• Users Online: 71
  • Print this page
  • Email this page


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 4  |  Issue : 2  |  Page : 196-201

Vitamin B12 deficiency in psychiatric patients admitted in a tertiary care hospital


1 M. K. Shah Medical College and Research Center and SMS Multispecialty Hospital, Ahmedabad, Gujarat, India
2 Department of Psychiatry, Smt. NHL Municipal Medical College and SVPIMSR Hospital, Ahmedabad, Gujarat, India

Date of Submission05-Jul-2020
Date of Decision10-Sep-2020
Date of Acceptance16-Sep-2020
Date of Web Publication25-Nov-2020

Correspondence Address:
Dr. Sunayna Pandey
A/2, Sannidhi Apartment, Bhaikaknagar, Thaltej, Ahmedabad - 380 059, Gujarat
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aip.aip_69_20

Rights and Permissions
  Abstract 


Context: Vitamin B12 also known as cobalamin is water-soluble vitamin which is required for cell metabolism in the body and its deficiency leads to various neuropsychiatric disorders including depression, schizophrenia, and anxiety disorders. Aims: To find out the prevalence of Vitamin B12 deficiency in admitted psychiatric patients and associated clinical features, hematological findings, and risk factors. Settings and Design: It was a cross-sectional, observational study. Subjects and Methods: One hundred and fifty consecutive psychiatric patients admitted in the psychiatry ward of a tertiary care hospital were enrolled in the study population. After taking written informed consent, blood sample was collected for each participant, which is otherwise also a routine investigation for all indoor patients. Sociodemographic data of the patients were collected by a semi-structured interview. Data pertaining to clinical and laboratory presentation and risk factors were also collected. Statistical Analysis Used: Analysis was done using Student's t-test, Chi-square test, and Fisher's exact test. Results: The prevalence of Vitamin B12 deficiency in indoor psychiatric patients was 33.33%. The prevalence of depression was high among these patients (36%). It is more prevalent in males (64%) and in rural population (50%). Hematological changes in peripheral smear in the form of macrocytes (10%), macroovalocytes, and target cells (12%) were common findings. Clinical symptoms such as hyperpigmentation of knuckles (24%), memory loss 16%), fatigue (70%), and tingling numbness (34%) were associated with B12 deficiency. Conclusions: The prevalence of Vitamin B12 deficiency in the study population is reasonably high. More than half of the patients with B12 deficiency were suffering from mood disorders.

Keywords: Cobalamin, mentally ill, psychiatric patients, Vitamin B12 deficiency


How to cite this article:
Pandey S, Parikh NC, Oza HJ, Bhowmick SS. Vitamin B12 deficiency in psychiatric patients admitted in a tertiary care hospital. Ann Indian Psychiatry 2020;4:196-201

How to cite this URL:
Pandey S, Parikh NC, Oza HJ, Bhowmick SS. Vitamin B12 deficiency in psychiatric patients admitted in a tertiary care hospital. Ann Indian Psychiatry [serial online] 2020 [cited 2021 Jan 17];4:196-201. Available from: https://www.anip.co.in/text.asp?2020/4/2/196/301439




  Introduction Top


Vitamin B12 also known as cobalamin is a water-soluble vitamin, which is essential for DNA synthesis and for cellular energy production.[1] The most common causes of megaloblastic anemia are Vitamin B12 and folate deficiency.[2],[3],[4] Folate or cobalamin deficiencies are usually detected by hematologic abnormalities, such as macrocytic megaloblastic anemia, or often milder signs such as hypersegmented neutrophils. Sometimes, vitamin deficiencies may be associated with clinical conditions in which anemia and/or macrocytosis are absent, such as neuropsychiatric disorders and inborn errors of folate or cobalamin metabolism. Other markers of Vitamin B12 deficiency are marked anisocytosis, poikilocytosis, macroovalocytes, and basophilic stippling, though not exclusive to it.[5]

The Vitamins B12 and folic acid are used for the synthesis of purines, which are building blocks of RNA and DNA. It is used to methylate homocysteine to form methionine, which is converted to S-adenosylmethionine (SAM), a universal donor of methyl groups, including DNA, RNA, hormones, neurotransmitters (e.g., serotonin), membrane lipids, proteins, and others.[6]

