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Depressive symptoms predispose females tometabolic syndrome: a 7-year follow-upstudy

Introduction

The metabolic syndrome (MetS) is a multifactorialdisorder encompassing abdominal obesity, alteredglucose and lipid metabolism, and elevated bloodpressure (14). In previous cross-sectional studies,MetS has been observed with a higher prevalence

in depressed than in non-depressed subgroups, andthe observed prevalence rates have ranged from8% to 38% (58). The only previous long-termstudy focusing on the interaction between depres-sion and MetS has shown that more severedepressive symptoms and stressful life events atbaseline increased the risk to develop MetS during

Vanhala M, Jokelainen J, Keina nen-Kiukaanniemi S, Kumpusalo E,Koponen H. Depressive symptoms predispose females to metabolicsyndrome: a 7-year follow-up study.

Objective: To evaluate the risk for developing metabolic syndromewhen having depressive symptoms.Method: The prevalence of depressive symptoms and metabolicsyndrome at baseline, and after a 7-year follow-up as measured with

Beck depression inventory (BDI), and using the modified NationalCholesterol Education Program Adult Treatment Panel III criteriafor metabolic syndrome (MetS) were studied in a middle-agedpopulation-based sample (n = 1294).Results: The logistic regression analysis showed a 2.5-fold risk (95%CI: 1.25.2) for the females with depressive symptoms (BDI 10) atbaseline to have MetS at the end of the follow-up. The risk was highestin the subgroup with more melancholic symptoms evaluated with asummary score of the melancholic items in BDI (OR 6.81, 95% CI:2.0922.20). In men, there was no risk difference.Conclusion: The higher risks for MetS in females with depressivesymptoms at baseline suggest that depression may be an importantpredisposing factor for the development of MetS.

M. Vanhala1, J. Jokelainen2,S. Keinnen-Kiukaanniemi2,3,E. Kumpusalo4, H. Koponen5

1Unit of Family Practice, Central Hospital of Middle

Finland, Jyvskyl, Finland, 2Institute of Health

Sciences, University of Oulu, and Unit of General

Practice, Oulu University Hospital, Oulu, Finland, 3Oulu

Health Center, City of Oulu, Finland, 4School of Public

Health and Clinical Nutrition, Department of Family

Medicine, University of Kuopio, and Unit of Family

Practice, Kuopio University Hospital, Kuopio, Finland

and 5Academy of Finland, Department of Psychiatry,

Kuopio University, and Kuopio University Hospital,

Kuopio, Finland

Key words: Beck depression inventory; cholesterol;

depression; metabolic syndrome; triglycerides

Prof. Hannu Koponen, Department of Psychiatry, Kuopio

University Hospital, PO Box 1777, FIN-70211 Kuopio,

Finland.

E-mail: [email protected]

Accepted for publication September 16, 2008

Significant outcomes

Females with depressive symptoms at baseline showed to have a 2.5-fold risk to have metabolicsyndrome at the end of the 7-year follow-up.

The risk was highest in the subgroup with more melancholic symptoms.

Limitations

The identification of depressive symptoms was based on a self-report scale, not a diagnosticinterview.

Our genetically homogenous study population may hamper the generalizability of the results. The effect of age and subtype of depressive symptoms should be interpreted with caution because the

small sample size in these subgroups.

Acta Psychiatr Scand 2009: 119: 137142All rights reservedDOI: 10.1111/j.1600-0447.2008.01283.x

Copyright 2008 The AuthorsJournal Compilation 2008 Blackwell Munksgaard

ACTA PSYCHIATRICASCANDINAVICA

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the 15-year follow-up in an exclusively femalestudy population (7). Previous studies have alsoshown that MetS increases its prevalence aftermenopause, and that the postmenopausal hormonereplacement therapy may reduce abdominal obes-ity, insulin resistance, lipid levels and bloodpressure (9).

Previous studies also suggest that depressionmay be a risk factor for several components ofMetS. Depression is associated with a tendencyto dyslipidaemias and visceral fat accumulation(10). The results are not, however, equivocal as,in the Alameda County Study, depression didnot increase the risk for future obesity (11).Depressed patients also frequently have insulinresistance (12), which may resolve after recoveryfrom depression (13). A recent meta-analysis hasalso shown that the presence of depressionincreases the risk for diabetes (14). Besides the

study of Ra ikko nen et al. (7), previous estima-tions of the risk to develop MetS when havingdepression are based on cross-sectional clinicalevaluation linked with previous history of depres-sive episode.

