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Open Access 01-12-2013 | Review

Understanding the somatic consequences of depression: biological mechanisms and the role of depression symptom profile

Authors: Brenda WJH Penninx, Yuri Milaneschi, Femke Lamers, Nicole Vogelzangs

Published in: BMC Medicine | Issue 1/2013

Abstract

Depression is the most common psychiatric disorder worldwide. The burden of disease for depression goes beyond functioning and quality of life and extends to somatic health. Depression has been shown to subsequently increase the risk of, for example, cardiovascular, stroke, diabetes and obesity morbidity. These somatic consequences could partly be due to metabolic, immuno-inflammatory, autonomic and hypothalamic-pituitary-adrenal (HPA)-axis dysregulations which have been suggested to be more often present among depressed patients. Evidence linking depression to metabolic syndrome abnormalities indicates that depression is especially associated with its obesity-related components (for example, abdominal obesity and dyslipidemia). In addition, systemic inflammation and hyperactivity of the HPA-axis have been consistently observed among depressed patients. Slightly less consistent observations are for autonomic dysregulation among depressed patients. The heterogeneity of the depression concept seems to play a differentiating role: metabolic syndrome and inflammation up-regulations appear more specific to the atypical depression subtype, whereas hypercortisolemia appears more specific for melancholic depression. This review finishes with potential treatment implications for the downward spiral in which different depressive symptom profiles and biological dysregulations may impact on each other and interact with somatic health decline.

Alonso J, Angermeyer MC, Bernert S, Bruffaerts R, Brugha TS, Bryson H, de Girolamo G, Graaf R, Demyttenaere K, Gasquet I, Haro JM, Katz SJ, Kessler RC, Kovess V, Lépine JP, Ormel J, Polidori G, Russo LJ, Vilagut G, Almansa J, Arbabzadeh-Bouchez S, Autonell J, Bernal M, Buist-Bouwman MA, Codony M, Domingo-Salvany A, Ferrer M, Joo SS, Martínez-Alonso M, Matschinger H: Prevalence of mental disorders in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project. Acta Psychiatr Scand Suppl. 2004, 21-27.

Mathers CD, Loncar D: Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006, 3: e442-10.1371/journal.pmed.0030442.PubMedPubMedCentral

Nicholson A, Kuper H, Hemingway H: Depression as an aetiologic and prognostic factor in coronary heart disease: a meta-analysis of 6362 events among 146 538 participants in 54 observational studies. Eur Heart J. 2006, 27: 2763-2774. 10.1093/eurheartj/ehl338.PubMed

Mezuk B, Eaton WW, Albrecht S, Golden SH: Depression and type 2 diabetes over the lifespan: a meta-analysis. Diabetes Care. 2008, 31: 2383-2390. 10.2337/dc08-0985.PubMedPubMedCentral

Cuijpers P, Vogelzangs N, Twisk J, Kleiboer A, Li J, Penninx BW: Differential mortality rates in major and subthreshold depression: a meta-analysis of studies that measured both. Br J Psychiatry. 2013, 202: 22-27. 10.1192/bjp.bp.112.112169.PubMed

Bogers RP, Bemelmans WJE, Hoogenveen RT, Boshuizen HC, Woodward M, Knekt P, van Dam RM, Hu FB, Visscher TL, Menotti A, Thorpe RJ, Jamrozik K, Calling S, Strand BH, Shipley MJ, BMI-CHD Collaboration Investigators: Association of overweight with increased risk of coronary heart disease partly independent of blood pressure and cholesterol levels: a meta-analysis of 21 cohort studies including more than 300 000 persons. Arch Intern Med. 2007, 167: 1720-1728. 10.1001/archinte.167.16.1720.PubMed

Mottillo S, Filion KB, Genest J, Joseph L, Pilote L, Poirier P, Rinfret S, Schiffrin EL, Eisenberg MJ: The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J Am Coll Cardiol. 2010, 56: 1113-1132. 10.1016/j.jacc.2010.05.034.PubMed

Huxley RR, Barzi F, Lam TH, Czernichow S, Fang X, Welborn T, Shaw J, Ueshima H, Zimmet P, Jee SH, Patel JV, Caterson I, Perkovic V, Woodward M, Asia Pacific Cohort Studies Collaboration and the Obesity in Asia Collaboration: Isolated low levels of high-density lipoprotein cholesterol are associated with an increased risk of coronary heart disease: an individual participant data meta-analysis of 23 studies in the Asia-Pacific region. Circulation. 2011, 124: 2056-2064. 10.1161/CIRCULATIONAHA.111.028373.PubMed

Buckley DI, Fu R, Freeman M, Rogers K, Helfand M: C-reactive protein as a risk factor for coronary heart disease: a systematic review and meta-analyses for the U.S. Preventive Services Task Force. Ann Intern Med. 2009, 151: 483-495. 10.7326/0003-4819-151-7-200910060-00009.PubMed

10.

Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, Shibuya K, Salomon JA, Abdalla S, Aboyans V, Abraham J, Ackerman I, Aggarwal R, Ahn SY, Ali MK, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Bahalim AN, Barker-Collo S, Barrero LH, Bartels DH, Basáñez MG, Baxter A, Bell ML, Benjamin EJ, Bennett D: Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012, 380: 2163-2196. 10.1016/S0140-6736(12)61729-2.PubMed

11.

Murray CJ, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C, Ezzati M, Shibuya K, Salomon JA, Abdalla S, Aboyans V, Abraham J, Ackerman I, Aggarwal R, Ahn SY, Ali MK, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Bahalim AN, Barker-Collo S, Barrero LH, Bartels DH, Basáñez MG, Baxter A, Bell ML, Benjamin EJ: Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012, 380: 2197-2223. 10.1016/S0140-6736(12)61689-4.PubMed

12.

Meng L, Chen D, Yang Y, Zheng Y, Hui R: Depression increases the risk of hypertension incidence: a meta-analysis of prospective cohort studies. J Hypertens. 2012, 30: 842-851. 10.1097/HJH.0b013e32835080b7.PubMed

13.