The deficiency of these vitamins results in hyperhomocysteinemia which causes a decrease in SAM followed by impaired metabolism of neurotransmitters, phospholipids, myelin, and receptors.[7] It also leads to activation of NMDA receptors, lesions in vascular endothelium, and oxidative stress.[8] All these effects are neurotoxic and promote the development of various psychiatric disorders including depression, schizophrenia, and anxiety disorders and various neurological disorders such as dementia, Parkinson's disorder, cognitive impairment, cerebral atrophy, and epilepsy.[9],[10],[11],[12] It is also associated with mania, obsessive-compulsive disorder, and alcohol dependence and is also an independent risk factor for stroke.[13]

Vitamin B12 deficiency not also predisposes to psychiatric illnesses but long-term psychiatric illness may also lead to Vitamin B12 deficiency, which, in turn, can lead to resistant cases or deterioration of the condition. Some other risk factors include chronic alcohol use, long term antiepileptic use and chronic and frequent hospitalization.[14],[15] Also, studies have also demonstrated that with the supplements of Vitamin B12, patients have responded well and the severity of illness has diminished drastically.[10],[16]

Vitamin B12 is majorly found in animal sources including dairy products, eggs, fish, meat, and poultry. The recommended daily allowance of B12 is the range of 2.4 microgram to 2.8 microgram. Since a vegetarian diet supplies only up to 0.5 μ/day, most of the vegetarians and more so vegans are at risk of Vitamin B12 deficiency.[16]

Apart from decreased intake, B12 can be deficient because of insufficient cobalamin absorption.[17] Causes are lack of secretion of intrinsic factor, atrophic gastritis, partial gastrectomy, patients with long history of Helicobacter pylori infection, patients on long-term antiacid therapy, and decreased pepsin or gastric secretion.[18],[19],[20]

Vitamin B12 deficiency can be strongly prevalent in our country because a huge chunk of people have vegetarian diet while B12 is mainly found in animal products. The development of megaloblastic anemia is usually gradual and hence the patients are often relatively asymptomatic because they have had time to adjust to the marked fall in hemoglobin levels. Even in the absence of anemia, B12 deficiency can be present. Despite being studied widely, B12 deficiency is routinely missed in clinical practice leading to misdiagnosis and mismanagement. So, in order to highlight the importance of routine B12 screening in patients with psychiatric disorders, this study was carried out to find the prevalence of Vitamin B12 deficiency in 150 psychiatric patients admitted in a tertiary care hospital, the clinical manifestations and hematological findings associated with B12 deficiency and risk factors.

Subjects and Methods

This cross-sectional observational study was conducted in admitted patients at the psychiatry ward of a tertiary care hospital over 4 months and those patients who did not give consent or were on Vitamin B12 supplements were excluded.

The study was started after approval of the institutional review board. Written informed consent was obtained from patient and relative. Blood sample was collected from each participant for determining serum Vitamin B12 levels, which was a routine for all indoor psychiatric patients irrespective of the patient getting enrolled in the study. Sociodemographic data of the patients were collected by a semi-structured interview comprising of information about age, sex, education, marital status, occupation, family income, and locality. Data pertaining to clinical presentation like hyperpigmentation of knuckles, memory loss, fatigue, tingling and numbness of extremities, poor balance, and breathlessness were collected. Laboratory data collected were hemoglobin levels, red blood cell [RBC] hemoglobinization (normochromic, hypochromic, hyperchromic), RBC size (normocytes, microcytes, macrocytes), RBC shape (target cells, macroovalocytes), and hypersegmented neutrophils. Risk factors such as duration of psychiatric illness, duration of hospitalization, alcohol, and anticonvulsant use were also recorded. Diagnosis was made using the Diagnostic and Statistical Manual of Mental Disorders 5.

