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@ARTICLE{AlDiwani:282905,
author = {Al-Diwani, Adam and Theorell, Jakob and Zghoul, Tarek and
Voruganti, Aniruddha and Townsend, Leigh and De Giorgi,
Riccardo and Griffin, Benjamin and Bajorek, Tomasz and Okai,
David and Lennox, Belinda and Leite, M Isabel and Kim, Carla
Y and Coughlin, Arielle and Martin, Kelsey and Glassberg,
Brittany and Lachner, Christian and Westerbeek, Nicola and
Bergink, Veerle and Thakur, Kiran T and Yeshokumar, Anusha K
and Prüss, Harald and Day, Gregory S and Finke, Carsten and
Handel, Adam E and Manohar, Sanjay G and Joyce, Dan W and
Irani, Sarosh R},
title = {{T}he distinctive psychopathology of {NMDAR}-antibody
encephalitis compared with primary psychoses: an
international, multicentre, retrospective phenotypic
analysis.},
journal = {The lancet / Psychiatry},
volume = {13},
number = {1},
issn = {2215-0366},
address = {Philadelphia, Pa.},
publisher = {Elsevier},
reportid = {DZNE-2025-01366},
pages = {47 - 61},
year = {2026},
abstract = {N-methyl-D-aspartate receptor (NMDAR)-antibody encephalitis
is a life-threatening neuropsychiatric disorder requiring
prompt immunotherapy. The earliest features are mental-state
changes, often mistaken for primary psychosis. Improved
clinical differentiation could assist rational diagnostic
investigation and expedite immunotherapy. Inspired by
patients' and relatives' lived experience, we aimed to
explore the psychiatric phenotype of NMDAR-antibody
encephalitis and the features common to and distinct from
real-world episodes of psychosis.In this international,
multicentre, retrospective phenotypic analysis we collected
data on episodes of NMDAR-antibody encephalitis from
specialised neurology services in Europe (UK, Germany, and
Sweden) and the USA. For comparison, we collected similar
data from de-identified accepted referrals to a UK early
intervention in psychosis service, including consecutively
presenting cases (unselected psychosis) and a group defined
by having been assessed and admitted to hospital under the
Mental Health Act (selected psychosis). Additionally, we
included episodes of postpartum psychosis from a mother and
baby unit in the Netherlands. In our mental-state inventory
we included core features from ICD-11, the Bush-Francis
catatonia score, and the Neuropsychiatric Inventory
encompassing anxiety, depression, mania, schizophrenia,
catatonia, and also more granular transdiagnostic
behavioural features including those common to
neuropsychiatric and neurobehavioural syndromes, such as
delirium and dementia. Ethnicity data were not available. We
compared and visualised the neuropsychiatric phenotype of
these cohorts.We collected data from 100 episodes of
NMDAR-antibody encephalitis from 96 patients between 2010
and 2022 (median age 22 years, female:male ratio 3·80), 135
episodes of psychosis from 135 patients between 2018 and
2019 (median age 27 years, female:male ratio 0·75), and ten
episodes of postpartum psychosis from ten patients between
2005 and 2012 (median age 30 years, all female sex).
Psychopathology in NMDAR-antibody encephalitis was abundant
(92 $[92\%]$ of 100 episodes) and ultra-rapid in onset
(median 1 day $[95\%$ CI 1-1; IQR 1-7]) versus unselected
primary psychoses (median 180 days [120-210; 91-365];
p<0·0001). 21 $(36\%)$ of 58 mental-state features,
including catatonic and visual hallucinations, were
over-represented in NMDAR-antibody encephalitis and 12
$(21\%)$ were under-represented, including features typical
of affective (eg, elated mood, flight of ideas, grandiose
delusions) and non-affective psychoses (eg, thought
broadcasting, thought withdrawal, paranoid delusions; false
discovery rate threshold <0·05). Typically, in
NMDAR-antibody encephalitis, the complexity sequentially
evolved from mood to psychotic to catatonic predominance
within 2 weeks.NMDAR-antibody encephalitis has a
rapid-onset, complex, and dynamic neuropsychiatric
phenotype, sufficiently distinctive to drive a clinical
approach to differentiation.UK NIHR, Wellcome, and UK
Medical Research Council (MRC)/UK Research and Innovation.},
keywords = {Humans / Psychotic Disorders: diagnosis / Psychotic
Disorders: psychology / Anti-N-Methyl-D-Aspartate Receptor
Encephalitis: psychology / Anti-N-Methyl-D-Aspartate
Receptor Encephalitis: diagnosis / Female / Retrospective
Studies / Male / Adult / Phenotype / Young Adult / Middle
Aged / Europe / Adolescent},
cin = {AG Prüß},
ddc = {610},
cid = {I:(DE-2719)1810003},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41386901},
doi = {10.1016/S2215-0366(25)00305-0},
url = {https://pub.dzne.de/record/282905},
}