Association of symptom severity and cerebrospinal fluid alterations in recent onset psychosis in schizophrenia-spectrum disorders - An individual patient data meta-analysis.

Neuroinflammation and blood-cerebrospinal fluid barrier (BCB) disruption could be key elements in schizophrenia-spectrum disorders(SSDs) etiology and symptom modulation. We present the largest two-stage individual patient data (IPD) meta-analysis, investigating the association of BCB disruption and cerebrospinal fluid (CSF) alterations with symptom severity in first-episode psychosis (FEP) and recent onset psychotic disorder (ROP) individuals, with a focus on sex-related differences. Data was collected from PubMed and EMBASE databases. FEP, ROP and high-risk syndromes for psychosis IPD were included if routine basic CSF-diagnostics were reported. Risk of bias of the included studies was evaluated. Random-effects meta-analyses and mixed-effects linear regression models were employed to assess the impact of BCB alterations on symptom severity. Published (6 studies) and unpublished IPD from n = 531 individuals was included in the analyses. CSF was altered in 38.8 % of individuals. No significant differences in symptom severity were found between individuals with and without CSF alterations (SMD = -0.17, 95 %CI -0.55-0.22, p = 0.341). However, males with elevated CSF/serum albumin ratios or any CSF alteration had significantly higher positive symptom scores than those without alterations (SMD = 0.34, 95 %CI 0.05-0.64, p = 0.037 and SMD = 0.29, 95 %CI 0.17-0.41p = 0.005, respectively). Mixed-effects and simple regression models showed no association (p > 0.1) between CSF parameters and symptomatic outcomes. No interaction between sex and CSF parameters was found (p > 0.1). BCB disruption appears highly prevalent in early psychosis and could be involved in positive symptoms severity in males, indicating potential difficult-to-treat states. This work highlights the need for considering BCB breakdownand sex-related differences in SSDs clinical trials and treatment strategies.

The Importance of Cerebrospinal Fluid Investigation in First-episode Psychosis.

Despite being a reliable first-hand source of data on neuronal pathology, cerebrospinal fluid (CSF) analysis remains an often-overlooked evaluation method in first-episode psychosis (FEP). In this paper, we begin by discussing the current role of CSF testing during FEP evaluation in clinical practice. Given that anti-N-methyl-D-aspartate receptor encephalitis presents with a clinical picture indistinguishable from FEP in >85% of cases, we debate the importance of testing for CSF neuronal antibodies in at least a subset of patients. Then, we continue by reviewing the most important recent studies which sought to identify potential CSF biomarkers in FEP caused by a primary psychiatric disorder. By circumventing traditional psychiatric classifications, characteristic biomarker profiles have the potential to become integral components of early diagnosis, disease stratification, treatment choice, and outcome prediction. Along these lines, we aim to provide an updated perspective on the importance of CSF investigation in FEP.

Emerging cycloid psychosis episodes during COVID-19 pandemic: a case series.

AIMS: Cycloid psychosis (CP) is a clinical entity characterized by sudden onset of psychotic polymorphic symptomatology and fluctuant course. It has a reported rate of psychosocial precipitating factors ranging 30-65%. The aim of the study was to describe all cases of CP, admitted in our Psychiatry ward, during the first two months of the COVID-19 pandemic. METHOD: In this retrospective and observational study, we reported a sample of eight patients who were treated as inpatients in the psychiatric ward of our hospital during the first two months of COVID-19 pandemic (mid-March to mid-May 2020) and compared it with previous years. All our patients fulfilled all four Perris & Brockington criteria for CP. We reported the sociodemographic, clinical and biological parameters. RESULTS: In our sample, all of the patients had maladaptive personality traits; the major external stressing factor was COVID-19; all our patients had short prodromal symptomatology, short Duration of Untreated Psychosis (DUP) and high score at the Positive Scale at Positive and Negative Syndrome Scale (PANSS-P) at hospital admission with the majority showing psychotic symptoms related to the actual COVID-19 pandemic. The predominant treatment during admission was olanzapine and a short time to full remission of psychotic symptoms was observed in all patients. CONCLUSION: We found an increase in the admission of patients with CP during the first two months of the actual pandemic. Stress caused by the COVID-19 situation has possibly incremented the frequency of stress-related disorders and it has also influenced its clinical presentation.

Erythrocyte membrane polyunsaturated fatty acid (pufa) levels in a sample of patients with schizophrenia and relation with clinical and progression variables.

