Japanese Psychological Research 2011, Volume 53, No.

2, 133139 Special issue: Psychobiological approaches to stress and health

doi: 10.1111/j.1468-5884.2011.00460.x

Life satisfaction and inammatory biomarkers: The 2008 Scottish 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 health outcomes, although the mechanisms remain poorly understood. This study examined associations between life satisfaction and inammatory biomarkers. Participants were 369 men and 428 women (aged 52.1 16.8 years) recruited from the general population. Participants were required to rate their life satisfaction on a scale ranging from 0 (extremely dissatised) to 10 (extremely satised). Blood was collected for the measurement of C-reactive protein (CRP) and brinogen. In comparison with participants that were dissatised with life (5.8% of the sample), those that reported high life satisfaction demonstrated a lower CRP concentration (beta coefcient = -.24, 95% CI, -.47, -.02) and lower brinogen (b = -.24, 95% CI, -.45, -.04) after adjusting for age, sex, education, smoking, body mass index, and depressive symptoms. Life dissatisfaction was also associated with smoking, lower education, and depressive symptoms. In summary, lower levels of circulating inammatory markers might be an important psychobiological process through which positive psychological attributes protect against disease risk. Key words: positive affect, depression, C-reactive protein, brinogen, cardiovascular disease, psychobiology.

An emerging body of evidence has suggested that positive psychological attributes are associated 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 (KoivumaaHonkanen, Kaprio, Honkanen, Viinamki, & Koskenvuo, 2004) and poor self-rated health and disability (Strine, Chapman, Balluz, Moriarty,& Mokdad,2008).As positive psychological

*Correspondence concerning this article should be sent to: Mark Hamer, Psychobiology Group, Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London, WC1E 6BT, UK. (E-mail: m.hamer@ucl.ac.uk)
1

The Scottish Health Survey is funded by the Scottish Executive. The views expressed in this article are those of the author and not necessarily of the funding bodies. Dr Hamer is supported by the British Heart Foundation (RG 05/006). Yoichi Chida, Happy Smile Clinic, West Canyon II 3F, 1-12-20, Mizonoguchi, Takatsu-ku, Kawasaki 213-0001, Japan. (E-mail: yoichi.chida@gmail.com) Dr. Chida was supported by a grant from the NOBUKO-DAIKOKU medical research funding.

2011 Japanese Psychological Association. Published by Blackwell Publishing Ltd.

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M. Hamer and Y. Chida

attributes are often inversely associated with negative affect such as depression and anxiety it is important to demonstrate that any associations of positive affect on health outcomes are independent from measures of negative affect. The biological mechanisms of positive psychology remain poorly understood. Positive affect has been associated with blunted cardiovascular, brinogen, and hypothalamicpituitary-adrenal (HPA) axis responses to standardized 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 associated with levels of C-reactive protein (CRP) and interleukin (IL)-6 in women but not men (Steptoe, ODonnell, Badrick, Kumari, & Marmot, 2008). As inammatory 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 benets of positive psychology. The aim of this study was to investigate the association between life satisfaction and inammatory biomarkers. It was hypothesized that high life satisfaction would be associated with lower inammatory 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 inammatory 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 body mass index, as it might be a key confounder in the association between life satisfaction and inammatory biomarkers.

nationally representative sample of the general population living in households (The Scottish Government, 2008). The sample was drawn using multistage stratied probability sampling with postcode sectors selected at the rst stage and household addresses selected at the second stage. The present analyses used data from the 2008 SHS in adults aged 18 years and older. Participants gave full informed consent to participate 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 to be 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 qualications, 24.4% vs. 24.5%). Assessment of behavioral and psychosocial variables Interviewers were fully briefed on the administration of the survey. They were given training in measuring height and weight, including a practice session. Survey interviewers visited eligible households and collected data on demographics (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 dissatised) to 10 (extremely satised). 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 consenting adults. All nurses were professionally qualied and procient in taking blood before joining the Health Survey team. They attended a 1.5-day training session at which they

