Technology transfer for the implementation of a clinical trials network on drug abuse and mental health treatment in Mexico.

Low- and middle-income countries (LMIC) lack the research infrastructure and capacity to conduct rigorous substance abuse and mental health effectiveness clinical trials to guide clinical practice. A partnership between the Florida Node Alliance of the United States National Drug Abuse Treatment Clinical Trials Network and the National Institute of Psychiatry in Mexico was established in 2011 to improve substance abuse practice in Mexico. The purpose of this partnership was to develop a Mexican national clinical trials network of substance abuse researchers and providers capable of implementing effectiveness randomized clinical trials in community-based settings. A technology transfer model was implemented and ran from 2011-2013. The Florida Node Alliance shared the "know how" for the development of the research infrastructure to implement randomized clinical trials in community programs through core and specific training modules, role-specific coaching, pairings, modeling, monitoring, and feedback. The technology transfer process was bi-directional in nature in that it was informed by feedback on feasibility and cultural appropriateness for the context in which practices were implemented. The Institute, in turn, led the effort to create the national network of researchers and practitioners in Mexico and the implementation of the first trial. A collaborative model of technology transfer was useful in creating a Mexican researcher-provider network that is capable of changing national practice in substance abuse research and treatment. Key considerations for transnational technology transfer are presented.

Validation of the Impulsive/Premeditated Aggression Scale in Mexican psychiatric patients.

INTRODUCTION: Aggression has been linked to several psychiatric disorders. None of the available instruments validated in Mexico is able to classify aggression as impulsive or premeditated. The Impulsive/Premeditated Aggression Scale (IPAS) is a self-report instrument designed to characterize aggressiveness as predominately impulsive or premeditated. OBJECTIVE: The aim of the study was to determine the validity and reliability of the IPAS in a sample of Mexican psychiatric patients. METHOD: A total of 163 patients diagnosed with affective, anxiety or psychotic disorder were included. A principal-component factor analysis was performed to obtain construct validity of the IPAS impulsive and premeditated aggression subscales; convergent validity as well as internal consistency of subscales were also determined. RESULTS: The rotated matrix accounted for 33.4% of the variance. Significant values were obtained for convergent validity and reliability of the IPAS subscales. CONCLUSION: The IPAS is an adequate instrument, which might be used to differentiate the type of aggressive behavior in Mexican psychiatric patients.

Melatonin attenuates antipsychotic metabolic effects: an eight-week randomized, double-blind, parallel-group, placebo-controlled clinical trial.

OBJECTIVE: Second-generation antipsychotics (SGAs) are among the first-line treatments for bipolar disorder and schizophrenia, but have a tendency to generate metabolic disturbances. These features resemble a metabolic syndrome for which a central autonomic imbalance has been proposed that may originate from the hypothalamic suprachiasmatic nuclei. In a clinical trial, we hypothesized that melatonin, a hormone that regulates the suprachiasmatic nucleus, could attenuate SGA-induced adverse metabolic effects. METHODS: In an eight-week, double-blind, randomized, placebo-controlled, parallel-group clinical trial, we evaluated the metabolic effect of melatonin in SGA-treated patients in terms of weight, blood pressure, lipid, glucose, body composition, and anthropometric measures. A total of 44 patients treated with SGAs, 20 with bipolar disorder and 24 with schizophrenia, randomly received placebo (n = 24) or melatonin 5 mg (n = 20). RESULTS: The melatonin group showed a decrease in diastolic blood pressure (5.1 versus 1.1 mmHg for placebo, p = 0.003) and attenuated weight gain (1.5 versus 2.2 kg for placebo, F = 4.512, p = 0.040) compared to the placebo group. The strong beneficial metabolic effects of melatonin in comparison to placebo on fat mass (0.2 versus 2.7 kg, respectively, p = 0.032) and diastolic blood pressure (5.7 versus 5.5 mmHg, respectively, p = 0.001) were observed in the bipolar disorder and not in the schizophrenia group. No adverse events were reported. CONCLUSIONS: Our results show that melatonin is effective in attenuating SGAs' adverse metabolic effects, particularly in bipolar disorder. The clinical findings allow us to propose that SGAs may disturb a centrally mediated metabolic balance that causes adverse metabolic effects and that nightly administration of melatonin helps to restore. Melatonin could become a safe and cost-effective therapeutic option to attenuate or prevent SGA metabolic effects.

