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Life satisfaction and inflammatory biomarkers: The 2008Scottish Health Survey1
MARK HAMER* University College London jpr_460 133..139
YOICHI CHIDA2 Happy Smile Clinic
Abstract: Positive psychological attributes have been associated with better healthoutcomes, although the mechanisms remain poorly understood. This study examinedassociations between life satisfaction and inflammatory biomarkers. Participants were369 men and 428 women (aged 52.1 16.8 years) recruited from the general popu-lation. Participants were required to rate their life satisfaction on a scale ranging from0 (extremely dissatisfied) to 10 (extremely satisfied). Blood was collected for the
measurement of C-reactive protein (CRP) and fibrinogen. In comparison with partici-pants that were dissatisfied with life (5.8% of the sample), those that reported highlife satisfaction demonstrated a lower CRP concentration (beta coefficient = -.24,95% CI, -.47, -.02) and lower fibrinogen (b = -.24, 95% CI, -.45, -.04) after adjustingfor age, sex, education, smoking, body mass index, and depressive symptoms. Lifedissatisfaction was also associated with smoking, lower education, and depressivesymptoms. In summary, lower levels of circulating inflammatory markers might be animportant psychobiological process through which positive psychological attributesprotect against disease risk.
Key words: positive affect, depression, C-reactive protein, fibrinogen, cardiovasculardisease, psychobiology.
An emerging body of evidence has suggested
that positive psychological attributes are associ-
ated with better health (Pressman & Cohen,
2005). Life satisfaction or perceived level of life
enjoyment represents a positive psychological
state, and has been associated with a lower risk
of future cardiovascular disease and mortality
(Chida & Steptoe, 2008; Koivumaa-Honkanen,
Honkanen, Viinamki, Heikkil, Kaprio, &
Koskenvuo, 2000; Shirai, Iso, Ohira, Ikeda,
Noda, Honjo, Inoue, Tsugane, & Japan Public
Health Center-Based Study Group, 2009). Life
dissatisfaction is associated with increased risk
of suicide (Koivumaa-Honkanen, Honkanen,
Viinamki, Heikkil, Kaprio, & Koskenvuo,
2001), future depression (Koivumaa-
Honkanen, Kaprio, Honkanen, Viinamki, &
Koskenvuo, 2004) and poor self-rated health
and disability (Strine, Chapman, Balluz, Mori-
arty,& Mokdad,2008).As positive psychological
*Correspondence concerning this article should be sent to: Mark Hamer, Psychobiology Group, Departmentof Epidemiology and Public Health, University College London, 1-19 Torrington Place, London, WC1E 6BT, UK.(E-mail: [email protected])
1The Scottish Health Survey is funded by the Scottish Executive. The views expressed in this article are thoseof the author and not necessarily of the funding bodies. Dr Hamer is supported by the British Heart Foundation(RG 05/006).
2Yoichi Chida, Happy Smile Clinic, West Canyon II 3F, 1-12-20, Mizonoguchi, Takatsu-ku, Kawasaki 213-0001,Japan. (E-mail: [email protected]) Dr. Chida was supported by a grant from the NOBUKO-DAIKOKUmedical research funding.
Japanese Psychological Research2011, Volume 53, No. 2, 133139Special issue: Psychobiological approaches to stress and health
2011 Japanese Psychological Association. Published by Blackwell Publishing Ltd.
doi: 10.1111/j.1468-5884.2011.00460.x
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attributes are often inversely associated with
negative affect such as depression and anxiety it
is important to demonstrate that any associa-
tions of positive affect on health outcomes are
independent from measures of negative affect.
The biological mechanisms of positivepsychology remain poorly understood. Positive
affect has been associated with blunted
cardiovascular, fibrinogen, and hypothalamic-
pituitary-adrenal (HPA) axis responses to stan-
dardized mental stress tasks, and with lower
cortisol output post-awakening and throughout
the day (Brummett, Boyle, Kuhn, Siegler, &
Williams, 2009; Chida & Hamer, 2008; Steptoe,
Wardle, & Marmot, 2005). In a sample of 2873
healthy participants from the Whitehall II
cohort, positive affect was inversely associatedwith levels of C-reactive protein (CRP) and
interleukin (IL)-6 in women but not men
(Steptoe, ODonnell, Badrick, Kumari, &
Marmot, 2008). As inflammatory processes
have been linked with various health outcomes,
such as cardiovascular disease and cancer
(Heikkil, Ebrahim, & Lawlor, 2007; Libby &
Crea, 2010), this could be a key mechanism in
explaining the protective health benefits of
positive psychology.
