Risperidone Decreases Expression of Serotonin Receptor-2A (5-HT2A) and Serotonin Transporter (SERT) but Not Dopamine Receptors and Dopamine Transporter (DAT) in PBMCs from Patients with Schizophrenia.

Dopamine and serotonin receptors and transporters play an essential role in the pathophysiology of schizophrenia; changes in their expression have been reported in neurons and leukocytes. Each antipsychotic induces a unique pattern in leukocyte function and phenotype. However, the use of polytherapy to treat schizophrenia makes it challenging to determine the specific effects of risperidone on peripheral blood mononuclear cells (PBMCs). The aim of this study was to evaluate the changes in the expression of D3, D5, DAT, 5-HT2A, and SERT in PBMCs from healthy volunteers (HV), drug-naive patients with schizophrenia (PWS), drug-free PWS, and PWS treated with risperidone for up to 40 weeks using quantitative PCR. Our study revealed elevated mRNA levels of D3, DAT, 5-HT2A, and SERT in unmedicated PWS. Treatment with risperidone led to a reduction only in the expression of 5-HT2A and SERT. Furthermore, we observed a moderate correlation between 5-HT2A expression and the positive and negative syndrome scale (PANSS), as well as SERT expression and PANSS scale. We also found a moderate correlation between 5-HT2A and SERT expression and the positive subscale. The duration of risperidone consumption had a significant negative correlation with the expression of 5-HT2A and SERT. Our study introduces the measurement of 5-HT2A and SERT expression in PBMCs as a useful parameter for assessing the response to risperidone in PWS.

Remote crisis intervention and suicide risk management in COVID-19 frontline healthcare workers.

Introduction: Despite the propagation of virtual mental health services for vulnerable groups during COVID-19 pandemic, the implementation and evaluation of remote evidence-based practices (EBP) to manage them in low- and middle-income countries remains scarce. In the current study, we describe and evaluate the implementation process and clinical impact of brief, remote, manualized EBP for crisis intervention and suicide risk management among healthcare workers attending patients with COVID-19 (COVID-19-HCWs) in Mexico. Methods: The implementation process comprised community engagement of volunteer mental health specialists, creation of new clinical teams with different disciplines and skills, intervention systematization through manuals and education through 4-h remote training as main strategies. Mexican COVID-19-HCWs who had used a free 24-h helpline rated their pre- and post-intervention emotional distress. Therapists recorded patients' pre-intervention diagnosis, severity, and suicide risk, the techniques used in each case, and their post-treatment perception of COVID-19-HCWs' improvement at the end of the intervention. Results: All techniques included in the intervention manual were employed at least in one case (n = 51). At the beginning of the intervention, 65.9% of the COVID-19-HCWs were considered moderately ill or worse according to Clinical Global Impression-Severity (CGI-S) scores, whereas at the end, 79.4% of them were perceived as much or very much improved according to CGI-Improvement scores (CGI-I), and their emotional distress had been significantly reduced (p < 0.001). Discussion: This prospective study provides evidence that implementation of remote EBP is feasible and useful to reduce emotional distress and suicide risk among COVID-19-HCWs from a middle-income country. However, this study was limited by lack of a control group, improvement ratings provided by therapists and non-anonymous satisfaction ratings.

A Proposal to Study the Safety and Efficacy of Psilocybe cubensis in Preclinical and Clinical Studies as a Therapeutic Alternative for Major Depressive Disorder.

The pharmacological treatment of depression consists of taking antidepressant drugs for prolonged periods; its modest therapeutic effect can often be associated with significant adverse effects, while its discontinuation can lead to relapses. Psilocybin is today a novel and breakthrough therapy for major depression. It is a natural alkaloid in Psilocybe mushrooms, which are endemic to Mexico. Research on a larger scale is lacking in various populations, including the Mexican people. This proposal contemplates the experimental design of a preclinical (toxicity and pharmacological evaluation of an extract in mice) and clinical study by including the chemical analysis of a species of Psilocybe cubensis mushroom to characterize its main constituents. The clinical study will consider the safety evaluation by exploring tolerated doses of Psilocybe cubensis by measuring pharmacokinetic parameters after oral administration in healthy adults and an open trial on a sample of patients with major depressive disorder to assess the safety and efficacy of fully characterized Psilocybe cubensis in a two-single doses treatment, (with assisted psychotherapy), compared with the traditional care model at the Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz in Mexico City. This report presents the design of a research project with preclinical and clinical experimental components.

