The Relationship Between Folate and B12 Levels and Clinical Features in Patients with Early-Onset Schizophrenia Spectrum Disorder
PDF

Original Article

The Relationship Between Folate and B12 Levels and Clinical Features in Patients with Early-Onset Schizophrenia Spectrum Disorder

Turk J Child Adolesc Ment Health 2025;32(1):15-20 DOI: 10.4274/tjcamh.galenos.2024.42650
, , , , ,
PDF
Permissions

Abstract

Objectives

This study aimed to compare the serum folate and B12 levels between patients with early-onset schizophrenia spectrum disorder (EOSSD) and healthy controls.

Materials and Methods

In this retrospective study, folic acid and vitamin B12 serum levels were assessed during the hospitalization of patients (n=127) with EOSSD who were admitted to the child and adolescent psychiatry inpatient service. The study evaluated the clinical features and serum folate and B12 levels of patients with EOSSD.

Results

In EOSSD patients, the serum B12 levels were significantly lower compared to the control group (F=8.4, p=0.004). Age did not have any effect on B12 and folic acid levels in the models, but gender had a significant impact on folate (F=7.6, p=0.006) and B12 levels (F=5.7, p=0.018). A negative correlation was observed between folate levels and PANSS-total (r=-0.308, p<0.001). Additionally, a significant negative correlation was found between patients’ B12 level and age (r=-0.188, p=0.034), and a positive correlation was observed between CGI-S (r=0.231, p=0.010). The correlation with drug dose showed a trend toward significance (r=-0.168, p=0.063).

Conclusion

The clinical features in EOSSD patients are associated with folate and B12 levels. It may be useful in clinical practice for clinicians to question the symptoms of B12 and folate deficiency in patients with psychotic symptoms, to conduct an examination, and to initiate treatment to detect deficiencies.

Keywords: Early-onset schizophrenia spectrum disorder, folate, B12 vitamin

References

1

Masi G, Liboni F. Management of schizophrenia in children and adolescents: focus on pharmacotherapy. Drugs. 2011;71:179-208.

2

Roffman JL, Lamberti JS, Achtyes E, Macklin EA, Galendez GC, Raeke LH, Silverstein NJ, Smoller JW, Hill M, Goff DC. Randomized multicenter investigation of folate plus vitamin B12 supplementation in schizophrenia. JAMA Psychiatry. 2013;70:481-489.

3

Kyriakopoulos M, Frangou S. Pathophysiology of early onset schizophrenia. Int Rev Psychiatry. 2007;19:315-324.

4

Kumanan T, Thomas N, Pirasath S. Vitamin B12 deficiency in resistant schizophrenia in tropics. Open Access Library Journal. 2017;4:1-4.

5

Stover PJ. Physiology of folate and vitamin B12 in health and disease. Nutr Rev. 2004;62:S3-12; discussion S13.

6

van Beynum IM, den Heijer M, Thomas CM, Afman L, Oppenraay-van Emmerzaal D, Blom HJ. Total homocysteine and its predictors in Dutch children. Am J Clin Nutr. 2005;81:1110-1116.

7

Bottiglieri T. Folate, vitamin B12, and neuropsychiatric disorders. Nutr Rev. 1996;54:382-390.

8

Kapoor A, Baig M, Tunio SA, Memon AS, Karmani H. Neuropsychiatric and neurological problems among Vitamin B12 deficient young vegetarians. Neurosciences (Riyadh). 2017;22:228-232.

9

Reynolds E. Vitamin B12, folic acid, and the nervous system. Lancet Neurol. 2006;5:949-960.

10

Cao B, Wang DF, Xu MY, Liu YQ, Yan LL, Wang JY, Lu QB. Lower folate levels in schizophrenia: a meta-analysis. Psychiatry Res. 2016;245:1-7.

11

Ding Y, Ju M, He L, Chen W. Association of folate level in blood with the risk of schizophrenia. Comb Chem High Throughput Screen. 2017;20:116-122.

12

Firth J, Stubbs B, Sarris J, Rosenbaum S, Teasdale S, Berk M, Yung AR. The effects of vitamin and mineral supplementation on symptoms of schizophrenia: a systematic review and meta-analysis. Psychol Med. 2017;47:1515-1527.

13

Wang D, Zhai JX, Liu DW. Comparison of serum folate between schizophrenic patients and healthy controls in Chinese Han adult population: a systematic review and meta-analysis. Comb Chem High Throughput Screen. 2023;26:906-915.

14

Aucoin ML, LaChance LR. Vitamin B12, vitamin B6, folic acid and psychosis: a review. J Orthomol Med. 2018;35.

15

Cohen E, Margalit I, Shochat T, Goldberg E, Krause I. Gender differences in homocysteine concentrations, a population-based cross-sectional study. Nutr Metab Cardiovasc Dis. 2019;29:9-14.

16

Zhilyaeva TV, Kasyanov ED, Pyatoikina AS, Blagonravova AS, Mazo GE. Assotsiatsiya urovnya folatov syvorotki krovi s klinicheskimi simptomami shizofrenii [The association of serum folate levels with schizophrenia symptoms]. Zh Nevrol Psikhiatr Im S S Korsakova. 2022;122:128-135. Russian.

17

Tomioka Y, Kinoshita M, Umehara H, Nakayama T, Watanabe SY, Nakataki M, Numata S, Ohmori T. Association between serum folate levels and schizophrenia based on sex. Psychiatry Clin Neurosci. 2020;74:466-471.

18

dos Reis FP, Duarte L, Cartaxo T, Santos V. Folic acid, vitamin B12, and psychotic symptoms among young psychiatric inpatients. Bırth And Growth Medıcal Journal. 2021;30:85-91.

