PhD Tomas Hemmingsson
email: tomas.hemmingsson@ki.se

Bo Melin

Peter Allebeck

Ingvar Lundberg

Cognitive ability in adolescence and mortality in middle age -a prospective life course study

Keywords: IQ, mortality, prospective study, mental health, socioeconomic position

Background: An association between childhood cognitive ability measured with IQ-tests and mortality has been reported recently. It is not clear from those studies to what extent the increased relative risk associated with lower IQ-scores may be attenuated by adjustment for other risk factors. This study aims to investigate the association between cognitive ability measured at age 18-20 and mortality among middle aged men adjusting for risk factors for mortality over the life course. Methods: Data on cognitive ability, and other risk factors for premature mortality (indicators of mental health and social adjustment and behavioural factors), was collected among 49 321 men, born in 1949-51, at conscription for compulsory military training in 1969/70.

Information on socioeconomic factors in childhood and adulthood, as well as information on mortality, was collected through national registers.

Results: Cognitive ability showed an inverse and graded association with mortality between 40-53 years of age (1297 cases, crude hazard ratio (HR) 1.15, CI95% 1.12-1.18, for one point decrease on the nine point IQ scale). Adjustment for indicators of social misbehaviour, mental health problems, and behavioural risk factors measured in late adolescence, and adult social circumstances strongly attenuated the increased risks of mortality and it was no longer significantly increased (adjusted HR 1.02, CI95% 0.99-1.06, for one point decrease on the nine point IQ scale).

Conclusion:

The association between IQ and mortality among men below 54 years of age was almost completely attenuated by adjustment for risk factors captured by our measures of achieved social positions.

INTRODUCTION

There are marked socioeconomic differences in mortality in industrialised countries. The background to those inequalities are not fully understood. There is a strong association between socioeconomic position and cognitive ability. It has recently been suggested that cognitive ability, or IQ, itself may be a risk factor for mortality and be responsible for health inequalities. The association between cognitive ability in childhood or adolescence and mortality in old age [START_REF] Whalley | Longitudinal cohort study of childhood IQ and survival up to age 76[END_REF] and in mid-life, [START_REF] O'toole | Ultimate validity of psychological tests[END_REF][START_REF] Hart | Childhood IQ, social class, deprivation, and their relationships with mortality and morbidity risk in later life: prospective observational study linking the Scottish Mental Survey 1932 and the Midspan studies[END_REF][START_REF] Kuh | Childhood cognitive ability and deaths up until middle age: a post-war birth cohort study[END_REF][START_REF] Osler | Socioeconomic position in early life, birth weight, childhood cognitive function, and adult mortality. A longitudinal study of Danish men born in 1953[END_REF][START_REF] Hemmingsson | The association between cognitive ability measured at ages 18-20 and mortality during 30 years of follow-up--a prospective observational study among Swedish males born 1949-51[END_REF][START_REF] Pearce | Childhood IQ and deaths up to middle age: The Newcastle Thousand Families Study[END_REF] has recently been documented in studies based on populations born 1921-1955. In a recent review of all studies on the association between IQ in early life and later mortality it was concluded that the association seems to be strong and not affected by adjustment for socioeconomic circumstances in childhood. [START_REF] Batty | Premorbid (early life) IQ and Later Mortality Risk: Systematic Review[END_REF] Only few studies have so far investigated the association between cognitive ability in early life and later mortality, and with limited possibilities to adjust in the analyses for risk factors for mortality over the the life course. 8 9 However, in two recently published studies the association between IQ and mortality was to a large extent mediated by adult social circumstances. 10 11 Here we will investigate the association between IQ test score, measured at ages 18-20, and mortality in middle age in a cohort of 49 321 Swedish males, born in 1949-51, and the possible impact on this association from risk factors for mortality measured in childhood, adolescence, and in adult life. We will consider indicators of a poor childhood environment measured at ages 9-11, mental health, social problems, and behavioural risk factors measured at age 18-20 as well as data on achieved education, adult socio-economic position, and income from the 1990 census, i.e. when the subjects were 40 years of age.

Methods

Study population

The study was based on data from a nation-wide survey of 49 321 Swedish males, born 1949-51, who were conscripted for compulsory military service in 1969/70. The background of the Swedish conscription surveys and the variables included has been presented in detail elsewhere. 12 13 At that time, only 2-3 % of all Swedish men were exempted from conscription, in most cases due to severe handicaps or congenital disorders. Those included in this study accounted for 97.7% of all conscripts in 1969/70, the remaining 2.3% were born before 1949. The data collection is described in Table 1.

Information collected at the 1969-70 conscription examination

The IQ tests performed included tests on logic/general intelligence; verbal test of synonym detection; of visuospatial/geometric perception; and technical/mechanical skills with mathematical/physics problems and has been described in detail elsewhere 14 15 . The outcome of each test was ranked 1-9. [START_REF] Carlstedt | Cognitive abilities -aspects of structure, process and measurement[END_REF] These standard-nine values were transformed into a new standard-nine scale as a measure of general ability and corresponding to approximate IQ bands of :<74, 74-81, 82-89, 90-95, 96-104, 105-110, 111-118, 119-126, >126. [START_REF] Zammit | A longitudinal study of premorbid IQ Score and risk of developing schizophrenia, bipolar disorder, severe depression, and other nonaffective psychoses[END_REF] Of the men 49 262 (99.9%) had a score on cognitive ability.

All conscripts were seen by a physician who diagnosed any disorders according to the Swedish version of the ICD, 8th revision (ICD-8). All the men were seen by a psychologist for structured interviews. Conscripts reporting or presenting psychiatric symptoms were seen by a psychiatrist and any diagnoses were recorded according to ICD-8.

At conscription all men went through a health examination where height and weight were measured. The following variables were used as possible confounders of the cognitive ability -mortality association. Body mass index (BMI) was calculated using body weight (kg) divided by height (m) squared. In the analyses BMI as well as body height was used as continuous variables.

During the conscription the men completed questionnaires concerning information on social background, behaviour and adjustment, psychological factors, health, and substance use, e.g. alcohol consumption and tobacco smoking. In the analyses smoking was divided into the following four categories: 1>20 cigarettes/day, 2=11-20 cigarettes/day, 3=1-10 cigarettes/day, and 4=none smokers. Alcohol consumption in grams 100%/alcohol/week was calculated on the basis of the answers to the questions on frequency and average consumed volume of beer, wine, and strong spirits. A composite variable, risky use of alcohol, included at least one of the following indicators of problem drinking: consumption of at least 250 gr 100% alcohol/week, to have taken an eye-opener during hangover, to have been apprehended for drunkenness, or to have often been drunk (alternatives given in the questionnaire were "often", "rather often", "sometimes", and "never"). The variable 'contact with police and child welfare authorities' (at least once) indicated problem behaviour and has been shown to be strongly related to later psychiatric diagnosis. [START_REF] Allebeck | Psychiatric diagnoses as predictors of suicide. A comparison of diagnoses at conscription and in psychiatric care in a cohort of 50,465 young men[END_REF] The variable 'emotional control' was assessed in the structured interview by the psychologist. Low emotional control, defined as a score of 1 or 2 on a scale from 1 (lowest) to 5 (highest) was reported for 20% of the cohort, and served as a summary assessment of mental stability, emotional maturity, and tolerance for stress and frustration.

Census data on childhood social circumstances

The conscripts and their parents, and other head of household when different from the parents, were linked to each other between censuses through their personal identification numbers by Statistics Sweden. Information on 'childhood socioeconomic position' and of "crowded housing" was obtained from the National Population and Housing Census of 1960 (response rate 99%), i.e. when the subjects were 9-11 years old. The classification, into the following six socioeconomic groups, was based on information on the occupation of the head of the household: (1) unskilled workers, (2) skilled workers, (3) assistant non-manual employees, (4) non-manual employees at intermediate or higher level, (5) farmers, (6) those not classified in a socioeconomic group. We here used a measure of 'crowded housing' (in the 1960 census > 2 people/room -kitchen not included -was classified as crowded).

Data on adulthood socioeconomic position, attained education, and income

Information on adulthood socioeconomic group for each conscript was obtained by record linkage with the National Population and Housing Census of 1990 held by Statistics Sweden.

This census had a response rate of over 98%. The classification into the following eight socioeconomic groups in 1990 was conducted at Statistics Sweden and is based on information on occupation and the educational level required for the occupations: (1) unskilled workers, (2) skilled workers, (3) assistant non-manual employees, (4) non-manual employees at intermediate level, (5) non-manual employees at higher level, (6) farmers, (7) self-employed (mostly skilled workers or drivers), ( 8) those for whom no occupation was reported (e.g. unemployed, early retired, or disabled). The data was also linked to the Longitudinal Database of Education, Income and Occupation (LOUISE) of 1990-2002 held by Statistics Sweden in order to receive information on achieved education for each study member and income for the year 1990. In the analyses achieved education was divided into five categories (<= 9 years, 10-11 years, 12-13 years, 14 years, 15 or more years) and income was divided into quartiles.

Information on outcomes

Information on mortality and age at death in the subjects between 1970 and 2003 was obtained from the National Cause of Death Register administered by the Centre for Epidemiology at the National Board of Health and Welfare in Sweden.

