Relationship between serum NMDA receptor antibodies and response to antipsychotic treatment in first episode psychosis

Thomas Pollak; Angela Vincent; Conrad Iyegbe; Maria Ester Freitas Barbosa Pereira Coutinho; Leslie W Jacobson; D Rujescu; James Stone; Julie Jezequel; Véronique Rogemond; Stéphane Jamain; Laurent Groc; Anthony David; Alice Egerton; R S Kahn; Jérôme Honnorat; Paola Dazzan; M Leboyer; Philip McGuire

Relationship between serum NMDA receptor antibodies and response to antipsychotic treatment in first episode psychosis

Thomas Pollak, Angela Vincent, Conrad Iyegbe, Maria Ester Freitas Barbosa Pereira Coutinho, Leslie W Jacobson, D Rujescu, James Stone, Julie Jezequel, Véronique Rogemond, Stéphane Jamain, Laurent Groc, Anthony David, Alice Egerton, R S Kahn, Jérôme Honnorat, Paola Dazzan, M Leboyer, Philip McGuire

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Abstract

Background When psychosis develops in NMDAR antibody encephalitis it usually has an acute or subacute onset, and antipsychotic treatment may be ineffective and associated with adverse effects. Serum NMDAR antibodies have been reported in a minority of patients with first episode psychosis (FEP), but their role in psychosis onset and response to antipsychotic treatment is unclear. Methods Sera from 387 patients with FEP (duration of psychosis < 2 years, minimally or never treated with antipsychotics) undergoing initial treatment with amisulpride as part of the OPTiMiSE trial (ClinicalTrials.gov number NCT01248195) were tested for NMDAR IgG antibodies using a live cell-based assay (CBA). Symptom severity was assessed using the Positive and Negative Symptom Scale (PANSS) and the clinical global impression (CGI) at baseline and again after 4 weeks of treatment with amisulpride. Results At baseline, 15 patients were seropositive for NMDAR antibodies and 372 were seronegative. Seropositive patients had similar symptom profiles and demographic features to seronegative patients but a shorter duration of psychosis (median 1.5 versus 4.0 months; p=0.031). 11 seropositive and 284 seronegative patients completed 4 weeks of amisulpride treatment: following treatment, there was no between-groups difference in improvement in PANSS scores, nor in the frequency of adverse medication effects. Conclusions These data suggest that, in FEP, NMDAR antibody seropositivity alone is not an indication for using immunotherapy instead of antipsychotic medications. Further studies are required to establish what proportion of NMDAR antibody seropositive FEP patients have coexisting CSF inflammatory changes or other paraclinical evidence suggestive of likely benefit from immunotherapy.

Original language	English
Journal	Biological psychiatry
Publication status	Accepted/In press - 17 Nov 2020

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Pollak, T., Vincent, A., Iyegbe, C., Freitas Barbosa Pereira Coutinho, M. E., Jacobson, L. W., Rujescu, D., Stone, J., Jezequel, J., Rogemond, V., Jamain, S., Groc, L., David, A., Egerton, A., Kahn, R. S., Honnorat, J., Dazzan, P., Leboyer, M., & McGuire, P. (Accepted/In press). Relationship between serum NMDA receptor antibodies and response to antipsychotic treatment in first episode psychosis. Biological psychiatry.

@article{b433e380fb7c4861bb92ca5067d4bf32,

title = "Relationship between serum NMDA receptor antibodies and response to antipsychotic treatment in first episode psychosis",

abstract = "Background When psychosis develops in NMDAR antibody encephalitis it usually has an acute or subacute onset, and antipsychotic treatment may be ineffective and associated with adverse effects. Serum NMDAR antibodies have been reported in a minority of patients with first episode psychosis (FEP), but their role in psychosis onset and response to antipsychotic treatment is unclear. Methods Sera from 387 patients with FEP (duration of psychosis < 2 years, minimally or never treated with antipsychotics) undergoing initial treatment with amisulpride as part of the OPTiMiSE trial (ClinicalTrials.gov number NCT01248195) were tested for NMDAR IgG antibodies using a live cell-based assay (CBA). Symptom severity was assessed using the Positive and Negative Symptom Scale (PANSS) and the clinical global impression (CGI) at baseline and again after 4 weeks of treatment with amisulpride. Results At baseline, 15 patients were seropositive for NMDAR antibodies and 372 were seronegative. Seropositive patients had similar symptom profiles and demographic features to seronegative patients but a shorter duration of psychosis (median 1.5 versus 4.0 months; p=0.031). 11 seropositive and 284 seronegative patients completed 4 weeks of amisulpride treatment: following treatment, there was no between-groups difference in improvement in PANSS scores, nor in the frequency of adverse medication effects. Conclusions These data suggest that, in FEP, NMDAR antibody seropositivity alone is not an indication for using immunotherapy instead of antipsychotic medications. Further studies are required to establish what proportion of NMDAR antibody seropositive FEP patients have coexisting CSF inflammatory changes or other paraclinical evidence suggestive of likely benefit from immunotherapy. ",