Mapping the research landscape of bauxite by-products (red mud): An evolutionary perspective from 1995 to 2022.

The global population growth has significantly impacted energy and raw material consumption, unmatched since the Industrial Revolution. Among metals, aluminium ranks second only to steel, with annual production exceeding 69 million tonnes. Due to its high demand, bauxite, the primary ore from which aluminium is extracted, is now classified as a critical material in the EU and the US, given the potential risk of supply shortages for essential applications. Geographical and production challenges surround bauxite, presenting geo-economic and environmental challenges. A critical concern in aluminium production is managing by-products, notably red mud, a bauxite residue, generating over 175 million tonnes annually worldwide. Comprehensive bibliometric research is imperative due to the high amount of bibliographical resources related to this topic, encompassing circular economy, re-valorisation, sustainability, and disposal. This study employs bibliometric methods to assess red mud valorisation, offering insights into research topics, influential authors, and key journals, shedding light on the past, present, and future of red mud research. Such bibliometric analysis not only highlights the current state of the field but also serves as a valuable tool for decision-making, enabling researchers and policymakers to identify trends, gaps, and areas for further exploration, fostering informed and sustainable advancements in the by-products of the aluminium industry.

[Translation into Spanish and validation of the Snaith-Hamilton Pleasure Scale (SHAPS) for anhedonia]. / Traducción al español y validación de la Escala de Placer Snaith-Hamilton para Anhedonia (SHAPS).

INTRODUCTION: The inability to experience pleasure, anhedonia, is recognized as al hallmark symptom of depression. A 14-item, self-report scale developed for the assessment of hedonic capacity: the Snaith-Hamilton Pleasure Scale (SHAPS) has proved to be a reliable and valid psychometric instrument. OBJECTIVE: Because there are no versions of the scale in other languages, our objective in this study was to translate the instrument into spanish and to determine if the new version maintained the validity and reliability of its original english version. METHODOLOGY: The scale was translated into spanish and after reaching final consensus applied to a group of depressed patients participating in a pharmacological trial. The Hamilton Depression Rating Scale (HDRS) was also applied for comparative purposes. RESULTS: Our results demonstrate that the SHAPS in its spanish version maintains the validity and reliability level of the original english version. A moderate internal consistency was determined by Cronbach alpha value of 0.77. CONCLUSION: our results demonstrate the the spanish version of the SHAPS has validity and reliability similar to its original version, and thus it represents a good alternative to evaluate anhedonia in spanish-speaking populations.

Acute exercise reduces the effects of a 35% CO2 challenge in patients with panic disorder.

BACKGROUND: Chronic exercise has been shown to have therapeutic effects in panic disorder (PD). The mechanism of these effects is unknown. Acute exercise reduces the effect of a panic challenge in healthy volunteers. Such an effect has not yet been demonstrated in PD patients. The present study aimed at exploring the antipanic effects of acute exercise on a 35% CO2 panic provocation in treatment-naïve PD patients to further elucidate the mechanisms of the beneficial effects of exercise on panic. METHODS: Eighteen PD patients performed either moderate/hard exercise or very-light exercise before a 35% CO2 challenge in a randomized, between-group design. The reactivity to CO2 was assessed with the Visual Analogue Anxiety Scale and the DSM-IV Panic Symptom List. RESULTS: Panic reactions to CO2 were smaller in patients that performed moderate/hard exercise in contrast to those that performed very-light exercise. Increments in both measurements and panic rates were consistently reduced by intense exercise. LIMITATIONS: Since this study focuses on the acute effects of exercise on CO2 sensitivity in patients with PD, the results of repetitive exercise sessions on the rate of spontaneous panic attacks and overall symptoms are warranted. The small sample size and other limitations are addressed. CONCLUSIONS: Exercise reduced the panicogenic effects of a CO2 challenge. In addition to its therapeutic potential, exercise may also be useful as a laboratory maneuver with heuristic value in experimental research into the mechanisms of antipanic treatment.

