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Aim: To determine whether thyroid hormone levels are associated with a specific clinical phenotype in patients with first-episode psychosis (FEP)., Methods: Ninety-eight inpatients experiencing FEP and with less than 6 weeks of antipsychotic treatment were included in the study and were followed up for one year. Baseline psychiatric evaluation included assessment of prodromal symptoms, positive and negative symptoms, depressive symptoms, stressful life events and cycloid psychosis criteria. Thyroid function (thyroid-stimulating hormone (TSH) and free thyroxin (FT4)) was determined at admission. Partial correlation analysis was conducted to analyse the correlation between levels of TSH/FT4 and symptoms. Logistic regression was performed to explore the association between psychopathological symptoms, 12-month diagnoses and thyroid hormones while adjusting for covariates., Results: Patients with prodromal symptomatology showed lower baseline FT4 levels (OR = 0.06; p  = 0.018). The duration of untreated psychosis (DUP) was inversely associated with FT4 concentrations ( r  =  - 0.243; p  = 0.039). FEP patients with sudden onset of psychotic symptoms (criteria B, cycloid psychosis) showed higher FT4 levels at admission (OR = 10.49; p  = 0.040). Patients diagnosed with affective psychotic disorders (BD or MDD) at the 12-month follow-up showed higher FT4 levels at admission than patients diagnosed with nonaffective psychosis (schizophrenia, schizoaffective) (OR = 8.57; p  = 0.042)., Conclusions: Our study suggests that higher free-thyroxine levels are associated with a specific clinical phenotype of FEP patients (fewer prodromal symptoms, shorter DUP duration and sudden onset of psychosis) and with affective psychosis diagnoses at the 12-month follow-up., Competing Interests: The authors declare there are no competing interests., (©2023 Gine-Serven et al.)

In recent years, multiple studies have investigated the role of biomarkers in first-episode psychosis (FEP) to facilitate early diagnosis, disease stratification, therapeutic choice and outcome prediction. Few studies have focused on cerebrospinal fluid (CSF) investigations. In this prospective observational study, 95 FEP inpatients were followed up for one year. A lumbar puncture was performed at index admission (baseline) to study the CSF parameters (glucose, total proteins, lactate dehydrogenase [LDH], and pleocytosis). At the baseline visit, the clinical assessment included prodromal (psychotic and non-psychotic) symptoms before the psychotic outbreak and psychopathology at admission. The SCID-I was administered to obtain a clinical diagnosis at baseline and at 12 months. The relationship between prodromal and psychopathology symptoms at the baseline visit was tested with multiple linear regression. Multinomial logistic regression was also used to explore the association between CSF biomarkers and longitudinal diagnoses at follow-up (schizophrenia/schizoaffective disorder vs unipolar/bipolar depression vs other psychoses). Higher CSF glucose was associated with depressive (Standardized beta = 0.27, p = 0.041) and disorganized/concrete symptoms (Standardized beta = 0.33, p = 0.023) and lower CSF LDH was associated with prodromal symptoms (Standardized beta = -0.25, p = 0.042). Lower LDH concentrations were also associated with social withdrawal (r = -0.342, p = 0.001). CSF glucose was a predictor of the long-term diagnosis (lower CSF concentrations were associated with schizophrenia or schizoaffective disorder diagnoses [OR = 0.88, CI95%: 0.77-0.99). Our study suggests that CSF biomarkers that involve bioenergetic systems are associated with prodromal symptoms and the phenotype of psychotic disorders during the early stages of the disease., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To ascertain the clinical characteristics of anti-NMDA receptor encephalitis (NMDARE) in older patients., Method: A systematic literature review using PubMed and Scopus of all published case reports of NMDARE was undertaken, from database inception to June 2020. From this, cases reporting on patients older than 65 years of age and whose diagnosis was confirmed by the presence of anti-NMDAR antibodies in CSF were selected., Results: 23 case reports fulfilling the study's criteria were found. Median age was 70.1 years (range 65-84), fourteen were female (60.9%), and mostly presented with acute behavioral and cognitive changes (95.7%). Atypical psychosis occurred in eleven patients (47.8%) with a sudden onset and fluctuating clinical pattern of delusions (39.1%), hallucinations (30.4%), and motility disturbances (34.8%) including catatonia (17.4%). Nine patients presented with seizures (39.1%). Pleocytosis in CSF (>5 WBC) was described in twelve cases (52.2%). Eleven cases (47.8%) had abnormal brain magnetic resonance imaging (MRI) scans with limbic inflammatory lesions. Thirteen patients had an abnormal EEG (56.5%)., Conclusion: NMDARE should be included in the differential diagnosis of older patients who present with new psychiatric episodes, especially when characterized by sudden onset psychotic polymorphic symptomatology, fluctuating course with marked cognitive decline, and with catatonic features., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., (© 2021 American Academy of Neurology.)

Objective: We reviewed the psychotic symptoms of anti-NMDA receptor encephalitis (NMDARE) to differentiate its presentation from those found in a primary psychiatric disorder. We hypothesized that the cycloid psychosis (CP) phenotype would be a frequent clinical presentation in the psychiatric phase of NMDARE., Method: A systematic literature review in PubMed of all case reports published on NMDARE was performed from database inception to March 2020. We included all cases where psychotic symptoms were reported and whose diagnoses were confirmed by the presence of anti-NMDAR antibodies in the cerebrospinal fluid (CSF). An email including a short test (CP phenotype, Perris and Brockington's criteria) was sent to all case report authors asking them to describe the psychotic symptoms., Results: We identified 335 case reports fulfilling our criteria, and the authors of 200 replied. Our analyses were based exclusively on those answers and data extracted from the articles. Median patient age was 25 years (+-11.4), 81% were female, and 39% had an ovarian teratoma. A complete CP phenotype was identified in 175 patients (87%). These were acute psychotic episodes with a sudden onset and a fluctuating clinical pattern mostly characterized by confusion (97%), delusions (75%), hallucinations (69%), motility disturbances (87%), and mood oscillations (80%)., Conclusion: The complete CP phenotype was frequently the expression of psychotic symptoms in NMDARE. We suggest that patients with a first psychotic episode who initially exhibit the CP phenotype should undergo CSF analysis to determine whether antibodies against neuronal cell surface or synaptic receptors are present to rule out a possible diagnosis of autoimmune encephalitis., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)