Prevalence of anti-NMDA receptor antibodies among adult Chinese patients presenting with first-episode psychosis in Hong Kong

Prevalence of anti-NMDA receptor antibodies among adult Chinese patients presenting with first-episode psychosis in Hong Kong | medRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-P4HH5NV'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Prevalence of anti-NMDA receptor antibodies among adult Chinese patients presenting with first-episode psychosis in Hong Kong View ORCID Profile Steven WH Chau , Charis KW Lam , Matthew PM Yu , Joseph CH Choi , Howan HW Leung doi: https://doi.org/10.1101/2025.10.09.25337289 Steven WH Chau 1 Department of Psychiatry, The Chinese University of Hong Kong , Hong Kong Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Steven WH Chau For correspondence: stevenwaihochau{at}cuhk.edu.hk Charis KW Lam 2 Department of Psychiatry, Prince of Wales Hospital , Hong Kong Find this author on Google Scholar Find this author on PubMed Search for this author on this site Matthew PM Yu 3 Faculty of Medicine, The Chinese University of Hong Kong , Hong Kong Find this author on Google Scholar Find this author on PubMed Search for this author on this site Joseph CH Choi 4 Division of Neurology, Department of Medicine and Therapeutics, Prince of Wales Hospital , Hong Kong Find this author on Google Scholar Find this author on PubMed Search for this author on this site Howan HW Leung 4 Division of Neurology, Department of Medicine and Therapeutics, Prince of Wales Hospital , Hong Kong Find this author on Google Scholar Find this author on PubMed Search for this author on this site Abstract Full Text Info/History Metrics Data/Code Preview PDF Abstract Background Studies on the presence of anti-NMDA receptor antibodies were done primarily on the European population. In addition, most of the existing studies did not collect samples during the acute phase of the psychosis. The prevalence of anti-NMDA receptor antibodies among the Asian population presenting with first-onset psychosis in an acute medical setting is under-investigated. Method We retrospectively recruited patients assessed by the consultation-liaison psychiatry team at an acute teaching hospital in Hong Kong, for first-onset psychosis who were unmedicated at the accident and emergency department or the acute medical wards from January 2015 to March 2025. Patients aged 65 were excluded. The presence of anti-NMDA receptor antibodies was tested by cell-based indirect immunofluorescence assay (EUROIMMUN) on serum and/or cerebrospinal fluid samples. Results We consecutively recruited 389 eligible patients. Among this population, 109 were tested for anti-NMDA receptor antibodies (Mean age = 36.0 years; 29.7% female; 97% ethnic Chinese, 82.6% diagnosed with primary psychotic disorders with no medical explanation). Cerebrospinal fluid (CSF) samples were taken from 60 of them. Among the tested patients, 2 (1.8%) were found to be positive for anti-NMDA autoantibodies (age 20s-30s; 1 female). The antibodies were detectable in both blood and CSF samples. Both of the patients exhibited the classic features of autoimmune encephalitis with marked CSF pleocytosis. Conclusion The prevalence of anti-NMDA receptor autoantibodies among our population presenting with first-episode psychosis is low, especially among patients with primary psychotic disorders. This prevalence is lower than that reported by studies mainly done among European-predominant populations. The prevalence of many known autoimmune diseases is known to vary among ethnic groups, and further studies are needed to explore the differences in anti-NMDA receptor positivity among these groups. Background Anti-NMDA receptor antibodies are the most common type of anti-neuronal antibodies. Since its description in 2007 1 , the phenomenon of anti-NMDA receptor autoimmune encephalitis has been well described. The fact that this condition can present as acute psychosis means that this is an uncommon but important differential diagnosis for patients presenting with first-episode psychosis. Recent research has expanded the enquiry into the presence of antineuronal autoantibodies in patients presenting with psychosis but without encephalitis. Studies from the past decade report the prevalence of anti-NMDA receptor antibodies among patients with primary (or so-called ‘functional’) psychotic disorders to be around 1-4%, with considerable variability among the studies 2 – 4 . The role of anti-NMDA receptor antibodies and other antineuronal autoantibodies in the pathophysiology of psychiatric disorders in these patients remains debated. However, the studies cited above were primarily conducted on the European population, and data from Asian populations are underrepresented. The epidemiology of autoimmune phenomena is known to be varied among ethnic groups. For example, multiple sclerosis is more common in the White population compared to the Asian population, while the reverse is true for systemic