Analysis

Analysis was performed by SPSS (Statistical Packages for Social Sciences) Version 20. Patients with and without deficiency were compared regarding sociodemographic variables, psychiatric diagnosis, risk factors, and clinical and laboratory findings. Student's t-test, Chi-square, and Fisher's exact test were used for analysis. Fisher's exact test was used when at least one cell frequency was <5. P < 0.05 was considered statistically significant.


  Results Top


Prevalence of Vitamin B12 deficiency

150 patients admitted in psychiatry ward were taken into the study. Out of 150 patients, 50 were having Vitamin B12 deficiency (S. Vitamin B12 levels < 211 pg/ml). The prevalence in this study population was 33.33%. Out of 50 patients, 32 (64%) were male and 18 (36%) were female.

Sociodemographic variables and Vitamin B12 deficiency

[Table 1] shows sociodemographic factors related to patients suffering from Vitamin B12 deficiency. The results are statistically significant for sex, occupation, and locality. It was more common in males (64%), professionals (20%), and rural areas (50%). The mean age of patients with Vitamin B12 deficiency was 36.12 years.
Table 1: Sociodemographic characteristics and vitamin B12 deficiency

Click here to view


Clinical features and Vitamin B12 deficiency

[Table 2] shows clinical features related to patients suffering from Vitamin B12 deficiency. Results are statistically significant for hyperpigmentation of knuckles (24%), memory loss (16%), fatigue (70%), and tingling numbness (34%).
Table 2: Clinical features and vitamin B12 deficiency

Click here to view


Laboratory investigations and Vitamin B12 deficiency

[Table 3] shows laboratory investigations related to patients suffering from Vitamin B12 deficiency. Macrocytes (10%), target cells, and macroovalocytes (12%) are more commonly seen in peripheral smears of patients having Vitamin B12 deficiency, which was statistically significant.
Table 3: Laboratory investigations and vitamin B12 deficiency

Click here to view


Risk factors and Vitamin B12 deficiency

[Table 4] shows risk factors such as duration of psychiatric illness, duration of hospitalization, substance use, and use of anticonvulsants in patients suffering from Vitamin B12 deficiency. The results were not statistically significant.
Table 4: Risk factors and vitamin B12 deficiency

Click here to view


Psychiatric diagnosis and Vitamin B12 deficiency

[Graph 1] shows that out of 50 patients suffering from Vitamin B12 deficiency, 27 (54%) patients had mood disorders, 13 (26%) patients had psychosis, 4 (8%) patients had substance use disorder, 2 (4%) patients had functional neurological symptom disorder, 1 (2%) patient had borderline personality disorder, 1 (2%) patient had somatic symptom disorder, 1 (2%) had agoraphobia, and 1 (2%) patient had dissociative disorder.




  Discussion Top


In our study, we found that around 33.33% (50) of patients had Vitamin B12 deficiency. According to various studies, the prevalence of Vitamin B12 deficiency in admitted psychiatry patients is in the range of 3.6%–28%.[14],[21],[22],[23] The higher rates in our study could be because of geographical and dietary variation. Also, using different cutoff levels for Vitamin B12 deficiency in different studies could be a reason for this variation.

The mean age of patients suffering from Vitamin B12 deficiency was 36.12 years. Out of 50 positive patients, 32 (64%) were male and 18 (36%) were female. Higher prevalence is found is males in other studies also.[14],[24],[25],[26] This could be because of genetic variation.[19] Also, estrogen might be a protective factor for B12 deficiency.[27],[28]

People having B12 deficiency were mostly from rural areas (50%) as compared to those who did not have any deficiency (29%). Chakraborty et al. also had similar findings as 43.9% of study population were from rural places as compared to 30.1% from urban places.[29] Nutritional deficiency could play a role.

Hyperpigmentation was seen in 24%, memory loss in 16%, fatigue in 70%, and tingling numbness in 34% of patients having B12 deficiency. These symptoms are commonly associated with Vitamin B12 deficiency.[30],[31],[32],[33] Hence, Vitamin B12 deficiency should be suspected in patients having these signs and symptoms.

Macrocytes were found in 10% of the patients suffering from B12 deficiency, whereas 12% of patients had target cells and macroovalocytes. Low hemoglobin levels (<12 g/dl) did not have any significant association with Vitamin B12 deficiency. Other studies also supports similar findings.[14],[16] Hence, when such abnormal findings are present in peripheral smear even in the presence of normal hemoglobin, B12 deficiency should be suspected.