Aims of the study

The aim of this study was to evaluate the putativerisk to develop MetS until the end of 7-year follow-up when having depressive symptoms at baseline ina large population-based study sample. Inaddition, the sex differences in risk levels were

scrutinized.

Material and methods

Subjects

The study was conducted in Pieksa ma ki area,South-Savo, Finland in order to determine theprevalence of risk factors and long-term course ofMetS between 1998 and 2005. All inhabitants bornin the years 1942, 1947, 1952, 1957 and 1962 inPieksa ma ki (n = 1294) were invited for a compre-

hensive health check-up during 1998 at the studybaseline. The addition of the last group, those bornin 1962, extends the age spectrum of the samplewhen compared with the previously reported 1993sampling (15). The study was carried out inaccordance with the latest version of the Declara-tion of Helsinki. All participants gave a writteninformed consent, and the study protocol wasapproved by the Ethics Committee of the KuopioUniversity Hospital and the University of Kuopio.The participation rate at baseline in 1998 was9231294, i.e. 71.3%. In 20042005, 688 (74.5%)

of the 1998 participants took part in the 7-yearfollow-up visit.

Procedures

At the 1998 and 20042005 study visits, allparticipants filled out a standard questionnaire

containing questions about the use of medicationsincluding antidepressants and hormone replace-ment therapy in females. In addition, data werecollected on both visits of smoking habits, use ofalcohol (number of drinks per week) and physicalactivity (number of over 30 min exercise sessionsper week). At baseline and at 7-year follow-upvisit, the depressive symptoms were evaluated withthe Beck depression inventory (BDI) (16), in whicha score of 10 points was used as a cut-off point fordepressive symptoms. In order to examine theeffect of the subtype of depressive symptomatol-

ogy, we used a summary score of the melancholicitems in BDI (sadness, past failure, loss of pleasure,guilty feelings, punishment feelings, loss of interest,irritability, change in sleeping and appetite) individing the cases with depressive symptoms intosubgroups with more frequent melancholic symp-toms and non-melancholic symptoms subgroups(17, 18).

At baseline and at 7-year follow-up, fastingblood samples including the glucose and lipid levelswere drawn between 8 and 11 Oclock after 12 h offasting. The physical examination included weight,height, waist circumference and blood pressure

taken on the same study visit. Height and weightwere measured in light clothing to the nearest0.5 cm and 0.1 kg respectively. The waist circum-ference was measured to the nearest 1.0 cm at themidpoint between the lateral iliac crest and lowestrib. The blood pressure was measured twice with amercury sphygmomanometer with subjects in sit-ting position after a 15-min rest. All measurementswere carried out by two nurses who were specif-ically trained to the procedures during 1-daycourse at the Unit of General Practice of theKuopio University. In the evaluation of MetS, we

used the modified National Cholesterol EducationProgram Adult Treatment Panel III criteria(NCEPATPIII criteria) with the 100 mgdLblood glucose cut-off point (1). Originally, NCEPdefines MetS as having three or more of thefollowing criteria: i) fasting serum glucose of110 mgdl or higher, ii) serum triglycerides of150 mgdl or higher, iii) serum high-densitylipoprotein (HDL) cholesterol 88 cm in women (4).

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Statistical methods

Logistic regression models were used to examinethe relationship between the MetS and depressivesymptoms by gender. In multivariate analyses, thefollowing possible confounding factors were used:age, education, marital status, smoking, physical

activity, alcohol consumptions and use of anti-depressive and hormone replacement therapy. Allstatistical testing were performed at a 5% level ofsignificance using sas for Windows version 9.2(SAS Institute Inc., Cary, NC, USA).

Results

The key variables for the 488 members (294 womenand 194 men) of the study population, who atbaseline visit did not have MetS and who alsoparticipated in the 7-year follow-up, are shown in

Table 1. The prevalence of MetS at 1998 baselinewas 33% (n = 96) for males and 26.5% (n = 106)in females. These 202 excluded participants whohad MetS at baseline did differ from the studygroup with regards to their age (the excluded wereon average 2 years older) and degree of basiceducation (cases with MetS at baseline had lowerbasic education). No other differences betweendemographic factors or life habits were observed.