INTRODUCTION: Previous studies have shown that erythrocyte cell membranes in patients with schizophrenia contain considerably less omega-3 fatty acids, particularly EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), reflecting the lower levels present in neuronal and central nervous system membranes. This phenomenon, linked to genetic, metabolic, or dietary factors, has been associated with the development of schizophrenia and the risk of developing and the severity of metabolic syndrome. METHODS: This study is an observational study conducted in a sample of 31 patients with schizophrenia treated at the Mataró Mental Health Center (Barcelona). Its aim was to relate the erythrocyte levels of omega 3 with the clinical severity of schizophrenia and dietary habits. EPA (eicosapentaenoic acid), DHA (docosahexaenoic acid) and other membrane lipid levels were determined, as well as psychopathology, cognitive, and social functioning measures, previous evolution, and finally a survey of dietary habits. RESULTS: Our results did not show a statistically significant correlation between erythrocyte omega-3 levels and psychopathological and clinical severity variables. Higher, statistically significant, levels were found in the group of women and in subjects with more days of admission to the day hospital. In contrast, lower values were obtained in subjects treated with long-acting antipsychotics and in sunflower oil consumers. CONCLUSIONS: Despite not being able to demonstrate our working hypothesis, significant correlations were found that were consistent with published findings in the current literature. The need for studies with larger samples and groups of healthy controls is postulated.

Corrigendum: Psychosocial stress moderates the relationship between cerebrospinal fluid lactate dehydrogenase and the duration of untreated psychosis in first-episode psychosis.

[This corrects the article DOI: 10.3389/fpsyt.2024.1327928.].

Psychosocial stress moderates the relationship between cerebrospinal fluid lactate dehydrogenase and the duration of untreated psychosis in first-episode psychosis.

Introduction: Previous research has shown that lower lactate dehydrogenase (LDH) concentrations in cerebrospinal fluid (CSF) are associated with longer prodromal symptoms in first-episode psychosis (FEP). We aimed to study whether there is a relationship between the duration of untreated psychosis (DUP) and LDH and other CSF biomarkers in FEP and whether stressful life events moderate this association. Methods: Ninety-five inpatients with FEP and with less than 6 weeks of antipsychotic treatment were included in the study. All participants were informed about the nature of the study, which was approved by the local ethics committee, and signed an informed consent form. A lumbar puncture was performed at index admission (baseline) to measure CSF parameters (glucose, total protein, LDH). The DUP was assessed with the Quick Psychosis Onset and Prodromal Symptoms Inventory (Q-POPSI). Stressful life events (SLEs) in the previous 6 months were assessed with the List of Threatening Experiences. We dichotomized the SLE variable into having experienced at least one SLE or no experience of SLEs. Statistical analyses were performed with SPSS v. 25.0. Total protein and LDH concentrations were natural log transformed (ln) to reduce skewness. Multiple linear regression analyses were conducted to explore the association between the DUP and CSF parameters (considered the dependent variable). Age, sex, DUP and SLEs were considered independent variables. We tested the DUP by SLE interaction. Significant interactions were included in the final model. The threshold for significance was set at p<0.05. Results: Fifty-four FEP patients (56.8%) reported an SLE in the previous 6 months. There were no significant differences in the DUP between patients with or without SLEs. There were no significant differences in CSF biomarkers between the SLE groups. In the multiple linear regression analyses, we found a significant DUP by SLE interaction effect on CSF LDH concentrations (standardized beta= -0.320, t= -2.084, p= 0.040). In patients with SLEs, a shorter DUP was associated with higher CSF LDH concentrations and vice versa. No significant associations were found between the DUP or SLEs and other CSF biomarkers (glucose, total proteins). Conclusions: Our study suggests that psychosocial stress moderates the relationship between the onset of psychosis and CSF biomarkers related to bioenergetic systems.

Association between free thyroxine levels and clinical phenotype in first-episode psychosis: a prospective observational study.

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.

Attempted suicide with intravenous methamphetamine and chemsex.

