A Short Checklist for Deciding Who Gets an Antibody Test in Psychosis
- In 754 people with psychosis at mental health services in Australia (352 early psychosis, 402 persistent psychosis), antineuronal antibodies were found in serum in 17 (2.3%): 12 of 352 (3.4%) with early and 5 of 402 (1.2%) with persistent psychosis.
- Clinicians rated each person as high or low risk before testing. Seropositivity was 8 of 122 (6.6%) in high-risk early psychosis, 4 of 230 (1.7%) in low-risk early, 4 of 290 (1.4%) in high-risk persistent and 1 of 112 (0.9%) in low-risk persistent psychosis.
- Autoimmune psychosis was confirmed in 2 of 754 (0.3%), one in each group. Both were rated high risk, both had NMDA receptor antibodies in cerebrospinal fluid, and both improved on immunotherapy. No seropositive person with negative or untested cerebrospinal fluid received immunotherapy.
- The criteria are not diagnostic. With only two confirmed cases the authors could not validate them statistically, and 8 seropositive people did not consent to follow-up, so their outcomes are unknown.
A positive antibody result is easier to order than to interpret. This Australian study proposed a short list of clinical features for deciding who should be tested for antineuronal antibodies, then followed what happened to those who came back positive.
Who counts as high risk
Clinicians at 14 services in three states rated each patient aged 14 to 60 before the blood draw. In early psychosis, high risk meant onset of the first episode in under a month plus at least one of six features: new neurological signs, severe new cognitive or language impairment, catatonia or intermittent agitation, unusual sensitivity to extrapyramidal side effects, illness severe enough to need ECT, or a fluctuating, delirium-like state. In persistent psychosis any one of six was enough: symptoms refractory to antipsychotics from onset, past neurological signs unrelated to medication, persistent severe cognitive or language impairment, past catatonia, past unusual sensitivity to extrapyramidal side effects, or past ECT. Of 754 people, 17 were seropositive. Two had autoimmune psychosis confirmed by a multidisciplinary panel. The other seropositive people were found in every risk group, and four with early psychosis were in remission at 12 months on standard psychiatric care.
Telling a client about a positive result
The authors write that most seropositive results are likely false positives for an immune-mediated illness, and that a serum result neither confirms nor excludes the diagnosis. That shapes the conversation. I would tell the client what the laboratory found, that it is one piece of a larger picture, and that a neurologist, and if needed a spinal fluid test, decides what it means. Avoid "you have an autoimmune illness" and avoid "this is nothing". Keep treating the psychosis meanwhile, and write down which listed features the person has, because the neurology referral rests on that list.
A positive antibody result is a reason to ask more questions, not an answer to give the client.
The authors could not statistically validate the criteria because far fewer cases were confirmed than expected, and recruitment fell short of its target of 1200 during the COVID-19 pandemic. Blood tests were declined or not possible for 15% of the original sample, more often in persistent psychosis, and lumbar puncture was not feasible for every seropositive person, so some cases may have gone undiagnosed.