Anti-GAD65 encephalitis

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.

Anti-GAD65 encephalitis is an autoimmune encephalitis with multisystemic involvement.

It can present with psychiatric features such as anxiety, mood symptoms, behavioural change, confusion, agitation, sleep disturbance, hallucinations, and psychosis, particularly in the context of limbic encephalitis or seizure-related presentations.

Other characteristic features include limbic encephalitis with seizures (which may be frequent or refractory), memory impairment, cognitive decline, and encephalopathy. Other neurological phenotypes associated with GAD65 autoimmunity include stiff-person spectrum disorder with progressive muscle stiffness, painful spasms, and stimulus-triggered spasms, as well as cerebellar ataxia in some cases.

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

  • Endocrine: association with autoimmune endocrine disorders, particularly type 1 diabetes mellitus; less commonly, autoimmune polyglandular clustering may occur.

  • Musculoskeletal: muscle stiffness and painful spasms may occur in stiff-person spectrum presentations.

Early diagnosis is important to enable prompt immunotherapy, identify and manage associated autoimmune conditions, reduce the risk of persistent seizures, progressive neurological disability, and functional decline, and improve prognosis and quality of life.

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.