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Annals of General Psychiatry
Published in: Annals of General Psychiatry 1/2012

Open Access 01-12-2012 | Primary research

The role of cytokines and hot flashes in perimenopausal depression

Authors: Sokratis E Karaoulanis, Alexandros Daponte, Katerina A Rizouli, Andreas A Rizoulis, Georgios A Lialios, Catherine T Theodoridou, Christos Christakopoulos, Nikiforos V Angelopoulos

Published in: Annals of General Psychiatry | Issue 1/2012

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Abstract

Background

An imbalance in the production of proinflammatory and anti-inflammatory cytokines may play a role in the pathophysiology of perimenopausal depression. The aim of this study was to examine serum levels of the proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNFα), and the anti-inflammatory cytokine IL-10, in perimenopausal women suffering from depression. Furthermore, to assess whether serum cytokine levels are associated with the presence of hot flashes or the use of selective serotonin reuptake inhibitors (SSRIs). We also evaluated the possible association of hot flashes and perimenopausal depression.

Methods

Serum samples from 65 perimenopausal women, 41 with depression and 24 without depression, were assessed for serum IL-6, TNFα and IL-10 by conventional enzyme-linked immunosorbent assays. Depression was evaluated by the 17-item Hamilton Depression Rating Scale (HAM-D 17) and a psychiatric interview. The presence and severity of hot flashes were examined using the Menopause Rating Scale (MRS).

Results

Serum levels cytokines did not differ between depressed women and normal controls. Serum levels of cytokines did not change significantly in depressed women with hot flashes or in depressed women treated with SSRIs. Hot flashes were strongly associated (P < 0.0001) with perimenopausal depression.

