Vitamin B12 deficiency

Page most recently updated 7 September 2026

This page focuses on the reported psychiatric associations, which may be the initial presenting manifestation, and on other clinical features that may assist the psychiatrist or primary care physician in identifying the underlying diagnosis, considered through the lenses of the diagnostic lenses framework.

Vitamin B12 deficiency is a clinically heterogeneous nutritional and metabolic disorder with neuropsychiatric, hematological, and gastrointestinal manifestations.

It can present with psychiatric features such as irritability, personality or behavioural change, apathy, depression, impaired concentration, memory impairment, and other cognitive changes. Less commonly, psychotic symptoms may occur as prominent or initial manifestations of B12 deficiency.

Other characteristic features include peripheral sensorimotor neuropathy, paraesthesia, impaired vibration and proprioception, gait disturbance, and subacute combined degeneration of the spinal cord, which may produce sensory ataxia, spasticity and weakness. Optic neuropathy and cognitive impairment may also occur. Respiratory symptoms such as dyspnoea and tachypnoea may occur, particularly in the setting of significant anaemia. Neurological manifestations can precede haematological abnormalities and may become irreversible if treatment is delayed.

From a multisystemic lens perspective, clinical features in other body systems include (but are not limited to):

  • Cardiovascular: Tachycardia and palpitations, particularly in the setting of significant anaemia; thromboembolic or ischaemic cardiovascular disease may also occur, potentially related to hyperhomocysteinaemia.

  • Hematologic: Megaloblastic anaemia, macrocytosis, hypersegmented neutrophils and, in more severe deficiency, pancytopenia. Importantly, neurological or psychiatric manifestations may occur without anaemia or macrocytosis.

  • Gastrointestinal: Anorexia, weight loss, glossitis, stomatitis and, less commonly, diarrhoea or other gastrointestinal symptoms.

  • Dermatologic: Hyperpigmentation, particularly affecting the hands, feet, palmar creases or flexures, as well as hair and nail changes; oral mucosal pigmentation and glossitis may also occur.

Early diagnosis is important because prompt vitamin B12 replacement can prevent progression to potentially irreversible neurological injury, particularly subacute combined degeneration and peripheral neuropathy, and may reverse neuropsychiatric manifestations. Because psychiatric and neurological manifestations can precede or occur without the typical haematological abnormalities, a high index of suspicion is important, particularly in people with risk factors such as pernicious anaemia or autoimmune gastritis, malabsorption, restrictive dietary intake, gastrointestinal surgery, older age, or medications that impair B12 absorption such as metformin and proton-pump inhibitors.

Selected references and further reading — Multisystemic lens

Cardinal RN, Bullmore ET. The diagnosis of psychosis. Cambridge: Cambridge University Press; 2011.

Sachdev PS, Keshavan MS, editors. Secondary schizophrenia. Cambridge: Cambridge University Press; 2010.

Levenson JL, editor. The American Psychiatric Association Publishing textbook of psychosomatic medicine and consultation-liaison psychiatry. 3rd ed. Washington (DC): American Psychiatric Association Publishing; 2019.

Stern TA, Beach SR, Smith FA, Freudenreich O, Vranceau AM, Fava M, editors. Massachusetts General Hospital handbook of general hospital psychiatry. 8th ed. Philadelphia: Elsevier; 2025.

Arciniegas DB, Yudofsky SC, Hales RE, editors. The American Psychiatric Association Publishing textbook of neuropsychiatry and clinical neurosciences. 6th ed. Washington (DC): American Psychiatric Association Publishing; 2018.

Agrawal N, Faruqui R, Bodani M, editors. Oxford textbook of neuropsychiatry. Oxford: Oxford University Press; 2020.

Boland R, Verduin M, editors. Kaplan and Sadock's comprehensive textbook of psychiatry. 11th ed. Philadelphia: Wolters Kluwer; 2024.

Loscalzo J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, editors. Harrison's principles of internal medicine. 22nd ed. New York: McGraw Hill; 2025.