Motivational enhancement treatment in outpatient addiction centers: A multisite randomized trial.

BACKGROUND/OBJECTIVES: Motivational Enhancement Treatment in Spanish (METS) is a brief intervention aimed at resolving patient ambivalence towards behavior change that has demonstrated efficacy in substance use disorder treatment to reduce use and increase treatment engagement in different populations. In order to have evidence for its implementation in Mexico, a multi-site, randomized, two-arm, controlled clinical trial was conducted at three outpatient addiction treatment centers in the country to compare the effect of METS with Counseling as Usual (CAU). METHOD: One hundred and twenty patients were randomized to receive three sessions of METS (n = 54) or CAU (n = 66) during the first four weeks of treatment and were assessed during the following 12 weeks. Primary outcome measures were self-reported days of substance use and of treatment services utilization, which were tested using Generalized Estimating Equations. RESULTS: Results associated both conditions with significant changes in substance use over, whereas there were no differences between conditions in substance use or in service utilization. CONCLUSIONS: Findings do not support the hypothesis that METS is more effective than CAU, but suggest that brief interventions at treatment initiation may improve patient outcomes.

Antecedentes/Objetivos: La Intervención de Incremento Motivacional (METS) es una intervención breve para resolver la ambivalencia del paciente con respecto a su comportamiento y ha demostrado eficacia en distintas poblaciones para reducir el consumo de sustancias e incrementar la asistencia al tratamiento en adicciones. Con el objetivo de generar evidencia para su implementación en México, se desarrolló un ensayo clínico controlado, multi-sede, aleatorizado, de dos brazos en tres centros de tratamiento ambulatorio para adicciones, para comparar el efecto de METS con el del tratamiento usual (CAU). Método: Ciento veinte pacientes fueron aleatorizados a tres sesiones de METS (n = 54) o CAU (n = 66) durante las primeras cuatro semanas de tratamiento y evaluados durante las siguientes doce. Se midieron resultados mediante autoinforme de días con consumo de sustancias y días de utilización de servicios, los cuales fueron analizados mediante ecuaciones de estimación generalizadas. Resultados: Los resultados asociaron ambas condiciones a cambios significativos en uso de sustancias a lo largo del tiempo, pero no demostraron diferencias entre condiciones en el uso de sustancias o en la utilización de servicios. Conclusiones: Los hallazgos contradicen la hipótesis de superioridad de METS sobre CAU, pero sugieren que las intervenciones breves al inicio del tratamiento pudieran mejorar la respuesta del paciente.

Different gender response to serotonergic and noradrenergic antidepressants. A comparative study of the efficacy of citalopram and reboxetine.

BACKGROUND: It is well established that depressive disorders are more prevalent in women; however gender differences in the pharmacological response to antidepressants are not a consistent finding in all reports. It is considered that this discrepancy can be explained by the fact that in most clinical trials drug use for comparative purposes is not completely different. In this study gender differences in antidepressant response with citalopram (CTP), a selective serotonin reuptake inhibitor and reboxetine (RBX), a selective noradrenaline reuptake inhibitor were evaluated in a group of young men and premenopausal women. METHOD: Eighty-six depressed patients 18 to 40 years old participated in an 8-week double-blind clinical trial. Subjects were divided in four groups according to sex and treatment assignation: females treated with CTP (n = 25) or RBX (n = 23), and males treated with CTP (n = 19) or RBX (n = 19). Response was determined using HDRS and BDI. RESULTS: ANOVA analysis considering change in HDRS scores from baseline to last evaluation found a significant interaction between gender and type of treatment. Females treated with CTP showed a significantly greater response than females treated with RBX, while in men no differences were observed for both drugs. LIMITATIONS: Replication using larger sample size and longer treatment periods is required. CONCLUSIONS: These results support previous findings which show that premenopausal women respond better than men to serotonergic antidepressants. They also support that a plausible interaction between gonadal hormones and serotonin may explain gender differences in antidepressant response.