Dong JY, Zhang YH, Tong J, Qin LQ: Depression and risk of stroke: a meta-analysis of prospective studies. Stroke. 2012, 43: 32-37. 10.1161/STROKEAHA.111.630871.PubMed

14.

Gao Y, Huang C, Zhao K, Ma L, Qiu X, Zhang L, Xiu Y, Chen L, Lu W, Huang C, Tang Y, Xiao Q: Depression as a risk factor for dementia and mild cognitive impairment: a meta-analysis of longitudinal studies. Int J Geriatr Psychiatry. 2013, 28: 441-449. 10.1002/gps.3845.PubMed

15.

Luppino FS, van Reedt Dortland AK, Wardenaar KJ, Bouvy PF, Giltay EJ, Zitman FG, Penninx BW: Symptom dimensions of depression and anxiety and the metabolic syndrome. Psychosom Med. 2011, 73: 257-264. 10.1097/PSY.0b013e31820a59c0.PubMed

16.

Chida Y, Hamer M, Wardle J, Steptoe A: Do stress-related psychosocial factors contribute to cancer incidence and survival?. Nat Clin Pract Oncol. 2008, 5: 466-475. 10.1038/ncponc1134.PubMed

17.

van Gool CH, Kempen GI, Bosma H, van Boxtel MP, Jolles J, van Eijk JT: Associations between lifestyle and depressed mood: longitudinal results from the Maastricht Aging Study. Am J Public Health. 2007, 97: 887-894. 10.2105/AJPH.2004.053199.PubMedPubMedCentral

18.

DiMatteo MR, Lepper HS, Croghan TW: Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med. 2000, 160: 2101-2107. 10.1001/archinte.160.14.2101.PubMed

19.

Esposito K, Chiodini P, Colao A, Lenzi A, Giugliano D: Metabolic syndrome and risk of cancer: a systematic review and meta-analysis. Diabetes Care. 2012, 35: 2402-2411. 10.2337/dc12-0336.PubMedPubMedCentral

20.

Profenno LA, Porsteinsson AP, Faraone SV: Meta-analysis of Alzheimer’s disease risk with obesity, diabetes, and related disorders. Biol Psychiatry. 2010, 67: 505-512. 10.1016/j.biopsych.2009.02.013.PubMed

21.

Eckel RH, Grundy SM, Zimmet PZ: The metabolic syndrome. Lancet. 2005, 365: 1415-1428. 10.1016/S0140-6736(05)66378-7.PubMed

22.

Pan A, Keum N, Okereke OI, Sun Q, Kivimaki M, Rubin RR, Hu FB: Bidirectional association between depression and metabolic syndrome: a systematic review and meta-analysis of epidemiological studies. Diabetes Care. 2012, 35: 1171-1180. 10.2337/dc11-2055.PubMedPubMedCentral

23.

Foley DL, Morley KI, Madden PA, Heath AC, Whitfield JB, Martin NG: Major depression and the metabolic syndrome. Twin Res Hum Genet. 2010, 13: 347-358. 10.1375/twin.13.4.347.PubMedPubMedCentral

24.

Hildrum B, Mykletun A, Midthjell K, Ismail K, Dahl AA: No association of depression and anxiety with the metabolic syndrome: the Norwegian HUNT study. Acta Psychiatr Scand. 2009, 120: 14-22. 10.1111/j.1600-0447.2008.01315.x.PubMed

25.

Kahl KG, Greggersen W, Schweiger U, Cordes J, Balijepalli C, Lösch C, Moebus S: Prevalence of the metabolic syndrome in unipolar major depression. Eur Arch Psychiatry Clin Neurosci. 2012, 262: 313-320. 10.1007/s00406-011-0277-4.PubMed

26.

Koponen H, Jokelainen J, Keinanen-Kiukaanniemi S, Kumpusalo E, Vanhala M: Metabolic syndrome predisposes to depressive symptoms: a population-based 7-year follow-up study. J Clin Psychiatry. 2008, 69: 178-182. 10.4088/JCP.v69n0202.PubMed

27.

Miettola J, Niskanen LK, Viinamaki H, Kumpusalo E: Metabolic syndrome is associated with self-perceived depression. Scand J Prim Health Care. 2008, 26: 203-210. 10.1080/02813430802117624.PubMedPubMedCentral

28.

Muhtz C, Zyriax BC, Klahn T, Windler E, Otte C: Depressive symptoms and metabolic risk: effects of cortisol and gender. Psychoneuroendocrinology. 2009, 34: 1004-1011. 10.1016/j.psyneuen.2009.01.016.PubMed

29.

Skilton MR, Moulin P, Terra JL, Bonnet F: Associations between anxiety, depression, and the metabolic syndrome. Biol Psychiatry. 2007, 62: 1251-1257. 10.1016/j.biopsych.2007.01.012.PubMed

30.

van Reedt Dortland AK, Giltay EJ, van Veen T, Zitman FG, Penninx BW: Metabolic syndrome abnormalities are associated with severity of anxiety and depression and with tricyclic antidepressant use. Acta Psychiatr Scand. 2010, 122: 30-39.PubMed

31.

Vogelzangs N, Suthers K, Ferrucci L, Simonsick EM, Ble A, Schrager M, Bandinelli S, Lauretani F, Giannelli SV, Penninx BW: Hypercortisolemic depression is associated with the metabolic syndrome in late-life. Psychoneuroendocrinology. 2007, 32: 151-159. 10.1016/j.psyneuen.2006.11.009.PubMedPubMedCentral

32.

Vogelzangs N, Beekman AT, Kritchevsky SB, Newman AB, Pahor M, Yaffe K, Rubin SM, Harris TB, Satterfield S, Simonsick EM, Penninx BW: Psychosocial risk factors and the metabolic syndrome in elderly persons: findings from the health, aging and body composition study. J Gerontol A Biol Sci Med Sci. 2007, 62: 563-569. 10.1093/gerona/62.5.563.PubMed

33.

Vogelzangs N, Beekman AT, Boelhouwer IG, Bandinelli S, Milaneschi Y, Ferrucci L, Penninx BW: Metabolic depression: a chronic depressive subtype? Findings from the InCHIANTI study of older persons. J Clin Psychiatry. 2011, 72: 598-604. 10.4088/JCP.10m06559.PubMed

34.

