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.

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.].

The nature of memory impairment in multiple sclerosis: understanding different patterns over the course of the disease.

Introduction: Memory deficit is one of the most common and severe cognitive impairments in patients with multiple sclerosis and can greatly affect their quality of life. However, there is currently no agreement as to the nature of memory deficit in multiple sclerosis. Methods: This cross-sectional study, carried out at the Dr. Josep Trueta and Santa Caterina hospitals in Girona (Spain), was designed to determine the semiology of verbal memory deficit in the different stages of the disease. To this end, a modification of Rey's verbal auditory test was created by introducing two recognition trials between the five learning trials, thus monitoring what happens in terms of acquisition versus the retrieval of information during the learning phase. Linear regression models were used to evaluate verbal episodic memory performance between-groups adjusting results by age, sex, educational level, and the presence of anxiety and/or depressive symptoms. Results: 133 patients with multiple sclerosis, clinically isolated syndrome, and radiologically isolated syndrome and 55 healthy controls aged 18-65 years were assessed. It was observed that the memory processes of multiple sclerosis patients worsen with the progression of the disease. In this respect, patients in pre-diagnostic phases (radiologically isolated syndrome and clinically isolated syndrome) show no differences in verbal episodic memory compared to the healthy controls. Patients in the inflammatory stage (relapsing-remitting multiple sclerosis) show a previously learned information retrieval deficit, while patients in progressive stages (secondary progressive multiple sclerosis and primary progressive multiple sclerosis) do not even correctly acquire information. Discussion: These results provide significant information to assist in understanding the nature of memory deficits in multiple sclerosis over the course of the disease. These results are discussed in terms of possible cognitive rehabilitation strategies depending on the evolutive stage and are related to neuropathological mechanisms involved in the progression of the disease.

Encefalitis antirreceptor de NMDA. Diagnóstico y tratamiento precoz en pacientes con sintomatología psicótica aguda-subaguda / Anti-NMDA receptor encephalitis. Early diagnosis and treatment in patients with acute-subacute psychotic symptoms

Introducción. La encefalitis por anticuerpos antirreceptor de NMDA es una entidad aguda y grave, cuya rápida identificación y tratamiento puede comportar recuperaciones sin secuelas. Es más prevalente en mujeres jóvenes y a menudo está asociada a un tumor subyacente. Los síntomas iniciales son habitualmente psiquiátricos y en días o semanas adquieren el perfil neurológico característico. Casos clínicos. Tres mujeres, de 17, 23 y 35 años, que ingresaron en el Servicio de Psiquiatría con clínica psicótica aguda. La mala respuesta a los antipsicóticos, las fluctuaciones del nivel de conciencia, la disautonomía y las crisis epilépticas fueron los síntomas que despertaron la sospecha clínica. El líquido cefalorraquídeo mostró leve pleocitosis y positividad para los anticuerpos antirreceptor de NMDA en todas las pacientes. Sólo una mostró alteraciones en la resonancia magnética cerebral, y dos, el patrón electroencefalográfico extreme delta brush. En todas se diagnosticó un teratoma ovárico, que fue resecado antes del mes. Dos se recuperaron sin secuelas y la tercera, a los seis meses del alta, presenta secuelas cognitivas. Conclusiones. Los casos descritos comenzaron con clínica psicótica aguda. La evolución psiquiátrica atípica y la clínica neurológica alertaron de la posibilidad de una encefalitis. El reconocimiento de la enfermedad y la coordinación entre servicios es fundamental para un diagnóstico y tratamiento precoz. El análisis sistemático de líquido cefalorraquídeo en pacientes con un primer episodio psicótico agudo-subagudo contribuiría a adelantar el diagnóstico. En mujeres jóvenes hay que buscar siempre un teratoma ovárico u otro tumor asociado

