Antidepressant- and anxiolytic-like activities and acute toxicity evaluation of the Psilocybe cubensis mushroom in experimental models in mice.

ETHNOPHARMACOLOGY RELEVANCE: Central nervous system (CNS) diseases can be diverse and usually present with comorbidity, as in the case of depression and anxiety. Despite alternatives like Psilocybe mushrooms for mental health there is no basic research to evidence their CNS benefits. AIM OF THE STUDY: To evaluate the anxiolytic- and antidepressant-like effects, as well as the acute toxicity of P. cubensis mushroom. MATERIAL AND METHODS: First, the acute toxicity (LD50) of P. cubensis (2000 mg/kg) was determined after the esophageal (p.o.) and intraperitoneal (i.p.) route of administration. The rota-rod test and electroencephalogram (EEG) were included to assess CNS toxicity in free moving mice. Anxiolytic (ambulatory or exploratory and rearing behaviors) and antidepressant behavioral responses were assayed in the open-field, plus-maze, and forced swimming test, respectively, after administration of 1000 mg/kg, p.o., of the whole P. cubensis mushroom or the polar aqueous (AQ) or methanolic (MeOH) extractions (1, 10, and/or 100 mg/kg, i.p.) in comparison to the reference drugs buspirone (4 mg/kg, i.p.), fluoxetine and/or imipramine (10 mg/kg, s.c. and i.p., respectively). A chemical analysis of the AQ and MeOH extractions was performed to detect psilocybin and/or psilocin by using UHPLC. RESULTS: Neurotoxic effects of P. cubensis mushroom administered at high doses were absent in mice assessed in the rota-rod test or for EEG activity. A LD50 > 2000 mg/kg was calculated by p.o. or i.p. administration. While significant and/or dose-response antidepressant-like effects were produced with the whole P. cubensis mushroom, p.o., and after parenteral administration of the AQ or MeOH extractions resembling the effects of the reference drugs. Behavioral responses were associated with an anxiolytic-like effect in the open-field as corroborated in the plus-maze tests. The presence of psilocybin and psilocin was mainly characterized in the AQ extraction. CONCLUSION: Our results provide preclinical evidence of the anxiolytic- and antidepressant-like effects of the P. cubensis mushroom without producing neurotoxicity after enteral or parenteral administration, where psilocybin and psilocin were identified mainly after AQ extraction. This study reinforces the benefits of the P. cubensis mushroom in mental health and therapy for anxiety and depression.

Toll-Like Receptor (TLR) 1, 2, and 6 Gene Polymorphisms Support Evidence of Innate Immune Factors in Schizophrenia.

Introduction: Schizophrenia is a complex psychiatric disorder with an important genetic contribution. Immunological abnormalities have been reported in schizophrenia. Toll-like receptor (TLR) genes play an important role in the activation of the innate immune response, which may help to explain the presence of inflammation in people with this disorder. The aim of this study was to analyze the association of TLR1, TLR2, and TLR6 gene polymorphisms in the etiology of schizophrenia. Methods: We included 582 patients with schizophrenia and 525 healthy controls. Genetic analysis was performed using allelic discrimination with TaqMan probes. Results: We observed significant differences between patients and controls in the genotype and allele frequencies of TLR1/rs4833093 (χ2 = 17.3, p = 0.0002; χ2 = 15.9, p = 0.0001, respectively) and TLR2/rs5743709 (χ2 = 29.5, p = 0.00001; χ2 = 7.785, p = 0.0053, respectively), and in the allele frequencies of TLR6/rs3775073 (χ2 = 31.1, p = 0.00001). Finally, we found an interaction between the TLR1/rs4833093 and TLR2/rs5743709 genes, which increased the risk of developing schizophrenia (OR = 2.29, 95% CI [1.75, 3.01]). Discussion: Our findings add to the evidence suggesting that the activation of innate immune response might play an important role in the development of schizophrenia.

Adverse effects of antipsychotics on sleep in patients with schizophrenia. Systematic review and meta-analysis.