Akbaraly TN, Ancelin ML, Jaussent I, Ritchie C, Barberger-Gateau P, Dufouil C, Kivimaki M, Berr C, Ritchie K: Metabolic syndrome and onset of depressive symptoms in the elderly: findings from the three-city study. Diabetes Care. 2011, 34: 904-909. 10.2337/dc10-1644.PubMedPubMedCentral

35.

Bove M, Carnevali L, Cicero AF, Grandi E, Gaddoni M, Noera G, Gaddi AV: Psychosocial factors and metabolic parameters: is there any association in elderly people? The Massa Lombarda Project. Aging Ment Health. 2010, 14: 801-806. 10.1080/13607861003713299.PubMedPubMedCentral

36.

Dunbar JA, Reddy P, Davis-Lameloise N, Philpot B, Laatikainen T, Kilkkinen A, Bunker SJ, Best JD, Vartiainen E, Kai Lo S, Janus ED: Depression: an important comorbidity with metabolic syndrome in a general population. Diabetes Care. 2008, 31: 2368-2373. 10.2337/dc08-0175.PubMedPubMedCentral

37.

Mast BT, Miles T, Penninx BW, Yaffe K, Rosano C, Satterfield S, Ayonayon HN, Harris T, Simonsick EM: Vascular disease and future risk of depressive symptomatology in older adults: findings from the Health, Aging, and Body Composition study. Biol Psychiatry. 2008, 64: 320-326. 10.1016/j.biopsych.2008.01.025.PubMed

38.

Petrlova B, Rosolova H, Hess Z, Podlipny J, Simon J: Depressive disorders and the metabolic syndrome of insulin resistance. Semin Vasc Med. 2004, 4: 161-165. 10.1055/s-2004-835374.PubMed

39.

Pyykkonen AJ, Raikkonen K, Tuomi T, Eriksson JG, Groop L, Isomaa B: Association between depressive symptoms and metabolic syndrome is not explained by antidepressant medication: results from the PPP-Botnia Study. Ann Med. 2012, 44: 279-288. 10.3109/07853890.2010.543921.PubMed

40.

Veen G, Giltay EJ, DeRijk RH, van Vliet IM, van Pelt J, Zitman FG: Salivary cortisol, serum lipids, and adiposity in patients with depressive and anxiety disorders. Metabolism. 2009, 58: 821-827. 10.1016/j.metabol.2009.02.009.PubMed

41.

Viscogliosi G, Andreozzi P, Chiriac IM, Cipriani E, Servello A, Marigliano B, Ettorre E, Marigliano V: Depressive symptoms in older people with metabolic syndrome: is there a relationship with inflammation?. Int J Geriatr Psychiatry. 2013, 28: 242-247. 10.1002/gps.3817.PubMed

42.

Gil K, Radzillowicz P, Zdrojewski T, Pakalska-Korcala A, Chwojnicki K, Piwonski J, Ignaszewska-Wyrzykowska A, Załuga L, Mielczarek M, Landowski J, Wyrzykowski B: Relationship between the prevalence of depressive symptoms and metabolic syndrome. Results of the SOPKARD Project. Kardiol Pol. 2006, 64: 464-469.PubMed

43.

Viinamaki H, Heiskanen T, Lehto SM, Niskanen L, Koivumaa-Honkanen H, Tolmunen T, Honkalampi K, Saharinen T, Haatainen K, Hintikka J: Association of depressive symptoms and metabolic syndrome in men. Acta Psychiatr Scand. 2009, 120: 23-29. 10.1111/j.1600-0447.2008.01333.x.PubMed

44.

Pulkki-Råback L, Elovainio M, Kivimäki M, Mattsson N, Raitakari OT, Puttonen S, Marniemi J, Viikari JS, Keltikangas-Järvinen L: Depressive symptoms and the metabolic syndrome in childhood and adulthood: a prospective cohort study. Health Psychol. 2009, 28: 108-116.PubMedPubMedCentral

45.

Toker S, Shirom A, Melamed S: Depression and the metabolic syndrome: gender-dependent associations. Depress Anxiety. 2008, 25: 661-669. 10.1002/da.20379.PubMed

46.

Vanhala M, Jokelainen J, Keinanen-Kiukaanniemi S, Kumpusalo E, Koponen H: Depressive symptoms predispose females to metabolic syndrome: a 7-year follow-up study. Acta Psychiatr Scand. 2009, 119: 137-142. 10.1111/j.1600-0447.2008.01283.x.PubMed

47.

McCaffery JM, Niaura R, Todaro JF, Swan GE, Carmelli D: Depressive symptoms and metabolic risk in adult male twins enrolled in the National Heart, Lung, and Blood Institute twin study. Psychosom Med. 2003, 65: 490-497. 10.1097/01.PSY.0000041545.52924.82.PubMed

48.

Takeuchi T, Nakao M, Nomura K, Yano E: Association of metabolic syndrome with depression and anxiety in Japanese men. Diabetes Metab. 2009, 35: 32-36. 10.1016/j.diabet.2008.06.006.PubMed

49.

Takeuchi T, Nakao M, Nomura K, Inoue M, Tsurugano S, Shinozaki Y, Yano E: Association of the metabolic syndrome with depression and anxiety in Japanese men: a 1-year cohort study. Diabetes Metab Res Rev. 2009, 25: 762-767. 10.1002/dmrr.1041.PubMed

50.

Raikkonen K, Matthews KA, Kuller LH: Depressive symptoms and stressful life events predict metabolic syndrome among middle-aged women: a comparison of World Health Organization, Adult Treatment Panel III, and International Diabetes Foundation definitions. Diabetes Care. 2007, 30: 872-877. 10.2337/dc06-1857.PubMed

51.

Vaccarino V, McClure C, Johnson BD, Sheps DS, Bittner V, Rutledge T, Shaw LJ, Sopko G, Olson MB, Krantz DS, Parashar S, Marroquin OC, Merz CN: Depression, the metabolic syndrome and cardiovascular risk. Psychosom Med. 2008, 70: 40-48.PubMed

52.