Data analysis

Associations between cognitive ability and mortality 1991-2003 were estimated using Cox's proportional-hazards models, yielding hazard ratios (HR:s) with 95 % confidence intervals, in both univariate and multivariate (including the potential confounders) models using the PHREG-procedure in the SAS computer package. Cognitive ability was modelled as a continouos variable, with HR:s given for an increase of 1 in the 9 point scale, as well as with dummy variables for each of nine categories using the highest test score as the reference category. In the adjusted models the relative hazard associated with a particular level of IQ score was estimated adjusting for the effect of the risk factors added to the model in order of their appearance in the life course. In order to calculate the proportions of the increased relative risk of mortality associated with IQ that was attenuated after adjustment for other risk factors we used the formulae ((RR crude -RR adjusted )/(RR crude -1))*100. Possible interaction effects between IQ (dichotomised IQ 1-4 versus IQ 5-9) and other early life factors was investigated according to the method proposed by Rothman. 17 18

Results

Of the 49 321 men conscripted for military service in 1969/70 there were 48 283 men still alive in 1990. Of them 47 678 (98.7%) participated in the census that year. Our presentations are based on those 43 834 men (94.0%) for whom there was information on all the variables included in the final analyses. In Table 2 the childhood and adolescent characteristics of the full cohort of those included in the analytical sample are shown. The differences in the prevalence of each risk factor between the full cohort and the sample are small.

In Table 3 the associations between cognitive ability, measured at conscription, and mortality between 40 and 54 years of age are shown. IQ was inversely associated with mortality (RR=1.15, CI95% 1.12-1.18, for each decrease of one on the nine-grade scale). In the multivariate analyses risk factors were added to the model in the order of their appearance in the life course, i.e. 1) childhood social circumstances, 2) adolescence behaviour and mental health, 3) adult social circumstances. Adjustments for indicators of poor social circumstances in childhood (low childhood SEP, crowded housing, and low body height) did not contribute to lower the increased risk found in the crude analyses. Adjustment for indicators of adolescent mental health and social adjustment, as well as for smoking and risky use of alcohol, contributed each to some attenuation of the association between IQ and mortality, while adjustment for overweight did not. After adjustment for all early life factors the relative risk was attenuated by 40%. Adjustment for all indicators of social circumstances in adulthood by themselves lowered the increased relative risk substantially (HR=1.04, CI95% 1.01-1.07, for each decrease of one on the nine-grade scale, i.e -73%). The single factor that contributed most to attenuate the increased relative risk found in the crude analyses was adult socioeconomic position. In the final model, taking all risk factors into account, the risks were strongly attenuated and the relative risks associated with an increase of 1 on the 9-point scale was on the limit to significantly increased (HR=1.02, CI95% 0.99-1.06, i.e. -87%). We investigated possible interaction effects between IQ and each confounding or mediating factor adjusting for the other factors. There were no indications of interaction effects.

A strong and graded increase of HR for mortality was seen on the nine-grade scale from high to low test scores (Table 4). After adjustment for risk factors over the life course no significantly increased risk remained. The HR in the lowest of nine IQ groups, in comparison with the highest, decreased from 3.3 (CI95% 2.3-4.6) to 1.2 (CI95% 0.9-1.8) after adjustment for all risk factors. Excluding information on achieved education from the fully adjusted model did not change the results.

Discussion

This is one of the very few studies on the association between IQ and mortality with possibilities to adjust in the analyses for a large number of risk factors for mortality over the life-course. It shows, in a cohort of Swedish males, that IQ test scores at ages 18-20 were associated with mortality between 40 and 54 years of age. A graded risk increase was seen across all IQ score groups. The increased risk was markedly attenuated by simultaneous adjustment for indicators of poor mental health and behavioural factors measured in late adolescence. Further adjustment for measures of adult social position almost entirely attenuated the increased risk found in the crude analyses indicating a strong mediating effect from adult circumstances.

Only a very small proportion of Swedish men are exempted from conscription, i.e. the cohort is highly representative of males born around 1950 in Sweden.

Many studies on early-life factors and health outcomes in adult life rely on retrospective information collected at some point of the subject's adult life which may introduce bias. [START_REF] Kauhanen | Social disadvantages in childhood and risk of all-cause death and cardiovascular disease in later life: a comparison of historical and retrospective childhood information[END_REF] In this study all information was collected at the time point when the conditions reported were actually present. This concerns socioeconomic positions and crowded housing in childhood as well as the behavioural factors measured at conscription (over-weight, smoking, risky use of alcohol) and the information obtained when the subjects were 39-41 years of age. Hence, the non-differential misclassification in this study is most likely smaller than in previous studies, leading to less dilution of relative risk estimates associated with the risk factors measured in early life and result in a higher explanatory power of each potential risk factor.

The psychiatric diagnoses given at conscription were categorised according to the International Classification of Diseases (ICD), version 8. At present, version 10 of ICD is in use. We believe that the measure of psychiatric illness used in this study quite well captures what would have been found using the updated version of ICD, although the specific diagnoses would differ somewhat.

All conscripts met with a psychologist for a face-to-face interview in order to assess their level of emotional control. We are not fully aware of any similar measure used in personality research today, but we have previously reported strong associations between the measure of low emotional control and smoking [START_REF] Hemmingsson | Smoking at age 18-20 and suicide during 26 years of followup-how can the association be explained?[END_REF] , alcoholism [START_REF] Hemmingsson | Explanations of social class differences in alcoholism among young men[END_REF] , early retirement [START_REF] Upmark | Predictors of disability pension among young men: The role of alcohol and psychosocial factors[END_REF] , and mortality [START_REF] Larsson | Self-rated health and mortality among young men: what is the relation and how may it be explained?[END_REF] .

This study only includes men and the reported associations may not be similar among women.

In the study based on the British 1946 birth cohort 4 men but not women showed an increased risk of mortality with low IQ. The men were followed for mortality between 40-53 years of age when mortality rates are still low. In a study by Hart et al there was an association between IQ and mortality among persons younger than 65 but not among persons older than 65. [START_REF] Hart | Childhood IQ and all-cause mortality before and after age 65: prospective observational study linking the Scottish Mental Survey 1932 and the Midspan studies[END_REF] In a previous study based on the 1969 conscription cohort we found that the strengths of association between IQ and mortality was the same over 35 years of follow up after the conscription examination. [START_REF] Hemmingsson | The association between cognitive ability measured at ages 18-20 and mortality during 30 years of follow-up--a prospective observational study among Swedish males born 1949-51[END_REF]

Comparison with previous studies

Only a limited number of previous studies have reported on the association between childhood IQ and mortality. [START_REF] Batty | Premorbid (early life) IQ and Later Mortality Risk: Systematic Review[END_REF] A Scottish study based on 922 subjects born in 1921 found an association, including males and females in the same analyses, between IQ measured at age 11 and mortality during a follow from middle age. An increased relative risk of mortality was found only in the lowest, compared with the highest, IQ-quartile (RR=1.47) and for those who died before the age of 65, but not among those who died later in life. 3 23 This study did not include information on other early life circumstances. In the British 1946 birth cohort IQ was measured at age eight and the study population was divided into IQ qurtiles and followed for mortality between 9-54 years of age. [START_REF] Kuh | Childhood cognitive ability and deaths up until middle age: a post-war birth cohort study[END_REF] In the crude analyses a doubled risk of mortality was found among men in the lowest IQ quartile. After adjustment for indicators of social circumstances in childhood and adulthood the increased risk was reduced by 63 % and was no longer significantly increased. No association between IQ and mortality was found among women. In a Scottish cohort based on just over 2000 men and women born in Aberdeen in 1921 a stronger association among women than among men was found between IQ at age 11 and mortality up to the age of 76. [START_REF] Whalley | Longitudinal cohort study of childhood IQ and survival up to age 76[END_REF] In a Danish cohort based on men born in Copenhagen in 1953 a graded association was found between IQ measured at age 12 and mortality followed up to the age of 47. [START_REF] Osler | Socioeconomic position in early life, birth weight, childhood cognitive function, and adult mortality. A longitudinal study of Danish men born in 1953[END_REF] The study did not include information on the participants adult life circumstances and adjustment for childhood social class only slightly attenuated the association. Batty et al (2008) investigated the association between IQ and mortality in a cohort consisting 4316 male former Vietnam-era US army personnel. [START_REF] Batty | IQ in late adolescence/early adulthood, risk factors in middle age and later all-cause mortality in men: the Vietnam Experience Study[END_REF] The men were tested for IQ at entry into the service in late adolescence and were interviewed in middle age concerning potential risk factors for mortality, e.g. smoking and social circumstances over the life course. The association between IQ and mortality found in the crude analysis was not affected by adjustment for childhood social circumstances but almost completely attenuated by adjustment for adult social circumstances. Very similar results have been reported from three other US cohorts with data on IQ collected in adolescence and mortality up to middle age. [START_REF] Link | The resources that matter: fundamental social causes of health disparities and the challenge of intelligence[END_REF] Our finding of a strong mediating effect from socioeconomic factors in middle age on the association between childhood IQ and mortality is in strong agreement with those recently published findings.

Is IQ a risk factor for mortality?

We found a gradually increased risk of mortality by decreasing test score on all nine levels among men 40-54 years of age. Adjustment for all risk factors almost entirely attenuated the increased risk of mortality found in the crude analysis.