author = "Thomas Pollak and Angela Vincent and Conrad Iyegbe and {Freitas Barbosa Pereira Coutinho}, {Maria Ester} and Jacobson, {Leslie W} and D Rujescu and James Stone and Julie Jezequel and V{\'e}ronique Rogemond and St{\'e}phane Jamain and Laurent Groc and Anthony David and Alice Egerton and Kahn, {R S} and J{\'e}r{\^o}me Honnorat and Paola Dazzan and M Leboyer and Philip McGuire",

year = "2020",

month = nov,

day = "17",

language = "English",

journal = "Biological psychiatry",

issn = "0006-3223",

publisher = "Elsevier",

}

Pollak, T, Vincent, A, Iyegbe, C , Freitas Barbosa Pereira Coutinho, ME, Jacobson, LW, Rujescu, D, Stone, J, Jezequel, J, Rogemond, V, Jamain, S, Groc, L, David, A , Egerton, A, Kahn, RS, Honnorat, J, Dazzan, P, Leboyer, M & McGuire, P 2020, 'Relationship between serum NMDA receptor antibodies and response to antipsychotic treatment in first episode psychosis', Biological psychiatry.

TY - JOUR

T1 - Relationship between serum NMDA receptor antibodies and response to antipsychotic treatment in first episode psychosis

AU - Pollak, Thomas

AU - Vincent, Angela

AU - Iyegbe, Conrad

AU - Freitas Barbosa Pereira Coutinho, Maria Ester

AU - Jacobson, Leslie W

AU - Rujescu, D

AU - Stone, James

AU - Jezequel, Julie

AU - Rogemond, Véronique

AU - Jamain, Stéphane

AU - Groc, Laurent

AU - David, Anthony

AU - Egerton, Alice

AU - Kahn, R S

AU - Honnorat, Jérôme

AU - Dazzan, Paola

AU - Leboyer, M

AU - McGuire, Philip

PY - 2020/11/17

Y1 - 2020/11/17

N2 - Background When psychosis develops in NMDAR antibody encephalitis it usually has an acute or subacute onset, and antipsychotic treatment may be ineffective and associated with adverse effects. Serum NMDAR antibodies have been reported in a minority of patients with first episode psychosis (FEP), but their role in psychosis onset and response to antipsychotic treatment is unclear. Methods Sera from 387 patients with FEP (duration of psychosis < 2 years, minimally or never treated with antipsychotics) undergoing initial treatment with amisulpride as part of the OPTiMiSE trial (ClinicalTrials.gov number NCT01248195) were tested for NMDAR IgG antibodies using a live cell-based assay (CBA). Symptom severity was assessed using the Positive and Negative Symptom Scale (PANSS) and the clinical global impression (CGI) at baseline and again after 4 weeks of treatment with amisulpride. Results At baseline, 15 patients were seropositive for NMDAR antibodies and 372 were seronegative. Seropositive patients had similar symptom profiles and demographic features to seronegative patients but a shorter duration of psychosis (median 1.5 versus 4.0 months; p=0.031). 11 seropositive and 284 seronegative patients completed 4 weeks of amisulpride treatment: following treatment, there was no between-groups difference in improvement in PANSS scores, nor in the frequency of adverse medication effects. Conclusions These data suggest that, in FEP, NMDAR antibody seropositivity alone is not an indication for using immunotherapy instead of antipsychotic medications. Further studies are required to establish what proportion of NMDAR antibody seropositive FEP patients have coexisting CSF inflammatory changes or other paraclinical evidence suggestive of likely benefit from immunotherapy.

AB - Background When psychosis develops in NMDAR antibody encephalitis it usually has an acute or subacute onset, and antipsychotic treatment may be ineffective and associated with adverse effects. Serum NMDAR antibodies have been reported in a minority of patients with first episode psychosis (FEP), but their role in psychosis onset and response to antipsychotic treatment is unclear. Methods Sera from 387 patients with FEP (duration of psychosis < 2 years, minimally or never treated with antipsychotics) undergoing initial treatment with amisulpride as part of the OPTiMiSE trial (ClinicalTrials.gov number NCT01248195) were tested for NMDAR IgG antibodies using a live cell-based assay (CBA). Symptom severity was assessed using the Positive and Negative Symptom Scale (PANSS) and the clinical global impression (CGI) at baseline and again after 4 weeks of treatment with amisulpride. Results At baseline, 15 patients were seropositive for NMDAR antibodies and 372 were seronegative. Seropositive patients had similar symptom profiles and demographic features to seronegative patients but a shorter duration of psychosis (median 1.5 versus 4.0 months; p=0.031). 11 seropositive and 284 seronegative patients completed 4 weeks of amisulpride treatment: following treatment, there was no between-groups difference in improvement in PANSS scores, nor in the frequency of adverse medication effects. Conclusions These data suggest that, in FEP, NMDAR antibody seropositivity alone is not an indication for using immunotherapy instead of antipsychotic medications. Further studies are required to establish what proportion of NMDAR antibody seropositive FEP patients have coexisting CSF inflammatory changes or other paraclinical evidence suggestive of likely benefit from immunotherapy.

M3 - Article

SN - 0006-3223

JO - Biological psychiatry

JF - Biological psychiatry

ER -

Relationship between serum NMDA receptor antibodies and response to antipsychotic treatment in first episode psychosis

Abstract

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