Abstract
BackgroundAutoantibodies to the N-methyl-D-aspartate receptor (NMDAR-Abs) in autoimmune encephalitis have been associated with prominent psychiatric symptoms. The aims of the present study are to identify the prevalence of NMDAR-Abs in adolescents with early onset psychosis disorders (EOP) and healthy controls (HC) and examine its clinical significance.MethodPlasma samples were acquired from 46 adolescent EOP patients and 69 age- and sex matched HC, and assessed for the presence of immunoglobulin G NMDAR-Abs. All participants underwent psychiatric evaluation, neurological examination and head magnetic resonance imaging.ResultsNMDAR-Abs were detected in three of 46 (6.5%) EOP patients and in two of 69 (2.9%) HC. One NMDAR-Abs EOP patient presented with unusual psychopathology and minor T1 weighted lesions of vasculopathological origin located bi-frontally and in the basal ganglia, and had a recent diagnosis of a separate autoimmune disease. One NMDAR-Ab HC displayed a T2 weighted FLAIR hyperintensity lesion in the left frontal lobe. The remaining three NMDAR-Ab participants were two EOP patients without neurological or radiological findings, and one HC without any clinical findings.ConclusionsWe report that a small number of EOP patients and HC have NMDAR-Abs with a similar frequency in both groups. The presence of the antibodies was not associated with any distinctive clinical or radiological features. Detection of the antibodies had no diagnostic implication, and a positive NMDAR antibody test must be carefully interpreted and reviewed within the individual clinical context.
Highlights
Psychosis, as observed in severe mental illness, is a condition with unknown pathophysiology
The dopamine hypothesis only partially explains the symptoms occurring in affected individuals [1, 2], but pharmacological studies in both humans and animals indicate that hypoactivation of N-methyl-D-aspartate receptors (NMDAR) may cause the presynaptic hyperdopaminergia related to schizophrenia [3, 4]
We found no evidence of the broad range of symptoms seen in Anti-NMDA receptor encephalitis (ANRE), nor did we find any positive neurological signs or brain MR imaging findings such as white matter hyper intensities on T2-weighted fluidattenuated inversion recovery (FLAIR) coinciding with ANRE
Summary
As observed in severe mental illness, is a condition with unknown pathophysiology. The dopamine hypothesis only partially explains the symptoms occurring in affected individuals [1, 2], but pharmacological studies in both humans and animals indicate that hypoactivation of N-methyl-D-aspartate receptors (NMDAR) may cause the presynaptic hyperdopaminergia related to schizophrenia [3, 4]. Anti-NMDA receptor encephalitis (ANRE) is an autoimmune neurological condition associated with IgG antibodies directed towards the NMDA receptor (NMDAR-Abs), which leads to NMDAR hypofunction [6]. There have been many studies examining the prevalence of antibodies in adult psychiatric patients compared to healthy controls [10]. Autoantibodies to the N-methyl-D-aspartate receptor (NMDAR-Abs) in autoimmune encephalitis have been associated with prominent psychiatric symptoms. The aims of the present study are to identify the prevalence of NMDAR-Abs in adolescents with early onset psychosis disorders (EOP) and healthy controls (HC) and examine its clinical significance
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