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Open Access 01.12.2013 | Research article

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

verfasst von: 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

Erschienen in: BMC Psychiatry | Ausgabe 1/2013

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.

Authors’ original file for figure 1

Electronic supplementary material

The online version of this article (doi:10.1186/1471-244X-13-145) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

Authors HK, PM, HO and MV designed the study. Authors OK, YO and MV participated in recruiting and interviewing the patients. Authors JGE, OK, HK, JL, SM, PM, YO, MV, MV and JS wrote the article. Author HK undertook the statistical analysis. All authors contributed to and have approved the final manuscript.

ANCOVA

Analysis of co-variance

BDI

the Beck depression inventory

BMI

Body mass index

CMIA

Chemiluminescent microparticle immuno assay

Coefficients of variation

Depressive symptoms

FIN-D2D

the Finnish diabetes prevention programme

LTPA

Leisure time physical activity

MDS

Melancholic depressive symptoms

MONICA

Monitoring trends and determinants in cardiovascular disease

NmDS

Non-melancholic depressive symptoms

RRR

Relative risk ratio

SAM

S-adenosylmethionine

WHO

World health organisation.

Background

Depression is a global public health problem particularly in developed countries. Recently, the World Health Organization estimated that unipolar depressive disorder remains one of the leading causes of total disability adjusted life years (DALY’s ) worldwide [1]. It accounts for 8% of total DALY’s in the Americas and 6% in Europe [2]. Overall, the 12-month and lifetime prevalence rates of depression are approximately 12% and 24% among U.S. men and women, respectively [3].

A wide array of etiological hypotheses has been suggested to underlie depression. Of the biological hypotheses, the monoamine hypothesis proposes an important etiological role for serotoninergic or noradrenergic dysfunction in depression [4]. Besides folate, vitamin B₁₂ is involved in single-carbon transfer reactions needed for the production of serotonin and other monoamine neurotransmitters [5]. Vitamin B₁₂ deficiency may also result in the accumulation of homocysteine, which has been suggested to lead to exito-toxic reactions and may enhance depression [6, 7]. Homocysteine can be remethylated to methionine, which requires vitamin B₁₂[8]. Methionine is the immediate precursor of S-adenosylmethionine (SAM), the methyl donor of numerous methylation reactions in the brain, many of which are directly involved in the synthesis and metabolism of dopamine, norepinephrine and serotonin [9]. These findings form a plausible link between vitamin B₁₂ and mood, and may also indicate that the association between depression and vitamin B₁₂ could be mediated through monoamine synthesis.

In clinical studies, lower vitamin B₁₂ levels have been found to be associated with severe depression [10, 11]. Low serum vitamin B₁₂ levels are also detected in approximately 20% of psychiatric patients [12]. On the other hand, high vitamin B₁₂ levels were associated with a good treatment outcome in patients with major depressive disorders in a clinical setting [13]. However, a small randomised trial found no improvement in depression after the administration of vitamin B₁₂ as an adjuvant [14].

The three cross-sectional studies and one prospective population-based study that have reported a connection between vitamin B₁₂ levels and DS or depressive disorders were conducted on older adults [15‐18]. In the Women’s Health and Aging Study B₁₂ deficiency was associated with a two-fold increased risk of severe depression [15]. The Rotterdam Study found that B₁₂ deficiency was independently associated with depressive disorder among older adults [16]. A study among Chinese older adults also found a correlation between deficient levels of vitamin B₁₂ and greater risk of DS [18]. The only existing community-based prospective study reported that lower levels of vitamin B₁₂ at baseline were associated with a higher risk of incident of depression on 2–3 year follow-up among older Korean people [17]. However, previous results have been somewhat inconsistent, since some studies, mainly conducted in younger populations, have found no association between vitamin B₁₂ levels and DS or depressive disorders [19‐23].

