Association Studies of Genetic Scores of Serum Vitamin B12 and Folate Levels with Symptoms of Depression and Anxiety in Two Danish Population Studies

Overview

Journal Eur J Clin Nutr

Specialty Nutritional Sciences

Date 2017 Jun 29

PMID 28656970

Citations 4

Authors

L T Mollehave

T Skaaby

K S Simonsen

B H Thuesen

E L Mortensen

C H Sandholt

O Pedersen

N Grarup

T Hansen

A Linneberg

Affiliations

Soon will be listed here.

Abstract

Background/objectives: Observational studies have suggested low serum levels of vitamin B12 or folate to be risk factors of depression and anxiety. However, these results may be biased by confounding and reverse causation. Mendelian randomization studies are not subject to these limitations. The aim was to examine the association of genetic scores of vitamin B12 and folate-associated alleles with depression and anxiety.

Subjects/methods: The study included 4126 participants from two Danish population-based studies. Serum vitamin B12 and folate were measured. Weighed allele scores were calculated as the sum of weights (genetic effect sizes) for 12 and two variants increasing circulating levels of vitamin B12 and folate, respectively. Symptoms of depression and anxiety were assessed by the Symptom Check List (SCL)-90-R, and self-reported doctor-diagnosed depression and anxiety.

Results: An increased weighed allele score for serum vitamin B12 was associated with decreased odds of a SCL-90-R score above the 90th percentile (OR 0.540 (95%CI 0.302-0.967)) in Health2006 but not in Inter99, in the pooled analysis (OR 0.817 (95%CI 0.331-2.018)) or with other outcomes. The weighed allele score for serum folate was not associated with any of the measured outcome variables: SCL-90-R scores of depression (pooled OR 0.603 (95%CI 0.101-3.602)), anxiety (pooled OR 0.619 (95%CI 0.110-3.495)), combined score or history of doctor-diagnosed depression or anxiety.

Conclusion: Our results do not provide evidence for a causal effect of circulating folate or vitamin B12 on the risk of depression or anxiety. However, we cannot rule out small to moderate effects, and thus large scale studies are needed.

Citing Articles

Micronutrients and Major Depression: A Mendelian Randomisation Study.

Carnegie R, Zheng J, Borges M, Jones H, Wade K, Sallis H Nutrients. 2024; 16(21).

PMID: 39519523 PMC: 11547740. DOI: 10.3390/nu16213690.

Mendelian randomisation for nutritional psychiatry.

Carnegie R, Zheng J, Sallis H, Jones H, Wade K, Evans J Lancet Psychiatry. 2019; 7(2):208-216.

PMID: 31759900 PMC: 6983323. DOI: 10.1016/S2215-0366(19)30293-7.

Egg consumption and prevalence of psychological disorders in adults.

Shafiei F, Keshteli A, Pouraram H, Afshar H, Salari-Moghaddam A, Esmaillzadeh A Eur J Nutr. 2018; 58(5):1923-1932.

PMID: 29948220 DOI: 10.1007/s00394-018-1739-5.

S100B, Homocysteine, Vitamin B12, Folic Acid, and Procalcitonin Serum Levels in Remitters to Electroconvulsive Therapy: A Pilot Study.

Maier H, Helm S, Toto S, Moschny N, Sperling W, Hillemacher T Dis Markers. 2018; 2018:2358451.

PMID: 29545905 PMC: 5818900. DOI: 10.1155/2018/2358451.

References

Beesdo K, Pine D, Lieb R, Wittchen H . Incidence and risk patterns of anxiety and depressive disorders and categorization of generalized anxiety disorder. Arch Gen Psychiatry. 2010; 67(1):47-57. DOI: 10.1001/archgenpsychiatry.2009.177. View

Thuesen B, Cerqueira C, Aadahl M, Ebstrup J, Toft U, Thyssen J . Cohort Profile: the Health2006 cohort, research centre for prevention and health. Int J Epidemiol. 2013; 43(2):568-75. DOI: 10.1093/ije/dyt009. View

DeRogatis L, Cleary P . Factorial invariance across gender for the primary symptom dimensions of the SCL-90. Br J Soc Clin Psychol. 1977; 16(4):347-56. DOI: 10.1111/j.2044-8260.1977.tb00241.x. View

Husemoen L, Skaaby T, Thuesen B, Grarup N, Sandholt C, Hansen T . Mendelian randomisation study of the associations of vitamin B12 and folate genetic risk scores with blood pressure and fasting serum lipid levels in three Danish population-based studies. Eur J Clin Nutr. 2016; 70(5):613-9. DOI: 10.1038/ejcn.2016.5. View