The aim of this study was to investigate the
association between life satisfaction and inflam-
matory biomarkers. It was hypothesized that
high life satisfaction would be associated with
lower inflammatory biomarkers, independently
from depressive symptoms and other related
factors such as smoking and obesity. Obesity is
strongly associated with CRP, as adiposity is a
major production site of inflammatory markers
(Hamer & Stamatakis, 2008). Because previous
evidence has suggested an association between
obesity and life satisfaction (Strine et al., 2008),
we made an a priori decision to adjust for bodymass index, as it might be a key confounder in
the association between life satisfaction and
inflammatory biomarkers.
Methods
Participants and study design
The Scottish Health Survey (SHS) is a periodic
survey (typically every 35 years) that draws a
nationally representative sample of the general
population living in households (The Scottish
Government, 2008). The sample was drawn
using multistage stratified probability sampling
with postcode sectors selected at the first stage
and household addresses selected at the secondstage. The present analyses used data from the
2008 SHS in adults aged 18 years and older.
Participants gave full informed consent to par-
ticipate in the study and ethical approval was
obtained from the Multi-Centre Research
Ethics Committee for Wales (REC reference
number: 07/ MRE09/55). The response rate to
the household survey was 61% and comprised
6313 participants. A subsample (n = 1835) of
participants was approached for a nurses
visit and 797 of them provided full data tobe included in the present analyses. Within
the nurse sample, those participants that were
excluded from the present analyses were
slightly younger (50.8 vs. 52.1 years, p = .02)
than those included, but did not differ in other
key characteristics such as education (% with
no qualifications, 24.4% vs. 24.5%).
Assessment of behavioral and
psychosocial variables
Interviewers were fully briefed on the adminis-
tration of the survey. They were given training
in measuring height and weight, including a
practice session. Survey interviewers visited eli-
gible households and collected data on demo-
graphics (e.g. education), health behaviors (e.g.
smoking), and took anthropometry variables
(height, weight). Participants were required to
rate their satisfaction with life on a scale ranging
from 0 (extremely dissatisfied) to 10 (extremely
satisfied). Anxiety and depressive symptoms
were measured using the revised version of the
Clinical Interview Schedule (CIS-R).
Nurse visit and biomarker data
On a separate visit, within several days of
the interview, nurses collected information on
medical history, and blood samples from con-
senting adults. All nurses were professionally
qualified and proficient in taking blood before
joining the Health Survey team. They attended
a 1.5-day training session at which they
M. Hamer and Y. Chida134
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received equipment training and were briefed
on the specific requirements of the survey with
respect to taking blood and other measures.Peripheral blood was collected in serum tubes
and spun at room temperature. All blood
samples were frozen at 70C until assay. The
analysis of CRP levels from serum was per-
formed using the N Latex high sensitivity CRP
mono immunoassay on the Behring Nephelom-
eter II analyser. The limit of detection was
0.17 mg/L and the coefficient of variation (CV)
was less than 6% for this assay. Fibrinogen
levels were determined using the Organon
Teknika MDA 180 analyser, using a modifica-
tion of the Clauss thrombin clotting method,
with a CV of less than 10%. All analyses were
carried out in the same laboratory according to
Standard Operating Procedures by State Reg-
istered Medical Laboratory Scientific Officers.
Statistical analysis
A large number of quality control measures
was built into the survey at both data collection
and subsequent stages to check on the quality
of interviewer and nurse performance. Life sat-
isfaction scores were recategorized into fourgroups, representing low satisfaction (rating
score of 04), moderate satisfaction (56), high
satisfaction (78), very high satisfaction (910).
Log transformations were used to normalize
CRP values. General linear models were
employed to examine associations between life
satisfaction and inflammatory biomarkers. In
the basic model we adjusted for age and sex,
and further models included adjustment for
education (university degree or higher; higher
national diploma; higher grade; standard grade;
other school qualification, no qualification),smoking (never; previous; current), body mass
index category (underweight, < 18.5; normal
18.525.0; overweight, > 2530; obese, > 30 kg/
m2). Finally the model was adjusted for anxious
and depressive symptoms (ranging from 04) in
order to examine if associations of life satisfac-
tion was independent from negative psycho-
logical states. Additionally, we performed linear
regression analyses treating the life satisfaction
score (010) as a continuous variable.All analy-
ses were performed using SPSS (version 14)
and all tests of statistical significance were
based on two-sided probability.
Results
The full sample consisted of 369 men and 428
women (aged 52.1 16.8 years) for all analyses
involving CRP, although a reduced sample size
was used for fibrinogen analyses because 185
participants had missing data.Very high life sat-
isfaction (a rating of 9 or 10) was reported in34.3% of the sample and 5.8% of participants
were dissatisfied with life (a rating score of
04). Participants reporting high life satisfac-
tion were more likely to be educated, not
smoke, and have lower anxious and depressive
symptoms (Table 1).
