bazzano L. A., He J., Muntner P., Vupputuri S. & Whelton P. K. Relationship between cigarette smoking and novel risk factors for cardiovascular disease in the United States. Ann. Intern. Med. 138, 891–897 (2003). [DOI] [PubMed] [Google Scholar]
  53. Hermsdorff H. H. M., Zulet M. Á., Puchau B. & Martínez J. A. Central Adiposity Rather Than Total Adiposity Measurements Are Specifically Involved in the Inflammatory Status from Healthy Young Adults. Inflammation 34, 161–170 (2011). [DOI] [PubMed] [Google Scholar]
  54. Yanbaeva D. G., Dentener M. A., Creutzberg E. C., Wesseling G. & Wouters E. F. M. Systemic effects of smoking. Chest 131, 1557–1566 (2007). [DOI] [PubMed] [Google Scholar]
  55. De Heredia F. P., Gómez-Martínez S. & Marcos A. Obesity, inflammation and the immune system. Proc. Nutr. Soc. 71, 332–338 (2012). [DOI] [PubMed] [Google Scholar]
  56. Singh B. & Chaudhuri T. K. Role of C-reactive protein in schizophrenia: An overview. Psychiatry Res. 216, 277–285 (2014). [DOI] [PubMed] [Google Scholar]
  57. Boyer L. et al. Neurophysiological correlates of metabolic syndrome and cognitive impairment in schizophrenia: A structural equation modeling approach. Psychoneuroendocrinology 50, 95–105 (2014). [DOI] [PubMed] [Google Scholar]
  58. Boyer L. et al. Association of metabolic syndrome and inflammation with neurocognition in patients with schizophrenia. Psychiatry Res. 210, 381–386 (2013). [DOI] [PubMed] [Google Scholar]
  59. Boyer L. et al. Insight into illness, neurocognition and quality of life in schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiatry 36, 271–276 (2012). [DOI] [PubMed] [Google Scholar]
  60. Tolman A. W. & Kurtz M. M. Neurocognitive Predictors of Objective and Subjective Quality of Life in Individuals With Schizophrenia: A Meta-Analytic Investigation. Schizophr. Bull. 38, 304–315 (2012). [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Scientific Reports are provided here courtesy of Nature Publishing Group

RESOURCES