Grarup N, Sulem P, Sandholt C, Thorleifsson G, Ahluwalia T, Steinthorsdottir V . Genetic architecture of vitamin B12 and folate levels uncovered applying deeply sequenced large datasets. PLoS Genet. 2013; 9(6):e1003530. PMC: 3674994. DOI: 10.1371/journal.pgen.1003530. View

Bottiglieri T . Homocysteine and folate metabolism in depression. Prog Neuropsychopharmacol Biol Psychiatry. 2005; 29(7):1103-12. DOI: 10.1016/j.pnpbp.2005.06.021. View

Biemans E, Hart H, Rutten G, Cuellar Renteria V, Kooijman-Buiting A, Beulens J . Cobalamin status and its relation with depression, cognition and neuropathy in patients with type 2 diabetes mellitus using metformin. Acta Diabetol. 2014; 52(2):383-93. DOI: 10.1007/s00592-014-0661-4. View

Jorgensen T, Borch-Johnsen K, Thomsen T, Ibsen H, Glumer C, Pisinger C . A randomized non-pharmacological intervention study for prevention of ischaemic heart disease: baseline results Inter99. Eur J Cardiovasc Prev Rehabil. 2003; 10(5):377-86. DOI: 10.1097/01.hjr.0000096541.30533.82. View

Koponen H, Kautiainen H, Eriksson J, Kampman O, Leiviska J, Mannisto S . Association between vitamin b12 levels and melancholic depressive symptoms: a Finnish population-based study. BMC Psychiatry. 2013; 13:145. PMC: 3674945. DOI: 10.1186/1471-244X-13-145. View

10.

De-Regil L, Pena-Rosas J, Fernandez-Gaxiola A, Rayco-Solon P . Effects and safety of periconceptional oral folate supplementation for preventing birth defects. Cochrane Database Syst Rev. 2015; (12):CD007950. PMC: 8783750. DOI: 10.1002/14651858.CD007950.pub3. View

11.

Prince M, Patel V, Saxena S, Maj M, Maselko J, Phillips M . No health without mental health. Lancet. 2007; 370(9590):859-77. DOI: 10.1016/S0140-6736(07)61238-0. View

12.

Saltin B, Grimby G . Physiological analysis of middle-aged and old former athletes. Comparison with still active athletes of the same ages. Circulation. 1968; 38(6):1104-15. DOI: 10.1161/01.cir.38.6.1104. View

13.

Forti P, Rietti E, Pisacane N, Olivelli V, Dalmonte E, Mecocci P . Blood homocysteine and risk of depression in the elderly. Arch Gerontol Geriatr. 2009; 51(1):21-5. DOI: 10.1016/j.archger.2009.06.009. View

14.

Kessler R, Aguilar-Gaxiola S, Alonso J, Chatterji S, Lee S, Ormel J . The global burden of mental disorders: an update from the WHO World Mental Health (WMH) surveys. Epidemiol Psichiatr Soc. 2009; 18(1):23-33. PMC: 3039289. DOI: 10.1017/s1121189x00001421. View

15.

VanderWeele T, Tchetgen Tchetgen E, Cornelis M, Kraft P . Methodological challenges in mendelian randomization. Epidemiology. 2014; 25(3):427-35. PMC: 3981897. DOI: 10.1097/EDE.0000000000000081. View

16.

Kumar N . Neurologic aspects of cobalamin (B12) deficiency. Handb Clin Neurol. 2013; 120:915-26. DOI: 10.1016/B978-0-7020-4087-0.00060-7. View

17.

Moulton C, Pickup J, Ismail K . The link between depression and diabetes: the search for shared mechanisms. Lancet Diabetes Endocrinol. 2015; 3(6):461-471. DOI: 10.1016/S2213-8587(15)00134-5. View

18.

Burgess S, Thompson S . Use of allele scores as instrumental variables for Mendelian randomization. Int J Epidemiol. 2013; 42(4):1134-44. PMC: 3780999. DOI: 10.1093/ije/dyt093. View

19.

Jorgensen T, Ladelund S, Borch-Johnsen K, Pisinger C, Schrader A, Thomsen T . Screening for risk of cardiovascular disease is not associated with mental distress: the Inter99 study. Prev Med. 2009; 48(3):242-6. DOI: 10.1016/j.ypmed.2008.12.010. View

20.

Brown T, Barlow D . Dimensional versus categorical classification of mental disorders in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders and beyond: comment on the special section. J Abnorm Psychol. 2005; 114(4):551-6. DOI: 10.1037/0021-843X.114.4.551. View