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Contents lists available at ScienceDirect

Schizophrenia Research

journal homepage: www.elsevier.com/locate/schres

Sedentary behaviour is associated with elevated C-reactive protein levels

in people with psychosis
Brendon Stubbs a,⁎, Poonam Gardner-Sood b, Shubulade Smith c,d, Khalida Ismail c,e, Kathryn Greenwood f,
Ross Farmer a, Fiona Gaughran g,h
a
Physiotherapy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, London, United Kingdom
b
Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
c
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
d
South London and Maudsley NHS Foundation Trust, London, United Kingdom
e
King's College Hospital NHS Foundation Trust, United Kingdom
f
School of Psychology, University of Sussex, Brighton and Early Intervention in Psychosis Service, Sussex Partnership NHS Foundation Trust, West Sussex, United Kingdom
g
National Psychosis Service, South London and Maudsley NHS Foundation Trust, United Kingdom
h
Institute of Psychiatry, Psychology and Neuroscience and the Biomedical Research Centre, BRC Nucleus, United Kingdom

a r t i c l e i n f o a b s t r a c t

Article history: Psychosis is associated with elevated inflammatory markers including C-reactive protein (CRP), a marker of car-
Received 6 March 2015 diovascular disease (CVD) risk. Using a cross sectional design, 250 participants with established psychosis
Received in revised form 10 June 2015 (48.2 years (SD 10.2), 39.2% female) were classified as having normal (b 5.0 mg/μl, N = 159) or high CRP levels
Accepted 4 July 2015
(N5.0 mg/μl, N = 91). Regression analysis demonstrated that higher sedentary behaviour was associated with
Available online xxxx
elevated CRP levels (β = .155, p = .01) after adjustment for confounding variables. Female gender (β = .229,
Keywords:
p = .001), waist circumference (β = .205, p = .003) and non-white ethnicity (β = .181, p = .005) were also
Psychosis associated with elevated CRP. Sedentary behaviour is modifiable and increasing physical activity may reduce
Inflammation CRP levels.
C-reactive protein © 2015 Elsevier B.V. All rights reserved.
Sedentary behaviour
Schizophrenia
Cardiovascular disease

1. Introduction
People with psychosis are at increased risk of cardiovascular disease
(CVD) (Mitchell et al., 2013) which accounts for a considerable
proportion of the premature mortality in this group (Lawrence et al.,
2013). In general medicine, inflammation is understood to be involved
in the pathogenesis of CVD. Consequently, interest has grown in the
role of inflammatory cytokines in predicting CVD with C-reactive
protein (CRP) receiving particular attention (Vepsäläinen et al., 2011).
Indeed, a meta-analysis confirmed that higher CRP is associated with
CVD in the general population (Kaptoge et al., 2012).
A recent meta-analysis (Miller et al., 2014) found that people with
schizophrenia have elevated CRP levels and called for more research
to investigate risk factors for this. Moreover, Sicras-Mainar (Sicras-
Mainar et al., 2013) found that high CRP levels are associated with a
greater 10 year risk of CVD mortality in schizophrenia. Although the
⁎ Corresponding author.
E-mail address: brendonstubbs@hotmail.com (B. Stubbs).
literature is sparse, recent research has found that female gender, higher
BMI, smoking and increased triglycerides and HBA1c levels are all
significantly associated with CRP levels in relatively modest samples
of people with psychosis (Dickerson et al., 2013; Dieset et al., 2012;
Sicras-Mainar et al., 2013).
Despite the robust evidence for a link between physical activity and
sedentary behaviour with CRP levels in the general population (Yu et al.,
2009), only one small study, to our knowledge, has investigated this re-
lationship in people with psychosis (Wang et al., 2012). Specifically
Wang et al. (2012) found that people with schizophrenia engaging in
lower levels of moderate physical activity had higher levels of CRP. No
study has investigated the impact of sedentary behaviour on CRP levels.
Sedentary refers to behaviours such as sitting, lying down, and reclining
during waking hours that do not increase energy expenditure
substantially above an individual's basal metabolic rate (Sedentary
Behaviour Research, 2012). People with schizophrenia are significantly
more sedentary than the general population (Soundy et al., 2013) but
it is not known if this influences CRP levels or CVD risk. We conducted
the first study to investigate if sedentary behaviour is associated with
CRP levels after adjusting for previously identified risk factors.

http://dx.doi.org/10.1016/j.schres.2015.07.003
0920-9964/© 2015 Elsevier B.V. All rights reserved.