Conclusion

The study supports the hypothesis that perimenopausal depression is not characterized by increased proinflammatory cytokines and decreased anti-inflammatory cytokines. Women with perimenopausal depression suffer from more severe and more frequent hot flashes than women without perimenopausal depression.
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Literature
1.
Bromberger JT, Matthews KA, Schott LL, Brockwell S, Avis NE, Kravitz HM, Everson-Rose SA, Gold EB, Sowers M, Randolph JF: Depressive symptoms during the menopausal transition: The Study of Women's Health Across the Nation (SWAN). J Affect Disord. 2007, 103: 267-272. 10.1016/j.jad.2007.01.034.PubMedCentralCrossRefPubMed
2.
Cohen LS, Soares CN, Vitonis AF, Otto MW, Harlow BL: Risk for new onset of depression during the menopausal transition: The Harvard Study of Moods and Cycles. Arch Gen Psychiatry. 2006, 63: 385-390. 10.1001/archpsyc.63.4.385.CrossRefPubMed
3.
Rasgon N, Shelton S, Halbreich U: Perimenopausal mental disorders: epidemiology and phenomenology. CNS Spectr. 2005, 10: 471-478.PubMed
4.
Anisman H: Cascading effects of stressors and inflammatory immune system activation: implications for major depressive disorder. J Psychiatry Neurosci. 2009, 34: 4-20.PubMedCentralPubMed
5.
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.PubMedCentralCrossRefPubMed
6.
Muller N, Schwartz MJ: The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression. Mol Psychiatry. 2007, 12: 988-1000. 10.1038/sj.mp.4002006.CrossRefPubMed
7.
Raison CL, Capuron L, Miller AH: Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006, 27: 24-31. 10.1016/j.it.2005.11.006.PubMedCentralCrossRefPubMed
8.
Schiepers OJG, Wichers MC, Maes M: Cytokines and major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2005, 29: 201-217. 10.1016/j.pnpbp.2004.11.003.CrossRefPubMed
9.
Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctôt KL: A meta-analysis of cytokines in major depression. Biol Psychiatry. 2009, 67: 446-457.CrossRefPubMed
10.
Maes M, Smith R, Scharpe S: The monocyte-T-lymphocyte hypothesis of major depression. Psychoneuroendocrinology. 1995, 20: 111-116. 10.1016/0306-4530(94)00066-J.CrossRefPubMed
11.
Hepgul N, Mondelli V, Pariante CM: Psychological and biological mechanisms of cytokine induced depression. Epidemiol Psichiatr Soc. 2010, 19: 98-102.PubMed
12.
Cioffi M, Esposito K, Vietri MT, Gazzerro P, D'Auria A, Ardovino I, Puca GA, Molinari AM: Cytokine pattern in postmenopause. Maturitas. 2002, 41: 187-192. 10.1016/S0378-5122(01)00286-9.CrossRefPubMed
13.
Ushiroyama T, Ikeda A, Ueki M: Elevated plasma interleukin 6 (IL-6) and soluble IL-6 receptor concentrations in menopausal women with and without depression. Int J Gynecol Obstet. 2002, 79: 51-52. 10.1016/S0020-7292(02)00189-3.CrossRef
14.
Yasui T, Uemura H, Tomita J, Miyatani Y, Yamada M, Kuwahara A, Matsuzaki T, Maegawa M, Tsuchiya N, Yuzurihara M, Takeda S, Irahara M: Association of interleukin-8 with hot flashes in premenopausal, perimenopausal and postmenopausal women and bilateral oophorectomized women. J Clin Endocrinol Metab. 2006, 91: 4805-4808. 10.1210/jc.2006-1100.CrossRefPubMed
15.
Gyllstrom EM, Schreiner PJ, Harlow BL: Perimenopause and depression: strength of association, causal mechanisms and treatment recommendations. Best Pract Res Clin Obstet Gynecol. 2007, 21: 275-292. 10.1016/j.bpobgyn.2006.11.002.CrossRef
16.
17.
Hauser GA, Huber IC, Keller PJ, Lauritzen C, Schneider HPG: Evaluation der klinischen Beschwerden (Menopause Rating Scale). Zentralbl Gynakol. 1994, 116: 16-23.PubMed
18.
Schneider HPG, Heinemann LAJ, Rosemeier HP, Potthoff P, Behre HM: The Menopause Rating Scale (MRS): reliability of scores of menopausal complaints. Climacteric. 2000, 3: 59-64. 10.3109/13697130009167600.CrossRefPubMed
19.
Blom EH, Lekander M, Ingvar M, Asberg M, Mobarrez F, Serlachius E: Pro-inflammatory cytokines are elevated in adolescent females with emotional disorders not treated with SSRIs. J Affect Disord. 2012, 136: 716-723. 10.1016/j.jad.2011.10.002.CrossRef
20.
Maes M, Meltzer HY, Bosmans E, Bergmans R, Vandoolaeghe E Ranjan R, Desnyder R: Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2 and transferrin receptor in major depression. J Affect Disord. 1995, 34: 301-309. 10.1016/0165-0327(95)00028-L.CrossRefPubMed
21.
Maes M, Yirmyia R, Noraberg J, Brene S, Hibbeln J, Perini G, Kubera M, Bob P, Lerer B, Maj M: The inflammatory & neurodegenerative (I & ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis. 2009, 24: 27-53. 10.1007/s11011-008-9118-1.CrossRefPubMed
