Plasma CRP Levels in Premenopausal Women with Major Depression: A 12-Month Controlled Study

Abstract

C-reactive protein (CRP), an inflammatory marker of cardiovascular risk, is often elevated in major depressive disorder (MDD). The magnitude and consistency of this elevation have not been previously characterized in premenopausal women with MDD. The aim of the study was to prospectively assess plasma CRP levels, body composition, endocrine and metabolic parameters, and depressive status in premenopausal women with MDD (n=77) and controls (n=41), aged 21 to 45. Women were enrolled in a 12-month, controlled study of bone turnover, the P.O.W.E.R. (Premenopausal, Osteoporosis, Women, Alendronate, Depression) Study. Blood samples were taken at Baseline, Month 6, and Month 12. Most subjects with MDD were in clinical remission. These women tended to have consistently higher CRP levels than controls over 12 months (p=0.077). BMI was positively related to log[CRP] in women with MDD only. Nine women with MDD had CRP levels greater than 10 mg/l, a value associated with a very high cardiovascular risk. This subset was obese and had significantly higher triglycerides, total cholesterol, LDL-cholesterol, fasting insulin, and HOMA-IR than the rest of women with MDD. The variations in CRP levels over time were high (intra- and inter-individual coefficients of variations of ∼30–50% and ∼70–140%, respectively). No control had CRP levels greater than 10 mg/l. Depression was associated with increased plasma CRP in women with MDD. The clinical significance of abnormal plasma CRP for cardiovascular risk needs to be assessed in large prospective studies of women with depression.

obesity - women's health - inflammation - cytokine - cardiovascular morbidity - metabolic syndrome