Methods
Participants and study design The Scottish Health Survey (SHS) is a periodic survey (typically every 35 years) that draws a
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Table 1 Descriptive characteristics of the study sample in relation to life satisfaction (n = 797)
Variable Lowest (n = 46) Age (years) Men (%) Education (% no qualication) Current smokers (%) Obesity (% > 30 kg/m2) Depressive symptoms (% any) Anxious symptoms (% any) 52.2 13.1 41.3 43.5 54.3 30.4 45.7 44.2 Life satisfaction group Moderate (n = 103) 54.1 18.4 47.6 27.2 26.2 24.3 28.2 27.4 High (n = 375) 49.9 16.0 43.5 21.3 22.4 29.6 10.7 17.0 Very high (n = 273) 54.4 17.4 50.5 22.7 13.6 30.4 4.8 8.4

received equipment training and were briefed on the specic 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 performed using the N Latex high sensitivity CRP mono immunoassay on the Behring Nephelometer II analyser. The limit of detection was 0.17 mg/L and the coefcient of variation (CV) was less than 6% for this assay. Fibrinogen levels were determined using the Organon Teknika MDA 180 analyser, using a modication 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 Registered Medical Laboratory Scientic Ofcers. 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 satisfaction scores were recategorized into four groups, 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 inammatory 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 qualication, no qualication), 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 satisfaction was independent from negative psychological states. Additionally, we performed linear regression analyses treating the life satisfaction score (010) as a continuous variable. All analyses were performed using SPSS (version 14) and all tests of statistical signicance 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 brinogen analyses because 185 participants had missing data. Very high life satisfaction (a rating of 9 or 10) was reported in 34.3% of the sample and 5.8% of participants were dissatised with life (a rating score of 04). Participants reporting high life satisfaction 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 brinogen (Table 3). These associations were
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Table 2 Association between life satisfaction and C-reactive proteina (n = 797). Data are adjusted regression coefcients (95% CI)
Life satisfaction Low Medium High Very high p-trend Mean C-reactive protein SEM (mg\L) 5.3 4.3 3.0 3.4 1.0 .6 .2 .3 Model 1 b (95% CI) Reference -.23 (-.48, .03) -.36 (-.58,-.14) -.34 (-.57,-.11) .008 Model 2 b (95% CI) Reference -.11 (-.35, .13) -.26 (-.47,-.05) -.22 (-.44, .00) .045 Model 3 b (95% CI) Reference -.10 (-.35, .14) -.24 (-.47,-.02) -.19 (-.42, .04) .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. a All regression coefcients are from log transformed data.

Table 3 Association between life satisfaction and brinogen (n = 612). Data are adjusted regression coefcients (95% CI)
Life satisfaction Low Medium High Very high p-trend Mean brinogen SEM (g\L) 3.5 3.3 3.2 3.2 .1 .1 .03 .03 Model 1 b (95% CI) Reference -.21 (-.42, -.03) -.32 (-.51, -.14) -.36 (-.55, -.18) < .001 Model 2 b (95% CI) Reference -.17 (-.37, .04) -.25 (-.44, -.08) -.29 (-.47, -.10) .011 Model 3 b (95% CI) Reference -.13 (-.34, .08) -.20 (-.40, -.01) -.23 (-.43, -.03) .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.

somewhat attenuated after adjustment for possible confounders, and remained marginally signicant 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 dissatised with life, those that had high life satisfaction demonstrated lower CRP concentration (multivariate adjusted beta coefcient = -.28, 95% CI, -.54, -.03, p = .03) and brinogen (b = -.28, 95% CI, -.48, -.07, p = .008). We repeated the analyses using life satisfaction as a continuous variable in linear regression models in order to retain greater statistical power. In these analyses, the life satisfaction
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score remained inversely associated with log CRP (b = -.028, 95% CI, -.056 to .000, p = .05) and brinogen (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 satisfaction and two inammatory markers, and these associations were independent of anxious and depressive symptoms. These ndings are partly consistent with a previous study of healthy participants 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

