Correlation between frailty and reduction in cortical thickness in patients with chronic obstructive pulmonary disease.

Physical inactivity and cognitive impairment in patients with chronic obstructive pulmonary disease (COPD) can lead to frailty and poor prognoses. However, little is known regarding the association between frailty and the human brain. We hypothesized that the brain structure could change according to frailty in patients with COPD and focused on cortical thickness. Cortical thickness measured by magnetic resonance imaging and frailty scores using the Kihon Checklist (KCL) were assessed in 40 patients with stable COPD and 20 healthy controls. Among the 34 regions assessed, multiple regions were thinner in patients with COPD than in healthy individuals (p < 0.05). We found significant negative correlations between the eight regions and the KCL scores only in patients with COPD. After adjusting for age and cognitive impairment, the association between the left and six right regions remained statistically significant. The correlation coefficient was the strongest in the bilateral superior frontal gyrus (left: ρ = - 0.5319, p = 0.0006) (right: ρ = - 0.5361, p = 0.0005). Interestingly, among the KCL scores, the daily activity domain showed the strongest correlation (sensitivity, 90%; specificity, 73%) with the bottom quartile of the reduction in the superior frontal gyrus. Frailty in patients with COPD is associated with a thickness reduction in the cortical regions, reflecting social vulnerability.

Aberrant brain dynamics of large-scale functional networks across schizophrenia and mood disorder.

INTRODUCTION: The dynamics of large-scale networks, which are known as distributed sets of functionally synchronized brain regions and include the visual network (VIN), somatomotor network (SMN), dorsal attention network (DAN), salience network (SAN), limbic network (LIN), frontoparietal network (FPN), and default mode network (DMN), play important roles in emotional and cognitive processes in humans. Although disruptions in these large-scale networks are considered critical for the pathophysiological mechanisms of psychiatric disorders, their role in psychiatric disorders remains unknown. We aimed to elucidate the aberrant dynamics across large-scale networks in patients with schizophrenia (SZ) and mood disorders. METHODS: We performed energy-landscape analysis to investigate the aberrant brain dynamics of seven large-scale networks across 50 healthy controls (HCs), 36 patients with SZ, and 42 patients with major depressive disorder (MDD) recruited at Wakayama Medical University. We identified major patterns of brain activity using energy-landscape analysis and estimated their duration, occurrence, and ease of transition. RESULTS: We identified four major brain activity patterns that were characterized by the activation patterns of the DMN and VIN (state 1, DMN (-) VIN (-); state 2, DMN (+) VIN (+); state 3, DMN (-) VIN (+); and state 4, DMN (+) VIN (-)). The duration of state 1 and the occurrence of states 1 and 2 were shorter in the SZ group than in HCs and the MDD group, and the duration of state 3 was longer in the SZ group. The ease of transition between states 3 and 4 was larger in the SZ group than in the HCs and the MDD group. The ease of transition from state 3 to state 4 was negatively associated with verbal fluency in patients with SZ. The current study showed that the brain dynamics was more disrupted in SZ than in MDD. CONCLUSIONS: Energy-landscape analysis revealed aberrant brain dynamics across large-scale networks between SZ and MDD and their associations with cognitive abilities in SZ, which cannot be captured by conventional functional connectivity analyses. These results provide new insights into the pathophysiological mechanisms underlying SZ and mood disorders.

Predicting postoperative delirium after cardiovascular surgeries from preoperative portable electroencephalography oscillations.

Introduction: Postoperative delirium (POD) is common and life-threatening, however, with intensive interventions, a potentially preventable clinical syndrome. Although electroencephalography (EEG) is a promising biomarker of delirium, standard 20-leads EEG holds difficulties for screening usage in clinical practice. Objective: We aimed to develop an accurate algorithm to predict POD using EEG data obtained from portable device. Methods: We recruited 128 patients who underwent scheduled cardiovascular surgery. Cognitive function assessments were conducted, and portable EEG recordings were obtained prior to surgery. Results: Among the patients, 47 (36.7%) patients with POD were identified and they did not significantly differ from patients without POD in sex ratio, age, cognitive function, or treatment duration of intensive care unit. However, significant differences were observed in the preoperative EEG power spectrum densities at various frequencies, especially gamma activity, between patients with and without POD. POD was successfully predicted using preoperative EEG data with a machine learning algorithm, yielding accuracy of 86% and area under the receiver operating characteristic curve of 0.93. Discussion: This study provides new insights into the objective and biological vulnerability to delirium. The developed algorithm can be applied in general hospitals without advanced equipment and expertise, thereby enabling the reduction of POD occurrences with intensive interventions for high-risk patients.

