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BMC Psychiatry
Published in: BMC Psychiatry 1/2013

Open Access 01-12-2013 | Research article

Association between vitamin b12 levels and melancholic depressive symptoms: a Finnish population-based study

Authors: Jussi Seppälä, Hannu Koponen, Hannu Kautiainen, Johan G Eriksson, Olli Kampman, Jaana Leiviskä, Satu Männistö, Pekka Mäntyselkä, Heikki Oksa, Yrjö Ovaskainen, Merja Viikki, Mauno Vanhala, Jussi Seppälä

Published in: BMC Psychiatry | Issue 1/2013

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Abstract

Background

An association between vitamin B12 levels and depressive symptoms (DS) has been reported in several epidemiological studies. The purpose of this study was to evaluate vitamin B12 levels in population-based samples with melancholic or non-melancholic DS as the relationship between vitamin B12 levels and different subtypes of DS has not been evaluated in previous studies.

Methods

Subjects without previously known type 2 diabetes, aged 45–74 years were randomly selected from the National Population Register as a part of the Finnish diabetes prevention programme (FIN-D2D). The study population (N = 2806, participation rate 62%) consisted of 1328 men and 1478 women. The health examinations were carried out between October and December 2007 according to the WHO MONICA protocol. The assessment of DS was based on the Beck Depression Inventory (BDI, cut-off ≥10 points). A DSM-IV- criteria based summary score of melancholic items in the BDI was used in dividing the participants with DS (N = 429) into melancholic (N = 138) and non-melancholic DS (N = 291) subgroups. In the statistical analysis we used chi-squared test, t-test, permutation test, analysis of covariance, multivariate logistic regression analysis and multinomial regression model.

Results

The mean vitamin B12 level was 331±176 pmol/L in those without DS while the subjects with non-melancholic DS had a mean vitamin B12 level of 324 ± 135 pmol/L, and those with melancholic DS had the lowest mean vitamin B12 level of 292±112 pmol/L (p < 0.001 after adjusted for age, sex, use of antidepressive medication and chronic diseases sum index). The adjusted difference of vitamin B12 levels between the non-melancholic and the melancholic group was 33 pmol/L (95%CI 8 to 57, p = 0.008). Melancholic DS and vitamin B12 levels showed an independent linearly inverse association. The relative risk ratio (RRR) for melancholic DS was 2.75 (95%CI 1.66 to 4.56) in the lowest vitamin B12 level tertile versus the highest (p for linearity <0.001) when those without DS formed the reference group. The RRR in the non-melancholic subgroup was nonsignificant.