The indicators of poor childhood social circumstances (socioeconomic position and crowded housing measured at ages 9-11, and body height measured at ages 18-20) did not contribute to decrease of the association between IQ and mortality. This is in accordance with findings in previous studies. 1 4-7 In this study we were able to adjust for psychiatric diagnoses, social misbehaviour (self-reported contact with police and childcare authorities), and low emotional control at conscription. All three factors contributed each somewhat to attenuate the increased risk found in the crude analyses. It may be that those factors indeed are indicators of negative childhood experiences not captured by our measures of childhood social circumstances. There is evidence that a poor psychosocial home environment may be associated with negative health outcomes, [START_REF] Felitti | Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The Adverse Childhood Experiences (ACE) Study[END_REF] negative health related behaviours, [START_REF] Anda | Adverse childhood experiences and smoking during adolescence and adulthood[END_REF] as well as hamper IQ development. 26 27 28 It may also be that persons with lower IQ have difficulties in interpreting signs of upcoming psychiatric symptoms and therefore have a lower ability to take preventive actions. 15 It has been suggested that persons with lower IQ may have more difficulties in understanding and interpreting health prevention messages, e.g. related to smoking, risky use of alcohol and physical activity. [START_REF] Gottfredson | Intelligence predicts health and longevity, but why? Current direction in psychological[END_REF] Previous investigations on the association between IQ and life style habits often point at the importance of socioeconomic factors. In this study smoking and risk use of alcohol, but not overweight, contributed somewhat to attenuate the increased risk found in the crude analyses. Taylor et al [START_REF] Taylor | Childhood mental ability and smoking cessation in adulthood: prospective observational study linking the Scottish Mental Survey 1932 and the Midspan studies[END_REF] found that childhood IQ was not associated with starting smoking, but with smoking cessation in adulthood among persons born 1921. However, after adjustment for adult social class and deprivation category the association was no longer significant. We have recently shown in this conscription cohort an association between IQ and smoking at age 18, which almost disappeared after adjustment for other predictors of smoking. No association was found between IQ and smoking cessation later in life. [START_REF] Hemmingsson | How does IQ affect onset of smoking and cessation of smoking -Linking the Swedish 1969 conscription cohort to the Swedish Survey of Living Conditions[END_REF] It is therefore not likely that the misclassification of smoking status during follow-up is related to IQ. It has been reported that persons with lower IQ more often report high alcohol consumption. [START_REF] Batty | Childhood IQ and life course socioeconomic position in relation to alcohol induced hangovers in adulthood: the Aberdeen children of the 1950s study[END_REF] In other studies a high alcohol consumption seems to be more common among persons with higher IQ. [START_REF] Hatch | Childhood cognitive ability and adult mental health in the British 1946 birth cohort[END_REF] In our study a measure of risky use of alcohol somewhat contributed to attenuate the association between IQ and mortality.

Cognitive ability is strongly associated with indicators of achieved social position. In the study by Kuh et al [START_REF] Kuh | Childhood cognitive ability and deaths up until middle age: a post-war birth cohort study[END_REF] on the association between IQ and all-cause mortality, 63% of the increased risk among men disappeared after adjustment for education and achieved socioeconomic circumstances indicating a strong importance of a path-way mechanism. [START_REF] Kuh | Childhood cognitive ability and deaths up until middle age: a post-war birth cohort study[END_REF] In this study we adjusted in the analyses for risk factors for mortality measured at different points in time during the life course. It turned out that adjustment in the analyses for indictors of adult social position strongly contributed to reduce the associations between IQ and mortality (-73% and fully adjusted -87%). Very similar results were shown in three US cohorts with data on IQ collected in early life. 10 11 This result is in line with a pathway effect where IQ determines adult social circumstances and those circumstances in turn determine risk of mortality. 34 35 Since IQ and education are strongly correlated, one might question the logic of adjusting the association between IQ and mortality for education. However, in this study the introduction of achieved education in the analytical model after accounting for all other factors did not change the results at all.

Conclusions

In our analyses of the association between childhood IQ score and later mortality we adjusted for indicators covering information on childhood circumstances, health behaviours, and adult social circumstances. We found that the association between IQ and mortality disappeared entirely after adjustment in the analyses for adult social circumstances and social and behavioural factors measured in late adolescence. The association between IQ and mortality was strongly mediated by adult social circumstances.

Table 1 .

 1 Data collection 1949-2003 Calender year

	Age of
	subject

Table 2 .

 2 Prevalence of childhood and adolescent risk factors in the full cohort and among those included in the analytic sample.

		Full	Analytical
		cohort	sample
		(n=49321)	(n=43834)
		%	%
	Father manual worker	54.5	54.8
	Crowded housing in	20.7	20.6
	childhood
	Body height <171 cm	11.0	10.9
	Psychiatric diagnosis	12.5	11.8
	Contact with police and	28.8	28.4
	child care
	Low emotional control	30.5	29.6
	Daily smoking	58.6	58.4
	Risky use of alcohol	13.6	13.1
	BMI>25	6.6	6.6

Table 4 .

 4 IQ-score and all cause mortality. Crude and adjusted relative risks (hazard ratios), with 95% confidence intervals, with the highest IQ score as reference category (9 = highest). all mental health indicators, behavioural factors and socioeconomic position, income, and achieved education ** all mental health indicators, behavioural factors and adult socioeconomic position, and income, but not including achieved education

			Crude		Adjusted*	Adjusted**
	IQ-level	RR	CI 95%	RR	CI 95%	RR	CI 95%
	9	1	---	1	---	1	---
	8	1.1	0.8-1.5	1.0	0.7-1.3	1.0	0.7-1.3
	7	1.3	0.9-1.7	1.0	0.7-1.4	1.0	0.7-1.4
	6	1.5	1.1-2.0	1.0	0.8-1.4	1.1	0.8-1.4
	5	1.7	1.2-2.2	1.0	0.8-1.4	1.1	0.8-1.5
	4	1.9	1.4-2.5	1.0	0.7-1.4	1.1	0.8-1.4
	3	2.0	1.5-2.7	1.0	0.7-1.4	1.0	0.8-1.5
	2	2.6	1.9-3.6	1.2	0.8-1.7	1.2	0.9-1.7
	1	3.3	2.3-4.6	1.2	0.9-1.8	1.3	0.9-1.9

*

Acknowledgements

Funding: This study was supported by the Swedish Council for Working Life and Social Research (Project No 2005-0960) Ethical approval: The ethics committee at the Karolinska Institute, Stockholm, approved the study.

What this paper adds:

What is already known on this subject? The association between IQ and mortality has been found in many studies. The mechanisms and causal pathways are not fully understood.

What does this study adds?

This is the largest study to date to investigate the potential confounding and mediating factors in the association between IQ and mortality. The association between IQ and mortality was strongly mediated by adult social circumstances and social and behavioural factors measured in late adolescence.


Zoltán Vokó
email: z.voko@sph.dote.hu

PhD Péter Csépe

MD, MSc Renáta Németh

MSc Karolina Kósa

PhD Zsigmond Kósa

PhD György Széles

PhD Róza Ádány

Does socioeconomic status fully mediate the effect of ethnicity on the health of Roma people in Hungary?

Keywords: health surveys, health status, health behaviour, gypsies, ethnic groups

page 3 of 26 "The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive licence (or non exclusive for government employees) on a worldwide basis to the BMJ Publishing Group Ltd and its Licensees to permit this article (if accepted) to be published in JECH editions and any other BMJPGL products to exploit all subsidiary rights, as set out in our licence (http://jech.bmj.com/ifora/licence.pdf)" page 4 of 26 ABSTRACT Background Several models were proposed to explain the association between ethnicity and health. We investigated whether the association between Roma ethnicity and health is fully mediated by socioeconomic status in Hungary. Methods Comparative health interview surveys were performed in 2003-2004 on representative samples of the Hungarian population and inhabitants of Roma settlements. Logistic regression models were applied to study whether the relationship between Roma ethnicity and health is fully mediated by socioeconomic status, and whether Roma ethnicity modifies the association between socioeconomic status and health.

Results

The health status of people living in Roma settlements was poorer than that of the general population (odds ratio of severe functional limitation after adjustment for age and gender 1.8 (95% confidence interval 1.4-2.3)). The difference in selfreported health and in functionality was fully explained by the socioeconomic status.

The less healthy behaviours of people living in Roma settlements was also related very strongly to their socioeconomic status, but remained significantly different from the general population when differences in the socioeconomic status was taken into account, (e.g., odds ratio of daily smoking 1.6 (95% confidence interval 1.3-2.0) after adjustment for age, gender, education, income, and employment).

Conclusion

Socioeconomic status is a strong determinant of health of people living in Roma settlements in Hungary. It fully explains their worse health status but only partially determines their less healthy behaviours. Efforts to improve the health of Roma people should include a focus on socioeconomic status, but it is important to note that cultural differences must be taken into account in developing public health

interventions. page 5 of 26

The association between ethnicity and health is well established. Though it is generally accepted that interpreting ethnicity as an independent determinant of health is a simplification, our knowledge of the complex causal network of ethnicity, socioeconomic status (SES), health behaviour, environment and health status is rather limited. [START_REF] Kósa | Studying vulnerable populations. Lessons from the Roma minority[END_REF] The majority of studies on ethnicity and health were published in the United States since the beginning of the 20 th century (comparing health and health determinates in white people, afro-Americans, Hispanics and Native Americans), [START_REF] Trask | The significance of the mortality rates of the colored population of the United States[END_REF][START_REF] Smith | Socioeconomic differentials in mortality risk among men screened for the Multiple Risk Factor Intervention Trial, 2: black men[END_REF][START_REF] Smith | Mortality differences between black and white men in the USA: contribution of income and other risk factors among men screened for the MRFIT[END_REF][START_REF] Borrell | Racial Identity Among Hispanics: Implications for Health and Well-Being[END_REF][START_REF]Race, Ethnicity and the Health of Americans[END_REF] and in Britain (study on indigenous population and different ethnic minorities like Asian, Indian etc.). [START_REF][END_REF][START_REF] Balarajan | Ethnic differences in mortality from ischaemic heart disease and cerebrovascular disease in England and Wales[END_REF] Data on the health status and its determinants of the Roma population living in Central-Eastern Europe are scarce, despite the fact that they are the largest minority in the European Union, especially in Bulgaria, Romania, Hungary, the Slovak and the Czech Republics. [START_REF] Kósa | Health status of the Roma population in Hungary [in Hungarian][END_REF][START_REF] Koupilova | Health needs of the Roma population in the Czech and Slovak Republics[END_REF][START_REF] Ambrus | Minorities, communication, health[END_REF] Of the small number of studies in this population, the majority were conducted on convenience samples and methodological problems frequently occurred. Data protection laws in these countries present a significant obstacle in designing and conducting state of the art epidemiological studies in this field. [START_REF] Farkas L | The Monkey That Does Not See[END_REF] Nevertheless, available data show that Roma people have much worse health status, exhibit much less favourable health behaviour and live in an unhealthier environment than the average population. [START_REF] Hajioff | The health of the Roma people: a review of the published literature[END_REF] Recently, we reported the results of two comparative health surveys of the general Hungarian adult population and of the inhabitants of Roma settlements. [START_REF] Kósa | Health of the inhabitants of Roma settlements in Hungary -a comparative health survey[END_REF] We found that the health status of people living in Roma settlements was poor and comparable to the health status of people in the lowest socioeconomic quartile of the general population. Our data suggested that the lifestyle of people living in Roma settlements page 6 of 26 is even less conducive to future health than that of the poorest of the general population.