Mental health problems among healthcare workers involved with the COVID-19 outbreak

Objective: The mental health problems and perceived needs of healthcare workers involved with coronavirus disease (COVID-19) may vary due to individual and contextual characteristics. The objective of this study was to evaluate healthcare workers' mental health problems during the common COVID-19 exposure scenario in Mexico, comparing those on the frontline with other healthcare workers according to gender and profession, determining the main risk factors for the most frequent mental health problems. Methods: A cross-sectional online study was conducted with a non-probabilistic sample of 5,938 Mexican healthcare workers who completed brief screening measures of mental health problems and ad hoc questions about sociodemographic professional characteristics, conditions related to increased risk of COVID-19 infection, life stressors during the COVID-19 emergency, and perceived need to cope with COVID-19. Results: The identified mental health problems were insomnia, depression, and posttraumatic stress disorder (PTSD), all of which were more frequent in frontline healthcare workers (52.1, 37.7, and 37.5%, respectively) and women (47.1, 33.0 %, and 16.3%, respectively). A lack of rest time was the main risk factor for insomnia (OR = 3.1, 95%CI 2.6-3.7, p ≤ 0.0001). Mourning the death of friends or loved ones due to COVID-19 was the main risk factor for depression (OR = 2.2, 95%CI 1.8-2.7, p ≤ 0.0001), and personal COVID-19 status was the main risk factor for PTSD (OR = 2.2, 95%CI 1.7-2.9, p ≤ 0.0001). Conclusion: The most frequent mental health problems during the common exposure scenario for COVID-19 in Mexico included the short-term psychological consequences of intense adversity. A comprehensive strategy for preventing mental health problems should focus on individuals with cumulative vulnerability and specific risk factors.

Mental Health Problems among COVID-19 Frontline Healthcare Workers and the Other Country-Level Epidemics: The Case of Mexico.

COVID-19 frontline healthcare workers (FHCW) are struggling to cope with challenges that threaten their wellbeing. We examine the frequency and predictors of the most frequent mental health problems (MHP) among FHCW during the first COVID-19 peak in Mexico, one of the most severely affected countries in terms of FHCW's COVID-19 mortality. A cross-sectional survey was conducted between May 8 and August 18, 2020. A total of 47.5% of the sample (n = 2218) were FHCW. The most frequent MHP were insomnia, depression, posttraumatic stress symptoms, and health anxiety/somatization (whole sample: 45.7, 37.4, 33.9, and 21.3%; FHCW: 52.4, 43.4, 40.3 and 26.1, respectively). As compared to during the initial COVID-19 phase, depression and health anxiety/somatization symptoms as well as experiences of grieving due to COVID-19, personal COVID-19 status, and having relatives and close friends with COVID-19 were more frequent during the COVID-19 peak. Obesity, domestic violence, personal COVID-19 status, and grieving because of COVID-19 were included in regression models for main FHCW's MHP during the COVID-19 peak. In conclusion, measures to decrease other country-level epidemics contributing to the likelihood of COVID-19 complications (obesity) and MHP (domestic violence) as well as FHCW´s probability of COVID-19 infection could safeguard not only their physical but also mental health.

Mental health problems among healthcare workers involved with the COVID-19 outbreak.

OBJECTIVE: The mental health problems and perceived needs of healthcare workers involved with coronavirus disease (COVID-19) may vary due to individual and contextual characteristics. The objective of this study was to evaluate healthcare workers' mental health problems during the common COVID-19 exposure scenario in Mexico, comparing those on the frontline with other healthcare workers according to gender and profession, determining the main risk factors for the most frequent mental health problems. METHODS: A cross-sectional online study was conducted with a non-probabilistic sample of 5,938 Mexican healthcare workers who completed brief screening measures of mental health problems and ad hoc questions about sociodemographic professional characteristics, conditions related to increased risk of COVID-19 infection, life stressors during the COVID-19 emergency, and perceived need to cope with COVID-19. RESULTS: The identified mental health problems were insomnia, depression, and posttraumatic stress disorder (PTSD), all of which were more frequent in frontline healthcare workers (52.1, 37.7, and 37.5%, respectively) and women (47.1, 33.0 %, and 16.3%, respectively). A lack of rest time was the main risk factor for insomnia (OR = 3.1, 95%CI 2.6-3.7, p ≤ 0.0001). Mourning the death of friends or loved ones due to COVID-19 was the main risk factor for depression (OR = 2.2, 95%CI 1.8-2.7, p ≤ 0.0001), and personal COVID-19 status was the main risk factor for PTSD (OR = 2.2, 95%CI 1.7-2.9, p ≤ 0.0001). CONCLUSION: The most frequent mental health problems during the common exposure scenario for COVID-19 in Mexico included the short-term psychological consequences of intense adversity. A comprehensive strategy for preventing mental health problems should focus on individuals with cumulative vulnerability and specific risk factors.