Introduction: Our objective was to conduct a systematic review and meta-analysis of adverse effects on sleep in patients with schizophrenia receiving antipsychotic treatment. Methods: A systematic search was performed in PubMed, Cochrane Central, Embase, Toxline, Ebsco, Virtual Health Library, Web of Science, SpringerLink, and in Database of abstracts of Reviews of Effects of Randomized Clinical Trials to identify eligible studies published from January 1990 to October 2021. The methodological quality of the studies was evaluated using the CONSORT list, and the Cochrane bias tool. Network meta-analysis was performed using the Bayesian random-effects model, with multivariate meta-regression to assess the association of interest. Results: 87 randomized clinical trials were identified that met the inclusion criteria, and 70 articles were included in the network meta-analysis. Regarding the methodological quality of the studies, 47 had a low or moderate bias risk. The most common adverse effects on sleep reported in the studies were insomnia, somnolence, and sedation. The results of the network meta-analysis showed that ziprasidone was associated with an increased risk of insomnia (OR, 1.56; 95% credible interval CrI, 1.18-2.06). Several of the included antipsychotics were associated with a significantly increased risk of somnolence; haloperidol (OR, 1.90; 95% CrI, 1.12-3.22), lurasidone (OR, 2.25; 95% CrI, 1.28-3.97) and ziprasidone (OR, 1.79; 95% CrI, 1.06-3.02) had the narrowest confidence intervals. In addition, perphenazine (OR, 5.33; 95% CrI, 1.92-14.83), haloperidol (OR, 2.61; 95% CrI, 1.14-5.99), and risperidone (OR, 2.41; 95% CrI, 1.21-4.80) were associated with an increased risk of sedation compared with placebo, and other antipsychotics did not differ. According to the SUCRAs for insomnia, chlorpromazine was ranked as the lowest risk of insomnia (57%), followed by clozapine (20%), while flupentixol (26 %) and perospirone (22.5%) were associated with a lower risk of somnolence. On the other hand, amisulpride (89.9%) was the safest option to reduce the risk of sedation. Discussion: Insomnia, sedation, and somnolence were the most frequent adverse effects on sleep among the different antipsychotics administered. The evidence shows that chlorpromazine, clozapine, flupentixol, perospirone, and amisulpride had favorable safety profiles. In contrast, ziprasidone, perphenazine, haloperidol, and risperidone were the least safe for sleep. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42017078052, identifier: PROSPERO 2017 CRD42017078052.

Genetic analysis of the ZNF804A gene in Mexican patients with schizophrenia, schizoaffective disorder and bipolar disorder.

BACKGROUND: Evidence suggests that schizophrenia (SCZ), schizoaffective disorder (SAD) and bipolar disorder (BPD) share genetic risk variants. ZNF804A gene has been associated with these disorders in different populations. GWAS and candidate gene studies have reported association between the rs1344706 A allele with SCZ, SAD and BPD in European and Asian populations. In Mexican patients, no studies have specifically analyzed ZNF804A gene variants with these disorders. The aim of the study was to analyze the rs1344706 and identify common and rare variants in a targeted region of the ZNF804A gene in Mexican patients with SCZ, BPD and SAD compared with a control group. METHODS: We genotyped the rs1344706 in 228 Mexican patients diagnosed with SCZ, SAD and BPD, and 295 controls. Also, an additional sample of 167 patients with these disorders and 170 controls was analyzed to identify rare and common variants using the Sanger-sequence analysis of a targeted region of ZNF804A gene. RESULTS: Association analysis of rs1344706 observed a higher frequency of A allele in the patients compared with the control group; however, did not show statistical differences after Bonferronís correction (χ2 = 5.3, p = 0.0208). In the sequence analysis, we did not identify rare variants; however, we identified three common variants: rs3046266, rs1366842 and rs12477430. A comparison of the three identified variants between patients and controls did not show statistical differences (p > 0.0125). Finally, haplotype analysis did not show statistical differences between SCZ, SAD and BPD and controls. CONCLUSIONS: Our findings did not support the evidence suggesting that ZNF804A gene participates in the etiology of SCZ, SAD and BPD. Future studies are needed in a larger sample size to identify the effect of this gene in psychiatric disorders.

Tratamiento de la esquizofrenia en México: recomendaciones de un panel de expertos.