However, the influence of Roma ethnicity on health and health behaviours remains unknown. As has already been pointed out: "Studies that inadequately account for socioeconomic circumstances when examining ethnic-group differences in health can reify ethnicity (and its supposed correlates); however, the reductionist attribution of all ethnic differences in health to socioeconomic factors is untenable.

The only productive way forward is through studies that recognize the contingency of the relations between socioeconomic position, ethnicity, and particular health outcomes." [START_REF] Smith | Learning to live with complexity: ethnicity, socioeconomic position, and health in Britain and the United States[END_REF] Using data from the National Health Interview Survey 2003 and the Roma Health Survey, we were able to investigate whether the effect of Roma ethnicity on health is fully mediated by socioeconomic status and whether Roma ethnicity modifies the strength of the association between socioeconomic status and health.

METHODS

The design of the Hungarian National Health Survey 2003 and of the Roma Health Survey has already been reported. [START_REF] Kósa | Health of the inhabitants of Roma settlements in Hungary -a comparative health survey[END_REF] Briefly, the National Health Survey was based on a representative sample of the non-institutionalised Hungarian adult population, and collected information on self-reported health status, as well as on the main behavioural and socioeconomic determinants of health. [16] The study population of the National Health Survey was randomly selected from the Central Data Processing, Registration and Election Office's registry using two-stage sampling. In the first stage, communities (cities, towns and villages) were stratified by county and by community size. Within counties, communities were chosen with a sampling page 7 of 26 probability proportional to size. Individuals were then selected at random from the selected communities. To maximise the cost-effectiveness of the field work, a minimum of 10 individuals was chosen from each community selected. 5072 of the planned 7000 interviews were completed in the National Health Interview Survey.

Fifteen per cent of participants selected could not be located during the period of field work, 8% refused to participate, and 4% were unable to participate for other reasons.

The Roma Health Survey collected the same information based on a representative sample of persons living in Roma settlements in the north-eastern part of Hungary, where the representation of Roma people is the highest in the country.

The settlements were mapped previously and this served as the basis for the health survey. A two stage sampling process was employed. First settlements were selected randomly, and then households were selected using the random walk method, based on a map of the settlement. All adults in the household selected were The questionnaires used in the two surveys were almost identical allowing us to merge the datasets of the two surveys and fit multiple regression models to study the details of the associations between ethnicity, socioeconomic factors, and health. [START_REF]The European Health Interview & Health Examination Surveys Database: hishes[END_REF] We investigated two dimensions of health: health status and health behaviour. Health page 8 of 26 status was characterized by self-reported health and functional limitations, while health behaviour was represented by smoking, consumption of fresh fruits and vegetables and types of fat used for cooking. Specifically, self-reported health was assessed using a standard single-item measure (How is your health in general?) with five response options recommended by the WHO to measure perceived health. [START_REF] Bruin | Health interview surveys towards international harmonization of methods and instruments[END_REF] The response categories good, very good and fair were combined, as were bad and very bad. Functional limitation was assessed by a single-item question "Do you have any complaints, injuries, diseases that limit your everyday activities, such as working, shopping, managing your life, playing sports or keeping contact with other people?" The answers -yes I do, I am severely limited in my daily activities; yes I do, I am moderately limited in my daily activities; no, I do not -were dichotomised for the analysis to either severe functional limitation or modest or no limitation. Smoking was measured using the instrument recommended by the EUROHIS project of the WHO for population surveys. [START_REF] Bruin | Health interview surveys towards international harmonization of methods and instruments[END_REF] Questions in the instrument ascertained whether or not someone smoked, and if yes, what. Cigarette smokers were asked about the frequency of smoking, and daily smokers were asked about the number of cigarettes smoked per day. Smoking habit was dichotomised for the regression analysis as daily smokers and others.

Consumption of fresh fruits and vegetables, use of different types of fat for cooking, date of birth, gender, education, employment and monthly household income were assessed by direct questioning. Consumption of fresh fruits and vegetables was dichotomised as less than weekly and more frequently, and use of different types of fat for cooking was dichotomised as use of only lard and other. Age was categorised as 18-29, 30-44, or 45-64 years old. Education level was categorised as only primary education, secondary education without leaving certificate and at least secondary page 9 of 26 education with leaving certificate. Employment was categorised as active worker, unemployed, pensioner, disability pensioner, and other inactive. Mean household equivalent monthly income was used in the analysis, calculated as the total household income per month divided by the square root of the number of persons in the household. This adjustment was necessary because the income required to provide the same living standards do not increase linearly as the number of people in a household increases. As ethnicity was not explicitly asked in the surveys it was assumed that all participants of the Roma Health Surveys were Roma.

The theoretical model we investigated is shown in Figure 1.

i) The solid arrows represent the simplest pathway: socioeconomic status fully mediates the association between Roma ethnicity and health ("full mediation model").

ii) The dashed arrows add another layer of complexity: socioeconomic status partially mediates the association between Roma ethnicity and health ("partial mediation model").

iii) Dotted arrows reflect the hypothesis that Roma ethnicity is not only a determinant of health but also modifies the association between socioeconomic status and health ("effect modification model") [START_REF] Baron | The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations[END_REF] We fitted logistic regression models in a stepwise manner to determine which model our data support.

First, we fitted logistic models with self-reported health, functional limitation, smoking, consumption of fresh fruits and vegetables, and using only lard as fat for cooking as outcome variables and living in Roma settlement as independent variable corrected for age and gender. Next, in each model we added income, education and employment one by one. Finally, we fitted full models with interaction terms between page 10 of 26 the variables "living in Roma settlement" and the SES variables. The Wald-test was applied to test the hypotheses of no interaction; p<0.01 was considered statistically significant.

RESULTS

The mediation models for health status

Table 1 shows that both self-reported health and functional limitation were strongly related to socioeconomic factors. The odds of reporting very bad or bad health was 2.2 (95% confidence interval (CI) 1.8-2.7) times higher among people who lived in Roma settlements than in the general population after adjustment for age and gender (Figure 2). As the figure shows, this association gradually disappears after adjustment for income and education. The relationship between Roma ethnicity and functional limitation was similar; the effect disappeared after adjustment for income (Figure 2). page 11 of 26

The mediation models for health behaviour

Just like health status, health behaviour was also strongly related to socioeconomic factors (Table 2). The odds of daily smoking, consuming fresh fruits less than weekly and using only lard as fat for cooking were much higher among those who lived in Roma settlements (Figure 3). The odds ratios were reduced, but remained statistically significant after adjustment for income, education and employment.

page 13 of 26

DISCUSSION

We found that socioeconomic status is strongly related to health status and health behaviour in people living in Roma settlements. Our results show that the differences in health status (as measured by self-reported health and functional limitation)

between the general population and people living in Roma settlements are fully explained by the differences in income, education and employment. However, the differences in health behaviour (notably smoking, consumption of fruits and vegetables, and type of fat used for cooking) could not be accounted for by socioeconomic factors alone, leaving room for ethnicity as an explanatory variable (i.e., ethnicity is statistically significantly related to elements of health behaviour after adjustment for the socioeconomic factors).