An international research agenda for clozapine-resistant schizophrenia.

Treatment-resistant symptoms occur in about a third of patients with schizophrenia and are associated with a substantial reduction in their quality of life. The development of new treatment options for clozapine-resistant schizophrenia constitutes a crucial, unmet need in psychiatry. Additionally, an overview of past and possible future research avenues to optimise the early detection, diagnosis, and management of clozapine-resistant schizophrenia is unavailable. In this Health Policy, we discuss the ongoing challenges associated with clozapine-resistant schizophrenia faced by patients and health-care providers worldwide to improve the understanding of this condition. We then revisit several clozapine guidelines, the diagnostic tests and treatment options for clozapine-resistant schizophrenia, and currently applied research approaches in clozapine-resistant schizophrenia. We also suggest methodologies and targets for future research, divided into innovative nosology-oriented field trials (eg, examining dimensional symptom staging), translational approaches (eg, genetics), epidemiological research (eg, real-world studies), and interventional studies (eg, non-traditional trial designs incorporating lived experiences and caregivers' perspectives). Finally, we note that low-income and middle-income countries are under-represented in studies on clozapine-resistant schizophrenia and propose an agenda to guide multinational research on the cause and treatment of clozapine-resistant schizophrenia. We hope that this research agenda will empower better global representation of patients living with clozapine-resistant schizophrenia and ultimately improve their functional outcomes and quality of life.

Three-Dimensional Analysis of Water Dynamics in Human Skin by Stimulated Raman Scattering.

The stratum corneum (SC), the outermost layer of the skin, has an important function to provide a barrier against dry environments. To evaluate the barrier function and the skin condition, it is crucial to investigate the ability of SC to absorb and retain water. In this study, we demonstrate stimulated Raman scattering (SRS) imaging of three-dimensional SC structure and water distribution when water is absorbed into dried SC sheets. Our results show that the process of water absorption and retention is dependent on the specific sample and can be spatially heterogeneous. We also found that acetone treatment leads to spatially homogeneous retention of water. These results suggest the great potential of SRS imaging in diagnosing skin conditions.

Effects of Diabetes and Voluntary Exercise on IgA Concentration and Polymeric Immunoglobulin Receptor Expression in the Submandibular Gland of Rats.

Background and Objectives: Patients with diabetes are more susceptible to upper respiratory tract infections (URTIs) because they are easily infected. Salivary IgA (sali-IgA) levels play a major role in transmitting URTIs. Sali-IgA levels are determined by salivary gland IgA production and polymeric immunoglobulin receptor (poly-IgR) expression. However, it is unknown whether salivary gland IgA production and poly-IgR expression are decreased in patients with diabetes. While exercise is reported to increase or decrease the sali-IgA levels, it is unclear how exercise affects the salivary glands of patients with diabetes. This study aimed to determine the effects of diabetes and voluntary exercise on IgA production and poly-IgR expression in the salivary glands of diabetic rats. Materials and Methods: Ten spontaneously diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats (eight-week-old) were divided into two groups of five rats each: a non-exercise group (OLETF-C) and a voluntary wheel-running group (OLETF-E). Five Long-Evans Tokushima Otsuka (LETO) rats without diabetes were bred under the same conditions as the OLETF-C. Sixteen weeks after the study began, the submandibular glands (SGs) were collected and analyzed for IgA and poly-IgR expression levels. Results: IgA concentrations and poly-IgR expression levels in SGs were lower in OLETF-C and OLETF-E than in LETO (p < 0.05). These values did not differ between the OLETF-C and OLETF-E. Conclusions: Diabetes decreases IgA production and poly-IgR expression in the salivary glands of rats. Moreover, voluntary exercise increases sali-IgA levels but does not increase IgA production and poly-IgR expression in the salivary glands of diabetic rats. Increasing IgA production and poly-IgR expression in the salivary glands, which is reduced in diabetes, might require slightly higher-intensity exercise than voluntary exercise under the supervision of a doctor.

Structural connectivity between the hippocampus and cortical/subcortical area relates to cognitive impairment in schizophrenia but not in mood disorders.