Immunoendocrine Peripheral Effects Induced by Atypical Antipsychotics.

Atypical antipsychotics (AAP) or second-generation antipsychotics are the clinical option for schizophrenia treatment during acute psychoses, but they are also indicated for maintenance during lifetime, even though they are being used for other psychiatric conditions in clinical practice such as affective disorders and autism spectrum disorder, among others. These drugs are differentiated from typical antipsychotics based on their clinical profile and are a better choice because they cause fewer side effects regarding extrapyramidal symptoms (EPS). Even though they provide clear therapeutic benefits, AAP induce peripheral effects that trigger phenotypic, functional, and systemic changes outside the Central Nervous System (CNS). Metabolic disease is frequently associated with AAP and significantly impacts the patient's quality of life. However, other peripheral changes of clinical relevance are present during AAP treatment, such as alterations in the immune and endocrine systems as well as the intestinal microbiome. These less studied alterations also have a significant impact in the patient's health status. This manuscript aims to revise the peripheral immunological, endocrine, and intestinal microbiome changes induced by AAP consumption recommended in the clinical guidelines for schizophrenia and other psychiatric disorders.

Association study between COMT, DRD2, and DRD3 gene variants and antipsychotic treatment response in Mexican patients with schizophrenia.

PURPOSE: The efficacy of schizophrenia treatments using antipsychotics (APs) has long been established, but the benefit obtained by several patients using conventional APs (typical or atypical) has not been enough. Currently, the genetic study of the primary mechanisms of action of the APs has been focused on the dopaminergic pathways. The objective of this study was to determine if the response phenotypes (responder, resistance to treatment, and ultra-resistance to treatment groups) are associated with six single-nucleotide polymorphisms: COMT (Val158Met), DRD2 (A-241G, C376G, C939T, Taq1A), and DRD3 (Ser9Gly). PATIENTS AND METHODS: We classified the patients through a retrospective/prospective methodology to define response phenotypes. RESULTS: COMT/Val158Met and DRD3/Ser9Gly were associated with the responder group (P<0.05). The single-nucleotide polymorphism A-241G of DRD2 gene was related with the resistant-to-treatment group (P<0.001). Finally, Met/Met of COMT and Ser/Gly of DRD3 genes showed a predictive effect associated with the resistant-to-treatment phenotype. CONCLUSION: Further analyses should be performed to validate these genetic markers as mediators for the response to APs.

Predicting functional remission in patients with schizophrenia: a cross-sectional study of symptomatic remission, psychosocial remission, functioning, and clinical outcome.

BACKGROUND: New approaches to assess outcome in schizophrenia include multidimensional measures such as remission, cognition, psychosocial functioning, and quality of life. Clinical and psychosocial measures have been recently introduced to assess functional outcome. OBJECTIVE: The study presented here was designed to examine the rates of symptomatic remission, psychosocial remission, global functioning, and clinical global impressions in a sample of schizophrenia outpatients in order to assess functional remission and to identify predictive factors for functional remission. METHODS: A total of 168 consecutive Mexican outpatients receiving pharmacological treatment at the National Institute of Psychiatry in Mexico City were enrolled in a cross-sectional study. Symptomatic remission was assessed according to the definition and criteria proposed by the Remission in Schizophrenia Working Group using the Positive and Negative Symptom Scale. Psychosocial remission was assessed according to Barak criteria using the Psychosocial Remission in Schizophrenia scale. Functioning was measured with the Global Assessment of Functioning, and clinical outcome with the Clinical Global Impressions (CGI) Scale. RESULTS: Findings showed that 45.2% of patients fulfilled the symptomatic remission criteria, 32.1% achieved psychosocial remission, and 53% reported adequate functioning. However, the combination of these three outcome criteria - symptomatic, psychosocial remission, and functioning - indicated that 14.9% of the patients achieved our predefined functional remission outcome. The logistic regression model included five predictive variables for functional remission: (1) being employed, (2) use of atypical antipsychotics, (3) lower number of medications, (4) lower negative symptom severity, and (5) lower excitement symptom severity. CONCLUSION: The study demonstrated that symptomatic remission, psychosocial remission, and functioning could be achievable goals for a considerable number of patients. The outcome of functional remission was achieved by a minority of patients, less than 15%. New approaches should include multidimensional measures to assess functional outcome in schizophrenia research.