At baseline, 48 women (16.3% of the baselinestudy population) and 16 men (8.2%) had depres-sive symptoms. At the 7-year follow-up, 55 initiallynon-depressed females (22.4%) had developedMetS; in females, with depressive symptoms atbaseline the corresponding figure was 20 (or41.7%; P = 0.01). After adjusting for age, educa-

tion, physical activity, smoking, alcohol use, mar-ital status and the use of antidepressive andhormone replacement therapy, the logistic regres-sion analysis showed a 2.5-fold risk for the femalecohort members with depressive symptoms atbaseline to have MetS at the end of the follow-up(OR 2.5, 95% CI: 1.25.2). In men, two out of 16males (12.5%) with depressive symptoms at base-line developed MetS during the follow-up; in non-depressed males the corresponding figures were45178 (25.3%; P = 0.25).

As the risk to develop MetS when having

depressive symptoms at the baseline was significantonly in women, we studied this subgroup in greaterdetail. At baseline, the depressed females had moresevere symptoms than depressed males (v2 = 6.7,d.f. = 1, P = 0.001). We also observed a higherprevalence of low HDL-cholesterol levels inwomen with depressive symptoms than non-depressed females. The frequencies of individualcriteria for MetS in women are presented in

Table 1. Study population characteristics at 20042005 follow-up

Characteristic, 1998

Women Men

MetS

(n = 75)

No MetS

(n = 219)

MetS

(n = 47)

No MetS

(n = 147)

Age, mean (SD) 49.5 (5.4) 44.7 (6.2) 47.3 (5.8) 45.6 (5.9)

Beck depression inventory (BDI) score 4 (110) 2 (16) 2 (05) 2 (05)

BDI 10 (%) 28.6 13.9 4.2 9.5

Basic education (%)

Elementary school 61.3 38.5 66.0 54.4

Middle school 16.0 33.5 21.2 32.7

Matriculation 22.7 28.0 12.8 12.9

Marital status (%)

Single 10.7 8.3 10.6 8.2

Married cohabit 77.3 80.3 85.1 86.4

Divorced

widowed 12.0 11.4 4.3 5.4Current smokers (%) 22.7 22.5 34.0 26.5

Physically active (%) 30.7 28.4 36.2 33.3

Alcohol use (%) 14.7 5.5 27.7 27.2

Waist circumference, mean (SD) 84.1 (8.5) 77.1 (7.6) 93.0 (7.3) 88.8 (7.0)

BMI, mean (SD) 25.9 (3.7) 23.3 (2.8) 26.7 (2.5) 24.9 (2.6)

Weight (kg), mean (SD) 69.8 (10.0) 64.3 (8.9) 80.6 (8.7) 78.2 (8.5)

Systolic BP, mean (SD) 135.3 (17.6) 126.0 (16.4) 130.9 (14.6) 134.4 (15.2)

Diastolic BP, mean (SD) 81.9 (8.9) 76.0 (9.0) 81.0 (8.3) 80.9 (9.0)

Hypertension (sys 135 and or dia 85) (%) 60.0 35.2 42.6 61.9

Triglycerides, mean (SD) 1.1 (0.5) 1.0 (0.4) 1.5 (0.7) 1.2 (0.6)

HDL cholesterol, mean (SD) 1.6 (0.3) 1.6 (0.3) 1.4 (0.2) 1.4 (0.3)

Glucose, mean (SD) 5.6 (0.5) 5.4 (0.4) 5.8 (0.6) 5.7 (0.5)

MetS, metabolic syndrome; SD, standard deviation; BMI, body mass index; HDL, high-density lipoprotein; sys, systolic blood pressure; dia, diastolic blood pressure.

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Table 2. When the subtype of depressive symptomswas scrutinized, the risk to develop MetS washigher in females with more frequent melancholicsymptoms at baseline (n = 28; OR 4.2, 95%CI: 1.412.3) when compared to females withnon-melancholic depression (n = 20; OR 1.8,95% CI: 0.74.5). The effect of age and menopause

were explored using the categorization by Luotoet al. (19): subjects in 3637 and 4142 years of agewere considered premenopausal; subjects in 4647and 5152 years of age were considered perimeno-pausal; and subjects in 5657 years of age post-menopausal. As the risk may be more clear-cut inmenopausal transition, we took into the analysesperi- and postmenopausal females at baseline(n = 114). In this subgroup when compared withpremenopausal females, it was more common todevelop MetS as 14 out of the 24 females withdepressive symptoms developed MetS during thefollow-up (v2 = 3.7, d.f. = 1, P = 0.055). We

also examined the effect of hormone replacementtherapy. At 1998, 49 women used hormonereplacement therapy, and 13 of them weredepressed. At the 7-year follow-up, six of themhad developed MetS. Women with depressivesymptoms at baseline not using hormone replace-ment therapy developed MetS in 14 cases out of 34(41% vs. 46%, NS).