Introduction. Encephalitis due to anti-NMDA receptor antibodies is an acute and severe condition, which, if identified and treated quickly, can entail recovery without any sequelae. It is more prevalent in young females and is often associated with an underlying tumour. The initial symptoms are usually of a psychiatric nature, and in a matter of days or weeks take on a characteristic neurological profile. Case reports. We report the cases of three women, 17, 23 and 35 years of age, who were admitted to Psychiatry with acute psychotic clinical features. The poor response to antipsychotics, the fluctuations in the level of consciousness, dysautonomia and epileptic seizures were the symptoms that led to the clinical suspicion. The cerebrospinal fluid revealed slight pleocytosis and gave positive for anti-NMDA receptor antibodies in all cases. Only one patient displayed alterations in the magnetic resonance brain scan, and in two cases there was an extreme delta brush electroencephalographic pattern. All three women were diagnosed with an ovarian teratoma which was resectioned within a month. Two of the patients recovered without any sequelae, and the third presents cognitive sequelae six months after being discharged. Conclusions. The cases described began with an acute psychotic clinical picture. The atypical psychiatric progression and the neurological symptoms indicated the possible presence of encephalitis. Recognition of the disease and coordination among the different services is essential for early diagnosis and treatment. The systematic analysis of cerebrospinal fluid in patients with a first acute-subacute psychotic episode would help to reach a diagnosis sooner. In young women, a search must always be carried out for an ovarian teratoma or other associated tumour

An update on the molecular analysis of classical galactosaemia patients diagnosed in Spain and Portugal: 7 new mutations in 17 new families

Background and objectives: Classical galactosaemia is an inherited metabolic disorder due to mutations in the galactose-1-phosphate uridytransferase gene (GALT). We previously reported molecular analysis of 83 Spanish and Portuguese unrelated galactosaemic patients. Here we present the results of another seventeen unreported affected individuals. Material and methods: DNA from patients was PCR-amplified and sequenced following standard protocols. Results: Twelve patients diagnosed in Spain were studied. We detected five alleles carrying p.Q188R, accounting for 21%. Other six alleles (25%) were identified with the mutation p.K285N. We also identified six novel mutations: p.Q9X, c.328+2T>C, p.I170N, p.C180F, p.V233L and p.P257L. Taking into account all the Spanish galactosaemic diagnosed patients, mutation p.Q188R is still the most frequent mutation identified (44.4%). In five new Portuguese patients, five alleles p.Q188R were detected, representing 50%. One novel mutation (p.F171C) was identified. Conclusions: Our results confirm our previous observations that p.Q188R is the most frequent mutation in Iberian Peninsula galactosaemic patients (49%), and that Portuguese and Spanish genotypes differ (AU)

Fundamento y objetivo: La galactosemia clásica es una enfermedad metabólica hereditaria debida a mutaciones en el gen de la galactosa-1-fosfato uridiltransferasa (GALT). Nuestro grupo ya publicó los resultados del análisis molecular de 83 pacientes galactosémicos de España y Portugal. Aquí se presentan los resultados de una nueva serie de pacientes. Material y método: El ADN de los 17 pacientes estudiados se amplificó por PCR y se secuenció siguiendo métodos ya descritos. Resultados: Se analizó a 12 doce pacientes diagnosticados en España y detectamos 5 alelos con la mutación p.Q188R (21%). Otros 6 alelos (25%) resultaron portadores de la mutación p.K285N. También se identificaron 6 mutaciones nuevas:p.Q9X,c.328+2T4C, p.I170N, p.C180F, p.V233L y p.P257L. Considerando a todos los pacientes diagnosticados en España, la mutación p.Q188R sigue siendo la mutación mas frecuente (44,4%). En 5 pacientes portugueses se detectaron 5 alelosp.Q188R(50%) y se identificó una nueva mutación (p.F171C). Conclusiones: Estos resultados confirman las observaciones previas, en las cuales se mostraba que la mutación más frecuente en la península Ibérica es p.Q188R(49%), pero que los genotipos españoles y portugueses difieren entre sí (AU)