Methods

Study population and the setting of the study

The Finnish type 2 diabetes (FIN-D2D) survey is the implementation project of a national programme for the prevention of type 2 diabetes covering a population of 1.5 million during the years 2003–2008 [24]. The specific aims were to improve the screening of people at risk of diabetes and the detection of undiagnosed diabetes, as well as the prevention of diabetes among national population.

A random sample of 4500 subjects without previously known type 2 diabetes, aged 45–74 years, stratified according to gender and 10-year age groups (45–54, 55–64 and 65–74 years), was selected from the National Population Register of Finland in August 2007. The sampling represented three separate geographical areas with both urban and rural populations. The study participants were invited by mail to a health examination. The study population (N = 2806, participation rate 62%) consisted of 1328 men and 1478 women. The participants and the nonparticipants (N = 1694) did not differ with regard to age or gender distribution. The Ethical Committee of the Hospital District of Helsinki and Uusimaa approved the study protocol. All participants gave their written informed consent prior to participation in the study.

Design of the study and measurements

Depressive symptoms

DS were assessed by using the Beck Depression Inventory (BDI), which is a 21-item self-report questionnaire consisting of symptoms and attitudes related to depression [25]. The items are summed in a total score with a range from 0 to 63. The cut-off point for DS was 10, which has been reported to be a feasible instrument for depression screening [26]. It has also been shown to be a useful tool for detecting depressive symptoms in various adult populations [27‐32]. Out of the whole study population, 429 (15%) subjects with a BDI score ≥10 were identified. In order to examine the effect of the subtype of DS, we used a summary score of melancholic symptoms in the BDI based on the DSM-IV- defined criteria for melancholic depression (sadness, past failure, loss of pleasure, guilty feelings, punishment feelings, loss of interest, irritability, change of sleeping and appetite) in dividing the participants with increased DS into melancholic and non-melancholic depressive symptom subgroups in a similar way that has been published to be useful in several previous studies. The subjects were defined to have DS with melancholic characteristics when the number of melancholic symptoms exceeded the number of non-melancholic symptoms [29, 33‐36]. When using this method the subject had to score 2 or 3 points in each chosen item in order to have a positive item (a melancholic or a non-melancholic item).

Laboratory analysis

The study methods followed the World Health Organization MONICA protocol [37]. After an overnight fast, blood samples were drawn for basic biochemical measurements, including serum vitamin B₁₂. The serum and plasma were separated within one hour by centrifugation at room temperature. The samples were then aliquoted into storage tubes and stored at a minimum of −20°C. The samples were later transported frozen to the National Institute for Health and Welfare and stored at −70°C until analyzed at the laboratory of the Disease Risk Unit.

Serum vitamin B₁₂ was measured with an Architect ci82000 analyzer (Abbott Laboratories, Abbott Park, IL) using the Chemiluminescent Microparticle Immuno Assay (CMIA). The reference range was 138–652 pmol/L for the normal serum vitamin B₁₂ level. The interassay coefficients of variation (CV) of B₁₂ vitamin were 6.2% and 5.0% at the levels of 150 pmol/L and 380 pmol/L, respectively.

Other measurements

Height was measured to the nearest 0.1 cm, and weight was measured in light clothing to the nearest 0.1 kg. The body mass index (BMI) was calculated as weight (kg) divided by the square of height (m). Waist circumference was measured midway between the lowest rib margin and the iliac crest. Education was assessed according to years of education. The participants reported their marital status, and were categorized as married, single, separated or widowed. Employment status was inquired, and the number of employed participants was counted. Current smoking and alcohol consumption were assessed with self-administered questionnaires, and dichotomized (no or yes). Leisure- time physical activity (LTPA) was assessed with the question: “How much physical activity do you practice during leisure- time?” Response categories were: In my leisure- time I 1) read, watch television and do things that do not require physical activity; 2) walk, ride a bicycle or exercise in other ways requiring physical activity for at least four hours a week; 3) have physical activities to maintain my condition such as jogging, cross-country skiing, aerobics, swimming or ball games at least three hours a week; and 4) practice regularly for competitions in running, cross-country skiing, orienteering, ball games, or other heavy physical exercise several times a week. The intensity of LTPA was classified as low (category 1), moderate (category 2) or high (categories 3 and 4) [31]. A chronic diseases sum index was based on the question “Have you had any of the following diseases that have been diagnosed or treated by a doctor in the last 12 months?” The diseases included elevated blood pressure, heart failure, angina pectoris/other cardiovascular event, diabetes, cancer, bronchial asthma/emphysema and rheumatoid arthritis/other arthropathy/spinal diseases. The chronic diseases sum index ranged from 0 to 7 [32]. The use of antidepressive medications was also recorded.