22.
O'Brien SM, Scott LV, Dinan TG: Cytokines: abnormalities in major depression and implications for pharmacological treatment. Hum Psychopharmacol. 2004, 19: 397-403. 10.1002/hup.609.CrossRefPubMed
23.
Alexander JL, Dennerstein L, Woods NF, McEwen BS, Halbreich U, Kotz K, Richardson G: Role of stressful life events and menopausal stage in wellbeing and health. Exp Rev Neurother. 2007, 7: s93-S113. 10.1586/14737175.7.11s.S93.CrossRef
24.
Hayley S: Toward an anti-inflammatoty strategy for depression. Front Behav Neurosci. 2011, 5: 1-7.CrossRef
25.
Pfeilschifter J, Koditz R, Pfohl M, Schatz : Changes in proinflammatory cytokine activity after menopause. Endocrine Rev. 2002, 23: 90-119. 10.1210/er.23.1.90.CrossRef
26.
Arnason PGW, Reder AT: Cell-mediated immunity and neurologic disease. Diseases of the Nervous System. Edited by: Mackhann GM, McDonald WI. 1991, Philadelphia, PA: WB Saunders
27.
Aziz N, Nishanian P, Mitsuyasu R, Detels R, Fahey JL: Variables that affect assays for plasma cytokines and soluble activation markers. Clin Diagn Lab Immunol. 1999, 6: 89-PubMedCentralPubMed
28.
Bromberger JT, Kravitz HM, Matthews K, Youk A, Brown C, Feng W: Predictors of first lifetime episodes of major depression in midlife women. Psychol Med. 2009, 39: 55-64. 10.1017/S0033291708003218.PubMedCentralCrossRefPubMed
29.
Freeman EW: Associations of depression with the transition to menopause. Menopause. 2010, 17: 823-827. 10.1097/gme.0b013e3181db9f8b.CrossRefPubMed
30.
Freeman EW, Sammel MD, Lin H: Temporal associations of hot flashes and depression in the transition to menopause. Menopause. 2009, 16: 728-734. 10.1097/gme.0b013e3181967e16.PubMedCentralCrossRefPubMed
31.
Joffe HJ, Hall JE, Soares CN, Hennen J, Reilly CJ, Carlson K, Cohen LS: Vasomotor symptoms are associated with depression in perimenopausal women seeking primary care. Menopause. 2002, 9: 392-398. 10.1097/00042192-200211000-00003.CrossRefPubMed
32.
Juang K-D, Wang S-J, Lu S-R, Lee S-J, Fuh J-L: Hot flashes are associated with psychological symptoms of anxiety and depression in peri- and post- but not premenopausal women. Maturitas. 2005, 52: 119-126. 10.1016/j.maturitas.2005.01.005.CrossRefPubMed
33.
Seritan AL, Iosif AM, Park JH, Deatheragehand D, Sweet RL, Gold EB: Self reported anxiety, depressive and vasomotor symptoms: a study of perimenopausal women presenting to a specialized midlife assessment center. Menopause. 2010, 17: 410-415. 10.1097/gme.0b013e3181bf5a62.CrossRefPubMed
34.
Ozturk O, Eraslan D, Mete HE, Ozsener S: The risk factors and symptomatology of perimenopausal depression. Maturitas. 2006, 55: 180-186. 10.1016/j.maturitas.2006.02.001.CrossRefPubMed
35.
Basterzi AD, Aydemir C, Kisa C, Aksaray S, Tuzer V, Yazici K, Goka E: IL-6 levels decrease with SSRI treatment in patients with major depression. Hum Psychopharmacol Clin Exp. 2005, 20: 473-476. 10.1002/hup.717.CrossRef
36.
Yasui T, Yamada M, Uemura H, Ueno S, Numata S, Ohmori T, Tsuchiya N, Noguchi M, Yuzurihara M, Kase Y, Irahara M: Changes in circulating cytokine levels in midlife women with psychological symptoms with selective serotonin reuptake inhibitors and Japanese traditional medicine. Maturitas. 2009, 62: 146-152. 10.1016/j.maturitas.2008.12.007.CrossRefPubMed
37.
O'Brien SM, Scully P, Fitzgerald P, Scott LV, Dinan TG: Plasma cytokine profiles in depressed patients who fail to respond to selective serotonin reuptake inhibitor therapy. J Psychiatric Res. 2007, 41: 326-331. 10.1016/j.jpsychires.2006.05.013.CrossRef
38.
Minghini A, Britt LD, Hill MA: Interleukin-1 and interleukin-6 mediated skeletal muscle arteriolar vasodilation: in vitro versus in vivo studies. Shock. 1998, 9: 210-215. 10.1097/00024382-199803000-00009.CrossRefPubMed
39.
Patel JN, Jager A, Schalkwijk C, Corder R, Douthwaite JA, Yudkin JS, Coppack SW, Stehouwer CD: Effects of tumour necrosis factor-α in the human forearm: blood flow and endothelin-1 release. Clin Sci. 2002, 103: 409-415.CrossRefPubMed
Metadata
Title
The role of cytokines and hot flashes in perimenopausal depression
Authors
Sokratis E Karaoulanis
Alexandros Daponte
Katerina A Rizouli
Andreas A Rizoulis
Georgios A Lialios
Catherine T Theodoridou
Christos Christakopoulos
Nikiforos V Angelopoulos
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Annals of General Psychiatry / Issue 1/2012
Electronic ISSN: 1744-859X
DOI
https://doi.org/10.1186/1744-859X-11-9

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