Life Satisfaction and Bio Markers

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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

Japanese Psychological Association 2011.


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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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