19

Ayesa-Arriola R, Pérez-Iglesias R, Rodríguez-Sánchez JM, Mata I, Gómez-Ruiz E, García-Unzueta M, Martínez-García O, Tabares-Seisdedos R, Vázquez-Barquero JL, Crespo-Facorro B. Homocysteine and cognition in first-episode psychosis patients. Eur Arch Psychiatry Clin Neurosci. 2012;262:557-564.

20

Haidemenos A, Kontis D, Gazi A, Kallai E, Allin M, Lucia B. Plasma homocysteine, folate and B12 in chronic schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31:1289-1296.

21

Kim TH, Moon SW. Serum homocysteine and folate levels in korean schizophrenic patients. Psychiatry Investig. 2011;8:134-140.

22

Misiak B, Frydecka D, Slezak R, Piotrowski P, Kiejna A. Elevated homocysteine level in first-episode schizophrenia patients--the relevance of family history of schizophrenia and lifetime diagnosis of cannabis abuse. Metab Brain Dis. 2014;29:661-670.

23

Cao B, Wang DF, Xu MY, Liu YQ, Yan LL, Wang JY, Lu QB. Vitamin B12 and the risk of schizophrenia: a meta-analysis. Schizophr Res. 2016;172:216-217.

24

Kapici Y, Han Almis B. Comparison of first-episode psychosis and first-episode mania patients with healthy controls regarding serum vitamin B12 and folate levels. Dusunen Adam J Psychiatr Neurol Sci. 2022;35:147-154.

25

Saedisomeolia A, Djalali M, Moghadam AM, Ramezankhani O, Najmi L. Folate and vitamin B12 status in schizophrenic patients. J Res Med Sci. 2011;16 Suppl 1(Suppl1):S437-441.

26

Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13:261-276.

27

Busner J, Targum SD. The clinical global impressions scale: applying a research tool in clinical practice. Psychiatry (Edgmont). 2007;4:28-37.

28

Leucht S, Samara M, Heres S, Davis JM. Dose equivalents for antipsychotic drugs: The DDD method. Schizophr Bull. 2016;42 Suppl 1(Suppl 1):S90-94.

29

Wang D, Zhai JX, Liu DW. Serum folate levels in schizophrenia: A meta-analysis. Psychiatry Res. 2016 Jan 30;235:83-89.

30

Song X, Fan X, Li X, Kennedy D, Pang L, Quan M, Chen X, Gao J, Zhang W, Zhang J, Lv L. Serum levels of BDNF, folate and homocysteine: in relation to hippocampal volume and psychopathology in drug naïve, first episode schizophrenia. Schizophr Res. 2014;159:51-55.

31

Ipcioglu OM, Ozcan O, Gultepe M, Ates A, Basoglu C, Cakir E. Reduced urinary excretion of homocysteine could be the reason of elevated plasma homocysteine in patients with psychiatric illnesses. Clin Biochem. 2008;41:831-835.

32

Kale A, Naphade N, Sapkale S, Kamaraju M, Pillai A, Joshi S, Mahadik S. Reduced folic acid, vitamin B12 and docosahexaenoic acid and increased homocysteine and cortisol in never-medicated schizophrenia patients: implications for altered one-carbon metabolism. Psychiatry Res. 2010;175:47-53.

33

Huemer M, Vonblon K, Födinger M, Krumpholz R, Hubmann M, Ulmer H, Simma B. Total homocysteine, folate, and cobalamin, and their relation to genetic polymorphisms, lifestyle and body mass index in healthy children and adolescents. Pediatr Res. 2006;60:764-769.

34

Wahlin A, Bäckman L, Hultdin J, Adolfsson R, Nilsson LG. Reference values for serum levels of vitamin B12 and folic acid in a population-based sample of adults between 35 and 80 years of age. Public Health Nutr. 2002;5:505-511.

35

Misiak B, Stańczykiewicz B, Wiśniewski M, Bartoli F, Carra G, Cavaleri D, Samochowiec J, Jarosz K, Rosińczuk J, Frydecka D. Thyroid hormones in persons with schizophrenia: A systematic review and meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2021;111:110402.

36

Sakuma K, Matsunaga S, Nomura I, Okuya M, Kishi T, Iwata N. Folic acid/methylfolate for the treatment of psychopathology in schizophrenia: a systematic review and meta-analysis. Psychopharmacology (Berl). 2018;235:2303-2314.

37

Hill M, Shannahan K, Jasinski S, Macklin EA, Raeke L, Roffman JL, Goff DC. Folate supplementation in schizophrenia: a possible role for MTHFR genotype. Schizophr Res. 2011;127:41-45.

38

Levine J, Stahl Z, Sela BA, Ruderman V, Shumaico O, Babushkin I, Osher Y, Bersudsky Y, Belmaker RH. Homocysteine-reducing strategies improve symptoms in chronic schizophrenic patients with hyperhomocysteinemia. Biol Psychiatry. 2006;60:265-269.

39

Xu X, Shao G, Zhang X, Hu Y, Huang J, Su Y, Zhang M, Cai Y, Zhou H. The efficacy of nutritional supplements for the adjunctive treatment of schizophrenia in adults: a systematic review and network meta-analysis. Psychiatry Res. 2022;311:114500.

40

Kowalski K, Bogudzińska B, Stańczykiewicz B, Piotrowski P, Bielawski T, Samochowiec J, Szczygieł K, Plichta P, Misiak B. The deficit schizophrenia subtype ıs associated with low adherence to the mediterranean diet: findings from a case-control study. J Clin Med. 2022;11:568.

41

Matrisciano F. Functional nutrition as ıntegrated ıntervention for ın- and outpatient with schizophrenia. Curr Neuropharmacol. 2023;21:2409-2423.