lupus erythematosus 5 , 6 . In addition, most of the existing studies did not collect samples during the acute phase of psychosis. For example, the only available study examining the prevalence of anti-NMDA receptor antibodies among Chinese with first-episode psychosis was done in the setting of a specialist outpatient for early psychosis in Hong Kong 7 , which would have excluded patients with a diagnosis of autoimmune encephalitis. The primary objective of the current study is to investigate the prevalence of anti-NMDA antibodies among Chinese adult patients presenting with unmedicated first-onset psychosis in an acute medical setting. The secondary objective is to explore the presentation of patients with psychosis and anti-NMDA receptor antibodies. Method This is a retrospective cross-sectional study. We reviewed all the cases being assessed by the consultation liaison psychiatry team at the Accident and Emergency Department or inpatient departments of is a major tertiary hospital of Hong Kong serving a catchment area of a population of 700 thousand people, for first-onset psychosis from January 2015 to March 2025. The inclusion criteria are: 1. Age 18-65 years old at the time of presentation; 2. Presenting with first-onset psychosis, regardless of etiologies; 3. Received test(s) for the presence of anti-NMDA receptor antibodies in serum or cerebrospinal fluid sample. The presence of anti-NMDA receptor antibodies was tested by cell-based indirect immunofluorescence assay (EUROIMMUN) in a certified laboratory of another teaching hospital. The study was approved by the Joint CUHK-NTEC CREC (ref no.: 2024.606). Result Among the 426 patients assessed for suspected first-onset psychosis over the recruitment period, 389 were confirmed to have first-onset psychotic symptoms. 109 of them were tested for anti-NMDA receptor antibodies (Mean age = 36.0 years; 71.6% female; 96% ethnic Chinese). The selection of patients for antibody testing was based on clinical suspicion; therefore, the patients tested had significantly different demographic and clinical characteristics, such as age, acuteness, presence of fever, and catatonia. (See Table 1 ). Cerebrospinal fluid (CSF) samples were tested in 60 of them. The comparison of the demographic and clinical characteristics of the patients of first-onset psychosis with and without anti-NMDA receptor autoantibodies testing is shown in Table 1 . Among the tested patients, 35 (32%) were diagnosed with non-specific psychosis, 21 (19%) were diagnosed with schizophrenia, 15 (14%) were diagnosed with acute and transient psychotic disorder, 10 (9%) were diagnosed with mood disorder with psychotic symptoms and 19 (17%) patients were diagnosed with psychosis secondary to substance use or other medical conditions. Two of the patients (1.8%) were found to be positive for anti-NMDA receptor antibodies (ages 20s to 30s; 1 female, both are Chinese). The antibodies were detectable from both blood and CSF samples in both patients, and they both exhibited the classic clinical features of autoimmune encephalitis with marked CSF pleocytosis: The first patient presented with abrupt-onset insomnia, cognitive impairment, and auditory and visual hallucinations within a week. The patient subsequently developed orofacial dyskinesia and seizures in the following two weeks. While the MRI of the brain with contrast did not reveal encephalitic changes, the CSF analysis showed marked pleocytosis without evidence of infection. The second patient presented with an acute onset of cognitive impairment, agitation, and insomnia for two weeks, followed by the onset of auditory hallucination two days before hospitalization. CSF analysis of the patient showed marked pleocytosis without evidence of infection. The MRI brain scan showed an abnormal T2W signal over the left temporal lobe, suggestive of encephalitis, which resolved after treatment. In both patients, extensive work-ups, including full-body PET-CT scans, did not reveal any malignancy. Both patients’ neuropsychiatric symptoms responded to aggressive immunotherapy. View this table: View inline View popup Download powerpoint Table 1. Comparison of demographical and clinical characteristics between patients with first-episode psychosis tested for anti-NMDA receptor antibodies and those untested. Discussion To the best of our knowledge, this is the first study investigating the prevalence of anti-NMDA receptor antibodies among patients presenting with first-episode psychosis in an acute medical setting in a predominantly Chinese population. Our results suggest that the prevalence of anti-NMDA receptor antibodies among patients with first-onset psychosis is low among our cohort. Particularly, we do not find any antibody-positive case among patients suffering from primary psychotic disorders. A previous study on the prevalence of anti-NMDA receptor antibodies among patients with psychotic disorders in an outpatient setting in Hong Kong Chinese also yielded a low prevalence of 1.5% 7 . The prevalence reported in the literature, predominantly based on the Western population, has been highly variable. This variability can be partly attributed to diverse sampling contexts among the studies. The different kinds of assay used by the study could also explain part of the variability, as live cell-based assay is shown to be more sensitive than fixed cell assay, especially for serum test 8 . However, whether ethnic disparity plays a part in the variability is under-investigated. A recent multi-center study from Europe, which reported the prevalence of anti-NMDA receptor antibodies in their cohort by ethnicity, showed marked variations in prevalence among the ethnic groups 9 . Thus, we hypothesize that there is a potential ethnic disparity in the prevalence of anti-NMDA receptor antibodies among patients with psychosis, and further studies are needed to test this hypothesis. The limitations of the current study include the small sample size and its single-center design. While the study samples were consecutively recruited, the selection of patients undergoing the test for anti-NMDA receptor antibodies is biased by clinical suspicion. However, such bias is more likely to result in an overestimation of the prevalence. The age-related inclusion criteria, which are a restriction due to the scope of our team’s service, mean that potentially some cases of young-onset psychosis or encephalitis are missed from the study. Data Availability All data produced in the present study are available upon reasonable request to the authors References 1. ↵ Dalmau J , Gleichman AJ , Hughes EG , et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies . Lancet Neurol . 2008 ; 7 ( 12 ): 1091 – 1098 . doi: 10.1016/S1474-4422(08)70224-2 OpenUrl CrossRef PubMed Web of Science 2. ↵ Pollak TA , McCormack R , Peakman M , Nicholson TR , David AS . Prevalence of anti-N-methyl-d-aspartate (NMDA) receptor antibodies in patients with schizophrenia and related psychoses: a systematic review and meta-analysis . Psychological Medicine . 2014 ; 44 ( 12 ): 2475 – 2487 . doi: 10.1017/S003329171300295X OpenUrl CrossRef PubMed 3. Lennox BR , Palmer-Cooper EC , Pollak T , et al. Prevalence and clinical characteristics of serum neuronal cell surface antibodies in first-episode psychosis: a case-control study . Lancet Psychiatry . 2017 ; 4 ( 1 ): 42 – 48 . doi: 10.1016/S2215-0366(16)30375-3 OpenUrl CrossRef PubMed 4. ↵ Ariño H , Coutinho E , Pollak TA , Stewart R. Real-world experience of assessing antibodies against the N-methyl-D-aspartate receptor (NMDAR-IgG) in psychiatric patients. A retrospective single-centre study . Brain, Behavior, and Immunity . 2021 ; 98 : 330 – 336 . doi: 10.1016/j.bbi.2021.08.233 OpenUrl CrossRef PubMed 5. ↵ Lewis MJ , Jawad AS . The effect of ethnicity and genetic ancestry on the epidemiology, clinical features and outcome of systemic lupus erythematosus . Rheumatology (Oxford) . 2017 ; 56 ( Suppl_1 ): i67 – i77 . doi: 10.1093/rheumatology/kew399 OpenUrl CrossRef PubMed 6. ↵ Langer-Gould A , Brara SM , Beaber BE , Zhang JL . Incidence of multiple sclerosis in multiple racial and ethnic groups . Neurology . 2013 ; 80 ( 19 ): 1734 – 1739 . doi: 10.1212/WNL.0b013e3182918cc2 OpenUrl CrossRef PubMed 7. ↵ Chong C , Lo W , Mak C , Chen S , Lau K , Sheng B. Prevalence of neuronal membrane target antibodies in first-episode psychosis: abridged secondary publication . 8. ↵ Thouin A , Gastaldi M , Woodhall M , Jacobson L , Vincent A. Comparison of N-methyl-d-aspartate receptor antibody assays using live or fixed substrates . J Neurol . 2021 ; 268 ( 5 ): 1818 – 1826 . doi: 10.1007/s00415-020-10329-0 OpenUrl CrossRef PubMed 9. ↵ Luykx JJ , Visscher R , Winter-van Rossum I , et al. Clinical symptoms and psychosocial functioning in patients with schizophrenia spectrum disorders testing seropositive for anti-NMDAR antibodies: a case–control comparison with patients testing negative . The Lancet Psychiatry . 2024 ; 11 ( 10 ): 828 – 838 . doi: 10.1016/S2215-0366(24)00249-9 OpenUrl CrossRef PubMed 10. Luykx JJ , Visscher R , Rossum IW van , et al. Clinical symptoms and psychosocial functioning in patients with schizophrenia spectrum disorders testing seropositive for anti-NMDAR antibodies: a case–control comparison with patients testing negative . The Lancet Psychiatry . 2024 ; 11 ( 10 ): 828 – 838 . doi: 10.1016/S2215-0366(24)00249-9 OpenUrl CrossRef PubMed View the discussion thread. Back to top Previous Next Posted October 13, 2025. Download PDF Data/Code Email Thank you for your interest in spreading the word about medRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Prevalence of anti-NMDA receptor antibodies among adult Chinese patients presenting with first-episode psychosis in Hong Kong Message Subject (Your Name) has forwarded a page to you from medRxiv Message Body (Your Name) thought you would like to see this page from the medRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. 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