La esquizofrenia es una enfermedad compleja que actualmente no tiene cura. Existen, sin embargo, numerosas terapias que, solas o en combinación, son eficaces para tratar los síntomas de la enfermedad y mantenerla bajo control. La elección del tratamiento debe ser siempre individualizada, y basarse en la presentación clínica de la enfermedad, el estado general del paciente y la eficacia del fármaco, si bien hay que considerar también el costo y el acceso a servicios y al fármaco, que en México tiene algunas limitaciones. Un panel de 12 expertos mexicanos se reunió de forma virtual para revisar los últimos datos publicados y establecer unas recomendaciones de tratamiento en México, basadas en la evidencia, que garanticen una atención médica integral, homogénea, eficiente y con calidad.Schizophrenia is a complex illness that currently has no cure. There are, however, numerous therapies that, alone or in combination, are effective in treating the symptoms of the disease and keeping it under control. The choice of treatment must always be individualized, and based on the clinical presentation of the disease, the general condition of the patient and the efficacy of the drug, although the cost and access to services and to the drug must also be considered, as in Mexico it has some limitations. A panel of 12 Mexican experts met virtually to review the latest published data and establish evidence-based treatment recommendations in Mexico that guarantee comprehensive, homogeneous, efficient, and quality medical care.

Neuropsychiatric Genetics of Psychosis in the Mexican Population: A Genome-Wide Association Study Protocol for Schizophrenia, Schizoaffective, and Bipolar Disorder Patients and Controls.

No large-scale genome-wide association studies (GWASs) of psychosis have been conducted in Mexico or Latin America to date. Schizophrenia and bipolar disorder in particular have been found to be highly heritable and genetically influenced. However, understanding of the biological basis of psychosis in Latin American populations is limited as previous genomic studies have almost exclusively relied on participants of Northern European ancestry. With the goal of expanding knowledge on the genomic basis of psychotic disorders within the Mexican population, the National Institute of Psychiatry Ramón de la Fuente Muñiz (INPRFM), the Harvard T.H. Chan School of Public Health, and the Broad Institute's Stanley Center for Psychiatric Research launched the Neuropsychiatric Genetics Research of Psychosis in Mexican Populations (NeuroMex) project to collect and analyze case-control psychosis samples from 5 states across Mexico. This article describes the planned sample collection and GWAS protocol for the NeuroMex study. The 4-year study will span from April 2018 to 2022 and aims to recruit 9,208 participants: 4,604 cases and 4,604 controls. Study sites across Mexico were selected to ensure collected samples capture the genomic diversity within the Mexican population. Blood samples and phenotypic data will be collected during the participant interview process and will contribute to the development of a local biobank in Mexico. DNA extraction will be done locally and genetic analysis will take place at the Broad Institute in Cambridge, MA. We will collect extensive phenotypic information using several clinical scales. All study materials including phenotypic instruments utilized are openly available in Spanish and English. The described study represents a long-term collaboration of a number of institutions from across Mexico and the Boston area, including clinical psychiatrists, clinical researchers, computational biologists, and managers at the 3 collaborating institutions. The development of relevant data management, quality assurance, and analysis plans are the primary considerations in this protocol article. Extensive management and analysis processes were developed for both the phenotypic and genetic data collected. Capacity building, partnerships, and training between and among the collaborating institutions are intrinsic components to this study and its long-term success.

Neurocognition in Bipolar and Depressive Schizoaffective Disorder: A Comparison with Schizophrenia.

INTRODUCTION: Schizoaffective disorder (SA) is classified into bipolar (bSA) and depressive (dSA) subtypes. Although clinical differences between both have been reported, there is no clear information regarding their specific cognitive profile. OBJECTIVE: To compare neurocognition between SA subtypes and schizophrenia (SC). METHODS: A total of 61 patients were assessed and divided into 3 groups: 35 SC, 16 bSA, and 10 dSA. All participants signed an informed consent letter. The MATRICS Consensus Cognitive Battery, Central and South American version was used to assess neurocognition. The study was performed at the Instituto Nacional de Psiquiatría "Ramón de la Fuente". Participants were identified by specialized psychiatrists. Trained neuropsychologists carried out the clinical and cognitive assessment, which lasted 2 h approximately. RESULTS: The cognitive assessment showed a significant difference in Trail Making Test part A subtest (F[2,58] = 4.043; p = 0.023]. Post hoc analyses indicated that dSA obtained a significantly higher score than SC (MD = -11.523; p = 0.018). The f test showed a large effect size (f = 0.401). No statistical differences were observed regarding other cognitive variables. CONCLUSIONS: The cognitive profile of SA subtypes and SC is similar since no differences were found in most subtests. However, dSA may be less impaired than SC in measures of processing speed. Further research with larger samples must be conducted.

