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Clinical, Neuroimmunologic, and CSF Investigations in First Episode Psychosis
Mar Guasp1, Eloi Giné-Servén1, Estibaliz Maudes1
1From the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (M.G., E.M., E.M.-H., M.B., Y.M.-O., G.S., I.P, L.S., A.S., F.G., J.C.-F., E.P., J.D.), Hospital Clínic, and Department of Medicine (M.B., A.S., J.C.-F., E.P.), Universitat de Barcelona; Neurology Department (M.G., E.M.-H., A.S., J.D.), Department of Child and Adolescent Psychiatry and Psychology (M.R.-J., G.S., J.C.-F.), Barcelona Clínic Schizophrenia Unit (BCSU) (M.B., E.P.), and Bipolar and Depressive Disorders Unit (I.P.), Institute of Neuroscience, Hospital Clínic; Centro de Investigación Biomédica en Red (M.G., E.M.-H., L.S., J.D.), Enfermedades Raras (CIBERER); Psychiatry Department (E.G.-S., E.B.-Q., E.D.-L.), Hospital de Mataró Consorci Sanitari del Maresme, Mataró; Centro de Investigación Biomédica en Red (M.B., G.S., I.P., J.C.-F., E.P.), Salud Mental (CIBERSAM); Neurology Department (V.C., N.G., D.M., C.T.-R.), Hospital de Mataró Consorci Sanitari del Maresme; Medical Statistics Core Facility (J.R.), IDIBAPS and Hospital Clínic, Barcelona, Spain; Department of Neurology (J.D.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Catalan Institute for Research and Advanced Studies (ICREA) (J.D.), Barcelona, Spain.
Objectives:
To report the neuropsychiatric features and frequency of NMDA receptor (NMDAR) and other neuronal immunoglobulin G antibodies in patients with first episode psychosis (FEP) and to assess the performance of reported warning signs and criteria for autoimmune psychosis (AP).
Methods:
This was a prospective observational study of patients with FEP assessed for neuropsychiatric symptoms, serum and CSF neuronal antibodies (brain immunohistochemistry, cell-based assays, live neurons), and warning signs and criteria of AP. Previous autoimmune FEP series were reviewed.
Results:
One hundred five patients were included; their median age was 30 (range 14-75) years, and 44 (42%) were female. None had neuronal antibodies. Two of 105 (2%) had CSF pleocytosis, 4 of 100 (4%) had brain MRI abnormalities, and 3 of 73 (4%) EEG alterations. Thirty-four (32%) and 39 (37%) patients fulfilled 2 sets of warning signs of AP, and 21 (20%) fulfilled criteria of possible or probable AP, yet none developed AP. The cause of FEP was psychiatric in 101 (96%) and nonpsychiatric in 4 (4%). During this study, 3 patients with psychosis caused by anti-NMDAR encephalitis were transferred to our center; 2 did not meet criteria for possible AP. Of 1,159 reported patients with FEP, only 7 (1%) had CSF studies; 36 (3%) had serum NMDAR antibodies (without definite diagnosis of AP), and 4 had CSF NMDAR antibodies (3 classic anti-NMDAR encephalitis and 1 with isolated psychiatric features).
Conclusions:
NMDAR antibodies were not found in patients with FEP unless they had anti-NMDAR encephalitis. Warning signs and criteria for AP have limited utility when neurologic symptoms are absent or paraclinical tests are normal. A diagnostic algorithm for autoimmune FEP is provided.
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