Please cite this article as: Stubbs, B., et al., Sedentary behaviour is associated with elevated C-reactive protein levels in people with psychosis,
Schizophr. Res. (2015), http://dx.doi.org/10.1016/j.schres.2015.07.003
2 B. Stubbs et al. / Schizophrenia Research xxx (2015) xxx–xxx

2. Method
2.1. Participants and setting
Cross-sectional study across 5 community health trusts in England
using the baseline data of participants from the Improving Physical
health and reducing substance use in Psychosis (IMPaCT) randomised
controlled trial (RCT) (Gaughran et al., 2013). Participants with
established psychosis were eligible for inclusion (defined as schizophre-
nia (ICD-10 code: F20), delusional Disorder (F22.0), schizoaffective
disorder (F25), bipolar affective disorder (F31), recurrent depressive
disorder (F32), current episode severe with psychotic symptoms
(F33.3)).
Recruitment of participants occurred in two waves; first, all eligible
care-coordinators in participating CMHTs were approached in a random
sequence and invited to participate. Once each participant provided
informed consent, the patients from each participating care coordinator's
caseload, meeting the inclusion criteria, were likewise approached in a
random order and sequentially invited to participate.
3. Clinical and sociodemographic variables
A range of sociodemographic data were collected including age, sex
and self-report ethnicity. Participants were invited to attend a session
with a trained researcher to have their blood pressure, weight, waist
circumference and other markers measured including the International
Diabetes Federation (IDF) criteria for the metabolic syndrome (Alberti
et al., 2005). Willing participants were invited to provide a fasting
blood sample for which they were required to fast without food for
12 h prior to the sample being collected. A trained phlebotomist was
responsible for all blood sampling. Fasting glucose and a full lipid
analysis was performed.
3.1. Psychiatric symptoms, functioning and quality of life
and high CRP levels groups were analysed with independent sample t
tests and chi squared tests. A hierarchical linear regression was conduct-
ed with CRP levels as the dependent variable. In the first stage of the
model, age and gender were inserted in the model. In the second
stage, variables from stage 1 were included in addition to ethnicity, dia-
stolic blood pressure, waist circumference, HbA1c (mmol/mol), smoker
(ever smoked more than 100 cigarettes) total cholesterol/High-density
lipoprotein ratio and moderate physical activity levels (IPAQ-SF). In the
final model, we inserted the variables from step two and sedentary be-
haviour (IPAQ-SF). Standardised beta co-efficients (β) were calculated
and multicollinearity was assessed ensuring the variation inflation fac-
tor (VIF) was b10 and tolerance N 0.2 (Field, 2013).
5. Results
From the sample, 250 participants (mean age 48.2 years (SD 10.2),
N = 98 female, 39.2%) had a valid high sensitivity CRP sample. The
most common primary diagnosis was schizophrenia (N = 158, 63.2%),
bipolar affective disorder (current manic episode, N = 27, 10.8%) and
schizoaffective disorder (N = 22, 8.8%). All participants were receiving
antipsychotic medication and the average duration of psychotic illness
was 17.9 years (SD 10.7). Just over half of participants reported they
were white (n = 136, 54.4%), one third were black British (n = 84,
33.6%) and the remaining were other non-white ethnicities.
5.1. C-reactive protein levels and correlates
Approximately one third (N = 91, 36.4%) of participants had high
CRP levels (N5.0 mg/μl) and 159 had normal CRP levels (b 5.0 mg/μl).
Full details of key demographic and clinical data of these groups are
summarised in Table 1. In brief, there was no difference in the propor-
tion of smokers in each group, the number receiving second generation
antipsychotics (including clozapine and olanzapine), although diastolic