Altered subcellular distribution of the 75-kDa DISC1 isoform, cAMP accumulation, and decreased neuronal migration in schizophrenia and bipolar disorder: implications for neurodevelopment.

BACKGROUND: DISC1 (Disrupted-In-Schizophrenia-1) is considered a genetic risk factor for schizophrenia (SZ) and bipolar disorder (BD). DISC1 regulates microtubule stability, migration, and cAMP signaling in mammalian cell lines and mouse brain tissue. cAMP is a regulator of microtubule organization and migration in neurons. Aberrant microtubule organization has been observed in olfactory neuronal precursors (ONP) derived from patients with SZ and BD, which suggests involvement of DISC1 and cAMP. However, the biology of DISC1 in the physiopathology of psychiatric conditions remains elusive. AIMS: Herein, utilizing ONP obtained from SZ, BD patients and healthy subjects, we have studied DISC1 expression, protein levels, and subcellular distribution by qRT-PCR, immunoblotting, subcellular fractionation, and confocal microscopy. Cell migration and cAMP accumulation were assessed by Transwell and PKA competition assays. RESULTS: We found increased levels of the 75-kDa DISC1 isoform in total cell extracts of ONP from patients with SZ and BD compared with controls. Subcellular distribution showed a significant decrease of cytoplasmic DISC1 concomitant with its augmented levels in transcription sites. Moreover, significant cAMP accumulation and diminished migration were also observed in patients' cells. CONCLUSION: Alterations of DISC1 levels and its cellular distribution, which negatively modify cAMP homeostasis, microtubule organization, and cell migration, in ONP from patients with SZ and BD, suggest that their presence in early stages of brain development may impact brain maturation and function.

Failure of tibolone to potentiate the pharmacological effect of fluoxetine in postmenopausal major depression.

BACKGROUND: Perimenopausal depression has been attributed to physiological progressive estrogen decline. Estrogen and derivatives have some mood-enhancing effects, although studies of using estrogen as an antidepressant have had mixed results. The gonadomimetic drug tibolone stimulates estrogen receptors in a tissue-selective fashion, increasing the gonadal activity without causing some of the usual side effects of other estrogen preparations. METHODS: A total of 31 postmenopausal outpatients with a major depressive disorder (MDD) participated in the study. Sixteen received the antidepressant fluoxetine (20 mg/day) plus tibolone (2.5 mg/day), and 15 received the same dose of fluoxetine plus placebo, assigned in a randomized fashion. RESULTS: After 8 weeks of treatment, the two groups had a similar level of improvement in their depressive symptoms. Both treatments were well tolerated, without significant side effects. Pretreatment and posttreatment serum hormonal levels did not predict the final response. CONCLUSIONS: Combining tibolone and fluoxetine did not represent a more robust antidepressant response than fluoxetine alone in postmenopausal women with MDD.

Mental illness recognition and beliefs about adequate treatment of a patient with schizophrenia: association with gender and perception of aggressiveness-dangerousness in a community sample of Mexico City.