Conclusions

The vitamin B12 level was associated with melancholic DS but not with non-melancholic DS.
Appendix
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Literature
1.
World Health Organization (WHO): World health report 2003. Shaping the future. 2003, Geneva: WHO
2.
Ustun T, Syuso-Mateos JL, Chatterji S, Mathers C, Murray CJL: Global burden of depressive disorders in the year 2000. Br J Psychiatry. 2004, 184: 386-392. 10.1192/bjp.184.5.386.CrossRefPubMed
3.
Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S, Wittchen HU, Kendler KS: Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry. 1994, 51: 8-19. 10.1001/archpsyc.1994.03950010008002.CrossRefPubMed
4.
Stahl SM: Stahl`s essential psychopharmacology. Neuroscientific basis and practical applications. 2008, Cambridge, UK: Cambridge University Press, 3
5.
Coppen A, Swade J, Jones SA, Armstrong RA, Blair JA, Leeming RJ: Depression and tetrahydrobiopterion: the folate connection. J Affect Disord. 1989, 16: 121-130. 10.1016/0165-0327(89)90065-7.CrossRef
6.
Stabler SP, Allen RH, Saavge DG, Lindebaum J: Clinical spectrum and diagnosis of cobalamin deficiency. Blood. 1990, 76: 871-881.PubMed
7.
Parnetti L, Bottiglieri T, Lowenthal D: Role of homocysteine in age-related vascular and non-vascular diseases. Ageing. 1997, 9: 241-257.
8.
Bottigieri T: Homocysteine and folate metabolism in depression. Prog Neuro-Psychopharmacol Biol Psychiatry. 2005, 29: 1103-1112. 10.1016/j.pnpbp.2005.06.021.CrossRef
9.
Bottiglieri T, Laundy M, Crellin R, Toone BK, Carney MW, Reynolds EH: Homocysteine, folate, methylation, and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry. 2000, 69: 228-232. 10.1136/jnnp.69.2.228.CrossRefPubMedPubMedCentral
10.
Bell IR, Edman JS, Morrow FD, Marby DW, Mirages S, Rerrone G: B complex vitamin patterns in geriatric and young adult inpatients with major depression. J Am Geriatr Soc. 1991, 39: 252-257.CrossRefPubMed
11.
Mischoulon D, Burger JK, Spillmann MK, Worthington JJ, Fava M, Alpert JE: Anemia and macrosytosis in the prediction of serum folate and vitamin B-12 status, and treatment outcome in major depression. J Psychosom Res. 2000, 49: 183-187. 10.1016/S0022-3999(00)00158-6.CrossRefPubMed
12.
Elsborg L, Hansen T, Rafaelsen OJ: Vitamin B12 concentrations in psychiatric patients. Acta Psych Scand. 1979, 59: 145-152. 10.1111/j.1600-0447.1979.tb06956.x.CrossRef
13.
Hintikka J, Tolmunen T, Tanskanen A, Viinamäki H: High vitamin B12 level and good treatment outcome may be associated in major depressive disorder. BMC Psychiatry. 2003, 3: 17-10.1186/1471-244X-3-17.CrossRefPubMedPubMedCentral
14.
Hvas AM, Juul S, Lauritzen L: No effect of vitamin B12 treatment on cognitive function and depression: a randomized placebo controlled study. J Affect Disord. 2004, 81: 269-273. 10.1016/S0165-0327(03)00169-1.CrossRefPubMed
15.
Penninx B, Guralnik J, Ferrucci L, Fried L, Allen R, Stabler S: Vitamin B12 deficiency and depression in physically disabled older women: epidemiological evidence from the women’s health and aging study. Am J Psychiatry. 2000, 157: 715-721. 10.1176/appi.ajp.157.5.715.CrossRefPubMed
16.
Tiemeier H, van Tuijl H, Hofman A, Meijer J, Kiliaan A, Breteler M: Vitamin B12, folate and homocysteine in depression: the Rotterdam study. Am J Psychiatry. 2002, 159: 2099-2101. 10.1176/appi.ajp.159.12.2099.CrossRefPubMed
17.
Kim JM, Stewart R, Kim SW, Yang SJ, Shin IS, Yoon JS: Predictive value of folate, vitamin B12 and homocysteine levels in late-life depression. Br J Psychiatry. 2008, 192: 268-274. 10.1192/bjp.bp.107.039511.CrossRefPubMed
18.
Ng T-P, Feng L, Niti M, Kua E-H, Yap K-B: Folate, vitamin B12, homocysteine, and depressive symptoms in a population sample of older Chinese adults. JAGS. 2009, 57: 871-876. 10.1111/j.1532-5415.2009.02229.x.CrossRef
19.
Lindeman R, Romero L, Koehler K, Liang H, LaRue A, Baumgartner R, Garry PJ: Serum vitamin B12, C and folate concentrations in the New Mexico elder health survey: correlations with cognitive and affective functions. J Am Coll Nutr. 2000, 19: 68-76.CrossRefPubMed