Discussion

The key findings in our population-based study

containing both sexes and different age groups arethe observation of 2.5-fold prevalence of MetSafter the 7-year follow-up in middle-aged femaleswith depressive symptoms at baseline and a higherrisk in females with more frequent melancholicsymptoms. In men there was no difference, andmales had less-severe depressive symptoms whencompared with females suggesting that the severityof depressive symptoms may also play a role. Theincreased risk for MetS in depressed females is inline with the results of Ra ikko nen et al. (7), whofound that more-severe depressive symptoms and

life stress at baseline were associated with 1.2- to2.1-fold risk to develop MetS over the 15-yearfollow-up. We also observed that the risk todevelop MetS was higher in peri- and postmeno-pausal women. This is in accordance with theresults of Everson-Rose et al. (20) showing thatdepressive symptoms were significantly related to

excess risk of diabetes and insulin resistance in afemale population at menopausal transition. Theconnection between depression and MetS is prob-ably reciprocal as we have recently demonstratedan increased risk to develop depression whenhaving MetS at study baseline (21).

Our finding of increased liability in females todevelop MetS when initially depressed is also inaccordance with previous results from cross-sec-tional studies. Kinder et al. (5) using the ThirdNational Health and Nutrition ExaminationSurvey data noted that history of depressiveepisode was associated with MetS in women; in

men the association was not statistically significant.Onyike et al. (22) using the same databaseobserved that obesity was associated with past-month depression in females; in males the associ-ation was non-significant. Carpenter et al. (23)using the National Longitudinal Alcohol Epidemi-ological Survey data observed an associationbetween increased body mass index and past-yearmajor depression in females; in males the relation-ship was inverse. In the study of Carnethon et al.(24), association of depressive symptoms andincident diabetes was strongest in women. Thus

there may be gender differences in the connectionbetween depression and MetS or its components,and the health risks linked to depression may bemore critical to women. The psychological factorsmay also be important for the development ofMetS as depression is associated with sedentarylifestyle and negative perception of oneself (23),and they may also differ between males andfemales (7, 25).

Multiple factors appear to predispose to MetS,e.g. genetic deficits in insulin signalling pathways,adipose tissue disorders, physical inactivity, mito-

Table 2. Prevalence of modified NCEPATPIII MetS criteria in women (2004 2005 data)

Criteria

Non-depressed

(n = 224) (%)

With more frequent

melancholic symptoms

(n = 20) (%)

Other

depression

(n = 28) (%)

With depressive

symptoms, total

(n = 48) (%)

P-value (cases with

depressive symptoms

vs. non-depressed)

Abdominal obesity 22.5 30.0 28.6 29.2 0.3159

Triglycerides 18.0 35.0 22.2 27.7 0.1243

HDL cholesterol 14.2 50.0 32.1 39.6


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chondrial dysfunction, individual genetic variabil-ity, advancing age and certain drugs. The MetS isa useful clinical concept as it identifies patientswho have twice the risk for atherosclerotic car-diovascular disease and five times the risk fordiabetes (26). In previous years, several differentdiagnostic criteria sets have been suggested for

MetS (2, 3). The US NCEPATPIII criteriaproposed easily applicable cut-off limits for waistcircumference; lipid levels, blood glucose andblood pressure (4), and they have been widelyused in both clinical practice and epidemiologicalstudies. The recent modification of the criteria (1)uses a lower cut-off point for glucose and takes theantihypertensive, antidiabetic or antidyslipidaemicmedication into account in the criteria. In addi-tion, insulin resistance, the key feature in MetS,has been suggested to be a metabolic link betweendepressive disorder and atherosclerotic vascular

diseases (27). Biological mechanisms that mayexplain the association between depression andMetS include cytokine-mediated inflammation (28,29), dysregulation of the hypothalamicpituitaryadrenal (HPA) axis, and the effects of physiolog-ical or psychological stress related to depression.Cortisol excess may antagonize the actions ofinsulin-mediated glucose disposal or cause deposi-tion of fat to abdomen resulting in visceraladiposity (24, 30). Depression has also previouslylinked with low total cholesterol levels (31); in thisstudy, we observed a higher prevalence of lowHDL-cholesterol levels in women with depressive

symptoms. Low levels of HDL cholesterol may berelated to high total cholesterol and the presenceof MetS, but according to the study of Komulai-nen et al. (32) it may also predispose to memoryimpairment as high HDL-cholesterol levels mayprotect against hippocampal atrophy and promotesynaptogenesis. More profound associationbetween melancholic subtype of depression anddisturbances in the HPA-axis or cytokine func-tioning may explain the higher risk for MetSassociated with more frequent melancholic symp-toms in females.