BACKGROUND: In developing countries, little is known about public recognition and beliefs about treatment of severe mental disorders, both emergent key elements in reducing stigma and the gap of treatment of such patients. It has been proposed that they may be related to gender and perception of patient's aggressiveness and/or dangerousness. AIMS: To assess mental illness recognition and beliefs about treatment of schizophrenia, and to determine their relationship with perception of patient's aggressiveness/dangerousness and gender of the perceiver in a community sample of Mexico City. METHODS: A convenience sample of 1038 subjects responded to a questionnaire that assesses all variables after reading a vignette of a patient with paranoid schizophrenia. RESULTS: Women were 1.88 times more likely to recognize the presence of mental illness and considered psychiatric interventions as the most adequate treatment of symptoms. In contrast, non-psychiatric interventions were more often considered by men (64.7%). Responders who recognize mental illness were more likely to perceive the patient as dangerous, which was related to the suggestion of more restrictive interventions. CONCLUSIONS: It is necessary to direct special efforts to increase mental health literacy among men. The general public needs objective information about aggression and dangerousness in anti-stigma campaigns among developing countries similar to Mexico.

Mental health literacy about bipolar disorder and schizophrenia among medical students: a comparative study of illness recognition, treatment, and attitudes according to perception of aggressiveness-dangerousness / Alfabetización en salud mental sobre el trastorno bipolar y la esquizofrenia en estudiantes de medicina: estudio comparativo del reconocimiento de la enfermedad, tratamiento y actitudes de acuerdo a la percepción de agresión-peligrosidad

Abstract Introduction Lack of information may result in health professionals' negative attitudes toward individuals with mental illness. Objective We sought to determine the association between the perception of aggressiveness-dangerousness and illness recognition, suggested treatment, and attitudes regarding schizophrenia and bipolar disorder in a group of medical students. Method This field study used a non-experimental, cross-sectional comparative design in a purposive sample of medical students. Mental illness recognition, beliefs about adequate treatment, perception of patient's aggressiveness-dangerousness, and attitudes toward severe mentally ill persons were assessed with previously validated instruments. Results Of the 104 participants, 54.8% identified a mental health condition in the schizophrenia vignette compared with only 3.8% in the case of bipolar disorder. Most students believed that both diagnoses could lead to aggressive behaviors. Dangerousness was more frequently perceived in the schizophrenia vignette. Discussion and conclusion It is necessary to sensitize and educate medical students so they have accurate information about symptoms and available treatments for individuals with mental illnesses.

Resumen Introducción La falta de información puede dar como resultado actitudes negativas de los profesionales de la salud hacia los individuos con trastornos mentales. Objetivo Determinar la asociación entre la percepción de agresión-peligrosidad y el reconocimiento de la enfermedad, tratamiento sugerido y actitudes sobre la esquizofrenia y el trastorno bipolar en un grupo de estudiantes de pregrado de medicina. Método El presente es un estudio no experimental, transversal comparativo en una muestra propositiva de estudiantes de medicina. El reconocimiento de la enfermedad, creencias acerca del tratamiento más adecuado, percepción de la agresión-peligrosidad del paciente y las actitudes hacia los trastornos mentales graves fueron evaluados con instrumentos previamente validados. Resultados El 54.8% de un total de 104 participantes identificaron un estado de salud mental en la viñeta de esquizofrenia en contraste con tan sólo el 3.8% para el caso de trastorno bipolar. La mayoría de los estudiantes consideraron que ambos diagnósticos se relacionaban con conductas agresivas. La peligrosidad fue percibida más frecuentemente en la viñeta del caso con esquizofrenia. Discusión y conclusión Es necesario sensibilizar y educar a los estudiantes de medicina para que tengan información clara y precisa sobre los síntomas y tratamientos disponibles para los individuos con trastornos mentales.

Technology transfer for the implementation of a clinical trials network on drug abuse and mental health treatment in Mexico / Transferencia de tecnología para la implantación de una red de investigaciones clínicas sobre el tratamiento de la drogadicción y los problemas de salud mental en México

