Striatal glutamate, subcortical structure and clinical response to first-line treatment in first-episode psychosis patients.

INTRODUCTION: Recent studies have observed that patients with treatment-resistant schizophrenia as well as patients with schizophrenia who do not respond within a medication trial exhibit excess activity of the glutamate system. In this study we sought to replicate the within-trial glutamate abnormality and to investigate the potential for structural differences and treatment-induced changes to improve identification of medication responders and non-responders. METHODS: We enrolled 48 medication-naïve patients in a 4-week trial of risperidone and classified them retrospectively into responders and non-responders using clinical criteria. Proton magnetic resonance spectroscopy and T1-weighted structural MRI were acquired pre- and post-treatment to quantify striatal glutamate levels and several measures of subcortical brain structure. RESULTS: Patients were classified as 29 responders and 19 non-responders. Striatal glutamate was higher in the non-responders than responders both pre- and post-treatment (F1,39 = 7.15, p = .01). Volumetric measures showed a significant group x time interaction (t = 5.163, <1%FDR), and group x time x glutamate interaction (t = 4.23, <15%FDR) were seen in several brain regions. Striatal volumes increased at trend level with treatment in both groups, and a positive association of striatal volumes with glutamate levels was seen in the non-responders. CONCLUSIONS: Combining anatomic measures with glutamate levels offers the potential to enhance classification of responders and non-responders to antipsychotic medications as well as to provide mechanistic understanding of the interplay between neuroanatomical and neurochemical changes induced by these medications. Ethical statement The study was approved by the Ethics and Scientific committees of the Instituto Nacional de Neurología y Neurocirugía in Mexico City. All participants over 18 years fully understood and signed the informed consent; in case the patient was under 18 years, informed consent was obtained from both parents. Participants did not receive a stipend.

Evaluación de síndrome metabólico en varones hospitalizados en Unidad de Corta Estadía Psiquiátrica Marzo 2017 / Evaluation of metabolic syndrome in Hospitalized Men in the Short Stay Psychiatric Unit. March 2017

El síndrome metabólico (SM) corresponde a un conjunto de factores de riesgo derivados de la obesidad visceral e insulinoresistencia. 35.3% de la población adulta chilena presentó SM en el período 2009 - 2010, con diferencia significativa entre hombres y mujeres (41.6% vs 30.9%, respectivamente). En Estados Unidos se ha calculado que la media de años potencialmente perdidos en pacientes con enfermedades mentales va de 25 a 30, comparada con la población general. La principal causa de muerte es la enfermedad coronaria. La mayoría de los pacientes en tratamiento neuroléptico en hospitales psiquiátricos no reciben control de factores de riesgo metabólicos. La evidencia señala que los pacientes esquizofrénicos no son adecuadamente pesquisados ni tratados por Dislipidemia (hasta un 88% de estos pacientes siguen sin tratamiento) ni por hipertensión (hasta un 62%). El objetivo de este trabajo es evaluar factores de riesgo cardiovascular en varones hospitalizados en unidad de corta estadía psiquiátrica del Instituto Psiquiátrico Dr. José Horwitz Barak. Se evaluó a 35 pacientes varones, de los cuales un 37% presentó SM, un 45.3% presentó sobrepeso.

The metabolic syndrome (MS) corresponds to a set of risk factors derived from visceral obesity and insulin resistance. 35.3% of the Chilean adult population had MS in the 2009-2010 period, with a significant difference between men and women (41.6% vs 30.9%, respectively). In the United States, it has been estimated that the average number of years potentially lost in patients with mental illness ranges from 25 to 30, compared with the general population. The main cause of death is coronary heart disease. Most patients on neuroleptic treatment in psychiatric hospitals do not receive control of metabolic risk factors. The evidence indicates that schizophrenic patients are not adequately researched or treated for dyslipidemia (up to 88% of these patients remain untreated) or hypertension (up to 62%). OBJECTIVE: To evaluate cardiovascular risk factors in hospitalized men in a short stay psychiatric unit of the Psychiatric Institute Dr. José Horwitz Barak. Thirty-five male patients were evaluated, of which 37% had MS, and 45.3% were overweight.

Increased platelet glycogen sysnthase kinase 3beta in first-episode psychosis.