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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 dissatised/very dissatised with life 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 ndings from that study, which showed associations of life dissatisfaction 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 life satisfaction 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 satisfaction among middle-aged men (Rosmond, Lapidus, Marin, & Bjorntorp, 1996). One possible explanation for the association between life satisfaction and circulating inammatory markers might be linked with HPA axis function. Glucocorticoids (GCs), the nal HPA axis effector hormones, are generally thought to inhibit the production of pro-inammatory cytokines of IL-6 and tumor necrosis factor (TNF)-a, at both the transcriptional and translational levels (Gonzalez, Johnson, Morrison, Freudenberg, Galanos, & Silverstein, 1993; Swain, Appleyard, Wallace, Wong, & Le, 1999). These cytokines critically contribute to the production 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 physiological range induce IL-6 and TNF-a when administered at either basal (35 ng/ml) or stressrelated (350 ng/ml) levels in an in situ liver perfusion, which suggests that GCs do not consistently suppress the production of proinammatory cytokines. Thus, given previous ndings 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 inammatory markers might be partly explained by HPA axis function. 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 glucocorticoid 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 mechanism. 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 sympathetic activation in participants with higher life satisfaction. Given that acute mental stress can evoke inammatory responses (Steptoe, Hamer, & Chida, 2007), stress perception may be involved in life satisfaction and may partly explain the present ndings. This study has several strengths and limitations. The strengths of the study include the sampling of a large, representative general population-based group, and the well characterized study members, which facilitates insights into the role of potential confounding factors. Several limitations should also be highlighted. Life satisfaction was assessed from one question and therefore may not effectively convey the diverse components comprising this construct. The inclusion of other measures on general positive affect would therefore have strengthened the results. Secondly, life satisfaction was only measured once, so the effects of changes in this variable cannot be accounted for. Previous evidence suggests that life satisfaction is stable and trait-like (KoivumaaHonkanen, Kaprio, Honkanen, Viinamki, & Koskenvuo, 2005), although others have suggested that it might be modied by experiences in the past decade and expectations of the
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M. Hamer and Y. Chida mation and haemostasis. Brain, Behavior and Immunity, 22, 10411043. Heikkil, K., Ebrahim, S., & Lawlor, D. A. (2007). A systematic review of the association between circulating concentrations of C reactive protein and cancer. Journal of Epidemiology and Community Health, 61, 824833. Koivumaa-Honkanen, H., Honkanen, R., Viinamki, H., Heikkil, K., Kaprio, J., & Koskenvuo, M. (2000). Self-reported life satisfaction and 20-year mortality in healthy Finnish adults. American Journal of Epidemiology, 152, 983991. Koivumaa-Honkanen, H., Honkanen, R., Viinamki, H., Heikkil, K., Kaprio, J., & Koskenvuo, M. (2001). Life satisfaction and suicide: A 20-year follow-up study. American Journal of Psychiatry, 158, 433439. Koivumaa-Honkanen, H., Kaprio, J., Honkanen, R., Viinamki, H., & Koskenvuo, M. (2004). Life satisfaction and depression in a 15-year follow-up of healthy adults. Social Psychiatry and Psychiatric Epidemiology, 39, 994999. Koivumaa-Honkanen, H., Kaprio, J., Honkanen, R. J., Viinamki, H., & Koskenvuo, M. (2005). The stability of life satisfaction in a 15-year follow-up of adult Finns healthy at baseline. BMC Psychiatry, 5, 4. Korkeila, M., Kaprio, J., Rissanen, A., Koshenvuo, M., & Sorensen, T. I. (1998). Predictors of major weight gain in adult Finns: Stress, life satisfaction and personality traits. International Journal of Obesity, 22, 949957. Liao, J., Keiser, J. A., Scales, W. E., Kunkel, S. L., & Kluger, M. J. (1995). Role of corticosterone in TNF and IL-6 production in isolated perfused rat liver. American Journal of Physiology, 268, R699R706. Libby, P., & Crea, F. (2010). Clinical implications of inammation for cardiovascular primary prevention. European Heart Journal, 31, 777783. Mehlsen, M., Platz, M., & Fromholt, P. (2003). Life satisfaction across the life course: Evaluations of the most and least satisfying decades of life. International Journal of Aging and Human Development, 57, 217236. Miller, G. E., Cohen, S., & Ritchey, K. A. (2002). Chronic psychological stress and the regulation of pro-inammatory cytokines: A glucocorticoid resistance model. Health Psychology, 21, 531541. Pressman, S. D., & Cohen, S. (2005). Does positive affect inuence health? Psychological Bulletin, 131, 925971. Rosmond, R., Lapidus, L., Marin, P., & Bjorntorp, P. (1996). Mental distress, obesity and body fat distribution in middle-aged men. Obesity Research, 4, 245252.

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 causality, that is, raised levels of inammatory markers caused by existing disease could inuence subjective ratings of life satisfaction. We cannot exclude the possibility of residual confounding from unmeasured variables. For example, other explanations of the ndings might involve the role of unmeasured positiveemotion related peptides, such as endorphins and oxytocin, which have a possible role in inhibiting inammatory 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 inammatory risk markers. Reduced levels of low-grade inammation 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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