20.
Morris MS, Fava M, Jacques PF, Selhub J, Rosenberg IH: Depression and folate status in the US population. Psychother Psychosom. 2003, 72: 80-87. 10.1159/000068692.CrossRefPubMed
21.
Bjelland I, Tell GS, Vollset SE, Refsum H, Ueland PM: Folate, vitamin B12, homocysteine, and the MTHFR 677→ T poymorphism in anxiety and depression: the Hordaland Homocysteine Study. Arch Gen Psychiatry. 2003, 60: 618-626. 10.1001/archpsyc.60.6.618.CrossRefPubMed
22.
Sachdev P, Parslow R, Lux O, Salonikas C, Wen W, Naidoo D, Christensen H, Jorm AF: Relationship of homocysteine, folic acid and vitamin B12 with depression in a middle-aged community sample. Psychol Med. 2005, 35: 529-538. 10.1017/S0033291704003721.CrossRefPubMed
23.
Beydoun M, Shroff M, Beydoun H, Zonderman A: Serum folate, vitamin B12, and homocysteine and their association with depressive symptoms among U.S. adults. Psychosom Med. 2010, 72: 862-873. 10.1097/PSY.0b013e3181f61863.CrossRefPubMedPubMedCentral
24.
Saaristo T, Peltonen M, Keinanen-Kiukaanniemi S, Vanhala M, Saltevo J, Niskanen L, Oksa H, Korpi-Hyövälti E, Tuomilehto J: For theFIN-D2D Study Group: National type 2 diabetes prevention programme in Finland: FIN-D2D. Int Journal of Circumpolar Health. 2007, 66: 101-112.CrossRef
25.
Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J: An inventory for measuring depression. Arch Gen Psychiatry. 1961, 4: 561-571. 10.1001/archpsyc.1961.01710120031004.CrossRefPubMed
26.
Beck AT, Steer RA, Garbin MG: Psychometric properties of the beck depression inventory: twenty-five years of evaluation. Clin Psychol Rev. 1988, 8: 77-100. 10.1016/0272-7358(88)90050-5.CrossRef
27.
Timonen M, Rajala U, Jokelainen J, Keinänen-Kiukaanniemi S, Meyer-Rochow VB, Räsänen P: Depressive symptoms and insulin resistance in young adult males: results from the Northern Finland 1966 birth cohort. Mol Psychiatry. 2006, 11: 929-933. 10.1038/sj.mp.4001838.CrossRefPubMed
28.
Räikkönen K, Matthews KA, Kuller LH: Depressive symptoms and stressful life events predict metabolic syndrome among middle-aged woman. 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.CrossRefPubMed
29.
Vanhala M, Jokelainen J, Keinänen-Kiukaaniemi S, Kumpusalo E, Koponen H: Depressive symptoms predispose females to metabolic syndrome: a 7-yers follow-up study. Acta Psychiatr Scand. 2009, 119: 137-142. 10.1111/j.1600-0447.2008.01283.x.CrossRefPubMed
30.
Koponen H, Jokelainen J, Keinäinen-Kiukaaniemi S, Vanhala M: Depressive symptoms and 10-year risk for cardiovascular morbidity and mortality. World J Biol Psychiatry. 2010, 11: 834-839. 10.3109/15622975.2010.486842.CrossRefPubMed
31.
Korniloff K, Häkkinen A, Kautiainen H, Koponen H, Peltonen M, Mäntyselkä P, Oksa H, Kampman O, Häkkinen A: Leisure-time physical activity and metabolic syndrome plus depressive symptoms in the FIN-D2D survey. Prev Med. 2010, 51: 466-470. 10.1016/j.ypmed.2010.09.007.CrossRefPubMed
32.
Mäntyselkä P, Korniloff K, Saaristo T, Koponen H, Eriksson J, Puolijoki H, Timonen M, Sundvall J, Kautiainen H, Vanhala M: Association of depressive symptoms with impaired glucose regulation, screen-detected, and previously known type 2 diabetes: findings from the Finnish D2D Survey. Diabetes Care. 2011, 34: 71-76. 10.2337/dc10-1044.CrossRefPubMed
33.
Steer R, Ball R, Ranieri W, Beck A: Dimensions of the beck depression inventory-II in clinically depressed outpatients. J Clin Psychol. 1999, 55: 117-128. 10.1002/(SICI)1097-4679(199901)55:1<117::AID-JCLP12>3.0.CO;2-A.CrossRefPubMed
34.
Ovaskainen Y, Koponen H, Jokelainen J, Keinänen-Kiukanniemi S, Kumpusalo E, Vanhala M: Depressive symptomatology is associated with decreased interleukin-1 beta and increased interleukin-1 receptor antagonist levels in males. Psychiatry Res. 2009, 167: 73-79. 10.1016/j.psychres.2007.12.004.CrossRefPubMed
35.
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.CrossRefPubMed
36.