Our study did not have any significant correlation between anticonvulsant use and B12 deficiency. This could be because the duration of anticonvulsant use, valproate in this case was for a lesser duration of time, i.e., only ranging from 3 months to 2 years and also the compliance could be poor. A study by Mintzer et al. also concluded that there was no B12 or folate deficiency in patients taking antiepileptic.[34] Alcohol use also did not have significant association in our study. This could be because the amount and duration of intake was not clearly specified and in a state like this where alcohol is banned, patients are reluctant to reveal their alcohol intake history. In other studies like Ssonko et al., risk factors like anticonvulsant use and alcohol use has been found to be significant.[14]

Most frequent diagnosis found in the study was mood disorders followed by psychotic disorders. Of 50 patients suffering from Vitamin B12 deficiency, 27 (54%) patients had mood disorders (thirteen patients had bipolar mood disorders, nine patients had major depressive disorder [MDD], two patients had MDD with anxious distress, one patient had MDD with social anxiety disorder, and 2 patient had persistent depressive disorder). Thirteen (26%) patients had psychosis (four had schizophrenia; eight had unspecified psychosis and one had delusional disorder). Four (8%) patients had substance use disorder (three patients had alcohol use disorder and one patient had cannabis use disorder along with alcohol use disorder). Two (4%) patients had functional neurological symptom disorder (conversion), one (2%) patient had borderline personality disorder, one (2%) patient had somatic symptom disorder, one (2%) had agoraphobia, and one (2%) patient had dissociative disorder. Depression has been commonly associated with B12 deficieny.[35] Also, depression can lead to decreased appetite which can lead to nutritional deficiency. Miskulin et al. in their study found out that 70% of the elderly patients who had Vitamin B12 deficiency had depressive symptoms.[36] Ssonko et al. found in their study that schizophrenia was the most common diagnosis.[14] This could have been aided by the largest population of patients suffering from schizophrenia in their study. Dementia is also commonly linked with B12 deficiency, but at the time of the study, there were no patients admitted with dementia in the ward.


  Conclusions Top


Low serum Vitamin B12 is quite prevalent in admitted patients suffering from psychiatric illness with a prevalence of 33.33%. More than half of the patients were suffering from mood disorders. It is more prevalent in males and in rural population. Hematologic changes in peripheral smear in form macrocytes, macroovalocytes and target cells were common findings even in the absence of anemia. Clinical symptoms like hyperpigmentation of knuckles, memory loss, fatigue, and tingling numbness were associated with B12 deficiency.

Clinical significance

This study highlights the significance of Vitamin B12 screening in patients with psychiatric illness. Due to the high prevalence of B12 deficiency, routine screening for Vitamin B12 is advised in all psychiatric patients and if not possible supplementation may be given in patients having symptoms of Vitamin B12 deficiency and hemogram suggestive of Vitamin B12 deficiency even in the absence of anemia.

Limitations and future recommendations

Sample size was small and single-center study, so results cannot be generalized to all psychiatric patients.

In the future, study should be done for a larger sample size and at multiple sites in order to confirm the findings of this study.

Ethical statement

This study was approved by Institutional Ethics Committee NHLIRB obtained on 17th January 2018.

Declaration of patient consent

Patient consent statement was taken from each patient as per institutional ethics committee approval along with consent taken for participation in the study and publication of the scientific results/clinical information/image without revealing their identity, name or initials. The patient is aware that though confidentiality would be maintained anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
O'Leary F, Samman S. Vitamin B12 in health and disease. Nutrients 2010;2:299-316.  Back to cited text no. 1
    
2.
Mahajan SK, Aundhakar SC. A study of the prevalence of serum Vitamin B12 and folic Acid deficiency in Western Maharashtra. J Family Med Prim Care 2015;4:64-8.  Back to cited text no. 2
[PUBMED]  [Full text]  
3.
Hall JA, Mason J, Choi J, Holguin M. B12 deficiency leading to marked poikilocytosis versus true schistocytosis, a pernicious problem. Transfus Apher Sci 2017;56:576-7.  Back to cited text no. 3
    