BACKGROUND: Undiagnosed attention deficit and hyperactivity disorder (ADHD) is frequent in the substance abuse disorder population, and has an intense repercussion in the daily life of the patients. That condition increases the risk of substance abuse disorders and risk conducts derived from impulsivity. There are not yet studies linking ADHD and the new emergent phenomenon of chemsex, that is, the action of use the intravenous injection of substances in sex parties, with the objective of maximising the practising time and sexual experience. In these sessions, different types of drug are used, for example, synthetic cathinone or mephedrone, and may lead to diverse medical and psychiatric complications like psychosis, aggressiveness and suicide ideation. CASE: We report the case of a 44-year-old man admitted into a psychiatric unit, presenting with 2nd time suicidal high risk attempt using intravenous methamphetamine and a dissolvent acid in the context of a depressive episode, after practising chemsex sessions almost every weekend with psychoactive substances taken orally, intravenously and intrarectally. The patient also presented psychotic symptoms from the use of these drugs. When we interviewed the patient during his hospital stay, we observed that there were symptoms of a possible attention and hyperactivity deficit, which was confirmed by study with ASRS-V1.1 and WURS scales. After three weeks, the patient improved substantially as his depressive symptoms and autolytic ideation disappeared. DISCUSSION: Look for "hidden" symptoms in substance abuse disorder patients. It is important not to delay important diagnostic tests and to prevent complications. Psychiatric and medical conditions related to chemsex have been reported in several European cities, and recently in Spain where it is an emergent phenomenon and a problem concerning medical and political institutions. The suicide attempt with metamphetamine and acid taken intravenously in the case we report, depressive and psychotic symptoms, addiction, suicide attempts and medical complications are described.

Routine cerebrospinal fluid parameters as biomarkers in first-episode psychosis: A prospective observational study.

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.

Anti-NMDA receptor encephalitis in older adults: A systematic review of case reports.

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.

Clinical, Neuroimmunologic, and CSF Investigations in First Episode Psychosis.

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.

Cycloid psychosis as a psychiatric expression of anti-NMDAR encephalitis. A systematic review of case reports accomplished with the authors' cooperation.

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.

Attempted Suicide with Intravenous Methamphetamine and Chemsex. / Intento de suicidio con metanfetamina endovenosa y chemsex.

BACKGROUND: Undiagnosed attention deficit and hyperactivity disorder (ADHD) is frequent in the substance abuse disorder population, and has an intense repercussion in the daily life of the patients. That condition increases the risk of substance abuse disorders and risk conducts derived from impulsivity. There are not yet studies linking ADHD and the new emergent phenomenon of chemsex, that is, the action of use the intravenous injection of substances in sex parties, with the objective of maximising the practising time and sexual experience. In these sessions, different types of drug are used, for example, synthetic cathinone or mephedrone, and may lead to diverse medical and psychiatric complications like psychosis, aggressiveness and suicide ideation. CASE: We report the case of a 44-year-old man admitted into a psychiatric unit, presenting with 2nd time suicidal high risk attempt using intravenous methamphetamine and a dissolvent acid in the context of a depressive episode, after practising chemsex sessions almost every weekend with psychoactive substances taken orally, intravenously and intrarectally. The patient also presented psychotic symptoms from the use of these drugs. When we interviewed the patient during his hospital stay, we observed that there were symptoms of a possible attention and hyperactivity deficit, which was confirmed by study with ASRS-V1.1 and WURS scales. After three weeks, the patient improved substantially as his depressive symptoms and autolytic ideation disappeared. DISCUSSION: Look for "hidden" symptoms in substance abuse disorder patients. It is important not to delay important diagnostic tests and to prevent complications. Psychiatric and medical conditions related to chemsex have been reported in several European cities, and recently in Spain where it is an emergent phenomenon and a problem concerning medical and political institutions. The suicide attempt with metamphetamine and acid taken intravenously in the case we report, depressive and psychotic symptoms, addiction, suicide attempts and medical complications are described.

Considerations of psychotic symptomatology in anti-NMDA encephalitis: Similarity to cycloid psychosis.

Most patients with anti-NMDA receptor (NMDAR) encephalitis present with acute psychosis which is difficult to differentiate from psychotic episodes related to a primarily psychiatric disease. A precise description of the psychiatric phenotype of this disease would greatly facilitate the early diagnosis of these patients. We provide here a detailed description of three of these patients and the similarity of the clinical features with cycloid psychosis. All three patients met Perris and Brockington's criteria for cycloid psychosis in the initial phase of the autoimmune process, including among other an acute and polysymptomatic onset, polymorphous psychotic symptomatology, mood swings, and changes in psychomotricity. In addition, none of the patients had experienced an extended psychiatric prodromal phase. External stress factors preceded symptom onset in the three patients, who also showed common base personality traits and intolerance to a range of antipsychotic treatments. Complementary studies disclosed that the three patients had ovarian teratoma as well as abnormal EEG, and CSF antibodies against NMDAR. Patients with anti-NMDAR encephalitis may present with clinical features that resemble cycloid psychosis. In addition, our patients did not have prodromal history of psychiatric symptoms and showed intolerance to antipsychotic medication, which all should raise concern for anti-NMDAR encephalitis, prompting CSF antibody testing.