Kahl KG: [The metabolic syndrome and mental illness: relevance, risk factors and practical consequences]. MMW Fortschr Med. 2005, 147: 32-34, 36.PubMed

53.

Seppälä J, Vanhala M, Kautiainen H, Eriksson J, Kampman O, Mäntyselkä P, Oksa H, Ovaskainen Y, Viikki M, Koponen H: Prevalence of metabolic syndrome in subjects with melancholic and non-melancholic depressive symptoms. A Finnish population-based study. J Affect Disord. 2012, 136: 543-549. 10.1016/j.jad.2011.10.032.PubMed

54.

Vogelzangs N, Beekman AT, Dik MG, Bremmer MA, Comijs HC, Hoogendijk WJ, Deeg DJ, Penninx BW: Late-life depression, cortisol, and the metabolic syndrome. Am J Geriatr Psychiatry. 2009, 17: 716-721. 10.1097/JGP.0b013e3181aad5d7.PubMed

55.

Kinder LS, Carnethon MR, Palaniappan LP, King AC, Fortmann SP: Depression and the metabolic syndrome in young adults: findings from the Third National Health and Nutrition Examination Survey. Psychosom Med. 2004, 66: 316-322. 10.1097/01.psy.0000124755.91880.f4.PubMed

56.

Raikkonen K, Matthews KA, Kuller LH: The relationship between psychological risk attributes and the metabolic syndrome in healthy women: antecedent or consequence?. Metabolism. 2002, 51: 1573-1577. 10.1053/meta.2002.36301.PubMed

57.

Xu Q, Anderson D, Lurie-Beck J: The relationship between abdominal obesity and depression in the general population: A systematic review and meta-analysis. Obes Res Clin Practice. 2011, 5: e267-e278. 10.1016/j.orcp.2011.04.007.

58.

Howren MB, Lamkin DM, Suls J: Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med. 2009, 71: 171-186. 10.1097/PSY.0b013e3181907c1b.PubMed

59.

Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctôt KL: A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010, 67: 446-457. 10.1016/j.biopsych.2009.09.033.PubMed

60.

Liu Y, Ho RC, Mak A: Interleukin (IL)-6, tumour necrosis factor alpha (TNF-alpha) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: a meta-analysis and meta-regression. J Affect Disord. 2012, 139: 230-239. 10.1016/j.jad.2011.08.003.PubMed

61.

Rottenberg J: Cardiac vagal control in depression: a critical analysis. Biol Psychol. 2007, 74: 200-211. 10.1016/j.biopsycho.2005.08.010.PubMed

62.

Kemp AH, Quintana DS, Gray MA, Felmingham KL, Brown K, Gatt JM: Impact of depression and antidepressant treatment on heart rate variability: a review and meta-analysis. Biol Psychiatry. 2010, 67: 1067-1074. 10.1016/j.biopsych.2009.12.012.PubMed

63.

Stetler C, Miller GE: Depression and hypothalamic-pituitary-adrenal activation: a quantitative summary of four decades of research. Psychosom Med. 2011, 73: 114-126. 10.1097/PSY.0b013e31820ad12b.PubMed

64.

Knorr U, Vinberg M, Kessing LV, Wetterslev J: Salivary cortisol in depressed patients versus control persons: a systematic review and meta-analysis. Psychoneuroendocrinology. 2010, 35: 1275-1286. 10.1016/j.psyneuen.2010.04.001.PubMed

65.

Esteve E, Ricart W, Fernandez-Real JM: Dyslipidemia and inflammation: an evolutionary conserved mechanism. Clin Nutr. 2005, 24: 16-31. 10.1016/j.clnu.2004.08.004.PubMed

66.

Osborn O, Olefsky JM: The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med. 2012, 18: 363-374. 10.1038/nm.2627.PubMed

67.

Zhang X, Zhang G, Zhang H, Karin M, Bai H, Cai D: Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity. Cell. 2008, 135: 61-73. 10.1016/j.cell.2008.07.043.PubMedPubMedCentral

68.

Krishnan V, Nestler EJ: Linking molecules to mood: new insight into the biology of depression. Am J Psychiatry. 2010, 167: 1305-1320. 10.1176/appi.ajp.2009.10030434.PubMedPubMedCentral

69.

Paz-Filho G, Wong ML, Licinio J: The procognitive effects of leptin in the brain and their clinical implications. Int J Clin Pract. 2010, 64: 1808-1812. 10.1111/j.1742-1241.2010.02536.x.PubMedPubMedCentral

70.

Alexopoulos GS: The vascular depression hypothesis: 10 years later. Biol Psychiatry. 2006, 60: 1304-1305. 10.1016/j.biopsych.2006.09.006.PubMed

71.

Bjorntorp P: Do stress reactions cause abdominal obesity and comorbidities?. Obes Rev. 2001, 2: 73-86. 10.1046/j.1467-789x.2001.00027.x.PubMed

72.

Tentolouris N, Argyrakopoulou G, Katsilambros N: Perturbed autonomic nervous system function in metabolic syndrome. Neuromolecular Med. 2008, 10: 169-178. 10.1007/s12017-008-8022-5.PubMed

73.

Maes M, Bosmans E, Meltzer HY, Scharpe S, Suy E: Interleukin-1 beta: a putative mediator of HPA axis hyperactivity in major depression?. Am J Psychiatry. 1993, 150: 1189-1193.PubMed

74.

Maes M: A review on the acute phase response in major depression. Rev Neurosci. 1993, 4: 407-416.PubMed

75.

Cesari M, Penninx BW, Newman AB, Kritchevsky SB, Nicklas BJ, Sutton-Tyrrell K, Rubin SM, Ding J, Simonsick EM, Harris TB, Pahor M: Inflammatory markers and onset of cardiovascular events: results from the Health ABC study. Circulation. 2003, 108: 2317-2322. 10.1161/01.CIR.0000097109.90783.FC.PubMed

76.

Kaptoge S, Di Angelantonio E, Lowe G, Pepys MB, Thompson SG, Collins R, Danesh J, Emerging Risk Factors Collaboration: C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet. 2010, 375: 132-140.PubMed

77.

Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB: Elevated C-reactive protein levels in overweight and obese adults. JAMA. 1999, 282: 2131-2135. 10.1001/jama.282.22.2131.PubMed

78.