4.
Ekem IA. Hypersegmented neutrophils and reversible hyperpigmentation in Vitamin B (12) deficiency in Ghana. BMJ Case Rep 2009;2009:bcr08.2008.0686.  Back to cited text no. 4
    
5.
Zittoun J, Zittoun R. Modern clinical testing strategies in cobalamin and folate deficiency. Semin Hematol 1999;36:35-46.  Back to cited text no. 5
    
6.
Selhub J. Folate, Vitamin B12 and Vitamin B6 and one carbon metabolism. J Nutr Health Aging 2002;6:39-42.  Back to cited text no. 6
    
7.
Poddar R, Paul S. Homocysteine-NMDA receptor-mediated activation of extracellular signal-regulated kinase leads to neuronal cell death. J Neurochem 2009;110:1095-106.  Back to cited text no. 7
    
8.
Karakuła H, Opolska A, Kowal A, Domański M, Płotka A, Perzyński J. Does diet affect our mood? The significance of folic acid and homocysteine. Pol Merkur Lekarski 2009;26:136-41.  Back to cited text no. 8
    
9.
Moustafa AA, Hewedi DH, Eissa AM, Frydecka D, Misiak B. Homocysteine levels in schizophrenia and affective disorders-focus on cognition. Front Behav Neurosci 2014;8:343.  Back to cited text no. 9
    
10.
Narayan SK, Verman A, Kattimani S, Ananthanarayanan PH, Adithan C. Plasma homocysteine levels in depression and schizophrenia in South Indian Tamilian population. Indian J Psychiatry 2014;56:46-53.  Back to cited text no. 10
[PUBMED]  [Full text]  
11.
Hermesh H, Weizman A, Shahar A, Munitz H. Vitamin B12 and folic acid serum levels in obsessive compulsive disorder. Acta Psychiatr Scand 1988;78:8-10.  Back to cited text no. 11
    
12.
Hector M, Burton JR. What are the psychiatric manifestations of Vitamin B12 deficiency? J Am Geriatr Soc 1988;36:1105-12.  Back to cited text no. 12
    
13.
Applebaum J, Shimon H, Sela BA, Belmaker RH, Levine J. Homocysteine levels in newly admitted schizophrenic patients. J Psychiatr Res 2004;38:413-6.  Back to cited text no. 13
    
14.
Ssonko M, Ddungu H, Musisi S. Low serum Vitamin B12 levels among psychiatric patients admitted in Butabika mental hospital in Uganda. BMC Res Notes 2014;7:90.  Back to cited text no. 14
    
15.
Streiff RR. Anemia and nutritional deficiency in the acutely ill hospitalized patients. Med Clin North Am 1993;77:911-8.  Back to cited text no. 15
    
16.
Coppen A, Bolander-Gouaille C. Treatment of depression: Time to consider folic acid and Vitamin B12. J Psychopharmacol 2005;19:59-65.  Back to cited text no. 16
    
17.
Carmel R. How I treat cobalamin (Vitamin B12) deficiency. Blood 2008;112:2214-21.  Back to cited text no. 17
    
18.
Antony AC. Vegetarianism and Vitamin B-12 (cobalamin) deficiency. Am J Clin Nutr 2003;78:3-6.  Back to cited text no. 18
    
19.
Pennypacker LC, Allen RH, Kelly JP, Matthews LM, Grigsby J, Kaye K, et al. High prevalence of cobalamin deficiency in elderly outpatients. J Am Geriatr Soc 1992;40:1197-204.  Back to cited text no. 19
    
20.
Lewerin C, Jacobsson S, Lindstedt G, Nilsson-Ehle H. Serum biomarkers for atrophic gastritis and antibodies against Helicobacter pylori in the elderly: Implications for Vitamin B12, folic acid and iron status and response to oral vitamin therapy. Scand J Gastroenterol 2008;43:1050-6.  Back to cited text no. 20
    