References

• 1 Carney RM, Rich MW, Tevelde A, Saini J, Clark K, Jaffe AS. Major depressive disorder in coronary artery disease.  Am J Cardiol. 1987;  60 1273-1275
• 2 Gonzalez MB, Snyderman TB, Colket JT, Arias RM, Jiang JW, O’Connor CM, Krishnan KR. Depression in patients with coronary artery disease.  Depression. 1996;  4 57-62
• 3 Ferketich AK, Schwartzbaum JA, Frid DJ, Moeschberger ML. Depression as an antecedent to heart disease among women and men in the NHANES I study National Health and Nutrition Examination Survey.  Arch Intern Med. 2000;  160 1261-1268
• 4 Rugulies R. Depression as a predictor for coronary heart disease. A review and meta-analysis.  Am J Prev Med. 2002;  23 51-61
• 5 Wassertheil-Smoller S, Shumaker S, Ockene J, Talavera GA, Greenland P, Cochrane B, Robbins J, Aragaki A, Dunbar-Jacob J. Depression and cardiovascular sequelae in postmenopausal women.  The Women's Health Initiative (WHI). Arch Intern Med. 2004;  164 289-298
• 6 Miller GE, Stetler CA, Carney RM, Freedland KE, Banks WA. Clinical depression and inflammatory risk markers for coronary heart disease.  Am J Cardiol. 2002;  90 1279-1283
• 7 Marques-Deak A, Cizza G, Sternberg E. Brain-immune interactions and disease susceptibility.  Mol Psychiatry. 2005;  10 239-250
• 8 Eskandari F, Mistry S, Martinez PE, Torvik S, Kotila C, Sebring N, Drinkard BE, Levy C, Reynolds JC, Csako G, Gold PW, Horne M, Cizza G. POWER (Premenopausal, Osteopenia/Osteoporosis, Women, Alendronate, Depression) Study Group . Younger, premenopausal women with major depressive disorder have more abdominal fat and increased serum levels of prothrombotic factors: implications for greater cardiovascular risk.  Metabolism. 2005;  54 918-924
• 9 Agatisa PK, Matthews KA, Bromberger JT, Edmundowicz D, Chang YF, Sutton-Tyrrell K. Coronary and aortic calcification in women with a history of major depression.  Arch Intern Med. 2005;  165 1229-1236
• 10 Jones DJ, Bromberger JT, Sutton-Tyrrell K, Matthews KA. Lifetime history of depression and carotid atherosclerosis in middle-aged women.  Arch Gen Psychiatry. 2003;  60 153-160
• 11 Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women.  N Engl J Med. 2000;  342 836-843
• 12 Ridker PM, Wilson PW, Grundy SM. Should C-reactive protein be added to metabolic syndrome and to assessment of global cardiovascular risk?.  Circulation. 2004;  109 2818-2825
• 13 Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive proteinand low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events.  N Engl J Med. 2002;  347 1557-1565
• 14 Penninx BW, Kritchevsky SB, Yaffe K, Newman AB, Simonsick EM, Rubin S, Ferrucci L, Harris T, Pahor M. Inflammatory markers and depressed mood in older persons: results from the Health, Aging and Body Composition study.  Biol Psychiatry. 2003;  54 566-572
• 15 Miller GE, Stetler CA, Carney RM, Freedland KE, Banks WA. Clinical depression and inflammatory risk markers for coronary heart disease.  Am J Cardiol. 2002;  90 1279-1283
• 16 Berk M, Wadee AA, Kuschke RH, O’Neill-Kerr A. Acute phase proteins in major depression.  J Psychosom Res. 1997;  43 529-534
• 17 Frasure-Smith N, Lesperance F, Irwin MR, Sauve C, Lesperance J, Theroux P. Depression, C-reactive protein and two-year major adverse cardiac events in men after acute coronary syndromes.  Biol Psychiatry. 2007;  62 302-308
• 18 Huang TL, Lin FC. High-sensitivity C-reactive protein levels in patients with major depressive disorder and bipolar mania.  Prog Neuropsychopharmacol Biol Psychiatry. 2007;  31 370-372
• 19 Empana JP, Sykes DH, Luc G, Juhan-Vague I, Arveiler D, Ferrieres J, Amouyel P, Bingham A, Montaye M, Ruidavets JB, Haas B, Evans A, Jouven X, Ducimetiere P. PRIME Study Group . Contributions of depressive mood and circulating inflammatory markers to coronary heart disease in healthy European men: the Prospective Epidemiological Study of Myocardial Infarction (PRIME).  Circulation. 2005;  111 2299-2305
• 20 Panagiotakos DB, Pitsavos C, Chrysohoou C, Tsetsekou E, Papageorgiou C, Christodoulou G, Stefanadis C. ATTICA study . Inflammation, coagulation, and depressive symptomatology in cardiovascular disease-free people; the ATTICA study.  Eur Heart J. 2004;  25 492-499
• 21 Kling MA, Alesci S, Csako G, Costello R, Luckenbaugh DA, Bonne O, Duncko R, Drevets WC, Manji HK, Charney DS, Gold PW, Neumeister A. Sustained low-grade pro-inflammatory state in unmedicated, remitted women with major depressive disorder as evidenced by elevated serum levels of the acute phase proteins C-reactive protein and serum amyloid A.  Biol Psychiatry. 2007;  62 309-313
• 22 Dogan E, Erkoc R, Eryonucu B, Sayarlioglu H, Agargun MY. Relation between depression, some laboratory parameters, and quality of life in hemodialysis patients.  Ren Fail. 2005;  27 695-699
• 23 O’Brien SM, Scott LV, Dinan TG. Antidepressant therapy and C-reactive protein levels.  Br J Psychiatry. 2006;  188 449-452
• 24 Lesperance F, Frasure-Smith N, Theroux P, Irwin M. The association between major depression and levels of soluble intercellular adhesion molecule 1, interleukin-6, and C-reactive protein in patients with recent acute coronary syndromes.  Am J Psychiatry. 2004;  161 271-277
• 25 Tiemeier H, van Tuijl HR, Hofman A, Kiliaan AJ, Breteler MM. Plasma fatty acid composition and depression are associated in the elderly: the Rotterdam Study.  Am J Clin Nutr. 2003;  78 40-46
• 26 Kuo HK, Yen CJ, Chang CH, Kuo CK, Chen JH, Sorond F. Relation of C-reactive protein to stroke, cognitive disorders, and depression in the general population: systematic review and meta-analysis.  Lancet Neurol. 2005;  4 371-380