Life satisfaction was linearly and inversely
associated with both CRP (Table 2) and
fibrinogen (Table 3). These associations were
Table 1 Descriptive characteristics of the study sample in relation to life satisfaction (n = 797)
Variable Life satisfaction group
Lowest
(n = 46)
Moderate
(n = 103)
High
(n = 375)
Very high
(n = 273)
Age (years) 52.2 13.1 54.1 18.4 49.9 16.0 54.4 17.4Men (%) 41.3 47.6 43.5 50.5
Education (% no qualification) 43.5 27.2 21.3 22.7
Current smokers (%) 54.3 26.2 22.4 13.6
Obesity (% > 30 kg/m2) 30.4 24.3 29.6 30.4
Depressive symptoms (% any) 45.7 28.2 10.7 4.8
Anxious symptoms (% any) 44.2 27.4 17.0 8.4
Life satisfaction and C-reactive protein 135
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somewhat attenuated after adjustment for pos-
sible confounders, and remained marginally
significant after accounting for anxious and
depressive symptoms. The covariate that
accounted for the largest attenuation in effect
size in model 2 was smoking. There were no
clear differences in our results between men
and women. These analyses were repeated
after removing 69 participants who reported a
history of cardiovascular disease (angina, heart
attack, or stroke), and the results were slightly
strengthened; in comparison with participants
that were dissatisfied with life, those that hadhigh life satisfaction demonstrated lower CRP
concentration (multivariate adjusted beta
coefficient = -.28, 95% CI, -.54, -.03, p = .03)
and fibrinogen (b = -.28, 95% CI, -.48, -.07,
p = .008).
We repeated the analyses using life satisfac-
tion as a continuous variable in linear regres-
sion models in order to retain greater statistical
power. In these analyses, the life satisfaction
score remained inversely associated with log
CRP (b = -.028, 95% CI, -.056 to .000, p = .05)
and fibrinogen (b = -.031, 95% CI, -.055 to
-.007, p = .01) after adjustments for age, sex,
education, smoking, body mass index, and
anxious and depressive symptoms.
Discussion and conclusions
The results of the present study demonstrate a
linear, inverse association between life satisfac-
tion and two inflammatory markers, and theseassociations were independent of anxious and
depressive symptoms. These findings are partly
consistent with a previous study of healthy par-
ticipants from the Whitehall II cohort, which
demonstrated an inverse association between
positive affect and levels of CRP and IL-6 in
women only (Steptoe et al., 2008). In the
present study there were no clear differences in
results between men and women, although the
Table 2 Association between life satisfaction and C-reactive proteina (n = 797). Data areadjusted regression coefficients (95% CI)
Life satisfaction Mean C-reactive
protein SEM (mg\L)
Model 1
b (95% CI)
Model 2
b (95% CI)
Model 3
b (95% CI)
Low 5.3 1.0 Reference Reference Reference
Medium 4.3 .6 -.23 (-.48, .03) -.11 (-.35, .13) -.10 (-.35, .14)
High 3.0 .2 -.36 (-.58,-.14) -.26 (-.47,-.05) -.24 (-.47,-.02)
Very high 3.4 .3 -.34 (-.57,-.11) -.22 (-.44, .00) -.19 (-.42, .04)
p-trend .008 .045 .096
Note. Model 1 adjusted from age and sex; Model 2 further adjusted for smoking, education, body mass index;
Model 3 further adjusted for anxious and depressive symptoms.aAll regression coefficients are from log transformed data.
Table 3 Association between life satisfaction and fibrinogen (n = 612). Data are adjustedregression coefficients (95% CI)
Life satisfaction Mean fibrinogen
SEM (g\L)
Model 1
b (95% CI)
Model 2
b (95% CI)
Model 3
b (95% CI)
Low 3.5 .1 Reference Reference Reference
Medium 3.3 .1 -.21 (-.42, -.03) -.17 (-.37, .04) -.13 (-.34, .08)
High 3.2 .03 -.32 (-.51, -.14) -.25 (-.44, -.08) -.20 (-.40, -.01)
Very high 3.2 .03 -.36 (-.55, -.18) -.29 (-.47, -.10) -.23 (-.43, -.03)
p-trend < .001 .011 .11
Note. Model 1 adjusted from age and sex; Model 2 further adjusted for smoking, education, body mass index;
Model 3 further adjusted for anxious and depressive symptoms.
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present sample contained participants from
the general population and was not restricted
to a working sample, as in the Whitehall II
study.