Symptom severity was assessed using the Positive and Negative Table 1
Comparison of key clinical and demographic characteristics of individuals with high and
Syndrome Scale (PANSS (Kay et al., 1987)). Global functioning among
normal levels of CRP.
participants was captured with the Global assessment of functioning
(GAF) (American Psychiatric Association, 2002). In addition, health Variable Normal CRP High CRP P value
(N = 159) (N = 91)
related quality of life (HRQOL) was measured with the Euroqol 5D
b5.0 mg/μl ≥5.0 mg/μl
(EQ 5D).
Age mean (SD) 47.2 (10.2) 49.9 (9.6) .035
Female N (%) 56 (35.2) 42 (46.2) .059
3.2. Sedentary behaviour and physical activity Caucasian N (%) 85 (53.4) 51 (56.0) .36
Current smoker N (%) 94 (59.1) 56 (61.5) .40
Physical activity and sedentary behaviour were assessed with the Diastolic BP mm hg π (SD) 80.5 (10.8) 85.5 (10.1) b.001
International Physical Activity Questionnaire (IPAQ-SF, (Craig et al., Waist circumference cm π (SD) 102.0 (16.8) 113.3 (15.0) b.001
HBA1c mmol/mmHB (SD) π 39.4 (7.1) 42.7 (9.9) .007
2003)). The IPAQ has been validated for use in people with schizophre-
Total cholesterol/HDL ratio 4.3 (1.5) 4.9 (1.5) .01
nia (Faulkner et al., 2006) and a recent systematic (Soundy et al., 2014) Fasting glucose 5.5 (2.2) 6.9 (4.1) .005
confirmed it has the most favourable psychometric properties of all self- Metabolic syndrome N (%)π 68 (45.3) 63 (75.0) b.001
report measures in people with serious mental illness. The number of Receiving SGA 110 (69.1) 70 (76.9) 0.34
hours and minutes of sedentary behaviour/physical activity per day PANSS total π (SD) 47.9 (13.1) 49.5 (12.4) .33
GAF score π (SD) 61.5 (13.0) 59.1 (14.1) .18
are calculated. HRQOL mean 0–100 (SD) 63.22 (21.9) 60.8 (23.1) .42
Meet 150 min moderate PA 40 (25.2) 23 (25.3) .54
3.3. High sensitivity C-reactive protein per week? Yes (%)
Vigorous PA per week (min) 33.4 (130.1) 19.1 (127.2) .35
High sensitivity CRP was collected and analysed utilising Siemens Key: SD = standard deviation, BMI = body mass index, GAF = global assessment of
Advia 2400 (Siemens Healthcare, UK). Participants were categorised functioning, HRQOL overall health state from 0–100 from EQ 5D, Moderate PA per week
(based on IPAQ questions and Vancampfort et al., 2012 recommendations of 150 min of
into two groups: normal vs. elevated using a 5.0 mg/μl cut off in
moderate physical activity per week; yes/no), Metabolic syndrome (based on IDF criteria).
accordance with previous research among people with psychosis π = Some Missing data in analysis: Systolic and diastolic BP N = 154 in normal CRP
(Dickerson et al., 2007). and N = 90 in high CRP, waist circumference N = 150 in normal CRP and N = 91 in
high CRP, HBA1c N = 156 in normal CRP and N = 82 in high CRP, PANSS negative N =
4. Statistical analysis 158 in normal CRP and N = 89 in high CRP, PANSS positive N = 158 in normal CRP and
N = 90 in high CRP, PANNS general N = 157 in normal CRP and N = 90 in high CRP,
PANNS total N = 157 in normal CRP and N = 89 in high CRP, GAF N = 158 in normal
Non-normally distributed data was log transformed (CRP levels, CRP and N = 91 in high CRP, HRQOL N = 158 in normal CRP and N = 91 in high CRP,
physical activity, sedentary behaviour, diastolic blood pressure). Differ- Total cholesterol N = 157 in normal CRP and N = 89 in high CRP, metabolic syndrome
ences between baseline demographic and key variables in the normal N = 150 normal CRP and N = 84 high CRP.

Please cite this article as: Stubbs, B., et al., Sedentary behaviour is associated with elevated C-reactive protein levels in people with psychosis,
Schizophr. Res. (2015), http://dx.doi.org/10.1016/j.schres.2015.07.003
 B. Stubbs et al. / Schizophrenia Research xxx (2015) xxx–xxx 3

Table 2
Hierarchical liner regression analysis investigating predictors of C-reactive protein levels in 222 people with psychosis.

Variable Model 1 Model 2 Model 3

β (SE) P value β (SE) P value β (SE) P value

Age .028 (.045) .67 .218 (.941) .90 .009 (.044) .889
Female gender .167 (.945) .01 −.162 (.092) .001 .229 (.932) .001
Non-white ethnicity .123 (.052) .010 .181 (.092) .005
HbA1c result (mmol/mmHB) .081 (.306) .058 .114 (.051) .074
Total cholesterol/HDL ratio .216 (.027) .227 .083 (.303) .212
Waist circumference .105 (.041) .002 .205 (.027) .003
Diastolic BP .123 (1.01) .110 .105 (.041) .107
Smoked more than 100 cigarettes .022 (.005) .061 .112 (1.00) .086
Moderate PA .218 (.941) .721 .049 (.006) .436
Sedentary behaviour .155 (.002) .011

Key: SE = standard error, β = standardised beta coefficients, BMI = body mass index, BP = blood pressure, PA = physical activity,
Variables entered in at Model 1: Age (years) and gender.
Variables entered in at Model 2: Step 1 variables and Ethnicity, diastolic blood pressure, waist circumference, HbA1c (mmol/mol), Smoked over 100 cigarettes, Total Cholesterol/HDL ratio,
Moderate physical activity levels (IPAQ).
Variables entered in at Model 3: Variables at step 1 and 2 and sedentary behaviour (IPAQ).