Statistical analysis

The data are presented as means with standard deviations or counts with percentages. Groups were statistically compared using the t-test, permutation test or chi-squared test, as appropriate. The statistical significance between groups was B12 level evaluated by bootstrap type analysis of covariance (ANCOVA) with appropriate contrast Multinomial logistic regression was used to analyze the relative risk ratios (RRR) and their 95% confidence intervals (95% CI) for the presence of non-melancholic and melancholic DS with appropriate contrasts. Adjusted continuous relationship between vitamin B12 levels and BDI score was analyzed using regression analysis (with bootstrap based standard error), squared term of the BDI score was added to an equation.

The multinomial (polytomous) logistic regression model is an extension of the binomial logistic regression model and is used when the dependent variable has more than two nominal (unordered) categories.

Results

The study population (N = 2806) included 429 subjects (15%) with a BDI score ≥10. Table 1 presents the sociodemographic characteristics of the two subgroups with BDI scores <10 or ≥10. Participants with elevated DS were more likely to be female or older, and to have a higher BMI, be less educated, unmarried or unemployed. They also used less alcohol and were less physically active than their non-depressed counterparts. Subjects with increased DS had a higher chronic diseases sum index, and more often used antidepressive medication.

Table 1

Demographic and clinical data at baseline according to depressive symptom status

	Depressive symptoms status		P-value
	BDI score <10 N = 2377	BDI score ≥10 N = 429
Female, n (%)	1215 (51)	263 (61)	<0.001
Age, years, mean (SD)	59 (8)	61 (9)	<0.001
Body mass index (kg/m²), mean (SD)	27.3 (4.7)	28.6 (5.6)	<0.001
Education years, mean (SD)	11 (8.14)	10 (8.13)	<0.001
Marital status, n (%)			<0.001
Married	1842 (78)	286 (67)
Single	181 (8)	47 (11)
Separated	215 (9)	61 (14)
Widowed	130 (5)	33 (8)
Employed, n (%)	1229 (52)	113 (26)	<0.001
Current smoker, n (%)	508 (21)	111 (26)	0.038
Using alcohol, n (%)	1465 (62)	225 (52)	<0.001
Leisure time physical activity, n (%)			<0.001
Low	375 (16)	141 (35)
Moderate	1391 (60)	218 (54)
High	561 (24)	46 (11)
Chronic diseases sum index (0–7), mean (SD)	0.60 (1.06)	1.12 (1.30)	<0.001
Use of antidepressive medication, n (%)	71 (3)	77 (18)	<0.001

Abbreviations. BDI-score ≥10 includes 291 subjects with non-melancholic DS and 138 subjects with melancholic DS.

BDI = Beck Depression Inventory.

DS = depressive symptoms.

Vitamin B₁₂ levels differed between males and females (serum vitamin B₁₂ 343 ± 168 pmol/L for females and 312 ± 171 pmol/L for males; p < 0.001). In order to further examine the vitamin B₁₂ levels in subjects with depressive symptoms they were subdivided into groups with predominantly melancholic (N = 138) and non-melancholic DS (N = 291). 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) (Figure 1A). 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). No difference was found between those without DS and the non-melancholic group (Figure 1A). The vitamin B₁₂ levels were significantly lower in the sub-group of melancholic depressive symptoms scoring 10–14 in the BDI. The association of vitamin B₁₂ levels with the non-melancholic and melancholic depressive symptoms when subdivided according to the BDI-scores is presented in Figure 1B.