Tratamiento de la esquizofrenia en México: recomendaciones de un panel de expertos / Treatment of schizophrenia in Mexico: recommendations from an expert panel

Resumen La esquizofrenia es una enfermedad compleja que actualmente no tiene cura. Existen, sin embargo, numerosas terapias que, solas o en combinación, son eficaces para tratar los síntomas de la enfermedad y mantenerla bajo control. La elección del tratamiento debe ser siempre individualizada, y basarse en la presentación clínica de la enfermedad, el estado general del paciente y la eficacia del fármaco, si bien hay que considerar también el costo y el acceso a servicios y al fármaco, que en México tiene algunas limitaciones. Un panel de 12 expertos mexicanos se reunió de forma virtual para revisar los últimos datos publicados y establecer unas recomendaciones de tratamiento en México, basadas en la evidencia, que garanticen una atención médica integral, homogénea, eficiente y con calidad.

Abstract Schizophrenia is a complex illness that currently has no cure. There are, however, numerous therapies that, alone or in combination, are effective in treating the symptoms of the disease and keeping it under control. The choice of treatment must always be individualized, and based on the clinical presentation of the disease, the general condition of the patient and the efficacy of the drug, although the cost and access to services and to the drug must also be considered, as in Mexico it has some limitations. A panel of 12 Mexican experts met virtually to review the latest published data and establish evidence-based treatment recommendations in Mexico that guarantee comprehensive, homogeneous, efficient, and quality medical care.

Development of the Mexican Version of the Empathy Quotient / Desarrollo de la versión mexicana del Cuestionario de Empatía

Abstract Introduction Empathy is defined as the ability or process to identify and understand other person's situation, feelings, and motives. These responses are essential for relationships and social behavior. Baron-Cohen et al. created the Empathy Quotient (EQ), a scale explicitly designed to have a clinical application. The instrument evaluates three constructs of empathy and several studies around worldwide, but not in Mexico. Objective To examine the psychometric properties and the factor congruence of the EQ in a community sample from Mexico City. Method Cronbach´s alpha coefficient and a correspondence factorial analysis was performed to test the relation between response options and factors from the Exploratory Factor Analysis 200 adults without Axis I disorders through the MINI, filled out the Spanish version of the short version (28-items) of the EQ. An exploratory factor analysis was performed while reliability was tested with Cronbach's alpha. In addition, correspondence factorial analysis and the factor congruence coefficient were determined. Results Five items were eliminated from the original 28-item EQ. From the 23 remaining items, only 16 were grouped in the three original proposed dimensions (cognitive empathy: 8 items, emotional reactivity: 4 items and social skills: 3 items), while one item showed communality with a different domain from the one originally proposed. Reliability was adequate (.82) as well as the congruence coefficients (.76 to .99). Discussion and conclusion The EQ Mexican 16-item version is a good tool to assess empathy in a Mexican population.

Resumen Introducción La empatía es definida como la capacidad para identificar y comprender las situaciones, sentimientos y motivaciones de otra persona. Estas respuestas son esenciales para relaciones y comportamientos sociales. Baron-Cohen et al. crearon el cociente de empatía (EQ), una escala diseñada para tener aplicación clínica. El instrumento evalúa tres constructos de empatía y ha probado sus propiedades psicométricas con resultados adecuados en varios estudios mundiales, pero no en México. Objetivo El propósito de este estudio fue examinar las propiedades psicométricas y la congruencia factorial del EQ en una muestra mexicana. Método El alpha de Cronbach y el análisis factorial fueron aplicados para probar la relación entre las opciones de respuesta y los factores en 200 adultos sin diagnóstico, a través de la entrevista MINI. Se utilizó la versión corta en español del EQ y se realizó un análisis factorial exploratorio dónde se probó la confiabilidad con el alfa de Cronbach y se determinó adecuada correspondencia y congruencia factorial. Resultados Se eliminaron cinco reactivos de la escala original de 28 reactivos. De los 23 reactivos restantes, solo 16 se agruparon en las tres dimensiones originales (empatía cognitiva: 8 reactivos, reactividad emocional: 4 reactivos y habilidades sociales: 3 reactivos) mientras que un reactivo mostró una comunalidad con un dominio diferente del original. La confiabilidad fue (.82), así como los coeficientes de congruencia (.76 a .99). Discusión y conclusión La versión del EQ es una buena herramienta para evaluar la empatía en población mexicana.