Ingelsson E, Hulthe J, Lind L: Inflammatory markers in relation to insulin resistance and the metabolic syndrome. Eur J Clin Invest. 2008, 38: 502-509. 10.1111/j.1365-2362.2008.01962.x.PubMed

79.

Anisman H, Hayley S, Turrin N, Merali Z: Cytokines as a stressor: implications for depressive illness. Int J Neuropsychopharmacol. 2002, 5: 357-373. 10.1017/S1461145702003097.PubMed

80.

Bonaccorso S, Marino V, Puzella A, Pasquini M, Biondi M, Artini M, Almerighi C, Verkerk R, Meltzer H, Maes M: Increased depressive ratings in patients with hepatitis C receiving interferon-alpha-based immunotherapy are related to interferon-alpha-induced changes in the serotonergic system. J Clin Psychopharmacol. 2002, 22: 86-90. 10.1097/00004714-200202000-00014.PubMed

81.

Shelton RC, Miller AH: Eating ourselves to death (and despair): the contribution of adiposity and inflammation to depression. Prog Neurobiol. 2010, 91: 275-299. 10.1016/j.pneurobio.2010.04.004.PubMedPubMedCentral

82.

Sublette ME, Postolache TT: Neuroinflammation and depression: the role of indoleamine 2,3-dioxygenase (IDO) as a molecular pathway. Psychosom Med. 2012, 74: 668-672. 10.1097/PSY.0b013e318268de9f.PubMed

83.

Wichers MC, Koek GH, Robaeys G, Verkerk R, Scharpe S, Maes M: IDO and interferon-alpha-induced depressive symptoms: a shift in hypothesis from tryptophan depletion to neurotoxicity. Mol Psychiatry. 2005, 10: 538-544. 10.1038/sj.mp.4001600.PubMed

84.

Maes M, Berk M, Goehler L, Song C, Anderson G, Galecki P, Leonard B: Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways. BMC Med. 2012, 10: 66-10.1186/1741-7015-10-66.PubMedPubMedCentral

85.

Anderson G, Maes M, Berk M: Inflammation-related disorders in the tryptophan catabolite pathway in depression and somatization. Adv Protein Chem Struct Biol. 2012, 88: 27-48.PubMed

86.

Maes M, Galecki P, Chang YS, Berk M: A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness. Prog Neuropsychopharmacol Biol Psychiatry. 2011, 35: 676-692. 10.1016/j.pnpbp.2010.05.004.PubMed

87.

Maes M, Kubera M, Leunis JC, Berk M: Increased IgA and IgM responses against gut commensals in chronic depression: further evidence for increased bacterial translocation or leaky gut. J Affect Disord. 2012, 141: 55-62. 10.1016/j.jad.2012.02.023.PubMed

88.

Schildkraut JJ, Orsulak PJ, Schatzberg AF, Gudeman JE, Cole JO, Rohde WA, LaBrie RA: Toward a biochemical classification of depressive disorders. I. Differences in urinary excretion of MHPG and other catecholamine metabolites in clinically defined subtypes of depressions. Arch Gen Psychiatry. 1978, 35: 1427-1433. 10.1001/archpsyc.1978.01770360031003.PubMed

89.

Linnoila M, Karoum F, Calil HM, Kopin IJ, Potter WZ: Alteration of norepinephrine metabolism with desipramine and zimelidine in depressed patients. Arch Gen Psychiatry. 1982, 39: 1025-1028. 10.1001/archpsyc.1982.04290090027006.PubMed

90.

Roy A, Pickar D, Linnoila M, Potter WZ: Plasma norepinephrine level in affective disorders. Relationship to melancholia. Arch Gen Psychiatry. 1985, 42: 1181-1185. 10.1001/archpsyc.1985.01790350055010.PubMed

91.

Esler M, Turbott J, Schwarz R, Leonard P, Bobik A, Skews H, Jackman G: The peripheral kinetics of norepinephrine in depressive illness. Arch Gen Psychiatry. 1982, 39: 295-300. 10.1001/archpsyc.1982.04290030035006.PubMed

92.

Veith RC, Lewis N, Linares OA, Barnes RF, Raskind MA, Villacres EC, Murburg MM, Ashleigh EA, Castillo S, Peskind ER: Sympathetic nervous system activity in major depression. Basal and desipramine-induced alterations in plasma norepinephrine kinetics. Arch Gen Psychiatry. 1994, 51: 411-422. 10.1001/archpsyc.1994.03950050071008.PubMed

93.

Barton DA, Dawood T, Lambert EA, Esler MD, Haikerwal D, Brenchley C, Socratous F, Kaye DM, Schlaich MP, Hickie I, Lambert GW: Sympathetic activity in major depressive disorder: identifying those at increased cardiac risk?. J Hypertens. 2007, 25: 2117-2124. 10.1097/HJH.0b013e32829baae7.PubMed

94.

Dekker JM, Crow RS, Folsom AR, Hannan PJ, Liao D, Swenne CA, Schouten EG: Low heart rate variability in a 2-minute rhythm strip predicts risk of coronary heart disease and mortality from several causes: the ARIC Study. Atherosclerosis risk in communities. Circulation. 2000, 102: 1239-1244. 10.1161/01.CIR.102.11.1239.PubMed

95.

Tsuji H, Larson MG, Venditti FJ, Manders ES, Evans JC, Feldman CL, Levy D: Impact of reduced heart rate variability on risk for cardiac events. The Framingham Heart Study. Circulation. 1996, 94: 2850-2855. 10.1161/01.CIR.94.11.2850.PubMed

96.

Porges SW: The polyvagal theory: phylogenetic substrates of a social nervous system. Int J Psychophysiol. 2001, 42: 123-146. 10.1016/S0167-8760(01)00162-3.PubMed

97.

Licht CM, de Geus EJ, Zitman FG, Hoogendijk WJ, van Dyck R, Penninx BW: Association between major depressive disorder and heart rate variability in the Netherlands Study of Depression and Anxiety (NESDA). Arch Gen Psychiatry. 2008, 65: 1358-1367. 10.1001/archpsyc.65.12.1358.PubMed

98.