Figure 1C shows adjusted continuous relationship between vitamin B12 levels and BDI score.

In the multinomial regression analysis there was an independent linearly inverse association between the vitamin B₁₂ tertiles and melancholic depressive symptoms: the relative risk ratio (RRR) was 2.75 (95% CI 1.66 to 4.56, p for linearity <0.001) in the lowest vitamin B₁₂ level tertile as compared to the highest when those without DS formed the reference group (Table 2). There was no association between B₁₂ vitamin tertiles and non-melancholic DS, since the RRR for the lowest vitamin B₁₂ level tertile versus the highest was 1.20 (95% CI 0.86 to 1.66, p for linearity 0.28) (Table 2).

Table 2

Relative risk ratios and their 95% confidence intervals (95% CI) from multinomial regression analysis for having non-melancholic or melancholic depressive symptoms

Variables	NmDS versus BDI < 10 RRR (95% CI)	P-value	MDS versus BDI < 10 RRR (95% CI)	P-value
Vitamin B₁₂ tertiles*
I	1 (reference)	0.28#	1 (reference)	<0.001#
II	1.01 (0.72 to 1.41)		1.90 (1.21 to 3.22)
III	1.20 (0.86 to 1.66)		2.75 (1.66 to 4.56)
Male sex	0.59 (0.44 to 0.79)	<0.001	0.82 (0.54 to 1.23)	0.34
Age	1.02 (1.00 to 1.04)	0.041	1.02 (1.00 to 1.05)	0.091
BMI	1.02 (1.00 to 1.05)	0.11	0.98 (0.94 to 1.02)	0.32
Smoking	1.23 (0.88 to 1.71)	0.23	1.41 (0.91 to 2.20)	0.13
Using alcohol	1.09 (0.81 to 1.45)	0.59	0.84 (0.56 to 1.26)	0.39
LTPA		<0.001#		0.006#
I	1 (reference)		1 (reference)
II	0.50 (0.37 to 0.68)		0.42 (0.27 to 0.64)
III	0.24 (0.15 to 0.39)		0.43 (0.24 to 0.76)
Years of education	0.98 (0.94 to 1.02)	0.24	1.00 (0.95 to 1.06)	0.99
Living alone	1.29 (0.95 to 1.75)	0.10	1.93 (1.30 to 2.88)	0.001
Energy intake	1.00 (1.00 to 1.00)	0.90	1.00 (1.00 to 1.00)	0.74
Use of antidepressive medication	5.51 (3.55 to 8.54)	<0.001	9.45 (5.63 to 15.86)	<0.001
Chronic diseases sum index	1.41 (1.26 to 1.59)	<0.001	1.21 (1.02 to 1.45)	0.031

* Gender specific tertiles: Male I > 340 pmol/L, II = 255–340 pmol/L, III < 255 pmol/L;

Female I > 380 pmol/L, II = 280–379 pmol/L, III = <280 pmol/L.

# P for linearity.

RRR = relative risk ratio.

BDI = Beck Depression Inventory.

NmDS = non-melancholic depressive symptoms.

MDS = melancholic depressive symptoms.

BMI = body mass index.

LTPA = leisure-time physical activity.

Discussion

The novel finding in our population-based study, controlled for multiple potential confounders, was that vitamin B₁₂ levels showed an independent linearly inverse association with the risk of melancholic DS but not with non-melancholic DS. This result is in line with the monoamine hypothesis of depressive disorders connecting a low vitamin B₁₂ level with diminished synthesis of serotonin and other monoamines [4]. In our study we observed an approximately three-fold increased RRR for melancholic DS in the lowest vitamin B₁₂ tertile. Thus, the risk is very much in the same range as the results from a recent study in which vitamin B₁₂ deficiency appeared to be associated with the occurrence of DS (OR = 2.68) [18]. Two earlier studies reported similar, but somewhat lower risk levels (OR 2.05 and 1.64, respectively) [15, 16]. Previously we have reported an association between low folate intake and increasing risk of melancholic DS in this material [36]. Homocysteine was not determined in this study.