There are several limitations in this study. Theidentification of depressive symptoms was based ona self-report scale, not a diagnostic interview,which is a limitation. Although not initially con-structed for a diagnostic scale, the BDI with a cut-of score of 10 points has been shown to be a usefulinstrument for detecting depressive disorders infollow-ups in various adult populations (see Ref. 7,17, 33). Secondly, our genetically homogenousstudy population may hamper the generalizabilityof the results. Thirdly, the effect of age and subtypeof depressive symptoms should be interpreted with

caution because of the small sample size in thesesubgroups.

Our results suggest that depressive symptoms,and in particular more frequent symptoms ofmelancholic depression, may be important predis-posing factors for the development of MetS infemales. Thus, effective treatment of depression

could also be important for the prevention ofMetS. In addition, insights into the pathophysio-logical links between depression and MetS wouldhelp to develop new treatments for depression.

Acknowledgements

This work was supported by grant from the Central Finland

Hospital District (MV), and grant number 113 760 from the

Academy of Finland (HK).

Declaration of interest

None.

References

1. Grundy SM, Cleeman JI, Daniels SRA et al. Diagnosis and

management of the metabolic syndrome: an American

Heart Association National heart, lung, and blood insti-

tute scientific statement: executive summary. Circulation

2005;112:e285e290.

2. Alberti KGMM, Zimmet P, Shaw J, for the IDF Epidemiol-

ogy Task Force Consensus Group (2005). The metabolic

syndrome a new worldwide definition. Lancet 2005;

366:10591062.

3. Alberti KGMM, Zimmet P, Shaw J. Metabolic syndrome a

new worldwide definition. A consensus statement from the

International Diabetes Federation. Diabet Med 2006;

23:469480.

4. Expert Panel on Detection, Evaluation, and Treatment ofHigh Blood Cholesterol in Adults (2001). Executive Sum-

mery of the Third Report of the National Cholesterol

Education Program (NCEP) Expert Panel on detection,

evaluation, and treatment of high blood cholesterol in

adults (Adult Treatment Panel III). JAMA 2001;285:2486

2497.

5. Kinder LS, Carnethon MR, Palaniappan LP, King AC,

Fortman SP. Depression and the metabolic syndrome in

young adults: findings from the third national health and

nutrition examination survey. Psychosom Med 2004;

66:316322.

6.Heiskanen TH

,Niskanen LK

,Hintikka JJ

et al. Metabolicsyndrome and depression: a cross-sectional analysis. J Clin

Psychiatry 2006;67:14221427.

7. Raikkonen K , Matthews KA, Kuller LH. Depressive

symptoms and stressful life events predict metabolic syn-

drome among middle-aged women. A comparison of

World Health Organization, Adult Treatment Panel III

and International Diabetes Foundation definitions. Dia-

betes Care 2007;30:872877.

8. Skilton MR, Moulin P, Terra J-L, Bonnet F. Associations

between anxiety, depression, and the metabolic syndrome.

Biol Psychiatry 2007;62:12511257.

9. Salpeter SR, Walsh JME, Ormiston TM, Greyber E, Buckley

NS, Salpeter EE. Meta-analysis: effect of hormone

Depression predisposes females to MetS

141


6/6

replacement therapy on components of the metabolic

syndrome in postmenopausal women. Diabetes Obes

Metab 2006;8:538554.

10. Weber-Hamann B, Werner M, Hentschel F et al. Metabolic

changes in elderly patients with major depression: evidence

for increased accumulation of visceral fat at follow-up.

Psychoneuroendocrinology 2006;31:347354.

11. Roberts RE, Deleger S, Strawbridge WJ, Kaplan GA. Pro-

spective association between obesity and depression: evi-

dence from the Alameda county study. Int J Obes 2003;

27:514521.

12. Timonen M, Rajala U, Jokelainen J, Keinanen-Kiukaanniemi

S, Meyer-Rochow VB, Rasanen P. Depressive symptoms

and insulin resistance in young adult males: results from

the Northern Finland 1966 birth cohort. Mol Psychiatry

2006;11:929933.