The utility and interpretation of ethnicity as a health determinant has long been debated in the scientific literature, with several models put forward to explain the page 15 of 26 relationship between ethnicity and health. [START_REF] Kaplan | Use of race and ethnicity in biomedical publication[END_REF][START_REF] Dressler | Race and ethnicity in public health research: models to explain health disparities[END_REF] There is evidence that genetic factors may have a more important role in explaining differences in health of different populations. For example nicotine dependence and smoking persistence are heritable, and are determined by a complex interplay of polygenic and environmental influences to a degree larger than previously thought. [START_REF] Lermann | Genetics and smoking cessation improving outcomes in smokers at risk[END_REF] Nevertheless, explanations attributing health disparities to genetic differences between various minority and majority groups have been increasingly challenged due to the recognition that ethnicity is more of a social, than a biological construct. [START_REF] Cooper | The biological concept of race and its application to public health and epidemiology[END_REF][START_REF] Krieger | Shades of difference: theoretical underpinnings of the medical controversy on black/white differences in the United States, 1830-1870[END_REF] Another set of theories proposes health behaviour variations among ethnic groups as an explanation for health disparities. [START_REF] Dressler | Race and ethnicity in public health research: models to explain health disparities[END_REF] Diet, exercise, and use of various psychoactive substances are well-known health determinants of major importance, and have been shown in our previous paper to substantially differ between Roma and non-Roma. [START_REF] Kósa | Health of the inhabitants of Roma settlements in Hungary -a comparative health survey[END_REF] However, health and health behaviour are influenced by more distal health determinants such as education, income, occupation, and other dimensions of the socioeconomic status. [START_REF] Krieger | Measuring social class in US public health research: concepts, methodologies, and guidelines[END_REF][START_REF] Galobardes | Indicators of socioeconomic position[END_REF] The socioeconomic model holds that ethnic health disparities are confounded with SES disparities, [START_REF] Dressler | Race and ethnicity in public health research: models to explain health disparities[END_REF] therefore all ethnic health variations must be adjusted for the widest possible range of socioeconomic factors. If significant ethnic differences in health behaviour not explicable by SES remain, as in our case, then the partial mediation model holds, and additional factors related to ethnicity can be hypothesized as health determinants. This was the case in an intervention study in a Slovenian Roma population, which revealed that smoking is a strong part of the cultural, ethnic, and individual identity of the Roma to the extent that even children smoke. Advice from a doctor to quit smoking is usually not followed, and the attempts to quit are usually unsuccessful. The study found that the Roma hold a tenacious belief that the harmful page 16 of 26 effects of smoking are in the hands of destiny and do not associate their smokingrelated illnesses with the habit. [START_REF] Petek | Attitudes of Roma toward smoking: qualitative study in Slovenia[END_REF] The material interpretation of health inequalities assigns a considerable part of ethnic health variations to differential access to material conditions such as food, shelter, access to services, etc. [287,[START_REF] Lynch | Income inequality and mortality: importance to health of individual income, psychosocial environment, or material conditions[END_REF] We found evidence in our study to support this model, since income was strongly related to health.

According to the psychosocial model, ethnic health behaviour variations could be attributed to stress due to the discrimination and social exclusion resulting from holding a low socioeconomic position. [START_REF] Dressler | Race and ethnicity in public health research: models to explain health disparities[END_REF][START_REF] Krieger | Racial discrimination and blood pressure: the CARDIA Study of young black and white adults[END_REF][START_REF] Marmot | Social determinants of health[END_REF] While discrimination against the Roma both in everyday life and specifically in health care have been reported, [START_REF]The situation of Roma in an enlarged European Union. Luxembourg[END_REF][START_REF] Danova-Russinova | Ambulance not on the way: the disgrace of health care for Roma in Europe[END_REF] we have not encountered publications on perceived stress among them. Increased odds of smoking among Roma settlement dwellers even after adjustment for SES in our study, and the high prevalence of smoking among pregnant Roma women might in part be attributed to such psychosocial factors. [START_REF] Kósa | Health status of the Roma population in Hungary [in Hungarian][END_REF][START_REF] Kósa | Health of the inhabitants of Roma settlements in Hungary -a comparative health survey[END_REF] Data on the early disadvantages of Roma children and the life course perspective would also deserve attention when the psychosocial explanation of the health behaviour of Roma are further elaborated. [START_REF] Kertesi | The Roma children of the transformation recession[END_REF][START_REF]Equal access to quality education for Roma. Monitoring Reports[END_REF][START_REF] Barker | Mothers, babies and health in later life[END_REF] Socioeconomic status in our study could not fully explain the increased odds of lard use for cooking as well as low consumption of fresh fruits and vegetables in the Roma. Psychosocial health determinants seem unlikely to account for these increased odds so other determinants including rurality, traditions, and beliefs should be considered as additional contributing factors. [START_REF] Probst | Person and place: the compounding effects of race/ethnicity and rurality on health[END_REF][START_REF] Hjelm | Beliefs about health and diabetes in men of different ethnic origin[END_REF][START_REF] Jasti | Dietary supplement use in the context of health disparities: cultural, ethnic and demographic determinants of use[END_REF] Our findings have shown that there is no unique model for the different aspects of the complex relationship of Roma ethnicity and health. The neo-material model, [START_REF] Lynch | Income inequality and mortality: importance to health of individual income, psychosocial environment, or material conditions[END_REF] the structural-constructivist model according to which our "ability to control page 17 of 26 disease and death are distributed according to resources of knowledge, money, power, prestige, and beneficial social connections", [START_REF] Phelan | Controlling Disease and Creating Disparities: A fundamental cause perspective. The Journals of Gerontology Series B[END_REF] and other models that emphasize both psychological and sociocultural factors [START_REF] Dressler | Race and ethnicity in public health research: models to explain health disparities[END_REF] have different explanatory power for the associations between ethnicity and specific dimensions of health.

One limitation of our study may lie in the methodology. We studied two dimensions of health: health status and health behaviour. The answers provided about health status might reflect a more global subjective rating of health and well being, whereas the answers about specific health behaviours were more clearly defined. Consequently, the former may be more likely to be affected by reporting biases such as negative response style, which might themselves be associated with socioeconomic status and ethnicity. This potential bias may explain why socioeconomic status was found to fully mediate health status, but not health behaviours. Nevertheless, the question about functionality was much more specific than the question about self-reported health, and the results about the two dimensions of health status were consistent. Furthermore, we used only income, education and employment as socioeconomic factors in the analysis. Including additional socioeconomic factors in the model might have shown a stronger mediational effect for socioeconomic status on heath behaviours.

Our study suffers from the obvious limitation that it is not representative of the overall Hungarian Roma population. It did not include those Roma that are assimilated with the majority population to various degrees. However, given the unwillingness of many people to self-define their ethnicity as Roma, this is a constraint that will be very difficult to overcome. As the Roma Health Survey involved page 18 of 26 the most disadvantaged section of the Roma population, our results do apply to the group whose needs are the most important to understand from a policy perspective.

Finally, as in any survey based on self-report, the data on diet must be interpreted with caution. Nevertheless, the probability of information bias in case of the simple questions we used to assess the frequency of fruit and vegetable consumption and about the types of fat used for cooking is much less than in a detailed dietary questionnaire.

Although the evidence gathered so far on the nature, magnitude, and causes of health inequities between Roma and non-Roma has already been sufficient to have immediate policy implications, the contextual factors are of fundamental importance to design and implement efficient programs to increase the health of Roma people.

Decent housing, education and employment should be the first marks on the long road to empower Roma people to improve their health. Understanding the role of their traditions and culture as health determinants may help increasing speed and avoiding dead ends along this road. What is already known on this subject?

ACKNOWLEDGMENTS

Ethnicity is a well established determinant of health behaviour and health status.

What does this study add?

The results highlight that socioeconomic status is a very strong determinant of the health of people living in Roma settlements. The paper shows that the association between Roma ethnicity and health status is fully mediated, and the association between Roma ethnicity and health behaviour is partially mediated by the socioeconomic status.

page 25 of 26 The dotted line represents an odds ratio of 1, which corresponds to no association.

  interviewed by the interviewers. 969 interviews were completed successfully of the planned 1000, 12 persons refused to participate, 19 interviews were incomplete (96.9% response rate). Given the low number of elderly persons in the Roma Health Survey, we limited our analysis to persons aged 18-64 years, reducing our sample size to 936 persons in the Roma Health Survey and 4121 individuals in the National Health Survey in the analysis. Both surveys were approved by the Ethical Committee of the Hungarian National Scientific Council on Health.

Theof 26 "

 26 National Health Interview Survey, 2003, was funded by the Hungarian Ministry of Health in the framework of the National Public Health Programme. The Roma Health Survey was funded from Hungarian research grants from the National Research and Development Program (NKFP-1B/0013/2002) and the Ministry of Environment (KvH-96/167/2000). This project was funded by the National Scientific Council on Health (ETT: 331/2006). The contribution of fieldworkers and other study personnel is gratefully acknowledged, as is the support of the Ministry of Health, Ministry of Environment, and Ministry of Education of Hungary. page 19 WHAT THIS PAPER ADDS"

Figure 1 .

 1 Figure 1. The theoretical model investigated in the study

Figure 2 .page 26 of 26 Legend Figure 3 Figure 3 .

 22633 Figure 2. The association between Roma ethnicity and health status

Table 1 .

 1 The association between socioeconomic status, Roma ethnicity and health status

	Odds ratio* (95% CI)

Table 2 .

 2 The association between socioeconomic status, Roma ethnicity and health behaviour

	Odds ratio* (95% CI)


PhD Judith G M Rosmalen
email: j.g.m.rosmalen@med.umcg.nl

BSc Eva M Kingma

MD Lineke M Tak

PhD Martijn Huisman

Intelligence is negatively associated with the number of functional somatic symptoms

Keywords: functional somatic symptoms, intelligence, somatization, general population, longitudinal

Background: Functional somatic symptoms (FSS), symptoms that cannot be conclusively explained by organic pathology, have a poorly understood aetiology. Our aim is to study intelligence as a risk factor for FSS. We hypothesize that intelligence is negatively associated with the number of FSS. To investigate the specific role of intelligence in FSS as opposed to medically explained symptoms (MES), we compared associations of intelligence with FSS with those of intelligence with MES. We hypothesize that lifestyle factors and socioeconomic factors mediate the relation between intelligence and both FSS and MES, whereas psychological distress is especially important for FSS.

Methods:

We performed all analyses in a longitudinal study with two measurement waves in a general population cohort of 947 participants (age 33-79 years, 47.9 % male). We used the Generalized Aptitude-Test Battery to derive an index for general intelligence, and the somatization section of the Composite International Diagnostic Interview to measure the number FSS and MES.

Results: General intelligence was significantly associated with the number of FSS. The association of intelligence and FSS but not MES was mediated by work-situation: participants of lower intelligence that report more FSS are more often (unwanted) economically inactive.

No evidence was found for a mediating role of psychological distress in the association of intelligence with FSS, even though distress was an important predictor of FSS.