The proportion of the sample that reported
that they were dissatisfied/very dissatisfied withlife is very similar to data reported from the
Behavioral Risk Factor Surveillance System,
which is a representative sample of the US
population (Strine et al., 2008). The present
data also replicated other findings from that
study, which showed associations of life dissat-
isfaction with poor education, smoking and
depressive symptoms. We did not observe any
association between life satisfaction and
obesity, which is not entirely consistent with
prior studies. For example, a low level of lifesatisfaction was associated with obesity in the
general adult US population (Strine et al.,
2008), predicted weight gain in older women
(Korkeila, Kaprio, Rissanen, Koshenvuo, &
Sorensen, 1998) and waist/hip circumference
ratio was negatively associated with life satis-
faction among middle-aged men (Rosmond,
Lapidus, Marin, & Bjorntorp, 1996).
One possible explanation for the association
between life satisfaction and circulating inflam-
matory markers might be linked with HPA axis
function. Glucocorticoids (GCs), the final HPA
axis effector hormones, are generally thought
to inhibit the production of pro-inflammatory
cytokines of IL-6 and tumor necrosis factor
(TNF)-a, at both the transcriptional and trans-
lational levels (Gonzalez, Johnson, Morrison,
Freudenberg, Galanos, & Silverstein, 1993;
Swain, Appleyard, Wallace, Wong, & Le, 1999).
These cytokines critically contribute to the pro-
duction of CRP from the liver. However, the
doses of GCs used in the above studies were in
the pharmacological range. By contrast, Liao,Keiser, Scales, Kunkel, and Kluger (1995)
showed that glucocorticoids in the physiologi-
cal range induce IL-6 and TNF-a when admin-
istered at either basal (35 ng/ml) or stress-
related (350 ng/ml) levels in an in situ liver
perfusion, which suggests that GCs do not
consistently suppress the production of pro-
inflammatory cytokines. Thus, given previous
findings that positive affect was associated with
blunted HPA axis responses to standardized
mental stress tasks and with lower cortisol
output post-awakening and throughout the day
(Brummett et al. 2009; Chida & Hamer, 2008;
Steptoe et al., 2005), the association between
life satisfaction and inflammatory markersmight be partly explained by HPA axis func-
tion. Indeed, dysregulated HPA activity may
promote glucocorticoid receptor resistance
and subsequent diminished responsiveness of
immune cells to regulation by cortisol (Miller,
Cohen, & Ritchey, 2002). However, because
direct measures of HPA activity and glucocor-
ticoid receptor resistance were not available
from this study we can only speculate about the
mechanisms. The sympathetic nervous system
might also be implicated as a potential mecha-nism. In the present study there was a weak
inverse association between life satisfaction
and systolic blood pressure (age and sex
adjusted b = -.51, 95% CI, -1.11 to .09 mmHg,
p = .096), which might suggest lower sympa-
thetic activation in participants with higher life
satisfaction. Given that acute mental stress
can evoke inflammatory responses (Steptoe,
Hamer, & Chida, 2007), stress perception may
be involved in life satisfaction and may partly
explain the present findings.
This study has several strengths and limita-
tions. The strengths of the study include the
sampling of a large, representative general
population-based group, and the well character-
ized study members, which facilitates insights
into the role of potential confounding factors.
Several limitations should also be highlighted.
Life satisfaction was assessed from one ques-
tion and therefore may not effectively convey
the diverse components comprising this con-
struct. The inclusion of other measures on
general positive affect would therefore havestrengthened the results. Secondly, life satisfac-
tion was only measured once, so the effects of
changes in this variable cannot be accounted
for. Previous evidence suggests that life satis-
faction is stable and trait-like (Koivumaa-
Honkanen, Kaprio, Honkanen, Viinamki, &
Koskenvuo, 2005), although others have sug-
gested that it might be modified by experiences
in the past decade and expectations of the
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future (Mehlsen, Platz, & Fromholt, 2003).
Because this study is cross-sectional, causality
cannot be inferred. Nevertheless, the results
remained robust after excluding participants
with existing cardiovascular disease, which
partly excludes the possibility of reverse causal-ity, that is, raised levels of inflammatory
markers caused by existing disease could influ-
ence subjective ratings of life satisfaction.
We cannot exclude the possibility of residual
confounding from unmeasured variables. For
example, other explanations of the findings
might involve the role of unmeasured positive-
emotion related peptides, such as endorphins
and oxytocin, which have a possible role in
inhibiting inflammatory responses (Straub,
Dorner, Riedel, Kubitza, Van Rooijen, Lang,Schlmerich, & Falk, 1998).
In summary, this study shows a linear,
inverse association between life satisfaction
and two inflammatory risk markers. Reduced
levels of low-grade inflammation might be
an important mechanism in explaining a
lower risk of future cardiovascular disease and
mortality in participants reporting high life
satisfaction.
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