All the previous studies showing positive relationships between vitamin B₁₂ levels and DS or depressive disorders have been conducted among older populations [15‐18]. On the other hand, most previous population-based studies not showing an association between vitamin B₁₂ levels and depressive disorders or DS have been conducted on younger populations than that in our study [20, 21, 23]. Exceptions are an American and an Australian study that failed to detect this association among older populations [19, 22]. These partly inconsistent results may suggest that the age of the study population is important although methodological differences in subject selection and in the measurement methods of depressive symptoms or depression, or in the B₁₂ status, may also contribute. The distribution of depressive subtypes may also be important as in our study vitamin B₁₂ levels were lower in the melancholic sub-group. In addition, the severity of DS is also relevant as the difference was significant only in the sub-group of mild to moderate depression i.e. 10–14 points in the BDI. The cut-off points for BDI tertiles were selected according to previous studies suggesting BDI-score of 10 [25, 26] or 14 as proper cut of values [38, 39]. Statistical reasons, such as a low number of subjects, or a large variety of vitamin B₁₂ levels in the sub-group having BDI-scores ≥15 may have affected the significance of the result.

These previous results suggest that the elderly may be more vulnerable to low vitamin B₁₂ levels. One plausible explanation for these findings is that vitamin B₁₂ deficiency is more common in the aged. Its prevalence was 12% in the Finnish population (aged 65–100 years) compared to the finding that 5% of Canadians (age 6–79 years) were vitamin B₁₂ deficient [40, 41]. Lifestyle factors such as smoking, alcohol consumption and a vegetarian diet have been linked with anincreased risk of vitamin B₁₂ deficiency in younger adults, [42, 43] but no such association was recorded in an aged Finnish population [40]. No specific risk group for lower vitamin B₁₂ levels could be defined among the aged [40]. It may also be possible that the brain effects of low vitamin B₁₂ do not manifest until much later in life.

The strengths of our study include a large population-based sample containing middle-aged and elderly subjects with a substantial prevalence of DS. The study population was also geographically representative, covering both urban and rural districts in three study areas. In addition, the study data were comprehensively examined, and we used a WHO-based study methodology [37]. The BDI with a cut-off score of 10 points has also been shown to be a useful instrument for detecting DS in various adult populations [27‐32].

The available evidence suggest some clinical utility and some validity for the concept of melancholic features [44]. Depression with melancholic or non-melancholic features can be established by using diagnostic interviews [45, 46]. Instead,we used a summary score of melancholic symptoms in the BDI based on the DSM-IV- defined criteria for melancholic depression in order to examine the effect of the subtype of DS [33]. The way of dividing the DS into melancholic or non-melancholic DS has been applied in several previous studies as well [29, 34‐36].

Unfortunately, we were not able to present sensitivity analysis due to a dicotomous, and not a continuous method established in dividing DS into melancholic and non-melancholic DS. Factor analysis was not used because symtom composition of the resultant factors may be dependant of the types of samples being studied [33]. Furthermore, due to population-based design of the study the amount of subjects having lower scores in the BDI was high.

However, the criteria that guided the choice for melancholic DS need to be discussed more thoroughly. The chosen melancholic symptoms in the BDI are based on the DSM-IV- defined criteria for melancholic depression [47]. Although e.g. irritability can occur in the non-demented and demented older populations it may be quite near to agitation which is one the criteria for melancholic depression in DSM-IV [47, 48]. The fatique and somatic factor symptoms, including irritability, may be major features of major and in particular of melancholic depression [49]. Irritability may be a symptom of mixed depression as well [50]. In addition, 11-21% of persons in Finland have DS assessed according to the BDI with the same, a rather low cut-off score of 10 points, which is in line with the prevalence of 15% shown in the present study [29, 51].