Conclusion:

Intelligence is negatively associated with the number of FSS in the general population. Part of the association of intelligence with FSS is explained by a more unfavourable work situation of adults of lower intelligence.

INTRODUCTION

Functional somatic symptoms (FSS) are somatic symptoms that cannot be conclusively explained in terms of conventionally defined organic pathology. 1;2 FSS constitute a major health care problem because they are common, disabling for patients and costly for society. [START_REF] Nimnuan | Medically unexplained symptoms -An epidemiological study in seven specialities[END_REF][START_REF] Katon | Medically unexplained symptoms in primary care[END_REF][START_REF] Barsky | Somatization increases medical utilization and costs independent of psychiatric and medical comorbidity[END_REF] Doctors often have difficulties in dealing with patients who present FSS. They want to reassure their patient, but at the same time fail to provide an acceptable explanation for the occurrence of FSS. Most doctors explain FSS as a result of psychological distress. 6;7 Patients are often dissatisfied with those psychological labels for their somatic symptoms [START_REF] Rief | Are somatoform disorders 'mental disorders'? A contribution to the current debate[END_REF] and prefer a somatic diagnosis. [START_REF] Bakal | An experiential mind-body approach to the management of medically unexplained symptoms[END_REF] This incorrect dualistic view of both patients and doctors on the nature of symptoms is a major obstacle to an effective treatment relation.

Although the aetiology of FSS is poorly understood, it is becoming increasingly clear that underlying processes are multifactorial. Recent research and theory in this area suggest complex interactions between biological, psychological and social factors in the development and perpetuation of FSS. [START_REF] Brown | Psychological mechanisms of medically unexplained symptoms: An integrative conceptual model[END_REF][START_REF] Rief | Explaining medically unexplained symptoms-models and mechanisms[END_REF][START_REF] Deary | The cognitive behavioural model of medically unexplained symptoms: A theoretical and empirical review[END_REF] Intelligence is an interesting vulnerability factor to study in the context of FSS, because it is associated with several risk factors for development and perpetuation of FSS. Although intelligence itself has never been studied as a risk factor for FSS, studies towards related constructs such as lower education level suggest an association with the occurrence of somatic symptoms in general practice. [START_REF] Van Der Windt | Impact of physical symptoms on perceived health in the community[END_REF][START_REF] Hiller | Somatization in the population: from mild bodily misperceptions to disabling symptoms[END_REF][START_REF] Mattila | Alexithymia and somatization in general population[END_REF][START_REF] Kroenke | Gender differences in the reporting of physical and somatoform symptoms[END_REF][START_REF] Gureje | Somatization in cross-cultural perspective: A World Health Organization study in primary care[END_REF][START_REF] Verhaak | Persistent presentation of medically unexplained symptoms in general practice[END_REF][START_REF] Karvonen | Somatization symptoms in young adult Finnish population -Associations with sex, educational level and mental health[END_REF] In contrast to FSS, various studies have looked at the relation between intelligence and various kinds of medically explained somatic health problems. These studies have consistently found a negative association between intelligence and somatic morbidity or mortality. 20 21;22 Two commonly studied non-exclusive mediating mechanisms in the relation between intelligence and health are socioeconomic factors and lifestyle factors. [START_REF] Deary | Why do intelligent people live longer[END_REF] Intelligence is associated with more education, and thereafter with more professional occupations that might place the person in healthier environments. In addition, intelligence is associated with a healthier diet, more exercise, and less smoking and problem drinking. Both mechanisms seem to be involved in the relation between intelligence and somatic morbidity and mortality, however, it is unknown to which degree these mechanisms are involved in the development of FSS. A third potential mediator is psychological distress, since both intelligence and somatic symptoms are known to be associated with an increased prevalence of anxiety and depression. [START_REF] Koenen | Childhood IQ and Adult Mental Disorders: A Test of the Cognitive Reserve Hypothesis[END_REF][START_REF] Henningsen | Medically unexplained physical symptoms, anxiety, and depression: A meta-analytic review[END_REF][START_REF] Iacovides | Comorbid mental and somatic disorders: an epidemiological perspective[END_REF] Given the fact that most doctors explain FSS as a result of psychological distress, 6;7 the question arises whether its mediating role might be more important in the relation of intelligence with FSS than in that with medically explained symptoms (MES).

This study aims to clarify the association between intelligence and FSS in a population-based cohort. We hypothesize that intelligence is negatively associated with the number of FSS. We hypothesize that socioeconomic factors, lifestyle factors and psychological distress mediate this relation. To investigate the specific role of intelligence in FSS as opposed to MES, we compared associations of intelligence with FSS with those of intelligence with MES. Whereas we expected more or less similar associations with both outcomes, we expected that distress would be a mediator of the association of intelligence with FSS but not with that of intelligence with MES.

METHODS

Population

The current study has been performed in a cohort derived from PREVEND (Prevention of REnal and Vascular ENd stage Disease), a major population cohort study at the University Medical Center Groningen investigating microalbuminuria as a risk factor for renal and cardiovascular disease. The recruitment of participants for PREVEND has been described elsewhere. [START_REF] Pinto-Sietsma | Urinary albumin excretion is associated with renal functional abnormalities in a nondiabetic population[END_REF] Basically, the PREVEND baseline population consists of 8592 subjects randomly selected from the population of the city of Groningen with oversampling for albuminuria. Selection of subjects for the purpose of the current study was aimed to recruit a sample representative of the general population of Groningen, while simultaneously rectifying PREVEND's oversampling for albuminuria. Research assistants handed over invitations to 2554 participants who visited the outpatient clinic of PREVEND. Measurements were completed by a total of 1094 participants (43%), forming the population cohort. PREVEND participants who were invited for the current study but did not participate and PREVEND participants who agreed to participate did not significantly differ concerning gender, age and scores on a 12-item neuroticism scale. [START_REF] Sanderman | Cross-Cultural Comparisons of Personality -the Netherlands and England[END_REF] Follow-up measurements, performed approximately two years later, were completed by a total of 976 participants. The study was approved by the medical ethics committee and was conducted in accordance with the guidelines of the declaration of Helsinki. Written informed consent was obtained from all participants.

Assessment of intelligence

At baseline, the intelligence of the participants was measured using the computerized version of the General Aptitude-Test Battery (GATB) version B 1002-B. [START_REF] Bosch | Manual Generalized Aptitude Test Battery[END_REF] The GATB consists of a combination of tests that measure nine aptitudes. The aptitude intelligence is measured by three tests: 1) a dimensional space test, 2) a vocabulary test, and 3) an arithmetic reasoning test. All participants performed the intelligence test in groups of at most nine persons. Before the start of each test, a test assistant provided test-instructions and provided computer help when necessary. Tests were not started before the test assistant was certain that all participants had successfully completed the practice sessions. To construct a general intelligence score, we summed standardized scores on each of the three subtests (a total of 1061 completed GATBs were available).

Assessment of somatic symptoms

Participants completed the somatization section of the Composite International Diagnostic Interview (CIDI). The CIDI is a fully structured diagnostic interview developed by the World Health Organization and has adequate test-retest reliability and validity. [START_REF] Andrews | The psychometric properties of the composite international diagnostic interview[END_REF] A fully computerized version of the CIDI 2.1, suitable for self-administration, was applied. Trained interviewers were present for questions and for people that needed computer help. In the CIDI somatization section, 43 FSS (listed in appendix 1) are assessed through asking "have you ever had" this symptom. Symptoms are considered present when they meet severity criteria, i.e. provoking a health care visit. If these criteria are met, the interview assesses in a hierarchical fashion whether a medical doctor diagnosed a symptom as due to physical illness or injury, or whether a symptom was caused by the use of medication, drugs or alcohol. If the participant reported that a medical doctor diagnosed the symptom as due to physical illness or injury, the symptom was scored as a MES. If all inquiries were negative for medical explanations, the symptom was scored as a FSS. Sexual indifference was excluded from the analyses since it is not surveyed in the CIDI whether this symptom provoked a health care visit. Participants first completed the CIDI lifetime version measuring lifetime FSS and lifetime MES (a total of 1088 completed CIDIs were available). Approximately two years later, participants were re-interviewed and completed the CIDI 12-months version, in which the occurrence of the 43 symptoms in the previous year is surveyed (964 completed CIDIs were available). Since we expect that the 12-months recall of symptoms is less likely to be affected by cognitive abilities than lifetime recall, we constructed sum scores of 12-months FSS and 12-months MES for our main analyses. Additionally, sum scores of new-onset FSS and MES were constructed by comparing the MES and FSS reported in the CIDI 12-months interview with those reported in the CIDI lifetime interview.

Assessment of lifestyle factors

Body mass index (BMI) was calculated as the ratio between weight and the square of height (kg/m²) measured at baseline. Smoking, alcohol consumption, and exercise frequency were assessed by written self-report at baseline. Smoking was categorized in non-smoker, 1-5, 6-10, 11-15, 16-20 or more than 20 cigarettes/day. Alcohol consumption was categorized in never or almost never, 1-4 units/month, 2-7 units/ week, 1-3 units/day and ≥4 units/day).

Exercise frequency was categorized as never, once/week, twice or more/week.

Assessment of socio-economic factors

Information on income, educational level, and work situation was retrieved from questionnaires that were filled in at the time of inclusion into PREVEND. Income was measured through the gross monthly household income (<1200, 1200 -1799, 1800 -2199, 2200 -2799, 2800 -3799, 3800 -5800, or >5800 guilders) divided by the square root of the number of people living in the household. [START_REF] Buhrman | Sensitivity estimates across ten countries using the Luxembourg income study (LIS) data base[END_REF] The variable education was made up of the following categories: not applicable, low, middle, or high educational level. Low educational level was defined as lower secondary education or less, middle education was defined as higher secondary education, and high education was defined as tertiary education. Working situation was categorized in the following categories: employed (i.e. currently having a job), willingly unemployed (i.e. housekeeping or retired), or unwillingly unemployed (i.e. job seeker or unable to work).