Cognitive impairment in schizophrenia and other psychiatric disorders is a challenge to be overcome in order to maintain patients' quality of life and social function. The neurological pathogenesis of cognitive impairment requires further elucidation. In general, the hippocampus interacts between the cortical and subcortical areas for information processing and consolidation and has an important role in memory. We examined the relationship between structural connectivity of the hippocampus and cortical/subcortical areas and cognitive impairment in schizophrenia, major depressive disorder and bipolar disorder. Subjects comprised 21 healthy controls, 19 patients with schizophrenia, 20 patients with bipolar disorder and 18 patients with major depressive disorder. Diffusion-weighted tensor images data were processed using ProbtrackX2 to calculate the structural connectivity between the hippocampus and cortical/subcortical areas. Cognitive function was assessed using the Brief Assessment of Cognition in schizophrenia composite score. Hippocampal structural connectivity index was significantly correlated with composite score in the schizophrenia group but not in the healthy control, major depressive disorder or bipolar disorder groups. There were no statistically significant differences in hippocampal structural connectivity index between the four groups. Structural connectivity between the hippocampus and cortical/subcortical areas is suggested to be a pathophysiological mechanism of comprehensive cognitive impairment in schizophrenia.

Computational modeling of electric fields for prefrontal tDCS across patients with schizophrenia and mood disorders.

This cross-diagnostic study aims to computationally model electric field (efield) for prefrontal transcranial direct current stimulation in mood disorders and schizophrenia. Enrolled were patients with major depressive disorder (n = 23), bipolar disorder (n = 24), schizophrenia (n = 23), and healthy controls (n = 23). The efield was simulated using SimNIBS software (ver.2.1.1). Electrodes were placed at the left and right prefrontal areas and the current intensity was set to 2 mA intensity. Schizophrenia and major depressive disorder groups showed significantly lower 99.5th percentile efield strength than healthy controls. In voxel-wise analysis, patients with schizophrenia showed a significant reduction of simulated efield strength in the bilateral frontal lobe, cerebellum and brain stem compared with healthy controls. Among the patients with schizophrenia, reduction of simulated efield strength was not significantly correlated with psychiatric symptoms or global functioning. The patients with bipolar disorder showed no significant difference in simulated efield strength compared with healthy controls, and there was no significant difference between the clinical groups. Our results suggest attenuated electrophysiological response to transcranial direct current stimulation to the prefrontal cortex in patients with schizophrenia, and to some extent in patients with major depressive disorder.

The Big Five personality traits and the fear of COVID-19 in predicting depression and anxiety among Japanese nurses caring for COVID-19 patients: A cross-sectional study in Wakayama prefecture.

Recent studies have found a relationship between fear of COVID-19 and mental health problems. Medical workers caring for COVID-19 patients tend to suffer from mental health problems; however, the impact of their personality traits, in the form of mental problems like depression and anxiety in Japan is unclear. In this study, we investigated the risk of nurses' depression and anxiety, predicted by the fear of COVID-19 and the Big Five personality traits. A total of 417 nurses working in hospitals providing care to COVID-19 patients in Wakayama prefecture of the Kansai region participated in this study. The questionnaires comprised items on nurses' basic characteristics and three scales: the Fear of COVID-19 Scale 2020, the Big-Five Scale, and the Japanese version of the Hospital Anxiety and Depression Scale (HADS). Depression and anxiety in the HADS were set as dependent variables, and basic attributes, fear, and personality traits as independent variables; multivariate logistic regression analyses were conducted. The questionnaire, with no missing items was distributed from February to March 2021. Neuroticism (OR = 1.06, 95%CI = 1.03-1.09) was the only significant factor associated with the depression symptom, and both FCV-19S scores (OR = 1.16, 95%CI = 1.09-1.23) and neuroticism (OR = 1.09, 95%CI = 1.06-1.13) were the significant factors associated with anxiety. The Nagelkerke's R squared was 0.171 in the depression model and 0.366 in the anxiety model. Thus, it was found that it is necessary to support nurses' mental health by developing methods suitable to their personalities.

Multiple comparison of different noninvasive brain stimulation and pharmacologic interventions in patients with methamphetamine use disorders: A network meta-analysis of randomized controlled trials.