Licht CM, de Geus EJ, van Dyck R, Penninx BW: Longitudinal evidence for unfavorable effects of antidepressants on heart rate variability. Biol Psychiatry. 2010, 68: 861-868. 10.1016/j.biopsych.2010.06.032.PubMed

99.

Light KC, Kothandapani RV, Allen MT: Enhanced cardiovascular and catecholamine responses in women with depressive symptoms. Int J Psychophysiol. 1998, 28: 157-166. 10.1016/S0167-8760(97)00093-7.PubMed

100.

Guinjoan SM, Bernabo JL, Cardinali DP: Cardiovascular tests of autonomic function and sympathetic skin responses in patients with major depression. J Neurol Neurosurg Psychiatry. 1995, 59: 299-302. 10.1136/jnnp.59.3.299.PubMedPubMedCentral

101.

Gold PW, Wong ML, Goldstein DS, Gold HK, Ronsaville DS, Esler M, Alesci S, Masood A, Licinio J, Geracioti TD, Perini G, DeBellis MD, Holmes C, Vgontzas AN, Charney DS, Chrousos GP, McCann SM, Kling MA: Cardiac implications of increased arterial entry and reversible 24-h central and peripheral norepinephrine levels in melancholia. Proc Natl Acad Sci USA. 2005, 102: 8303-8308. 10.1073/pnas.0503069102.PubMedPubMedCentral

102.

Koschke M, Boettger MK, Schulz S, Berger S, Terhaar J, Voss A, Yeragani VK, Bär KJ: Autonomy of autonomic dysfunction in major depression. Psychosom Med. 2009, 71: 852-860. 10.1097/PSY.0b013e3181b8bb7a.PubMed

103.

Ahrens T, Deuschle M, Krumm B, van der Pompe G, den Boer JA, Lederbogen F: Pituitary-adrenal and sympathetic nervous system responses to stress in women remitted from recurrent major depression. Psychosom Med. 2008, 70: 461-467. 10.1097/PSY.0b013e31816b1aaa.PubMed

104.

Licht CM, Penninx BW, de Geus EJ: Effects of antidepressants, but not psychopathology, on cardiac sympathetic control: a longitudinal study. Neuropsychopharmacology. 2012, 37: 2487-2495. 10.1038/npp.2012.107.PubMedPubMedCentral

105.

Licht CM, Vreeburg SA, van Reedt Dortland AK, Giltay EJ, Hoogendijk WJ, DeRijk RH, Vogelzangs N, Zitman FG, de Geus EJ, Penninx BW: Increased sympathetic and decreased parasympathetic activity rather than changes in hypothalamic-pituitary-adrenal axis activity is associated with metabolic abnormalities. J Clin Endocrinol Metab. 2010, 95: 2458-2466. 10.1210/jc.2009-2801.PubMed

106.

Miller AH, Maletic V, Raison CL: Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry. 2009, 65: 732-741. 10.1016/j.biopsych.2008.11.029.PubMedPubMedCentral

107.

Belmaker RH, Agam G: Major depressive disorder. N Engl J Med. 2008, 358: 55-68. 10.1056/NEJMra073096.PubMed

108.

Vreeburg SA, Hoogendijk WJ, van Pelt J, Derijk RH, Verhagen JC, van Dyck R, Smit JH, Zitman FG, Penninx BW: Major depressive disorder and hypothalamic-pituitary-adrenal axis activity: results from a large cohort study. Arch Gen Psychiatry. 2009, 66: 617-626. 10.1001/archgenpsychiatry.2009.50.PubMed

109.

Vreeburg SA, Hartman CA, Hoogendijk WJ, van Dyck R, Zitman FG, Ormel J, Penninx BW: Parental history of depression or anxiety and the cortisol awakening response. Br J Psychiatry. 2010, 197: 180-185. 10.1192/bjp.bp.109.076869.PubMed

110.

Nelson JC, Davis JM: DST studies in psychotic depression: a meta-analysis. Am J Psychiatry. 1997, 154: 1497-1503.PubMed

111.

de Kloet ER, Joels M, Holsboer F: Stress and the brain: from adaptation to disease. Nat Rev Neurosci. 2005, 6: 463-475. 10.1038/nrn1683.PubMed

112.

Silverman MN, Sternberg EM: Glucocorticoid regulation of inflammation and its functional correlates: from HPA axis to glucocorticoid receptor dysfunction. Ann N Y Acad Sci. 2012, 1261: 55-63. 10.1111/j.1749-6632.2012.06633.x.PubMedPubMedCentral

113.

Pace TW, Miller AH: Cytokines and glucocorticoid receptor signaling. Relevance to major depression. Ann N Y Acad Sci. 2009, 1179: 86-105. 10.1111/j.1749-6632.2009.04984.x.PubMedPubMedCentral

114.

Ripke S, Wray NR, Lewis CM, Hamilton SP, Weissman MM, Breen G, Byrne EM, Blackwood DH, Boomsma DI, Cichon S, Heath AC, Holsboer F, Lucae S, Madden PA, Martin NG, McGuffin P, Muglia P, Noethen MM, Penninx BP, Pergadia ML, Potash JB, Rietschel M, Lin D, Müller-Myhsok B, Shi J, Steinberg S, Grabe HJ, Lichtenstein P, Magnusson P, Perlis RH, Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium: A mega-analysis of genome-wide association studies for major depressive disorder. Mol Psychiatry. 2013, 18: 497-511. 10.1038/mp.2012.21.PubMed

115.

Lamers F, De Jonge P, Nolen WA, Smit JH, Zitman FG, Beekman AT, Penninx BW: Identifying depressive subtypes in a large cohort study: results from the Netherlands Study of Depression and Anxiety (NESDA). J Clin Psychiatry. 2010, 71: 1582-1589. 10.4088/JCP.09m05398blu.PubMed

116.

Lamers F, Burstein M, He J, Avenevoli S, Angst J, Merikangas KR: Structure of major depressive disorder in adolescents and adults in the US general population. Br J Psychiatry. 2012, 201: 143-150. 10.1192/bjp.bp.111.098079.PubMedPubMedCentral

117.