• 27 Henningsson S, Baghaei F, Rosmond R, Holm G, Landén M, Anckarsäter H, Ekman A. Association between serum levels of C-reactive protein and personality traits in women.  Behav Brain Funct. 2008;  4 16
• 28 Whooley MA, Caska CM, Hendrickson BE, Rourke MA, Ho J, Ali S. Depression and inflammation in patients with coronary heart disease: findings from the Heart and Soul Study.  Biol Psychiatry. 2007;  62 314-320
• 29 Pan A, Ye X, Franco OH, Li H, Yu Z, Wang J, Qi Q, Gu W, Pang X, Liu H, Lin X. The association of depressive symptoms with inflammatory factors and adipokines in middle-aged and older Chinese.  PLoS ONE. 2008;  3 e1392
• 30 Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush JA, Walter EE, Wang PS. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R).  JAMA. 2003;  289 3095-3105
• 31 Riese H, Vrijkotte TG, Meijer P, Kluft C, De Geus EJ. Diagnostic strategies for C-reactive protein.  BMC Cardiovasc Disord. 2002;  2 9
• 32 Rudnicka AR, Rumley A, Lowe GD, Strachan DP. Diurnal, seasonal, and blood-processing patterns in levels of circulating fibrinogen, fibrin D-dimer, C-reactive protein, tissue plasminogen activator, and von Willebrand factor in a 45-year-old population.  Circulation. 2007;  115 996-1003
• 33 Eskandari F, Martinez P, Torvik S, Phillips TM, Sternberg EM, Mistry S, Ronsaville D, Wesley R, Toomey C, Sebring NG, Reynolds JC, Blackman MC, Calis KA, Gold PW, Cizza G. for the Power Study Group . Low bone mass in premenopausal women with depression.  Arch Intern Med. 2007;  167 2329-2336
• 34 Sabatine MS, Morrow DA, Jablonski KA, Rice MM, Warnica JW, Domanski MJ, Hsia J, Gersh BJ, Rifai N, Ridker PM, Pfeffer MA, Braunwald E. PEACE Investigators . Prognostic significance of the Centers for Disease Control/American Heart Association high-sensitivity C-reactive protein cut points for cardiovascular and other outcomes in patients with stable coronary artery disease.  Circulation. 2007;  115 1528-1536
• 35 Ladwig KH, Marten-Mittag B, Lowel H, Doring A, Koenig W. Influence of depressive mood on the association of CRP and obesity in 3 205 middle aged healthy men.  Brain Behav Immun. 2003;  17 268-275
• 36 Dietrich T, Garcia RI, de Pablo P, Schulze PC, Hoffmann K. The effects of cigarette smoking on C-reactive protein concentrations in men and women and its modification by exogenous oral hormones in women.  Eur J Cardiovasc Prev Rehabil. 2007;  14 694-700
• 37 Raum E, Gebhardt K, Buchner M, Schiltenwolf M, Brenner H. Long-term and short-term alcohol consumption and levels of C-reactive protein.  Int J Cardiol. 2007;  121 224-226
• 38 Cizza G, Marques AH, Eskandari F, Christie IC, Torvik S, Silverman MN, Phillips TM, Sternberg EM. POWER Study Group. Elevated neuroimmune biomarkers in sweat patches and plasma in premenopausal women with major depressive disorder in remission: the POWER Study.  Biol Psychiatry. 2008 Nov 15;  64 ((10)) 907-911 , Epub 2008 Jul 26
• 39 Devaraj S, O’Keefe G, Jialal I. Defining the proinflammatory phenotype using high sensitive C-reactive protein levels as the biomarker.  J Clin Endocrinol Metab. 2005;  90 4549-4554
• 40 Sesso HD, Wang L, Buring JE, Ridker PM, Gaziano JM. Comparison of interleukin-6 and C-reactive protein for the risk of developing hypertension in women.  Hypertension. 2007;  49 304-310
• 41 Cook NR, Buring JE, Ridker PM. The effect of including C-reactive protein in cardiovascular risk prediction models for women.  Ann Intern Med. 2006;  145 21-29
• 42 Mohamed-Ali V, Goodrick S, Rawesh A, Katz DR, Miles JM, Yudkin JS, Klein S, Coppack SW. Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo.  J Clin Endocrinol Metab. 1997;  82 4196-4200
• 43 Kinder LS, Carnethon MR, Palaniappan LP, King AC, Fortmann. Depression and the metabolic syndrome in young adults: findings from the Third National Health and Nutrition Examination Survey.  Psychosom Med. 2004;  66 316-322
• 44 Jensen GL. Drug-induced hyperphagia: what can we learn from psychiatric medications?.  J Parenter Enteral Nutr. 2008;  32 578-581
• 45 Ridker PM, Rifai N, Cook NR, Bradwin G, Buring JE. Non-HDL cholesterol, apolipoproteins A-I and B100, standard lipid measures, lipid ratios, and CRP as risk factors for cardiovascular disease in women.  JAMA. 2005;  294 326-333
• 46 Bogaty P, Boyer L, Simard S, Dauwe F, Dupuis R, Verret B, Huynh T, Bertrand F, Dagenais GR, Brophy JM. Clinical utility of C-reactive protein measured at admission, hospital discharge, and 1 month later to predict outcome in patients with acute coronary disease. The RISCA (recurrence and inflammation in the acute coronary syndromes) study.  J Am Coll Cardiol. 2008;  51 2339-2346
• 47 Kluft C, de Maat MP. Determination of the habitual low blood level of C-reactive protein in individuals.  Ital Heart J. 2001;  3 172-180
• 48 Kathiresan S, Larson MG, Vasan RS, Guo CY, Gona P, Keaney  Jr JF, Wilson PW, Newton-Cheh C, Musone SL, Camargo AL, Drake JA, Levy D, O’Donnell CJ, Hirschhorn JN, Benjamin EJ. Contribution of clinical correlates and 13 C-reactive protein gene polymorphisms to interindividual variability in serum C-reactive protein level.  Circulation. 2006;  113 1415-1423
• 49 Kelly GS. Seasonal variations of selected cardiovascular risk factors.  Altern Med Rev. 2005;  10 307-320
• 50 Kao PC, Shiesh SC, Wu TJ. Serum C-reactive protein as a marker for wellness assessment.  Ann Clin Lab Sci. 2006;  36 163-169
• 51 Lanquillon S, Krieg JC, Bening-Abu-Shach U, Vedder H. Cytokine production and treatment response in major depressive disorder.  Neuropsychopharmacology. 2000;  22 370-379
• 52 Selvin E, Paynter NP, Erlinger TP. The effect of weight loss on C-reactive protein: a systematic review.  Arch Intern Med. 2007;  167 31-39

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