Association study between the MDR1 gene and clinical characteristics in schizophrenia

Objective: Schizophrenia is a complex psychiatric disorder, characterized by disturbed patterns of thought and affecting 0.3-2.0% of the world population. Previously, the multidrug resistance 1 (MDR1) gene has been associated with schizophrenia in treatment response studies in psychotic patients. The aim of this study was to determine the association between MDR1 gene polymorphisms and clinical characteristics in patients with schizophrenia. Methods: Positive and negative symptoms of schizophrenia were assessed with the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS) in 158 Mexican patients with schizophrenia. Analyses of MDR1 gene polymorphisms were performed using TaqMan technology. A multivariate ANOVA was performed with MDR1 polymorphisms and gender as independent variables. Results: Males with the G/G genotype of MDR1 rs2032582 presented significantly higher levels of delusions (p = 0.02). When comparing female vs. male groups, the difference was statistically significant (p = 0.0003). Analyses of the MDR1 gene rs1045642 variant showed no significant differences. Conclusion: Our findings suggest that male carriers of the G allele of variant rs2032582 exhibit greater severity of delusions; however, these results should be taken as preliminary, and replication studies in other populations of different ethnic origins are required to confirm these findings. .

Association study between the MDR1 gene and clinical characteristics in schizophrenia.

OBJECTIVE: Schizophrenia is a complex psychiatric disorder, characterized by disturbed patterns of thought and affecting 0.3-2.0% of the world population. Previously, the multidrug resistance 1 (MDR1) gene has been associated with schizophrenia in treatment response studies in psychotic patients. The aim of this study was to determine the association between MDR1 gene polymorphisms and clinical characteristics in patients with schizophrenia. METHODS: Positive and negative symptoms of schizophrenia were assessed with the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS) in 158 Mexican patients with schizophrenia. Analyses of MDR1 gene polymorphisms were performed using TaqMan technology. A multivariate ANOVA was performed with MDR1 polymorphisms and gender as independent variables. RESULTS: Males with the G/G genotype of MDR1 rs2032582 presented significantly higher levels of delusions (p = 0.02). When comparing female vs. male groups, the difference was statistically significant (p = 0.0003). Analyses of the MDR1 gene rs1045642 variant showed no significant differences. CONCLUSION: Our findings suggest that male carriers of the G allele of variant rs2032582 exhibit greater severity of delusions; however, these results should be taken as preliminary, and replication studies in other populations of different ethnic origins are required to confirm these findings.

History of religious delusions and psychosocial functioning among Mexican patients with paranoid schizophrenia.

The association between global functionality and religiosity among patients from developing and predominantly Catholic countries warrants attention. To compare religiosity and psychosocial functioning in Mexican schizophrenia patients with and without a history of religious delusions, seventy-four patients with paranoid schizophrenia were recruited. Patients with a history of religious delusions had more psychiatric hospitalizations and poorer psychosocial functioning compared with those without a history of religious delusions. No differences emerged between groups in the total scores of religiosity scales. A history of religious delusions rather than religiosity itself may have an influence on psychosocial functioning among Mexican patients with schizophrenia.

Monoamine oxidase a and B gene polymorphisms and negative and positive symptoms in schizophrenia.

Given that schizophrenia is a heterogeneous disorder, the analysis of clinical characteristics could help to identify homogeneous phenotypes that may be of relevance in genetic studies. Linkage and association studies have suggested that a locus predisposing to schizophrenia may reside within Xp11. We analyzed uVNTR and rs1137070, polymorphisms from MAOA and rs1799836 of MAOB genes to perform single SNP case-control association study in a sample of 344 schizophrenia patients and 124 control subjects. Single polymorphism analysis of uVNTR, rs1137070 and rs1799836 SNPs did not show statistical differences between cases and controls. Multivariate ANOVA analysis of clinical characteristics showed statistical differences between MAOB/rs1799836 and affective flattening scores (F = 4.852, P = 0.009), and significant association between MAOA/uVNTR and affective flattening in female schizophrenia patients (F = 4.236, P = 0.016) after Bonferroni's correction. Our preliminary findings could suggest that severity of affective flattening may be associated by modifier variants of MAOA and MAOB genes in female Mexican patients with schizophrenia. However, further large-scale studies using quantitative symptom-based phenotypes and several candidate variants should be analyzed to obtain a final conclusion.