Angst J, Gamma A, Benazzi F, Silverstein B, Ajdacic-Gross V, Eich D, Rössler W: Atypical depressive syndromes in varying definitions. Eur Arch Psychiatry Clin Neurosci. 2006, 256: 44-54. 10.1007/s00406-005-0600-z.PubMed

118.

Williamson DE, Birmaher B, Brent DA, Balach L, Dahl RE, Ryan ND: Atypical symptoms of depression in a sample of depressed child and adolescent outpatients. J Am Acad Child Adolesc Psychiatry. 2000, 39: 1253-1259. 10.1097/00004583-200010000-00012.PubMed

119.

Angst J, Gamma A, Sellaro R, Zhang H, Merikangas K: Toward validation of atypical depression in the community: results of the Zurich cohort study. J Affect Disord. 2002, 72: 125-138. 10.1016/S0165-0327(02)00169-6.PubMed

120.

Sullivan PF, Kessler RC, Kendler KS: Latent class analysis of lifetime depressive symptoms in the national comorbidity survey. Am J Psychiatry. 1998, 155: 1398-1406.PubMed

121.

Sullivan PF, Prescott CA, Kendler KS: The subtypes of major depression in a twin registry. J Affect Disord. 2002, 68: 273-284. 10.1016/S0165-0327(00)00364-5.PubMed

122.

Kendler KS, Eaves LJ, Walters EE, Neale MC, Heath AC, Kessler RC: The identification and validation of distinct depressive syndromes in a population-based sample of female twins. Arch Gen Psychiatry. 1996, 53: 391-399. 10.1001/archpsyc.1996.01830050025004.PubMed

123.

Anisman H, Ravindran AV, Griffiths J, Merali Z: Endocrine and cytokine correlates of major depression and dysthymia with typical or atypical features. Mol Psychiatry. 1999, 4: 182-188. 10.1038/sj.mp.4000436.PubMed

124.

Kaestner F, Hettich M, Peters M, Sibrowski W, Hetzel G, Ponath G, Arolt V, Cassens U, Rothermundt M: Different activation patterns of proinflammatory cytokines in melancholic and non-melancholic major depression are associated with HPA axis activity. J Affect Disord. 2005, 87: 305-311. 10.1016/j.jad.2005.03.012.PubMed

125.

Huang TL, Lee CT: T-helper 1/T-helper 2 cytokine imbalance and clinical phenotypes of acute-phase major depression. Psychiatry Clin Neurosci. 2007, 61: 415-420. 10.1111/j.1440-1819.2007.01686.x.PubMed

126.

Yoon HK, Kim YK, Lee HJ, Kwon DY, Kim L: Role of cytokines in atypical depression. Nord J Psychiatry. 2012, 66: 183-188. 10.3109/08039488.2011.611894.PubMed

127.

Lamers F, Vogelzangs N, Merikangas KR, de Jonge P, Beekman AT, Penninx BW: Evidence for a differential role of HPA-axis function, inflammation and metabolic syndrome in melancholic versus atypical depression. Mol Psychiatry. 2012, [Epub ahead of print.]

128.

Karlovic D, Serretti A, Vrkic N, Martinac M, Marcinko D: Serum concentrations of CRP, IL-6, TNF-alpha and cortisol in major depressive disorder with melancholic or atypical features. Psychiatry Res. 2013, 47: 162-167. 10.1016/j.jpsychires.2012.09.017.

129.

Wong ML, Kling MA, Munson PJ, Listwak S, Licinio J, Prolo P, Karp B, McCutcheon IE, Geracioti TD, DeBellis MD, Rice KC, Goldstein DS, Veldhuis JD, Chrousos GP, Oldfield EH, McCann SM, Gold PW: Pronounced and sustained central hypernoradrenergic function in major depression with melancholic features: relation to hypercortisolism and corticotropin-releasing hormone. Proc Natl Acad Sci USA. 2000, 97: 325-330. 10.1073/pnas.97.1.325.PubMedPubMedCentral

130.

De Jonge P, Mangano D, Whooley MA: Differential association of cognitive and somatic depressive symptoms with heart rate variability in patients with stable coronary heart disease: findings from the Heart and Soul Study. Psychosom Med. 2007, 69: 735-739. 10.1097/PSY.0b013e31815743ca.PubMedPubMedCentral

131.

Rottenberg J, Chambers AS, Allen JJ, Manber R: Cardiac vagal control in the severity and course of depression: the importance of symptomatic heterogeneity. J Affect Disord. 2007, 103: 173-179. 10.1016/j.jad.2007.01.028.PubMedPubMedCentral

132.

Miller GE, Cohen S, Ritchey AK: Chronic psychological stress and the regulation of pro-inflammatory cytokines: a glucocorticoid-resistance model. Health Psychol. 2002, 21: 531-541.PubMed

133.

Wirtz PH, von Kanel R, Schnorpfeil P, Ehlert U, Frey K, Fischer JE: Reduced glucocorticoid sensitivity of monocyte interleukin-6 production in male industrial employees who are vitally exhausted. Psychosom Med. 2003, 65: 672-678. 10.1097/01.PSY.0000062529.39901.C7.PubMed

134.

Sorrells SF, Caso JR, Munhoz CD, Sapolsky RM: The stressed CNS: when glucocorticoids aggravate inflammation. Neuron. 2009, 64: 33-39. 10.1016/j.neuron.2009.09.032.PubMedPubMedCentral

135.

Munhoz CD, Lepsch LB, Kawamoto EM, Malta MB, Lima Lde S, Avellar MC, Sapolsky RM, Scavone C: Chronic unpredictable stress exacerbates lipopolysaccharide-induced activation of nuclear factor-kappaB in the frontal cortex and hippocampus via glucocorticoid secretion. J Neurosci. 2006, 26: 3813-3820. 10.1523/JNEUROSCI.4398-05.2006.PubMed

136.

Vogelzangs N, Duivis HE, Beekman AT, Kluft C, Neuteboom J, Hoogendijk W, Smit JH, de Jonge P, Penninx BW: Association of depressive disorders, depression characteristics and antidepressant medication with inflammation. Transl Psychiatry. 2012, 2: e79-10.1038/tp.2012.8.PubMedPubMedCentral

137.