Association between prolactin serum levels and cognitive function in chronic schizophrenia patients / Asociación de los niveles de prolactina con el funcionamiento cognitivo en pacientes con esquizofrenia crónic

Abstract Introduction Several studies have explored the relationship between serum prolactin levels, symptomatology, and cognitive dysfunction in individuals at high risk for psychosis and patients with a first psychotic episode. However, the relationship between such variables is poorly understood in the case of chronic patients. Objective To assess the relationship between prolactin levels, neuropsychological impairment, and symptom severity in patients with chronic schizophrenia. Method A total of 31 patients with diagnosis of schizophrenia were evaluated between May and December 2018. The age range was 18 to 60 years, with patients receiving antipsychotic treatment during a month at least. Data was obtained from clinical records, interviews, clinimetry, and with the application of the PANSS and the MCCB battery. For the prolactin measurement, the analysis was performed on a sample of 500 microliters of serum, with a chemiluminescence technique. Results The sample was comprised mostly by men (77.4%), with a mean age of 37.65 years, 13.29 years of formal education, and disease duration of 11.58 years. No correlations were observed between prolactin levels and PANSS components and subscales. Only in male patients is there a negative correlation was found between prolactin levels with the overall combined score of the MCCB battery and cognitive domains of reasoning and verbal learning. Discussion and conclusions Men diagnosed with schizophrenia may be particularly vulnerable to the negative effects of hyperprolactinemia on cognition. These preliminary data have clinical implications for close monitoring of prolactin and cognitive decline in males with schizophrenia. Theoretically, these data are suggestive of a protective effect of hormones in women with this condition.

Resumen Introducción Diversos estudios han explorado la relación entre los niveles de prolactina sérica, la sintomatología y la disfunción cognitiva en individuos con alto riesgo de psicosis y pacientes con un primer episodio psicótico. Sin embargo, la relación entre tales variables es poco comprendida en el caso de los pacientes crónicos con esquizofrenia. Objetivo Evaluar la relación entre los niveles de prolactina, el deterioro neuropsicológico y la severidad de los síntomas en pacientes crónicos. Método Se evaluó un total de 31 pacientes. El rango de edad fue de 18 a 60 años, quienes recibieron tratamiento antipsicótico durante un mes como mínimo. Los datos se obtuvieron de entrevistas y de la aplicación de la PANSS y la MCCB. La medición de la prolactina se realizó con una muestra de 500 microlitros de suero, con una técnica de quimioluminiscencia. Resultados La muestra estuvo compuesta en su mayoría por hombres (77.4%), con una edad media de 37.65 años, 13.29 años de escolaridad y una duración de la enfermedad de 11.58 años. No se observaron correlaciones entre los niveles de prolactina y los componentes y subescalas del PANSS. Sólo en los pacientes varones se da una correlación negativa entre los niveles de prolactina con la puntuación global combinada de la batería de MCCB y los dominios cognitivos de razonamiento y aprendizaje verbal. Discusión y conclusiones Los hombres diagnosticados con esquizofrenia pueden ser particularmente vulnerables a los efectos negativos de la hiperprolactinemia sobre la cognición. Teóricamente, estos datos sugieren un efecto protector de las hormonas en las mujeres con esta enfermedad.

Processing speed differences between schizophrenia and schizoaffective disorder: A pilot study.

We aimed to compare processing speed (PS) and its subcomponents in schizophrenia (SC) and schizoaffective disorder (SA). Thirty-five patients were divided into two groups (SC=18; SA=17). PS tasks from the MATRICS Consensus Cognitive Battery Central/South America version were used. Additional PS subcomponents were analyzed (i.e., behavioral execution, response processing, and accuracy). SA obtained significant higher scores than SC in response processing, verbal fluency and the PS general domain. Our results indicate that PS is a potential cognitive marker to differentiate between SC and SA. Further research with larger samples must be conducted.