AIM: In recent decades, the prevalence of amphetamine and methamphetamine use disorders has at least doubled in some regions/countries, with accompanying high risks of drug overdose-associated mortality. Noninvasive brain stimulation (NIBS) methods may be effective treatments. However, the comparative efficacy of the NIBS protocol for amphetamine/methamphetamine use disorder (AUD/MUD) remains unknown to date. The aim of this network meta-analysis (NMA) was to compare the efficacy and acceptability of various NIBS methods/protocols for AUD/MUD management. METHODS: A frequentist model-based NMA was conducted. We included randomized controlled trials (RCTs) that investigated the efficacy of NIBS and guideline-recommended pharmacologic treatments to reduce craving severity in patients with either AUD or MUD. RESULTS: Twenty-two RCTs including 1888 participants met the eligibility criteria. Compared with the sham/placebo group (study = 19, subjects = 891), a combination of intermittent theta burst stimulation over the left dorsolateral prefrontal cortex (DLPFC) and continuous TBS over the left ventromedial prefrontal cortex (study = 1, subjects = 19) was associated with the largest decreases in craving severity [standardized mean difference (SMD) = -1.50; 95% confidence intervals (95%CIs) = -2.70 to -0.31]. High-frequency repetitive transcranial magnetic stimulation over the left DLPFC was associated with the largest improvements in depression and quality of sleep (study = 3, subjects = 86) (SMD = -2.48; 95%CIs = -3.25 to -1.71 and SMD = -2.43; 95%CIs = -3.38 to -1.48, respectively). The drop-out rate of most investigated treatments did not significantly differ between groups. CONCLUSION: The combined TBS protocol over the prefrontal cortex was associated with the greatest improvement in craving severity. Since few studies were available for inclusion, additional large-scale randomized controlled trials are warranted.

Probable progressive supranuclear palsy in a patient with chronic schizophrenia: A case report.

Rare neurodegenerative disorders may be considered in the differential diagnosis of Parkinsonism in patients with schizophrenia who show worsening signs of Parkinsonism under treatment with antipsychotics. To the best of our knowledge, the present study is the first report describing probable progressive supranuclear palsy (PSP) in a patient with chronic schizophrenia. A 64-year-old man presented with hallucinations, delusions and asociality. He had received treatment with both typical and atypical antipsychotics for ~13 years. He began experiencing short-term memory impairment and bradykinesia two years before presentation, and then showed increased dysphagia, upper-limb muscle rigidity, extrapyramidal symptoms, vision loss and photophobia. Psychological manifestations included chronic depression, irritability and, occasionally, euphoria. His gait worsened, leading to repeated falls. Antipsychotics were discontinued, and the patient was almost completely dependent on a wheelchair in daily life. In a neurology consultation, he was diagnosed with probable progressive supranuclear palsy-Richardson's syndrome presenting as vertical supranuclear gaze palsy and prominent postural instability with falls. Brain magnetic resonance imaging (MRI) revealed atrophy of the mesencephalic tegmentum, and 123I-ioflupane single-photon emission computed tomography (SPECT) revealed reduced bilateral striatal reuptake. Overall, PSP should be considered in patients with schizophrenia with worsening Parkinsonism, especially when it is accompanied by supranuclear ophthalmoplegia, pseudobulbar palsy, dysarthria and dystonic stiffness of the neck and upper body. In the present case, the combination of brain MRI and 123I-ioflupane SPECT helped to discriminate PSP from other Parkinsonian syndromes, including drug-induced Parkinsonism, in the differential diagnosis.

Assessment of Noninvasive Brain Stimulation Interventions for Negative Symptoms of Schizophrenia: A Systematic Review and Network Meta-analysis.

