TY  - JOUR
A1  - Bien, Christian G.
A1  - Rohleder, Cathrin
A1  - Müller, Juliane K.
A1  - Bien, Corinna I.
A1  - Köthe, Dagmar
A1  - Leweke, F. Markus
T1  - Neural autoantibodies in cerebrospinal fluid and serum in clinical high risk for psychosis, first-episode psychosis, and healthy volunteers
T2  - Frontiers in psychiatry
N2  - The pathophysiological role of neural autoantibodies in acute psychotic disorders is receiving increased attention. However, there is still an ongoing debate, whether predominantly psychotic manifestations of autoimmune encephalitides exist that may remain undetected and, thus, untreated. Furthermore, it is discussed if such conditions can be diagnosed based on serum antibody results or if a reliable diagnosis requires additional cerebrospinal fluids (CSF) results. In this study, we screened pairs of serum and CSF samples from antipsychotic-naïve individuals with first-episode schizophrenic psychosis (FEP, n = 103), clinical high risk for psychosis (CHR, n = 47), and healthy volunteers (HV, n = 40) for eight different antibodies against various antigens that have been shown to be associated with autoimmune encephalitides: N-methyl-D-aspartate receptor (NMDAR, NR1 subunits only), glutamic acid decarboxylase (GAD65), leucine-rich glioma inactivated protein 1 (LGI1), contactin-associated protein-like 2 protein (CASPR2), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit 1, AMPAR subunit 2, γ-aminobutyric acid-B receptors (GABABR), and glycine receptors. All patients were within the norm with regards to a careful neurological examination, a magnetic resonance imaging (MRI) of the brain, an electroencephalogram (EEG), and routine blood pathology. All CSF samples were autoantibody-negative. In three serum samples of individuals with FEP, we detected low-titer CASPR2 immunoglobulin (Ig) G antibodies (≤1:160, n = 2) and non-IgG antibodies against NMDAR (n = 1) (overall serum-autoantibody prevalence in FEP: 2.91%). However, the IgG titers were below the laboratory cut-off defined for positivity, and non-IgG antibodies are of no clinical relevance. This suggests that there were no cases of autoimmune encephalitis in our cohort. Our results highlight the importance and the high specificity of CSF analysis to reliably detect autoantibodies. They confirm the hypothesis that pure psychotic manifestations of antibody-associated autoimmune encephalitides without any additional neuropsychiatric findings are very rare. However, special attention must be paid to those presenting with atypical mental illnesses with additional neurological symptoms, evidence of clinically-significant cognitive involvement, profound sleep-wake perturbations, seizures, electroencephalographic, or magnetic resonance imaging pathologies to be able to identify cases with autoimmune-mediated psychiatric syndromes.
KW  - autoimmune-mediated psychosis
KW  - autoimmune encephalitis
KW  - anti-neural autoantibodies
KW  - at-risk mental state
KW  - clinical high at-risk mental state
KW  - ultra-high risk for psychosis
KW  - schizophrenia
KW  - healthy control
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62015
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-620153
SN  - 1664-0640
N1  - This study was supported by grants from the Stanley Medical Research Institute (FML), the Koeln Fortune Program (FML), and intramural funds from the Central Institute of Mental Health (FML). The funding sources had no influence on the design of the study or the analysis and interpretation of the results.
VL  - 12
IS  - art. 654602
SP  - 1
EP  - 7
PB  - Frontiers Research Foundation
CY  - Lausanne
ER  -