Spectrum of Novel Anti-Central Nervous System Autoantibodies in the Cerebrospinal Fluid of 119 Patients With Schizophreniform and Affective Disorders.

BACKGROUND: Autoimmune psychosis may be caused by well-characterized anti-neuronal autoantibodies, such as those against the NMDA receptor. However, the presence of additional anti-central nervous system (CNS) autoantibodies in these patients has not been systematically assessed. METHODS: Serum and cerebrospinal fluid (CSF) from patients with schizophreniform and affective syndromes were analyzed for immunoglobulin G anti-CNS autoantibodies using tissue-based assays with indirect immunofluorescence on unfixed murine brain tissue as part of an extended routine clinical practice. After an initial assessment of patients with red flags for autoimmune psychosis (n = 30), tissue-based testing was extended to a routine procedure (n = 89). RESULTS: Based on the findings from all 119 patients, anti-CNS immunoglobulin G autoantibodies against brain tissue were detected in 18% (n = 22) of patients (serum 9%, CSF 18%) following five principal patterns: 1) against vascular structures, most likely endothelial cells (serum 3%, CSF 8%); 2) against granule cells in the cerebellum and/or hippocampus (serum 4%, CSF 6%); 3) against myelinated fibers (serum 2%, CSF 2%); 4) against cerebellar Purkinje cells (serum 0%, CSF 2%); and 5) against astrocytes (serum 1%, CSF 1%). The patients with novel anti-CNS autoantibodies showed increased albumin quotients (p = .026) and white matter changes (p = .020) more frequently than those who tested negative for autoantibodies. CONCLUSIONS: The study demonstrates five novel autoantibody-binding patterns on brain tissue of patients with schizophreniform and affective syndromes. CSF yielded positive findings more frequently than serum analysis. The frequency and spectrum of autoantibodies in these patient groups may be broader than previously thought.

Event-related potentials in insomnia reflect altered perception of sleep.

STUDY OBJECTIVES: Insomnia is defined by the subjective complaint of poor sleep as well as daytime impairments. Since polysomnography (PSG) typically shows only modest sleep impairment, some still unidentified property of sleep, not mirrored in PSG, may be modified in insomnia.One possible mechanistic hypothesis is that insomnia patients may be more sensitive to inevitably occurring internal or external stimuli during the night, causing brief sleep disruptions then perceived as wake time. METHODS: Auditory event-related potentials (ERP) to low intensity (50 dB SPL) synthesized guitar tones played continuously throughout two nights of polysomnographically registered sleep were obtained in fifty patients with insomnia disorder (ID, without comorbidities) and 50 age- and sex-matched good sleeper controls (GSC) for each sleep stage and NREM/REM cycle. Phasic and tonic REM were treated as separate stages. Latencies and amplitudes of components P1, N1 and P2 were measured and analyzed by multivariate repeated-measures ANCOVA including effects of group, night, cycle, and age. RESULTS: ID showed reduced P2 amplitudes relative to GSC specifically in phasic REM sleep. The same reduction also correlated with the amount of sleep misperception across groups. Independent component analysis showed a frontal negativity to contribute most to this group difference. CONCLUSIONS: The present finding can be interpreted as increased mismatch negativity (MMN) in ID, reflecting automated detection of change in the auditory system and a concomitant orienting response. Specifically phasic REM sleep appears to be vulnerable to sensory afferences in ID patients, possibly contributing to the perception of being awake. CLINICAL TRIAL INFORMATION: Short name "PERSLEEP 2," URL https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00008965, Registration DRKS00008965.