Importance: Negative symptoms have a detrimental impact on functional outcomes and quality of life in people with schizophrenia, and few therapeutic options are considered effective for this symptomatic dimension. Studies have suggested that noninvasive brain stimulation (NIBS) interventions may be effective in treating negative symptoms. However, the comparative efficacy of different NIBS protocols for relieving negative symptoms remains unclear. Objective: To compare the efficacy and acceptability of different NIBS interventions for treating negative symptoms. Data Sources: The ClinicalKey, Cochrane CENTRAL, Embase, ProQuest, PubMed, ScienceDirect, ClinicalTrials.gov, and Web of Science electronic databases were systematically searched from inception through December 7, 2021. Study Selection: A frequentist model network meta-analysis was conducted to assess the pooled findings of trials that evaluated the efficacy of repetitive transcranial magnetic stimulation (rTMS), theta-burst stimulation, transcranial random noise stimulation, transcutaneous vagus nerve stimulation, and transcranial direct current stimulation on negative symptoms in schizophrenia. Randomized clinical trials (RCTs) examining NIBS interventions for participants with schizophrenia were included. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. Data were independently extracted by multiple observers. The pair-wise meta-analytic procedures were conducted using a random-effects model. Main Outcomes and Measures: The coprimary outcomes were changes in the severity of negative symptoms and acceptability (ie, dropout rates owing to any reason). Secondary outcomes were changes in positive and depressive symptoms. Results: Forty-eight RCTs involving 2211 participants (mean [range] age, 38.7 [24.0-57.0] years; mean [range] proportion of female patients, 30.6% [0%-70.0%]) were included. Compared with sham control interventions, excitatory NIBS strategies (standardized mean difference [SMD]: high-definition transcranial random noise stimulation, -2.19 [95% CI, -3.36 to -1.02]; intermittent theta-burst stimulation, -1.32 [95% CI, -1.88 to -0.76]; anodal transcranial direct current stimulation, -1.28 [95% CI, -2.55 to -0.02]; high-frequency rTMS, -0.43 [95% CI, -0.68 to -0.18]; extreme high-frequency rTMS, -0.45 [95% CI, -0.79 to -0.12]) over the left dorsolateral prefrontal cortex with or without other inhibitory stimulation protocols in the contralateral regions of the brain were associated with significantly larger reductions in negative symptoms. Acceptability did not significantly differ between the groups. Conclusions and Relevance: In this network meta-analysis, excitatory NIBS protocols over the left dorsolateral prefrontal cortex were associated with significantly large improvements in the severity of negative symptoms. Because relatively few studies were available for inclusion, additional well-designed, large-scale RCTs are warranted.

TMS Database Registry Consortium Research Project in Japan (TReC-J) for Future Personalized Psychiatry.

The registry project led by the Japanese Society for Clinical Transcranial Magnetic Stimulation (TMS) Research aims to establish a centralized database of epidemiological, clinical, and biological data on TMS therapy for refractory psychiatric disorders, including treatment-resistant depression, as well as to contribute to the elucidation of the therapeutic mechanism of TMS therapy and to the validation of its efficacy by analyzing and evaluating these data in a systematic approach. The objective of this registry project is to collect a wide range of complex data linked to patients with various neuropsychiatric disorders who received TMS therapy throughout Japan, and to make effective use of these data to promote cross-sectional and longitudinal exploratory observational studies. Research utilizing this registry project will be conducted in a multicenter, non-invasive, retrospective, and prospective observational research study design, regardless of the framework of insurance medical care, private practice, or clinical research. Through the establishment of the registry, which aims to make use of data, we will advance the elucidation of treatment mechanisms and identification of predictors of therapeutic response to TMS therapy for refractory psychiatric disorders on a more real-world research basis. Furthermore, as a future vision, we aim to develop novel neuromodulation medical devices, algorithms for predicting treatment efficacy, and digital therapeutics based on the knowledge generated from this TMS registry database.

Differences in electric field strength between clinical and non-clinical populations induced by prefrontal tDCS: A cross-diagnostic, individual MRI-based modeling study.

INTRODUCTION: Prefrontal cortex (PFC) regions are promising targets for therapeutic applications of non-invasive brain stimulation, e.g. transcranial direct current stimulation (tDCS), which has been proposed as a novel intervention for major depressive disorder (MDD) and negative symptoms of schizophrenia (SCZ). However, the effects of tDCS vary inter-individually, and dose-response relationships have not been established. Stimulation parameters are often tested in healthy subjects and transferred to clinical populations. The current study investigates the variability of individual MRI-based electric fields (e-fields) of standard bifrontal tDCS across individual subjects and diagnoses. METHOD: The study included 74 subjects, i.e. 25 patients with MDD, 24 patients with SCZ, and 25 healthy controls (HC). Individual e-fields of a common tDCS protocol (i.e. 2 mA stimulation intensity, bifrontal anode-F3/cathode-F4 montage) were modeled by two investigators using SimNIBS (2.0.1) based on structural MRI scans. RESULT: On a whole-brain level, the average e-field strength was significantly reduced in MDD and SCZ compared to HC, but MDD and SCZ did not differ significantly. Regions of interest (ROI) analysis for PFC subregions showed reduced e-fields in Sallet areas 8B and 9 for MDD and SCZ compared to HC, whereas there was again no difference between MDD and SCZ. Within groups, we generally observed high inter-individual variability of e-field intensities at a higher percentile of voxels. CONCLUSION: MRI-based e-field modeling revealed significant differences in e-field strengths between clinical and non-clinical populations in addition to a general inter-individual variability. These findings support the notion that dose-response relationships for tDCS cannot be simply transferred from healthy to clinical cohorts and need to be individually established for clinical groups. In this respect, MRI-based e-field modeling may serve as a proxy for individualized dosing.