13. Okamura F, Tashiro A, Utumi A et al. Insulin resistance in

patients with depression and its changes during the clinical

course of depression: minimal model analysis. Metabolism

2000;49:12551260.

14. Knol MJ, Twisk JWR, Beekman ATF et al. Depression as a

risk factor for the onset of type 2 diabetes mellitus. A meta-

analysis. Diabetologia 2006;49:837845.

15.Vanhala P

,Vanhala M

,Kumpusalo E

,Keinanen

-Kiukaan-

niemi S. The quantitative insulin sensitivity check index

QUICKI predicts the onset of type 2 diabetes better than

fasting plasma insulin in obese subjects; a 5-year follow-up

study. J Clin Endocrinol Metab 2002;87:58345837.

16. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An

inventory for measuring depression. Arch Gen Psychiatry

1961;4:561571.

17. Steer RA, Ball R, Ranieri WF, Beck AT. Dimensions of the

Beck depression inventory-II in clinically depressed out-

patients. J Clin Psychol 1999;55:117128.

18. Sheehan DV, Lecrubier Y. Mini-International Neuropsy-

chiatric Interview (MINI). Tampa, FL: University of

South Florida, Institute for Research in Psychiatry; Paris:

INSERM-Hopital de la Salpetriere, 1994.

19.Luoto R

,Kaprio J

,Uutela A

. Age at natural menopauseand sociodemographic status in Finland. Am J Epidemiol

1994;139:6476.

20. Everson-Rose SA, Meyer PM, Powell LH et al. Depressive

symptoms, insulin resistance, and risk of diabetes in

women at midlife. Diabetes Care 2004;27:28562862.

21. Koponen H, Jokelainen J, Keinanen-Kiukaanniemi S, Kumpu-

salo E, Vanhala M. Metabolic syndrome predisposes to

depression. A population-based 7-year follow-up study.

J Clin Psychiatry 2008;69:178182.

22. Onyike CU, Crum RM, Lee HB, Lyketsos CG, Eaton WW. Is

obesity associated with major depression? Results from the

Third National Health and Nutrition Examination Survey

Am J Epidemiol 2003;158:11391147.

23. Carpenter KM, Hasin DS, Allison DB, Faith MS. Rela-

tionship between obesity and DSM-IV major depressive

disorder, suicide ideation, and suicide attempts: results

from a general population study. Am J Public Health

2000;90:251257.

24. Carnethon MR, Kinder LS, Fair JM, Stafford RS, Fortman

SP. Symptoms of depression as a risk factor for incident

diabetes: findings from the National Health and Nutrition

Examination Epidemiologic Follow-Up Study, 19711992.

Am J Epidemiol 2003;158:416423.

25. Bonnet F, Irving K, Terra J-L, Nony P, Berthezene F,

Moulin P. Depressive symptoms are associated with

unhealthy lifestyles in hypertensive patients with the

metabolic syndrome. J Hypertens 2005;23:611617.

26. Grundy SM. Metabolic syndrome: a multiplex cardiovas-

cular risk factor. J Clin Endocrinol Metab 2007;92:399

404.

27.Ramasubbu R

. Insulin resistance: a metabolic link betweendepressive disorder and atherosclerotic vascular diseases.

Med Hypothesis 2002;59:537551.

28. Charo IF, Taubman MB. Chemokines in the pathogenesis of

vascular disease. Circ Res 2004;95:858866.

29. Dunn AJ, Swiergiel AH, de Beaurepaire R. Cytokines as

mediators of depression: what can we learn from animal

studies? Neurosci Biobehav Rev 2005;29:891909.

30. Brown ES, Varghese FP, McEwen BS. Association of

depression with medical illness: does cortisol play a role?

Biol Psychiatry 2004;55:19.

31. Olusi SO, Fido AA. Serum lipid concentrations in patients

with major depressive disorder. Biol Psychiatry

1996;40:11281131.

32. Komulainen P, Lakka TA, Kivipelto M et al. Metabolic

syndrome and cognitive function: a population-based fol-low-up study in elderly women. Dement Geriatr Cogn

Disord 2007;23:2934.

33. Timonen M, Laakso M, Jokelainen J et al. Insulin resistance

and depression: cross-sectional study. BMJ 2005;330:17

18.

Vanhala et al.

142

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