Past studies have linked intracellular pathways related to psychotic disorders to the GSK3B enzyme. This study aimed to investigate GSK3B protein expression and phosphorylation in drug-naïve first-episode psychosis patients (n=43) at baseline and following symptom remission, and in healthy controls (n=77). At baseline GSK3B total level was higher in patients (p<0.001). In schizophrenia spectrum patients (n=25) GSK3B total and phosphorylated levels were higher than in controls and patients with other non-affective psychotic disorders (n=18) (p<0.001; p=0.027; p=0.05 respectively). No enzyme changes were found after clinical remission. The implication of this finding for the biology of psychoses warrants further studies to clarify whether increased GSK3B may be useful as a biomarker for psychosis in general, and schizophrenia in particular.

Post-stroke psychosis: how long should we treat? / Psicose após acidente vascular cerebral: até quando devemos tratar?

Abstract Objective: To describe a rare case of a patient who developed psychotic symptoms after a right stroke that disappeared with antipsychotic treatment, but appears to need low-dose maintenance antipsychotic therapy. Case description: A 65-year-old man presented at the psychiatric emergency service with a history of persistent delusional jealousy, visual illusions and agitation with onset about 1 month after a right posterior cerebral artery ischemic stroke. These symptoms only disappeared with therapeutic dosages of an antipsychotic drug (3 mg/day of risperidone). At 2-year follow-up, he no longer had delusional activity and the antipsychotic treatment was gradually discontinued over the following year. However, 1 week after full cessation, the patient once more became agitated and suspicious and was put back on risperidone at 0.25 mg/day, resulting in rapid clinical remission. One year after the return to low-dose risperidone, the patient's psychopathology is still under control and he is free from psychotic symptoms. Comments: Psychosis is a relatively rare complication after stroke. To our knowledge, no cases of post-stroke psychosis that apparently require continuous low-dose antipsychotic treatment have been reported to date. Our case suggests that low-dose maintenance antipsychotic therapy may be needed for certain patients with post-stroke psychosis, especially for those with risk factors and non-acute onset.

Resumo Objetivo: Descrever o caso raro de um paciente que desenvolveu sintomas psicóticos após um acidente vascular cerebral (AVC) no nível do hemisfério direito que remitiram com tratamento antipsicótico, mas parece precisar de uma terapêutica de manutenção com antipsicótico em baixa dosagem. Descrição de caso: Um homem de 65 anos apresentou-se no serviço de urgência psiquiátrica por um quadro persistente de delírio de ciúmes, ilusões visuais e agitação com início cerca de 1 mês após AVC isquêmico no nível da artéria cerebral posterior direita. Esses sintomas só desapareceram com doses terapêuticas de antipsicótico (risperidona 3 mg/dia). Após 2 anos de seguimento, o paciente não mais apresentava atividade delirante, e o tratamento antipsicótico foi progressivamente descontinuado durante o ano seguinte. No entanto, 1 semana após a suspensão total, o paciente começou a ficar agitado e desconfiado, tendo-se reiniciado a risperidona 0,25 mg/dia, com rápida remissão clínica. O paciente está medicado com esta baixa dose de antipsicótico há um ano, permanecendo psicopatologicamente compensado e sem sintomas psicóticos. Comentários: A psicose é uma complicação relativamente rara após AVC. Segundo nosso conhecimento, não há casos descritos até ao momento de psicose após AVC que, aparentemente, requerem uma dose baixa contínua de antipsicótico. Nosso caso sugere que uma terapêutica de manutenção com antipsicótico em baixa dosagem pode ser necessária para determinados pacientes com psicose após AVC, especialmente para aqueles com fatores de risco e início não agudo dos sintomas.

