Influence of glutathione-related genetic variants on the oxidative stress profile of Mexican patients with psychotic disorders

Objective: The clinical trajectories of patients with psychotic disorders have divergent outcomes, which may result in part from glutathione (GSH)-related high-risk genotypes. We aimed to determine pharmacokinetics of clozapine, GSH levels, GSH peroxidase (GPx) activity, gene variants involved in the synthesis and metabolism of GSH, and their association with psychotic disorders in Mexican patients on clozapine monotherapy and controls. Methods: The sample included 75 patients with psychotic disorders on clozapine therapy and 40 paired healthy controls. Plasma clozapine/N-desmethylclozapine, GSH concentrations, and GPx activity were determined, along with genotyping of GCLC and GSTP1 variants and copy number variations of GSTP1, GSTT1, and GSTM1. Clinical, molecular and biochemical data were analyzed with a logistic regression model. Results: GSH levels were significantly reduced and, conversely, GPx activity was higher among patients than controls. GCLC_GAG-7/9 genotype (OR = 4.3, 95%CI = 1.40-14.31, p = 0.019) and hetero-/homozygous genotypes of GCLC_rs761142 (OR = 6.09, 95%CI = 1.93-22.59, p = 0.003) were found to be risk factors for psychosis. The genetic variants were not related to clozapine/N-desmethylclozapine levels or metabolic ratio. Conclusions: GCLC variants were associated with the oxidative stress profile of patients with psychotic disorders, raising opportunities for intervention to improve their antioxidant defenses. Further studies with larger samples should explore this proposal.

Síntomas depresivos inducidos por el retiro de benzodiacepinas en el trastorno esquizoafectivo. Reporte de un caso / Depressive symptoms induced by benzodiazepine withdrawal in schizoaffective disorder. Case report

Resumen Introducción: Dentro del espectro de las enfermedades psiquiátricas, una de las más complejas es el trastorno esquizoafectivo debido al reto diagnóstico y al manejo psicofarmacológico. Esta enfermedad combina síntomas cardinales de la esquizofrenia con síntomas de trastornos del afecto. El tratamiento se enfoca entonces a mejorar los síntomas psicóticos y regular el estado de ánimo. Dentro de los fármacos que se utilizan se encuentran las benzodiacepinas, que deben retirarse gradualmente para evitar recaídas o síntomas de abstinencia. En este reporte comentamos el caso de una paciente que después del retiro gradual hasta la suspensión de clonazepam presentó síntomas depresivos que remitieron tras la reinstalación del fármaco. Reporte del caso: Mujer de 31 años de edad sin antecedentes de importancia para su padecimiento actual. Inició con síntomas psicóticos que requirieron hospitalización, donde se agregaron síntomas maniatiformes y se integró el diagnostico de episodio maniaco con síntomas psicóticos. Se manejó con un antipsicótico, estabilizador del estado de ánimo y benzodiacepinas, con lo que sus síntomas remitieron. A los dos años presentó un cuadro psicótico sin síntomas afectivos y se diagnosticó como trastorno esquizoafectivo según el DSM V. Por su mejoría se disminuyeron los fármacos de forma gradual. Tras la suspensión del clonazepam, la paciente presentó síntomas depresivos que remitieron al reinstalar el fármaco. Discusión: La aparición súbita de síntomas depresivos se consideró como una posible recaída dada la patología de base. Estrictamente hablando, la paciente no cumplía criterios para diagnosticar un síndrome de abstinencia a benzodiacepinas. En la literatura se reporta que en algunos casos los síntomas depresivos pueden ser parte de este espectro, sin embargo no se especifica ni temporalidad ni alguna otra característica relevante. Tras el reinicio del fármaco a la dosis mínima que utilizaba la paciente, en menos de dos semanas se logró la remisión total de un episodio que cumplía los criterios diagnósticos para un trastorno depresivo mayor. Esto nos permitió establecer una relación directa entre la suspensión del clonazepam y la aparición de dichos síntomas. Conclusiones: A pesar de que el manejo dependerá de las características de cada paciente y las preferencias de su médico, vale la pena tener en mente la aparición de síntomas poco usuales asociados con el uso de los fármacos aun a pesar de seguir los lineamientos establecidos para el cambio y suspensión, en este caso, de las benzodiacepinas.

Abstract Introduction: Within the spectrum of psychiatric illnesses one of the most complex is the schizoaffective disorder due to the fact that both, its diagnosis and pharmacological management are challenging. This disease combines cardinal symptoms of schizophrenia and mood disorders symptoms. The aim of the treatment focuses on improving both psychotic symptoms and mood stabilization. Benzodiazepines are frequently used, and should be gradually reduced in order to prevent either a relapse or withdrawal symptoms. Here, we report the case of a 31-year-old female patient that after a gradual reduction of benzodiazepines and the suspension of clonazepam developed depressive symptoms, which subsided after the drug reinstatement. Case report: A 31-year-old female with no relevant past medical history developed psychotic symptoms that required hospitalization. Maniac symptoms appeared and therefore, the diagnosis was a manic episode with psychotic symptoms. Antipsychotic drugs, a mood stabilizer and benzodiazepines were the treatment used and the patient showed clinical improvement. She was free of clinical manifestations for two years, until the patient presented a psychotic episode without mood symptoms; therefore she was diagnosed with schizoaffective disorder according to the DSM V criteria. After clinical improvement drugs were decreased gradually. Following the suspension of clonazepam the patient had depressive symptoms that disappeared after the reinstatement of the drug. Discussion: The sudden appearance of depressive symptoms was considered as a possible relapse linked to the underlying disease. Strictly speaking, the patient did not meet the criteria for benzodiazepine withdrawal syndrome. The literature reports that in some cases depressive symptoms may be part of this spectrum, however neither a temporality nor any other relevant characteristics were specified. After restarting the drug at the lowest dose that the patient used, total remission of the major depressive disorder was achieved in less than two weeks. This allowed us to establish, at our discretion, a direct link between the suspension of clonazepam and the appearance of these symptoms. Conclusion: Although the management depends on the characteristics of each patient and the physician preferences, it is worth keeping in mind the possibility of unusual symptoms that may appear even by following the correct guidelines established for a correct decrease doses and the suspension of benzodiazepines.

Infarto del miocardio y cocaína: presentación de un caso / Myiocardial infarction and cocaine: presentation of an case

Se presenta un nuevo caso de infarto del miocardio relacionado con el uso de cocaína por vía intranasal en nuestro medio. Se trata de un paciente masculino de 40 años de edad sin antecedente de: enfermedad coronaria familiar o personal, diabetes mellitus, obesidad, ni de hipertensión arterial, el cual refirió ser consumidor de cocaína desde los 25 años de edad y haber consumido cocaína 1 hora antes de presentar la sintomatología clásica de oclusión coronaria aguda