Seppälä J, Koponen H, Kautiainen H, Eriksson JG, Kampman O, Männistö S, Mäntyselkä P, Oksa H, Ovaskainen Y, Viikki M, Vanhala M: Association between folate intake and melancholic depressive symptoms. A Finnish population-based study. J Affect Disord. 2012, 138: 473-478. 10.1016/j.jad.2012.01.007.CrossRefPubMed
37.
World Health Organization: The World Health Organization MONICA Project (monitoring trends and determinants in cardiovascular disease): a major international collaboration. WHO MONICA Project Principal Investigators. J Clin Epimediol. 1988, 41: 105-114. 10.1016/0895-4356(88)90084-4.CrossRef
38.
Seppälä J, Vanhala M, Kautiainen H, Järvenpää S, Eriksson J, Kampman O, Oksa H, Ovaskainen Y, Viikki M, Koponen H: Beck depression inventory (BDI) as a screening tool for depression. A population-based Finnish cross-sectional study. Psychiatr Fenn. 2010, 41: 42-52.
39.
Viinamäki H, Tanskanen A, Honkalampi K, Koivumaa-Honkanen H, Haatainen K, Kaustio O, Hintikka J: Is the beck depression inventory suitable for screening major depression in different phases of the disease?. Nord J Psychiatry. 2004, 58: 49-53. 10.1080/08039480310000798.CrossRefPubMed
40.
Loikas S, Koskinen P, Irjala K, Löppönen M, Isoaho R, Kivelä S-L, Pelliniemi T: Vitamin B12 deficiency in the aged: a population-based study. Age Ageing. 2007, 36: 177-183. 10.1093/ageing/afl150.CrossRefPubMed
41.
MacFarlane AJ, Greene-Finestone LS, Shi Y: Vitamin B12 and homocysteine status in a folate-replete population: results from the Canadian Health Measures Survey. Am J Clin Nutr. 2011, Oct, 94: 1079-1084. 10.3945/ajcn.111.020230.CrossRefPubMed
42.
Herrmann W, Geisel J: Vegetarian lifestyle and monitoring of vitamin B12 status. Clin Chim Acta. 2002, 326: 47-59. 10.1016/S0009-8981(02)00307-8.CrossRefPubMed
43.
Wolters M, Strohle A, Hahn A: Cobalamin: a critical vitamin in the elderly. Prev Med. 2004, 39: 1256-1266. 10.1016/j.ypmed.2004.04.047.CrossRefPubMed
44.
Rush AJ, Weissenburger JE: Melancholic symptom features and DSM-IV. Am J Psychiatry. 1994, 151: 489-498.CrossRefPubMed
45.
Mitchell P, Parker G, Gladstone G, Wilhelm K, Austin M-P: Severity of stressful life events in first and subsequent episodes of depression: the relevance of depressive subtype. J Affect Disord. 2003, 73: 245-252. 10.1016/S0165-0327(01)00479-7.CrossRefPubMed
46.
Whithall A, Harris L, Cumming S: A longitudinal study of cognitive function in melancholic and non-melancholic subtypes of major depressive disorder. J Affect Disord. 2010, 123: 150-157. 10.1016/j.jad.2009.07.012.CrossRef
47.
American Psychiatric Association: Diagnostic and statistical manual of mental disorders. 2000, Washington DC: American Psychiatric Publishing, 4
48.
van der Linde R, Stephan B, Savva G, Dening T, Brayne C: Systematic review on behavioural and psychological symptoms in the older or demented population. Alzheimers Res Ther. 2012, 4: 28-10.1186/alzrt131.CrossRefPubMedPubMedCentral
49.
Maes M: “Functional” or “psychosomatic” symptoms, e.g. a flu-like malaise, aches and pain and fatique, are major features of major and in particular of melancholic depression. Neuro Endocrinol Lett. 2009, 30: 564-573.PubMed
50.
Benazzi F: Irritability in depression can be a symptom of mixed depression. Acta Psychiatr Scand. 2010, 121: 80-CrossRefPubMed
51.
Väänänen A, Buunk AP, Kivimäki M, Vahtera J, Koskenvuo M: Change in reciprocity as a predictor of depressive symtoms: a prospective cohort study of Finnish women and men. Soc Sci Med. 2008, 67: 1907-1916. 10.1016/j.socscimed.2008.09.015.CrossRefPubMed
Metadata
Title
Association between vitamin b12 levels and melancholic depressive symptoms: a Finnish population-based study
Authors
Jussi Seppälä
Hannu Koponen
Hannu Kautiainen
Johan G Eriksson
Olli Kampman
Jaana Leiviskä
Satu Männistö
Pekka Mäntyselkä
Heikki Oksa
Yrjö Ovaskainen
Merja Viikki
Mauno Vanhala
Jussi Seppälä
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Psychiatry / Issue 1/2013
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/1471-244X-13-145

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