Incremento del glutamato en el estriado de asociación en esquizofrenia. Resultados preliminares de un estudio longitudinal con espectroscopia con resonancia magnética / Glutamate increase in the associative striatum in schizophrenia: a longitudinal magnetic resonance spectroscopy preliminary study

Objetivo: Comparar los niveles de glutamato en el núcleo caudado dorsal, región rica en dopamina, y el cerebelo, región pobre en dopamina, en pacientes con esquizofrenia, durante un episodio psicótico agudo, después de recibir tratamiento antidopaminérgico (risperidona) y en controles sanos. Métodos: Se incluyeron 14 pacientes con esquizofrenia aguda sin tratamiento y 14 controles sanos. A los pacientes se les realizaron dos estudios de espectroscopia por resonancia magnética de protones (ERM1H). El primero antes de tratamiento y el segundo a las seis semanas de tratamiento efectivo. Los controles fueron evaluados en una ocasión. Los niveles de glutamato fueron normalizados con la concentración de creatina. Resultados: Los niveles de glutamato/creatina fueron mayores en el caudado dorsal de los pacientes previo a tratamiento (t=-2.16, p=0.03) y después del tratamiento en comparación con los controles (t=2.12, p=0.04). Los niveles de glutamato en el cerebelo no cambiaron con el tratamiento y fueron iguales a los controles. Conclusiones: Nuestros resultados indican que el incremento delglutamato en el caudado dorsal se encuentra en relación con la enfermedad y no cambia después de seis semanas de tratamiento antipsicótico efectivo. Más aún, la ausencia de diferencias en el cerebelo sugiere que el incremento del glutamato presente en la esquizofrenia se podría relacionar a regiones con abundante inervación dopaminérgica.

OBJECTIVE: To compare glutamate levels (Glu) found in the dorsal-caudate nucleus (a dopamine rich region) and in the cerebellum (a low dopamine region) among: 1) schizophrenia patients undergoing an acute psychotic episode, 2) after receiving antidopaminergic treatment (Risperidone), and 3) healthy controls. METHODS: Fourteen drug-free patients with schizophrenia and fourteen healthy controls were included. Patients underwent two proton magnetic resonance spectroscopy (1H-MRS) studies, one prior to treatment and the second after 6-weeks of daily Risperidone treatment. Controls underwent one 1H-MRS study. Glutamate levels were normalized according to the relative concentration of Creatine (Cr). RESULTS: The dorsal-caudate nucleus among schizophrenia patients showed higher levels of Glu/Cr during the drug-free condition (t = -2.16, p = 0.03) and after antipsychotic treatment (t = 2.12, p = 0.04) compared with controls. No difference was observed in the cerebellum between the drug-free, post-treatment and controls conditions. CONCLUSIONS: Our results suggest that the Glu increase observed in the dorsal-caudate in schizophrenia is illness-mediated and does not change after 6-weeks of antipsychotic treatment. Moreover, the lack of change detected in the cerebellum suggests that the Glu increase in schizophrenia is not ubiquitous within the brain and that may be associated with dopamine target regions.

Crises epilépticas e uso de olanzapina: relato de dois casos / Epileptic seizures and olanzapine use: two cases report

INTRODUÇÃO: Lentificação difusa ou focal da atividade de base e atividade epileptiforme ao eletrencefalograma, assim como desenvolvimento de crises epilépticas foram descritas, na literatura, em pacientes em uso de drogas antipsicóticas, como os fenotiazidicos e a butirofenona. No entanto, há relatos de baixo risco de ocorrência de crises epilépticas relacionadas ao uso da olanzapina. OBJETIVO: Avaliar a relação de olanzapina e crises epilépticas em dois casos. MÉTODO: São Relatados os casos de dois acientes de 45 e 37 anos de idade, com diagnóstico de esquizofrenia, que apresentaram crises epilépticas generalizadas, respectivamente, quatro meses e um mês após o início do uso de olanzapina. No eletrencefalograma havia complexos de ponta-onda generalizados em um paciente e focais em outro. CONCLUSÃO: Houve associação de crises epilépticas e uso de olanzapina em dois casos.

INTRODUCTION: Slowing and epileptiform activity in EEG-patterns as well as epileptic seizures have been published during antipsychotic therapy with phenothiazines and butyrophenones. More recently, olanzepine, a new class of antipsychotic drug for use in treatment of refractory schizophrenics has been associated with a low risk of epileptic seizure occurrence. METHODS: We studied two patients, 45 and 37 years old, with schizophrenia and generalized epileptic seizures appearing, respectively, four and one month after starting olanzapine treatment. Their electroencephalogram showed spike-wave discharges generalized in one case and focal in the second patient. CONCLUSION: It was observed an association between epileptic seizures and olanzapine use.