blood pressure, HBA1c, fasting glucose, metabolic syndrome rates and
waist circumference were higher in the elevated CRP group. There was
no evidence of differences in PANSS, GAF, physical activity or HRQOL
scores. The group with high CRP spent approximately 1.5 h more a
day being sedentary (8.78 h) compared to the group with normal CRP
(7.3 h, p = .007).
5.2. Factors associated with C-reactive protein levels
Within the final model of the hierarchical regression analysis the
largest unique predictors of high CRP levels were female gender (β =
.229, p = .001), increasing waist circumference (β = .205, p = .003),
and non-white ethnicity (β = .181, p = .005), followed by higher levels
of sedentary behaviour (β = .155, p = .01). Full details are summarised
in Table 2.
6. Discussion
To our knowledge this is the first study to establish that increased
sedentary behaviour is associated with higher levels of CRP in a large
multi-ethnic sample of people with psychosis. The relationship between
sedentary behaviour and CRP remained when we accounted for previ-
ously established confounding factors (gender, smoking, total/HDL cho-
lesterol, diabolic blood pressure, HBA1c levels). In line with previous
research we also found that female gender, increased waist circumfer-
ence and non-white ethnicity predicted high CRP (Dickerson et al.,
2013; Wang et al., 2012).
The reasons why sedentary behaviour is associated with high CRP in
psychosis are unclear. It may reflect inflammation associated with the
weight gain and metabolic syndrome, which may also be secondary to
excessive sedentary behaviour in this group (Vancampfort et al.,
2014) although antipsychotic medication may also play a role (Dieset
et al., 2012). Nevertheless, our results remained after adjusting for
known cardio-metabolic risk factors.
This research indicates that encouraging an active lifestyle should be
given a high priority in clinical practice in people with psychosis. Robust
research in the general population has demonstrated that physical ac-
tivity can reduce inflammatory cytokines including CRP (Hamer et al.,
2012). Unlike Wang et al. (2012) we did not find any association be-
tween moderate physical activity and CRP levels in our sample. Previous
research has also highlighted that sedentary behaviour is detrimental to
the cardiovascular health of people with psychosis independent of
physical activity (Vancampfort et al., 2014). Given the heightened risk
of cardiovascular disease, our results suggest that strategies to reduce
excessive sedentary behaviour in psychosis require urgent attention.
Some limitations must be noted. First, the study is cross sectional
and directionality of the relationships cannot be deduced. Second,
although validated for this population (Faulkner et al., 2006), the IPAQ
is a self-report measure and these are often inaccurate (Harvey, 2011).
Therefore, future research should prioritise objective measurement
(e.g. accelerometers) in order to obtain a more precise measure of the
relationship we observed. Third, chlorpromazine dose equivalents of
antipsychotic medication were not available within our sample and
future research should consider the impact of this. Nevertheless,
allowing for these caveats our study has for the first time found that
sedentary behaviour is associated with high levels of CRP among people
with psychosis even after adjusting for previously established risk
factors – and ultimately may allow the development and evaluation of
strategies to reduce early cardiovascular mortality in psychosis. More-
over, the study had some distinct advantages including utilising a
multi-ethnic sample (45.6% were non-Caucasian) with good power
and included controlling for relevant confounding factors. Since CRP is
a readily available laboratory biomarker, it could potentially be used
to track changes in CVD risk and prospective research is required to ad-
dress this.
Contributors
Data acquisition PGS, SS, KI, KG, AP, KI and FG. Data analysis BS, FG and PS.
BS, PS and FG wrote the manuscript and all authors provided critical revisions. All
authors have approved the final version.
Role of funding source
The National Institute for Health Research (NIHR) funds the IMPACT programme
at King's College London and South London and Maudsley NHS Foundation Trust (ref:
RP-PG-0606-1049). The views expressed are those of the author(s) and not necessarily
those of the National Health Service (NHS), the NIHR or the Department of Health. The
funder had no role at any stage of the research or influenced the decision to publish.
Conflict of interest
BS, PGS, SS, KI, KG, AP and RF report no conflict of interest related to this work. FG has
no direct conflict of interest but has received honoraria for advisory work and lectures
from Roche, BMS, Lundbeck, and Sunovion and has a family member with professional
links to Lilly and GSK. KI has received honorarium for educational meetings for Eli Lilly
and Janssen.
Acknowledgement
The National Institute for Health Research (NIHR) funds the IMPACT programme
at King's College London and South London and Maudsley NHS Foundation Trust (ref:
RP-PG-0606-1049). The views expressed are those of the author(s) and not necessarily
those of the National Health Service (NHS), the NIHR or the Department of Health.
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