Immunoglobulin G4-related disease accompanying a small intestinal ulcer: A case.

Immunoglobulin (Ig)G4-related disease (IgG4-RD) is a systemic condition associated with fibroinflammatory lesions and is characterized by elevated serum IgG4 levels and IgG4-positive cell infiltration into the affected tissues. It has been reported that IgG4-RD affects a variety of organs but uncommonly affects the gastrointestinal tract. In particular, there are few cases of lesions in the small intestine, except for sclerosing mesenteritis, which were mostly diagnosed from surgical specimens. Herein, we describe the case of a 70-year-old man who initially presented with abdominal pain, headache, later cognitive decline, and gait disturbance caused by IgG4-RD. Colonoscopy revealed irregular ulcers in the terminal ileum, and computed tomography of the head showed hypertrophic pachymeningitis. Numerous IgG4-positive cells were detected in the ileal and dural biopsies. We diagnosed the patient with IgG4-RD and started steroid pulse therapy. After initiation of treatment, the symptoms quickly improved. The patient was discharged from the hospital after starting oral prednisolone treatment (30 mg). The dosage was gradually reduced to 10 mg. A follow-up colonoscopy revealed scarring of the ileal ulcers. This case may provide valuable information regarding the endoscopic findings of small intestinal lesions in IgG4-RD.

Phase locking of squeezed vacuum generated by a single-pass optical parametric amplifier.

In high-precision optical measurements, squeezed vacuum states are a promising resource for reducing the shot noise. To utilize a squeezed vacuum, it is important to lock the phase of the local oscillator (LO) to the squeezed light. The coherent control sideband (CCSB) scheme has been established for the precise phase locking, while the previous CCSB scheme was designed for the squeezed vacuum generated with an optical parametric oscillator (OPO). Thus the previous CCSB scheme is not applicable to squeezing by a single-pass optical parametric amplifier (OPA), which is attractive for generating broadband squeezed vacuum states. In this study, we propose a variant of CCSB scheme, which is applicable to the squeezing by single-pass OPA. In this scheme, we inject pump light and frequency-shifted signal light into an OPA crystal in the same way as the previous CCSB scheme. The parametric process in the OPA crystal generates a squeezed vacuum, amplifies the signal light, generates an idler light, and causes the pump depletion reflecting the interference of the amplified signal light and the idler light. Through the lock-in detection of the pump depletion, we can phase-lock the injected signal light to the pump light. Then, after the heterodyne detection of the signal and the idler light, we get the error signal of LO and realize the precise phase locking of LO to the squeezed quadrature. We show the feasibility of the proposed scheme by deriving the signal-to-noise ratio (SNR) of the modulated pump signal. We experimentally demonstrate the proposed scheme on pulsed squeezing by a single-pass OPA.

Ankle arthrodesis using a retrograde intramedullary rod with fins for highly destructive joints in elderly patients with rheumatoid arthritis: A report of two cases.

Herein, we present two cases of older adult patients with highly destructive changes in ankle joints (Larsen grade IV) who underwent retrograde intramedullary ankle nail fixation with fins. In both patients, bony union was achieved, and full weight-bearing was attained at 3 months after surgery.

Schizophrenia after remission of anti-NMDA receptor encephalitis.

N-methyl-D-aspartate receptor (NMDAR) dysfunction is an attractive hypothesis regarding the etiology of schizophrenia. We present the unprecedented case of a woman diagnosed with schizophrenia without anti-NMDAR antibodies after history of NMDAR encephalitis. A first episode of psychosis was antibody-positive and was improved with steroid and immunoglobulin treatment. Second and third episodes were antibody-negative, each about three months postpartum (different pregnancies) and were improved with antipsychotics. Without NMDAR encephalitis-related findings, we diagnosed schizophrenia. After anti-NMDAR encephalitis, NMDAR dysfunction may decrease the threshold for the onset of psychosis. This case provides insight into NMDAR dysfunction on etiology of schizophrenia.