Hamer M, Batty GD, Marmot MG, Singh-Manoux A, Kivimaki M: Anti-depressant medication use and C-reactive protein: results from two population-based studies. Brain Behav Immun. 2011, 25: 168-173. 10.1016/j.bbi.2010.09.013.PubMed

138.

Hannestad J, DellaGioia N, Bloch M: The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis. Neuropsychopharmacology. 2011, 36: 2452-2459. 10.1038/npp.2011.132.PubMedPubMedCentral

139.

Hiles S, Baker A, de Malmanche T, Attia J: Interleukin-6, C-reactive protein and interleukin-10 after antidepressant treatment in people with depression: a meta-analysis. Psychol Med. 2012, 42: 2015-2026. 10.1017/S0033291712000128.PubMed

140.

Kenis G, Maes M: Effects of antidepressants on the production of cytokines. Int J Neuropsychopharmacol. 2002, 5: 401-412. 10.1017/S1461145702003164.PubMed

141.

Janssen DG, Caniato RN, Verster JC, Baune BT: A psychoneuroimmunological review on cytokines involved in antidepressant treatment response. Hum Psychopharmacol. 2010, 25: 201-215. 10.1002/hup.1103.PubMed

142.

Fava M: Weight gain and antidepressants. J Clin Psychiatry. 2000, 61: 37-41.PubMed

143.

Licht CM, de Geus EJ, Seldenrijk A, van Hout HP, Zitman FG, van Dyck R, Penninx BW: Depression is associated with decreased blood pressure, but antidepressant use increases the risk for hypertension. Hypertension. 2009, 53: 631-638. 10.1161/HYPERTENSIONAHA.108.126698.PubMed

144.

Shimizu S, Akiyama T, Kawada T, Shishido T, Mizuno M, Kamiya A, Yamazaki T, Sano S, Sugimachi M: In vivo direct monitoring of interstitial norepinephrine levels at the sinoatrial node. Auton Neurosci. 2010, 152: 115-118. 10.1016/j.autneu.2009.08.017.PubMed

145.

Grant MM, Weiss JM: Effects of chronic antidepressant drug administration and electroconvulsive shock on locus coeruleus electrophysiologic activity. Biol Psychiatry. 2001, 49: 117-129. 10.1016/S0006-3223(00)00936-7.PubMed

146.

Elam M, Thoren P, Svensson TH: Locus coeruleus neurons and sympathetic nerves: activation by visceral afferents. Brain Res. 1986, 375: 117-125. 10.1016/0006-8993(86)90964-9.PubMed

147.

Ising M, Horstmann S, Kloiber S, Lucae S, Binder EB, Kern N, Künzel HE, Pfennig A, Uhr M, Holsboer F: Combined dexamethasone/corticotropin releasing hormone test predicts treatment response in major depression - a potential biomarker?. Biol Psychiatry. 2007, 62: 47-54. 10.1016/j.biopsych.2006.07.039.PubMed

148.

Lanquillon S, Krieg JC, Bening-Abu-Shach U, Vedder H: Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology. 2000, 22: 370-379. 10.1016/S0893-133X(99)00134-7.PubMed

149.

Eller T, Vasar V, Shlik J, Maron E: Pro-inflammatory cytokines and treatment response to escitalopram in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2008, 32: 445-450. 10.1016/j.pnpbp.2007.09.015.PubMed

150.

Zhu CB, Blakely RD, Hewlett WA: The proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha activate serotonin transporters. Neuropsychopharmacology. 2006, 31: 2121-2131.PubMed

151.

Widner B, Laich A, Sperner-Unterweger B, Ledochowski M, Fuchs D: Neopterin production, tryptophan degradation, and mental depression–what is the link?. Brain Behav Immun. 2002, 16: 590-595. 10.1016/S0889-1591(02)00006-5.PubMed

152.

Neurauter G, Schröcksnadel K, Scholl-Bürgi S, Sperner-Unterweger B, Schubert C, Ledochowski M, Fuchs D: Chronic immune stimulation correlates with reduced phenylalanine turnover. Curr Drug Metab. 2008, 9: 622-627. 10.2174/138920008785821738.PubMed

153.

Raison CL, Rutherford RE, Woolwine BJ, Shuo C, Schettler P, Drake DF, Haroon E, Miller AH: A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry. 2013, 70: 31-41. 10.1001/2013.jamapsychiatry.4.PubMedPubMedCentral

154.

You T, Nicklas BJ: Effects of exercise on adipokines and the metabolic syndrome. Curr Diab Rep. 2008, 8: 7-11. 10.1007/s11892-008-0003-4.PubMed

155.

Mead GE, Morley W, Campbell P, Greig CA, McMurdo M, Lawlor DA: Exercise for depression. Cochrane Database Syst Rev. 2009, CD004366.

156.

Rethorst C, Toups M, Greer T, Nakonezny P, Carmody T, Grannemann B, Huebinger RM, Barber RC, Trivedi MH: Pro-inflammatory cytokines as predictors of antidepressant effects of exercise in major depressive disorder. Mol Psychiatry. 2012, [Epub ahead of print.]

157.

Uher R, Dernovsek MZ, Mors O, Hauser J, Souery D, Zobel A, Maier W, Henigsberg N, Kalember P, Rietschel M, Placentino A, Mendlewicz J, Aitchison KJ, McGuffin P, Farmer A: Melancholic, atypical and anxious depression subtypes and outcome of treatment with escitalopram and nortriptyline. J Affect Disord. 2011, 132: 112-120. 10.1016/j.jad.2011.02.014.PubMed

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1741-7015/11/129/prepub

Title: Understanding the somatic consequences of depression: biological mechanisms and the role of depression symptom profile
Authors: Brenda WJH Penninx
Yuri Milaneschi
Femke Lamers
Nicole Vogelzangs
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: BMC Medicine / Issue 1/2013
Electronic ISSN: 1741-7015
DOI: https://doi.org/10.1186/1741-7015-11-129

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Understanding the somatic consequences of depression: biological mechanisms and the role of depression symptom profile

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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