Intento de suicidio con metanfetamina endovenosa y chemsex / Attempted Suicide with Intravenous Methamphetamine and Chemsex

RESUMEN Introducción: El trastorno de déficit de atención e hiperactividad no diagnosticado es una condición comórbida frecuente en los trastornos por abuso de sustancias, y tiene un importante impacto en la vida de los pacientes, pues incrementa el riesgo de abuso de sustancias y el riesgo derivado de conductas impulsivas. En el momento actual no existen trabajos que estudien la relación entre el TDAH y el fenómeno emergente del chemsex, es decir, el uso de sustancias psicoactivas en el contexto de fiestas sexuales para maximizar el tiempo de práctica sexual y de las experiencias subjetivas. En estas sesiones se usan diferentes sustancias como, por ejemplo, las catinonas sintéticas como la mefedrona, que podría inducir complicaciones médicas y psiquiátricas como psicosis, agresividad e ideación suicida. Caso: Un varón de 44 arios ingresó en la unidad de agudos de psiquiatría tras un segundo intento de suicidio de alto riesgo con el uso de metanfetamina endovenosa mezclada con un ácido queratolítico, en el contexto de un episodio depresivo y práctica activa de sesiones de chemsex con una frecuencia semanal, en las que tomaba mefedrona vía transrectal, que provoca episodios puntuales de psicosis tóxica autolimatada. Se objetivó clínica compatible con TDAH no diagnosticado, y se aplicaron ASRS-V1.1 y WURS, que indicaron TDAH. Se ajustó el tratamiento antidepresivo y remitieron los síntomas depresivos y la ideación autolítica. Discusión: La búsqueda de síntomas de TDAH «ocultos¼ en el contexto del abuso de sustancias es importante para no retrasar diagnósticos con importancia esencial y prevenir complicaciones. Complicaciones médicas y psiquiátricas relacionadas con la práctica del chemsex se han comunicado en Europa y recientemente en España, donde es un fenómeno emergente que preocupa. Se describen el intento de suicidio con metanfetamina, síntomas depresivos y psicóticos, abuso de sustancias y complicaciones médicas.

ABSTRACT Background: Undiagnosed attention deficit and hyperactivity disorder (ADHD) is frequent in the substance abuse disorder population, and has an intense repercussion in the daily life of the patients. That condition increases the risk of substance abuse disorders and risk conducts derived from impulsivity. There are not yet studies linking ADHD and the new emergent phenomenon of chemsex, that is, the action of use the intravenous injection of substances in sex parties, with the objective of maximising the practising time and sexual experience. In these sessions, different types of drug are used, for example, synthetic cathinone or mephedrone, and may lead to diverse medical and psychiatric complications like psychosis, aggressiveness and suicide ideation. Case: We report the case of a 44-year-old man admitted into a psychiatric unit, presenting with 2nd time suicidal high risk attempt using intravenous methamphetamine and a dissolvent acid in the context of a depressive episode, after practising chemsex sessions almost every weekend with psychoactive substances taken orally, intravenously and intrarectally. The patient also presented psychotic symptoms from the use of these drugs. When we interviewed the patient during his hospital stay, we observed that there were symptoms of a possible attention and hyperactivity deficit, which was confirmed by study with ASRS-V1.1 and WURS scales. After three weeks, the patient improved substantially as his depressive symptoms and autolytic ideation disappeared. Discussion: Look for "hidden" symptoms in substance abuse disorder patients. It is impor-tant not to delay important diagnostic tests and to prevent complications. Psychiatric and medical conditions related to chemsex have been reported in several European cities, and recently in Spain where it is an emergent phenomenon and a problem concerning medical and political institutions. The suicide attempt with metamphetamine and acid taken intravenously in the case we report, depressive and psychotic symptoms, addiction, suicide attempts and medical complications are described.