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Approximately one-third of patients with first-episode schizophrenia-spectrum disorders develop treatment-resistant schizophrenia (TRS) within five years, yet reliable early predictors remain lacking. Routine cerebrospinal fluid (CSF) biomarkers may offer insights into TRS pathophysiology and enable early prognostic stratification. In this longitudinal study, we examined whether baseline CSF parameters—total protein, glucose, and lactate dehydrogenase (LDH)—predicted TRS, defined according to TRRIP consensus criteria and clozapine use. Forty-four patients with first-episode schizophrenia spectrum disorders underwent lumbar puncture during index hospitalization and were followed clinically for five years at the Mataró Mental Health Care Centre. TRS status was confirmed through detailed electronic health record review. Thirteen patients (29.5%) met TRS criteria. At baseline, these individuals had significantly lower CSF LDH concentrations compared to non-TRS patients (p = 0.014), while glucose and protein levels showed no significant differences. In adjusted logistic regression models, lower LDH remained independently associated with TRS (OR = 0.043, p = 0.031). A combined model incorporating LDH and early antipsychotic response achieved an AUC of 0.86, outperforming LDH alone (AUC = 0.73), and demonstrating good discriminative accuracy. Lower baseline CSF LDH concentrations predicted treatment resistance at five years, especially when combined with poor early antipsychotic response. This two-variable prognostic model—BIOERES (Bioenergetic and Early Response Stratification)—may facilitate early identification of high-risk patients and support personalized treatment strategies. Validation in larger, independent cohorts is needed.

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. It is of the utmost importance to precisely describe the initial psychiatric phenotype of anti‐NMDARE to perform an early diagnosis and to ameliorate prognosis. The complete cycloid psychosis phenotype was a frequent clinical presentation of anti‐NMDA receptor encephalitis cases with psychotic symptoms. This phenotype has an acute and sudden onset and a fluctuating course and is characterized by confusion, delusions, hallucinations, mood swings, and motility disturbances.

To determine whether thyroid hormone levels are associated with a specific clinical phenotype in patients with first-episode psychosis (FEP). 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. Patients with prodromal symptomatology showed lower baseline FT4 levels (OR = 0.06;  = 0.018). The duration of untreated psychosis (DUP) was inversely associated with FT4 concentrations (  =  - 0.243;  = 0.039). FEP patients with sudden onset of psychotic symptoms (criteria B, cycloid psychosis) showed higher FT4 levels at admission (OR = 10.49;  = 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;  = 0.042). 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.