Chronic Psychosis Associated with Vitamin B12 Deficiency
AP Rajkumar*, P Jebaraj**
B12 deficiency is widely prevalent and usually presents with haematologic and neuropsychiatric manifestations. Psychiatric symptoms seldom precede anaemia and present as the principal manifestation of B12 deficiency. A report an unusual presentation of long standing psychotic symptoms without anaemia in a 31 year old male, who presented to a tertiary care psychiatric facility. His physical examination revealed hyper pigmentation of extremities and posterior column involvement. Laboratory investigations confirmed normal haemoglobin and low serum B12 levels. He recovered dramatically with short term anti psychotic medication and intramuscular cobalamin supplementation. He remained asymptomatic and functionally independent at two years follow up. ©
Vitamin B12 deficiency is common in developing countries and its prevalence ranges up to 67% among Indian men.1 It results in neuro psychiatric manifestations such as peripheral neuropathy, myeloneuropathy, cerebellar ataxia, optic atrophy, delirium, dementia, psychosis and mood disorders.2 Reports of patients initially presenting to psychiatric facilities without associated haematological manifestations are rare.3 Here, we report a case of B12 deficiency that presented with two years history of psychosis without anaemia and responded well to short term antipsychotic treatment and parenteral cobalamin supplementation. He has remained well on a 2 year followup.
Mr. V, a 31 years single male labourer, without past or family history of any neuropsychiatric morbidity was brought by his relatives to a tertiary care psychiatric hospital. He had two years continuous history of insomnia, suspiciousness, hearing multiple female voices, social withdrawal, personal deterioration and functional impairment. History of any known medical illness or substance abuse was absent. He was on non-vegetarian diet and had family history of iron deficiency anaemia in his elder brother.
On examination, his cognitive functions were intact. Persecutory delusions and third person auditory hallucinations were present. He had blunted affect and poor insight. Hyperpigmentation of his extremities provided the impetus for further evaluation. Cranial nerves and motor system were normal. He had ataxic gait and impaired proprioception below both ankles. Rhomberg’s sign was positive. Signs of cerebellar or autonomic dysfunction were absent. Examination of other systems was uneventful. His serum B12 level (201pgm/ml; normal range: 220-900pgm/ml) confirmed the possibility of vitamin B12 deficiency. Serum electrolytes, renal and hepatic parameters were normal. Other pertinent laboratory parameters were presented in Table 1.
We made the diagnosis of organic delusional (schizophrenia like) disorder (ICD-10: F 06.2).4 We hospitalised him and consulted with departments of internal medicine, neurology, endocrinology and dermatology. We ruled out Addison’s disease, folate deficiency and hemochromatosis. He received intramuscular vitamin B12 daily during the first week and once weekly for the next four weeks. We added Tab. Risperidone up to 6 mg/day for acute management of his psychotic symptoms. His psychosis and subtle neurological signs improved dramatically within three weeks. His personal care and social functioning were restored. His score on Brief Psychiatric Rating Scale5 (BPRS) improved from 54 to 20 at the time of discharge. We started tapering Risperidone after four weeks and stopped it after three months. Parenteral B12 administration was continued once a month. He remained asymptomatic and was functioning well at two years follow up.
Absence of prior psychiatric morbidity, presence of hyper pigmentation and low B12 levels suggested the diagnosis of organic psychosis secondary to cobalamin deficiency. In view of high prevalence of vitamin B12 deficiency in Indian population1, coexistence of B12 deficiency and psychosis is insufficient to establish a causal association. However, marked improvement of psychosis in this patient with short term anti psychotics and parenteral vitamin B12 therapy as well as maintenance treatment only with vitamin B12 supplementation further strengthened the possibility of such diagnosis. This demonstrates the possibility of psychiatric symptoms antedating anaemia and the importance of evaluating for underlying remediable causes in patients with new onset psychosis.
Serum B12 levels need not be very low to produce severe neuro psychiatric morbidity. This case provides an apt example for that. During deficiency, vitamin B12 levels in the neuronal tissues fall much earlier than that in the serum.6 Hence, even a normal serum B12 level does not rule out metabolic deficiency of vitamin B12. In such cases, bone marrow smear examination, neuro imaging, electro physiological studies and homocysteine and methylmalonic acid assays increase the specificity of the diagnosis of B12 deficiency. As we managed this patient in a psychiatric facility and had cost constraints, we did not employ such endeavours but confirmed our diagnosis with treatment response and follow up data with parenteral cobalamin supplementation.
Vitamin B12 and folate are essential for methylation of homocysteine to methionine and for synthesis of s-adenosyl methionine. S-adenosyl methionine is involved in the metabolism of proteins, phospholipids and neuro transmitters. A defect in methylation process is hypothesized to be the biochemical basis of neuropsychiatric manifestations of vitamin B12 deficiency.7 Hence, It is desirable to check for raised serum levels of homocysteine and methylmalonic acid to demonstrate whether the low serum B12 levels imply significant metabolic deficiency. B12 and folate also increase tetrahydrobiopterin synthesis in the brain, which is pivotal for the synthesis of monoamine neurotransmitters.2 B12 deficiency results in diffuse and focal areas of degeneration in the cerebral white matter with relatively little gliosis and grey matter changes. Methytetrahydrofolate, a potential excitatory neuro toxin, levels are markedly elevated in vitamin B12 deficiency and may be responsible for such neuronal destruction.8
Earlier surveys have shown that a large number of psychiatric patients have low serum B12 levels, ranging from 6-15%.9 They reveal the magnitude of this often overlooked nutritional deficiency, which directly causes, contributes or compounds the disease process. In developing countries, underlying B12 deficiency should be considered for all patients with new onset psychosis. As psychosis can precede anaemia and other physical findings, we suggest directly investigating serum B12 levels. If serum B12 levels are low, early cobalamin supplementation to prevent possible neuronal degeneration, and the option of maintenance therapy with once monthly intra muscular B12 injections should be considered. Though comorbidity of B12 deficiency in a psychotic patient is more frequent than the organic psychosis secondary to B12 deficiency, such early initiation of parenteral cobalamin supplementation may be beneficial for both clinical scenarios.
1. Yajnik CS, Deshpande SS, Lubree HG, Naik SS, Bhat DS, Uradey BS, et al. Vitamin B12 deficiency and hyperhomocysteinemia in rural and urban Indians. J Assoc Physicians India 2006;54:775-82.
2. Hutto BR. Folate and cobalamin in psychiatric illness. Compr Psychiatry 1997;38:305-14.
3. Masalha R, Chudakov B, Muhamad M, Rudoy I, Volkov I, Wirguin I. Cobalamin-responsive psychosis as the sole manifestation of vitamin B12 deficiency. Isr Med Assoc J 2001;3:701-3.
4. World Health Organization. The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Description and Diagnostic Guidelines. Geneva: WHO; 1992.
5. Overall JE, Gorham DR. The brief psychiatric rating scale. Psychol Rep 1962;10:799-812.
6. Aaron S, Kumar S, Vijayan J, Jacob J, Alexander M, Gnanamuthu C. Clinical and laboratory features and response to treatment in patients presenting with vitamin B12 deficiency related neurological syndromes. Neurol India 2005;53:55-8.
7. Bottiglieri T. Folate, vitamin B12, and neuropsychiatric disorders. Nutr Rev 1996;54:382-90.
8. Kumar S. Vitamin B12 deficiency presenting with an acute reversible extra pyramidal syndrome. Neurol India 2004;52:507-9.
9. Shulman R. A survey of vitamin B12 deficiency in an elderly psychiatric population. Br J Psychiatry 1967;113:241-51.