Assessment of psychological distress

Psychological distress was measured using the Dutch translation of the 12-item General Health Questionnaire (GHQ-12) measuring current psychological distress. [START_REF] Koeter | Validity of the Ghq and Scl Anxiety and Depression Scales -A Comparative-Study[END_REF] This questionnaire was completed at home before the visit to the research facilities at baseline. The GHQ-12 comprises 12 questions dealing with two major classes of phenomena: inability to continue to carry out one's normal healthy functions and the appearance of new phenomena of a distressing nature (e.g., being able to enjoy day-to-day activities, losing sleep over worry, thinking of yourself as worthless). The respondent is asked whether he or she has recently experienced a particular symptom or item of behavior on a scale ranging from "less than usual" to "much more than usual". No items pertaining to somatic symptoms are included in the GHQ-12. The GHQ-12 exceeded the criterion for acceptable instrument internal consistency reliability of 0.70 or greater. [START_REF] Rosmalen | The association between neuroticism and self-reported common somatic symptoms in a population cohort[END_REF] We calculated a GHQ sum score using the traditional GHQ scoring method of 0-0-1-1. [START_REF] Goldberg | The validity of two versions of the GHQ in the WHO study of mental illness in general health care[END_REF] Missing data were imputed according to the method of corrected item mean substitution, if at least half of the items were completed. [START_REF] Huisman | Imputation of missing item responses: Some simple techniques[END_REF]

Statistical analyses

We used SPSS 16.0 (SPSS Inc, Chicago, IL, USA) to perform our statistical analyses.

Variables that were not normally distributed (sum scores of FSS and MES) were log transformed. The association between the log-transformed sum scores of FSS and MES was tested using Pearson's correlation coefficient. We performed univariable linear regression analyses to test whether subject characteristics (age, sex, body mass index, smoking, alcohol consumption, exercise frequency, income, educational level, work situation, and psychological distress) were associated with general intelligence, 12-months FSS, or with 12months MES. We performed multivariable linear regression analyses to test whether general intelligence was associated with the number of 12-months FSS or 12-months MES. We performed multivariable linear regression analyses to test whether general intelligence was associated with the number of 12-months FSS or 12-months MES. In addition, we repeated these analyses using, instead of general intelligence, scores on the dimensional space subtest, vocabulary subtest and arithmetic reasoning subtest as separate predictors. Next, we performed multivariable regression analyses, including potential mediators of the associations with FSS and MES. Factors were only included if they proved to be associated with both intelligence and the outcome. Since FSS and MES are correlated, we repeated all analyses adjusting FSS for MES and vice versa. Additionally, we tested whether intelligence predicted new-onset FSS and MES applying the same steps. All multivariable analyses were adjusted for the potential confounders gender (0 = M and 1 = F) and age (in years to one decimal place), since these variables are both associated with intelligence 36 37-39 and FSS. [START_REF] Turner | Sex-Differences in Wais Item Performance[END_REF][START_REF] Escobar | Abridged somatization: A study in primary care[END_REF][START_REF] Kroenke | Symptoms in the Community -Prevalence, Classification, and Psychiatric Comorbidity[END_REF][START_REF] Smith | Patients with Multiple Unexplained Symptoms -Their Characteristics, Functional Health, and Health-Care Utilization[END_REF] .

RESULTS

Demographic characteristics

The current study cohort consisted of 947 participants for which intelligence sores and symptom scores were available (47.9 % males), with a mean age of 52.7 (SD 11.2 years, minimum 33 years, maximum 79 years). Of the participants, 25.5% had a certificate of lower education; 27.0% a certificate of middle education and 43.1% a certificate of higher education. Test scores of general intelligence were normally distributed (skewness = -0.099, kurtosis = -0.476). The correlation between the sum scores of FSS and MES was 0.172 (p<0.001).

Associations between subject characteristics and intelligence

Table 1 summarizes the univariable associations between subject characteristics and intelligence. Intelligence was significantly associated with lower age and being male.

Considering lifestyle factors, higher intelligence was associated with having a lower BMI, less smoking, more alcohol consumption, and exercising. Higher intelligence was also associated with a higher educational level, a more favourable work situation and a higher income. However, intelligence was not associated with psychological distress (β=-0.019, t=-0.591, p=0.554). This means that psychological distress could not be a mediator of the association of intelligence with both outcomes, and this factor was therefore not examined in multivariable analyses.

Associations between subject characteristics and somatic symptoms

Table 2 summarizes the univariable associations between subject characteristics and the number of 12-months FSS or 12-months MES. Older age was related to having more MES but not FSS; females had more MES and FSS than males. Both FSS and MES were associated with a higher BMI, not consuming alcohol and a low exercise frequency. Smoking was associated with FSS but not with MES. All socio-economic factors were negatively associated with both FSS and MES, indicating that participants with a lower income, a lower educational level and less favourable work situation more often reported somatic symptoms.

Psychological distress was positively associated with both FSS and MES, but the effect size for FSS is about twice the size of the effect size for MES. When repeating these analyses using new-onset FSS and MES as an outcome, the results remained essentially the same.

Associations between intelligence and somatic symptoms

Table 3 summarizes the multivariable associations between intelligence and the number of 12-months FSS or MES. Linear regression analyses indicated that general intelligence was negatively associated with the number of FSS (β=-0.084, t=-2.299, p=0.022) and MES (β=-0.095, t=-2.652, p=0.008). When studying the subtests that composed general intelligence, we found that the association was explained by the vocabulary subtest and the arithmetic reasoning subtest, but not by the dimensional space subtest. Introduction of the potential mediators into the model removed the association of intelligence with somatic symptoms, but evidence for mediation was limited to work-situation in the relation of intelligence with FSS.

DISCUSSION

This study demonstrated that intelligence was negatively associated with the number of reported FSS and MES. The association of intelligence with FSS was mediated by the worksituation of participants, suggesting that adult men and women of lower intelligence that report more functional somatic symptoms are more often (unwanted) economically inactive.

In contrast to our expectations, no evidence was found for a mediating role of psychological distress in the association of intelligence with FSS, even though distress was an important predictor of FSS.

There are several strengths of this study. First, we collected detailed information on a large number of FSS and performed our analyses on a continuous variable for the number of FSS.

In many studies concerning FSS, arbitrary cut-off scores are used despite the lack of consensus about where to put the cut-off and the loss of information as a result of artificial dichotomizing of variables. 40;43 Second, we measured both FSS and MES using the same instrument, enabling comparisons between these types of symptoms and their associations with intelligence. Third, generalizability of our results is good, because we used a large population cohort without applying strict inclusion criteria.

When interpreting our study results, the following limitations should be taken into account.

First, we measured intelligence in adult participants. Although general intelligence is regarded as a trait that is stable from infancy into middle age, [START_REF] Gottfredson | Dissecting practical intelligence theory: Its claims and evidence[END_REF] it can not be excluded that reverse causality, in which somatic symptoms contribute to lower intelligence scores, is playing a role. We performed additional analyses (results not shown) including only new-onset symptoms (i.e. onset after measurement of intelligence) as outcomes, which provided essentially the same results as the analyses that are reported here, indicating that the effect of reverse causality may have been negligible. However, this does not exclude the possibility that pre-existing morbidity causes both low intelligence scores and new somatic symptoms.

Second, recall bias may have attenuated the reliability of the CIDI to measure FSS and MES, [START_REF] Leiknes | Methodological issues concerning lifetime medically unexplained and medically explained symptoms of the Composite International Diagnostic Interview: a prospective 11-year follow-up study[END_REF] and recall bias is likely to be associated with intelligence because people with lower intelligence have lower memory capacity. [START_REF] Duff | The relationship between executive functioning and verbal and visual learning and memory[END_REF] We limited our analyses to symptoms that occurred in the last 12 months, which will have reduced the effect of recall bias. Moreover, it should be noted that the expected effect of recall bias on our results would be to reduce associations of intelligence with reported symptoms, indicating that our results are more likely to be underestimations rather than overestimates. Finally, the fact that we measured symptoms via self-report may be regarded as a limitation. However, symptoms were only defined as being functional if it was reported that a medical doctor had indicated that all inquiries were negative for medical explanations. Moreover, the finding that psychological distress as measured by GHQ-scores was much more strongly associated with FSS than with MES underlines the etiological difference between those symptoms.