Treatment discontinuation and clinical outcomes in the 1-year naturalistic treatment of patients with schizophrenia at risk of treatment nonadherence.

BACKGROUND: This study aimed to improve physicians' understanding of the treatment circumstances and needs of outpatients with schizophrenia at risk of nonadherence, by naturalistically assessing antipsychotic treatment patterns, clinical outcomes, and health care service use in this little-studied patient population. METHODS: In this one-year, prospective, multicenter, noninterventional, observational study, patients considered at risk of nonadherence by their physicians were switched from their primary oral antipsychotic to another oral or a depot antipsychotic at study entry. All cause treatment discontinuation (antipsychotic switch, augmentation, or discontinuation) during the study was assessed using Kaplan-Meier survival analyses and descriptive statistics. Patients' illness severity, quality of life, attitude towards medication, patient-reported adherence, and health care resource utilization were assessed during the study. RESULTS: Of the 406 enrolled patients, 43 (10.6%) were switched to depot and 363 (89.4%) were switched to oral antipsychotics at study entry. During the study, 99 (24.4%) patients switched, augmented, or discontinued their antipsychotic (all cause treatment discontinuation). Of the 99 patients who switched, augmented, or discontinued their antipsychotic, 8 (18.6%) were taking depot and 91 (25.0%) were taking oral antipsychotics. These patients were switched to either depot (n = 15) or oral (n = 78) antipsychotics, or discontinued their antipsychotic medication (n = 6). Inadequate response was the most frequently reported reason for medication discontinuation. During the study, patients' clinical and functional status improved significantly and service use was low. Most patients considered themselves to be adherent at study entry, and this favorable self-perception increased during the study (from 68.5% to 88.1%). CONCLUSION: Although identified as at risk of nonadherence, few patients in this naturalistic study discontinued their prescribed antipsychotic medication during the study. The discrepancy between the physicians' perception of their patient's medication adherence and the patients' self-perceived adherence highlights the need to better understand the underlying reasons for this phenomenon.

Baseline characteristics and initial treatment decisions for patients with schizophrenia at risk of treatment nonadherence.

In this year-long, prospective observational study, sociodemographic, clinical, and functional characteristics were assessed in outpatients with schizophrenia from Australia, Mexico, Romania, and Taiwan who were switched from their primary oral antipsychotic to another oral or depot antipsychotic at study entry because of physician-perceived nonadherence risks. Patients (N = 406) rated their quality of life and functioning level as low. Few patients (10.6%, 43/406) were switched to depot antipsychotics, with country-specific differences (P < 0.001). Although illness severity was similar between subgroups, the depot switch subgroup had: a documented history of nonadherence (32.6% versus oral: 4.7%); recent alcohol (48.8% versus 23.2%; P < 0.001) or illicit drug use (16.3% versus 5.0%; P = 0.010); recent depot antipsychotic (20.7% versus 7.5%; P = 0.030) and mood stabilizer use (51.7% versus 26.3%; P = 0.008); poorer attitudes towards medication (P = 0.004); and poorer illness awareness (P = 0.041). Findings indicate that even when a risk of nonadherence has been identified, few patients with schizophrenia receive depot antipsychotics, despite being prime candidates for depot therapy. Findings suggest physicians may select depot therapy based on previous nonadherence, substance use, recent depot antipsychotic and mood stabilizer use, poor attitudes towards medications, and poor illness awareness.

Application in Mexico of psychosocial rehabilitation with schizophrenia patients.

To determine whether evidence-based, psychosocial treatments developed in the United States and England are applicable to Mexican outpatients with schizophrenia, the present study was carried out to evaluate the relative effectiveness of family psycho-education and psychosocial skills training added to customary treatment vs. customary treatment alone. Clinically stable outpatients with schizophrenia participated in a 12-month randomized, controlled trial at the National Institute of Psychiatry in Mexico City. An experimental group (N = 47) received the combination of psychosocial skills training, family psycho-education and customary pharmacotherapy while the comparison group (N = 36) received customary treatment alone. Patients were assessed at baseline and one year after commencement of treatment. Significant differences favoring the group that received psychosocial rehabilitation were found in ratings of adherence to medication, attendance at appointments, symptoms, social functioning, relapse, and re-hospitalization. While some adaptations were made in the psychosocial treatments to resolve cultural differences, the results provide cross-national validation of evidence-based treatments for persons with schizophrenia.