In addition, as the study population was in advanced middle age, the generalizability of the results to younger age groups may be limited. Furthermore, due to the cross-sectional study design, we cannot make inferences of causality. However, cross-sectional studies can produce new associations or hypotheses that can be futher studied in observational settings.

Conclusions

In our study we observed that a higher risk of melancholic depressive symptoms was associated with lower vitamin B₁₂ levels. Our findings suggest that vitamin B₁₂ may contribute to the pathogenesis of DS, although further studies are needed to evaluate the possible associations between DS and vitamin B₁₂ levels among populations with different ages and depressive subtypes.

Acknowledgements

FIN-D2D was supported by funding from the hospital districts of Pirkanmaa, Southern Ostrobothnia, North Ostrobothnia, Central Finland and Northern Savo, the National Institute for Health and Welfare, the Finnish Diabetes Association, the Ministry of Social Affairs and Health in Finland and Finland’s Slot Machine Association in cooperation with the FIN-D2D Study Group, and the Steering Committee: J. Huttunen, A. Kesäniemi, S. Kiuru, L. Niskanen, H. Oksa, J. Pihlajamäki, J. Puolakka, P. Puska, T. Saaristo, M. Vanhala, and M. Uusitupa.

None of the sponsors influenced the design or conduct of the study or the analysis or interpretation of the findings.

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

Authors’ original submitted files for images

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Authors’ original file for figure 1

World Health Organization (WHO): World health report 2003. Shaping the future. 2003, Geneva: WHO

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

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

Stahl SM: Stahl`s essential psychopharmacology. Neuroscientific basis and practical applications. 2008, Cambridge, UK: Cambridge University Press, 3

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

Stabler SP, Allen RH, Saavge DG, Lindebaum J: Clinical spectrum and diagnosis of cobalamin deficiency. Blood. 1990, 76: 871-881.PubMed

Parnetti L, Bottiglieri T, Lowenthal D: Role of homocysteine in age-related vascular and non-vascular diseases. Ageing. 1997, 9: 241-257.

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

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 B_12, 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 B_12, 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 B_12, 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 B_12, 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 B_12, 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

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-244X/13/145/prepub

Titel: Association between vitamin b12 levels and melancholic depressive symptoms: a Finnish population-based study
verfasst von: 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
Publikationsdatum: 01.12.2013
Verlag: BioMed Central
Erschienen in: BMC Psychiatry / Ausgabe 1/2013
Elektronische ISSN: 1471-244X
DOI: https://doi.org/10.1186/1471-244X-13-145

Neu im Fachgebiet Psychiatrie

23.04.2024 | Demenz | Nachrichten

Springer Medizin

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

Abstract

Background

Methods

Results

Conclusions

Electronic supplementary material

Competing interests

Authors’ contributions

Background

Methods

Study population and the setting of the study

Design of the study and measurements

Depressive symptoms

Laboratory analysis

Other measurements

Statistical analysis

Results

Discussion

Conclusions

Acknowledgements

Competing interests

Authors’ contributions

Authors’ original submitted files for images

Neu im Fachgebiet Psychiatrie

Demenzkranke durch Antipsychotika vielfach gefährdet

Weniger postpartale Depressionen nach Esketamin-Einmalgabe

„Psychotherapie ist auch bei sehr alten Menschen hochwirksam!“

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Springer Medizin

Abstract

Background

Methods

Results

Conclusions

Electronic supplementary material

Competing interests

Authors’ contributions

Background

Methods

Study population and the setting of the study

Design of the study and measurements

Depressive symptoms

Laboratory analysis

Other measurements

Statistical analysis

Results

Discussion

Conclusions

Acknowledgements

Competing interests

Authors’ contributions

Authors’ original submitted files for images

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