Our study demonstrates that intelligence is negatively associated with the number of FSS and MES. We are the first to study the direct relation between FSS and intelligence, but a negative association between intelligence and morbidity or mortality has been a consistent finding. [START_REF] Batty | IQ in late adolescence/early adulthood, risk factors in middle age and later all-cause mortality in men: the Vietnam Experience Study[END_REF][START_REF] Batty | Premorbid (early life) IQ and later mortality risk: Systematic review[END_REF][START_REF] Singh-Manoux | The role of cognitive ability (intelligence) in explaining the association between socioeconomic position and health: Evidence from the Whitehall II prospective cohort study[END_REF] Focusing on the association of intelligence with covariates, most of our results seemed to be in line with findings from previous studies. Socioeconomic factors and most lifestyle factors were negatively associated with intelligence. Only for alcohol consumption did we observe a positive association (i.e. more alcohol consumption in those with higher intelligence). Some studies have found the same result 47;48 whereas other studies found the opposite. [START_REF] Batty | Childhood IQ and life course socioeconomic position in relation to alcohol induced hangovers in adulthood: the Aberdeen children of the 1950s study[END_REF] It should be realized that we used a continuous measure of alcohol consumption, mainly indicating social drinking (which might be related to higher socioeconomic status [START_REF] Fillmore | Alcohol consumption and mortality. I. Characteristics of drinking groups[END_REF] with only a minority being problem drinkers. Another unexpected finding might be that psychological distress was not related to intelligence. Our initial hypothesis that one of the major differences between the associations of intelligence with FSS and MES would be that the association with FSS was mediated by distress therefore was not confirmed. Previous studies towards intelligence and GHQ-scores have been contrasting, with either a negative association between childhood intelligence and the GHQ-28 in middle-aged women [START_REF] Hatch | Childhood cognitive ability and adult mental health in the British 1946 birth cohort[END_REF] or no association between current intelligence and GHQ-30 scores in middle-aged participants from the Whitehall II study. [START_REF] Singh-Manoux | The role of cognitive ability (intelligence) in explaining the association between socioeconomic position and health: Evidence from the Whitehall II prospective cohort study[END_REF] The associations of socioeconomic and lifestyle factors with somatic symptoms were in the expected directions, with the exception of smoking in relation to MES. Despite its wellknown association with morbidity and mortality, [START_REF] Ezzati | Estimates of global mortality attributable to smoking in 2000[END_REF] we observed no association of smoking with MES. This lack of association might be due to the fact that we measure somatic complaints and not diagnoses, and most complaints included in the CIDI are not associated with smoking-related diseases such as cardiovascular and pulmonary disease.

Our multivariable models show that the association of intelligence with FSS and MES is removed after adding lifestyle and socioeconomic factors into the model. However, there was only clear evidence for mediation of the association with FSS by work-situation. The interpretation of these findings is not obvious, but one possibility is that participants without a job do not have a day-to-day distraction from their physical complaints. Furthermore, unemployment and especially unwanted employment is clearly linked to devastating individual effects, such as financial hardship. [START_REF] Evans | Employment, social inclusion and mental health[END_REF] It could be hypothesized that the resulting psychological distress is responsible for the association between work situation and FSS.

Although we did indeed find an association between psychological distress and FSS, this association was not responsible for the relation between work-situation and FSS. Finally, our results indicate that verbal components of intelligence are more important than performance components of intelligence in predicting somatic complaints. One explanation for this finding could be that linguistic skills might be of more use when it comes to communicating with doctors and when seeking social support when suffering from somatic complaints or psychosocial stress. Psychosocial stress has been assumed to play a role in development and perpetuation of FSS 4;12;53 and MES. [START_REF] Mcewen | Central effects of stress hormones in health and disease: Understanding the protective and damaging effects of stress and stress mediators[END_REF] In conclusion, lower general intelligence was associated with a higher number of FSS and MES in the general population. Part of the association of intelligence with FSS was explained by a more unfavourable work situation of adults of lower intelligence.

FUNDING

Funding for this study was provided by the Netherlands Organization for Scientific Research (Pionier 900-00-002). This organization had no further role in study design; in the collection and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

BOX: "What this paper adds" Paragraph 1: What is already known on this subject?

Recent research and theory in this area suggest complex interactions between biological, psychological and social factors in the development and perpetuation of Functional Somatic Symptoms (FSS). Intelligence is an interesting vulnerability factor to study in the context of FSS, because it is associated with several risk factors for development and perpetuation of FSS.

Paragraph 2: What does this study add?

Our results reveal a significant negative association between intelligence and the number of FSS in a general population-cohort. Part of the association of intelligence with FSS is explained by a more unfavourable work situation of adults of lower intelligence. No evidence was found for a mediating role of psychological distress in the association of intelligence with FSS, even though distress was an important predictor of FSS.

Table 2 : Univariable associations between subject characteristics and the number of 12- months FSS and the number of 12-months MES 12-months FSS 12-months MES

 2

		β	t	β	t
		(R²)		(R²)
	Age 1	0.013	0.402	0.194***	6.086
		(0.000)		(0.037)
	Female gender 2	0.184***	5.758	0.163***	5.082
		(0.033)		(0.026)
	Lifestyle factors
	BMI 3

Smoking 4 Alcohol consumption 5 Exercise frequency 6

Table 3 : Multivariable associations between intelligence and 12-months FSS and 12- months MES (all adjusted for age 1 and gender 2 ) 12-months FSS 12-months MES

 3

		β	t	β	t
		(R²)		(R²)
	General intelligence	-0.084*	-2.299	-0.095**	-2.652
		(0.037)		(0.074)
	Dimensional space subtest	-0.035	-0.968	-0.018	-0.496
		(0.031)		(0.067)
	Vocabulary subtest	-0.071*	-2.059	-0.086*	-2.521
		(0.036)		(0.073)
	Arithmetic reasoning subtest	-0.094**	-2.732	-0.116**	-3.438
		(0.038)		(0.078)
	General intelligence +

lifestyle factors + socio-economic factors Intelligence BMI 3 Smoking 4 Alcohol consumption 5 Exercise 6 Educational level 7

Distress measured by General Health Questionnaire (GHQ)-12 scores

 [START_REF] Stone | What should we say to patients with symptoms unexplained by disease? The "number needed to offend[END_REF]Gender with "0" = male, "1" = female [START_REF] Nimnuan | Medically unexplained symptoms -An epidemiological study in seven specialities[END_REF] Body mass index in kg/m 2 4 Smoking in number of cigarettes/day with "0" = 0, "1" = 1-5, "2" = 6-10, "3" = 11-15, "4" = 16-20", "5" = >20 [START_REF] Barsky | Somatization increases medical utilization and costs independent of psychiatric and medical comorbidity[END_REF] Alcohol consumption in number of units with "0" = no, almost never, "1"= 1-4/month, "2"= 2-7/week, "3" = 1-3/day, "4" = 4 or more/day [START_REF] Woivalin | Medically unexplained symptoms: perceptions of physicians in primary health care[END_REF] Frequency of exercise with "0" = no exercise, "1" = once/week, "2" = twice or more/week [START_REF] Wileman | Medically unexplained symptoms and the problem of power in the primary care consultation: a qualitative study[END_REF] Educational level with "1" = none, "2" = low, "3"= middle, "4" = high [START_REF] Rief | Are somatoform disorders 'mental disorders'? A contribution to the current debate[END_REF] Working situation with "1" = unwillingly unemployed, "2" = willingly unemployed, "3" = employed [START_REF] Bakal | An experiential mind-body approach to the management of medically unexplained symptoms[END_REF] Household income divided by the square root of number of people living of this income [START_REF] Stone | What should we say to patients with symptoms unexplained by disease? The "number needed to offend[END_REF] Gender with "0" = male, "1" = female [START_REF] Nimnuan | Medically unexplained symptoms -An epidemiological study in seven specialities[END_REF] Body mass index in kg/m 2 4 Smoking in number of cigarettes/day with "0" = 0, "1" = 1-5, "2" = 6-10, "3" = 11-15, "4" = 16-20", "5" = >20 [START_REF] Barsky | Somatization increases medical utilization and costs independent of psychiatric and medical comorbidity[END_REF] Alcohol consumption in number of units with "0" = no, almost never, "1" = 1-4/month, "2" = 2-7/week, "3" = 1-3/day, "4" = 4 or more/day [START_REF] Woivalin | Medically unexplained symptoms: perceptions of physicians in primary health care[END_REF] Frequency of exercise with"0" = no exercise, "1" = once/week, "2" = twice or more/week [START_REF] Wileman | Medically unexplained symptoms and the problem of power in the primary care consultation: a qualitative study[END_REF] Educational level with "1" = none, "2" = low, "3" = middle, "4" = high [START_REF] Rief | Are somatoform disorders 'mental disorders'? A contribution to the current debate[END_REF] Working situation with "1" = unwillingly unemployed, "2" = willingly unemployed, "3" = employed [START_REF] Bakal | An experiential mind-body approach to the management of medically unexplained symptoms[END_REF] Household income divided by the square root of people living of this income 2 Abbreviations: FSS, functional somatic symptoms; MES, medically explained symptoms All β's are standardized, *p < 0.05, **p < 0.01, ***p < 0.001 [START_REF] Fink | Classification of somatization and functional somatic symptoms in primary care[END_REF] Age in years [START_REF] Stone | What should we say to patients with symptoms unexplained by disease? The "number needed to offend[END_REF] Gender with "0" = male, "1" = female [START_REF] Nimnuan | Medically unexplained symptoms -An epidemiological study in seven specialities[END_REF] Body mass index in kg/m 2 4 Smoking in number of cigarettes/day with "0" = 0, "1" = 1-5, "2" = 6-10, "3" = 11-15, "4" = 16-20, "5" = >20 [START_REF] Barsky | Somatization increases medical utilization and costs independent of psychiatric and medical comorbidity[END_REF] Alcohol consumption in number of units with "0" = no, almost never, "1" = 1-4/month, "2" = 2-7/week, "3" = 1-3/day, "4" = 4 or more/day [START_REF] Woivalin | Medically unexplained symptoms: perceptions of physicians in primary health care[END_REF] Frequency of exercise with "0" = no exercise, "1" = once/week, "2" = twice or more/week [START_REF] Wileman | Medically unexplained symptoms and the problem of power in the primary care consultation: a qualitative study[END_REF] Educational level with "1" = none, "2" = low, "3" = middle, "4" = high [START_REF] Rief | Are somatoform disorders 'mental disorders'? A contribution to the current debate[END_REF] Working situation with "1" = unwillingly unemployed, "2" = willingly unemployed, "3" = employed [START_REF] Bakal | An experiential mind-body approach to the management of medically unexplained symptoms[END_REF] Household income divided by the square root of number of people living of this income 3 3

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