21.
Stabler SP. Clinical practice. Vitamin B12 deficiency. N Engl J Med 2013;368:149-60.  Back to cited text no. 21
    
22.
Bell IR, Edman JS, Marby DW, Satlin A, Dreier T, Liptzin B, et al. Vitamin B12 and folate status in acute geropsychiatric inpatients: Affective and cognitive characteristics of a vitamin nondeficient population. Biol Psychiatry 1990;27:125-37.  Back to cited text no. 22
    
23.
Silver H. Vitamin B12 levels are low in hospitalized psychiatric patients. Isr J Psychiatry Relat Sci 2000;37:41-5.  Back to cited text no. 23
    
24.
Margalit I, Cohen E, Goldberg E, Krause I. Vitamin B12 deficiency and the role of gender: A cross-sectional study of a large cohort. Ann Nutr Metab 2018;72:265-71.  Back to cited text no. 24
    
25.
Sánchez H, Albala C, Herlramp F E, Verdugo R, Lavados M, Castillo JL, et al. Prevalence of Vitamin B-12 deficiency in older adults. Rev Med Chil 2010;138:44-52.  Back to cited text no. 25
    
26.
Hao L, Ma J, Zhu J, Stampfer MJ, Tian Y, Willett WC, et al. Vitamin B-12 deficiency is prevalent in 35- to 64-year-old Chinese adults. J Nutr 2007;137:1278-85.  Back to cited text no. 26
    
27.
Berenson AB, Rahman M. Effect of hormonal contraceptives on Vitamin B12 level and the association of the latter with bone mineral density. Contraception 2012;86:481-7.  Back to cited text no. 27
    
28.
Sütterlin MW, Bussen SS, Rieger L, Dietl J, Steck T. Serum folate and Vitamin B12 levels in women using modern oral contraceptives (OC) containing 20 microg ethinyl estradiol. Eur J Obstet Gynecol Reprod Biol 2003;107:57-61.  Back to cited text no. 28
    
29.
Chakraborty S, Chopra M, Mani K, Giri AK, Banerjee P, Sahni NS, et al. Prevalence of Vitamin B (12) deficiency in healthy Indianschool-going adolescents from rural and urban localities and its relationship with various anthropometric indices: A cross-sectional study. J Hum Nutr Diet 2018;31:513-22.  Back to cited text no. 29
    
30.
Kannan R, Ng MJ. Cutaneous lesions and Vitamin B12 deficiency: An often-forgotten link. Can Fam Physician 2008;54:529-32.  Back to cited text no. 30
    
31.
Issac TG, Soundarya S, Christopher R, Chandra SR. Vitamin B12 deficiency: An important reversible co-morbidity in neuropsychiatric manifestations. Indian J Psychol Med 2015;37:26-9.  Back to cited text no. 31
[PUBMED]  [Full text]  
32.
Huijts M, Duits A, Staals J, van Oostenbrugge RJ. Association of Vitamin B12 deficiency with fatigue and depression after lacunar stroke. PLoS One 2012;7:e30519.  Back to cited text no. 32
    
33.
Staff NP, Windebank AJ. Peripheral neuropathy due to vitamin deficiency, toxins, and medications. Continuum (Minneap Minn) 2014;20:1293-306.  Back to cited text no. 33
    
34.
Mintzer S, Skidmore CT, Sperling MR. B-vitamin deficiency in patients treated with antiepileptic drugs. Epilepsy Behav 2012;24:341-4.  Back to cited text no. 34
    
35.
Tiemeier H, van Tuijl HR, Hofman A, Meijer J, Kiliaan AJ, Breteler MM. Vitamin B12, folate, and homocysteine in depression: The Rotterdam study. Am J Psychiatry 2002;159:2099-101.  Back to cited text no. 35
    
36.
Miskulin M, Kristic M, Vlahovic J. Vitamin B12 deficiency and depression in elderly: Cross sectional study in Eastern Croatia: Journal of health Sciences. 2014;4:143-8.  Back to cited text no. 36
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Results
Discussion
Conclusions
References
Article Tables

 Article Access Statistics
    Viewed219    
    Printed6    
    Emailed0    
    PDF Downloaded26    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]