Low- and middle-income countries (LMIC) lack the research infrastructure and capacity to conduct rigorous substance abuse and mental health effectiveness clinical trials to guide clinical practice. A partnership between the Florida Node Alliance of the United States National Drug Abuse Treatment Clinical Trials Network and the National Institute of Psychiatry in Mexico was established in 2011 to improve substance abuse practice in Mexico. The purpose of this partnership was to develop a Mexican national clinical trials network of substance abuse researchers and providers capable of implementing effectiveness randomized clinical trials in community-based settings. A technology transfer model was implemented and ran from 2011-2013. The Florida Node Alliance shared the "know how" for the development of the research infrastructure to implement randomized clinical trials in community programs through core and specific training modules, role-specific coaching, pairings, modeling, monitoring, and feedback. The technology transfer process was bi-directional in nature in that it was informed by feedback on feasibility and cultural appropriateness for the context in which practices were implemented. The Institute, in turn, led the effort to create the national network of researchers and practitioners in Mexico and the implementation of the first trial. A collaborative model of technology transfer was useful in creating a Mexican researcher-provider network that is capable of changing national practice in substance abuse research and treatment. Key considerations for transnational technology transfer are presented.

Los países de ingresos bajos o medios (PIBM) carecen de una infraestructura de investigación y de la capacidad para llevar a cabo investigaciones clínicas rigurosas sobre la eficacia del tratamiento de la drogadicción y los problemas de salud mental que orienten la práctica clínica. Se estableció una asociación entre la Florida Node Alliance de la National Drug Abuse Treatment Clinical Trials Network de los Estados Unidos y el Instituto Nacional de Psiquiatría de México con objeto de mejorar la práctica en materia de tratamiento de la drogadicción en México. La finalidad de esta asociación fue la de crear una red nacional mexicana de investigaciones clínicas constituida por investigadores y proveedores de tratamiento de la drogadicción capaces de ejecutar ensayos clínicos aleatorizados de eficacia en entornos comunitarios. Se implantó un modelo de transferencia de tecnologías. La Florida Node Alliance compartió el el conocimiento y la experiencia para la creación de la infraestructura de investigación con objeto de ejecutar investigaciones clínicas aleatorizadas en programas comunitarios, por medio de módulos de capacitación común y específica, entrenamiento en funciones específicas, emparejamientos, modelado, vigilancia y retroalimentación. El proceso de transferencia de tecnología fue de tipo bidireccional en cuanto se basó en la retroalimentación sobre la viabilidad y la adecuación cultural para el contexto en el que se llevaron a cabo las prácticas. El Instituto, a su vez, lideró la iniciativa para crear la red nacional de investigadores y profesionales de México y llevar a cabo el primer ensayo. Un modelo colaborativo de transferencia de tecnología resultó útil para la creación de una red mexicana de investigadores y proveedores de tratamiento capaz de cambiar las prácticas nacionales de investigación y tratamiento en materia de drogadicción. Se exponen las consideraciones clave para la transferencia transnacional de tecnología.

Endophenotypes and biomarkers: an approach to molecular genetic studies of mental disorders / Endofenotipos y biomarcadores: un enfoque hacia el estudio genético molecular de los trastornos mentales

Many precise aspects of the etiology and pathophysiology of mental disorders are still unknown. Susceptibility to these disorders depends in part on variability in the genome sequence among individuals. The genotype, a given environment, a specific epigenetic profile and stochastic factors affect the phenotype, which includes body structures, physiological processes, and behavior. Since the access to the Central Nervous System is generally difficult and in most cases there are still no biological tests that necessarily contribute to diagnosis, psychiatric phenotypes are usually limited to clinical symptoms and functioning. Therefore, researchers are currently seeking alternatives to facilitate the identification of genetic risk factors. One strategy is to identify measurable biological, cognitive, and behavioral markers, intermediate phenotypes, or endophenotypes, which in the best case may be simpler than general psychiatric diagnoses, ideally with a precise biological meaning and a more direct relationship with the action of specific genes. Endophenotypes have been very useful in other fields of medicine. Currently, there are several proposed criteria and specifications for endophenotypes. Examples of possible types of endophenotypes or biomarkers, as well as treatment response phenotypes in some psychiatric disorders will be discussed in this review.

Aún se desconocen diversos aspectos de la etiología y fisiopatología de los trastornos mentales. La susceptibilidad a éstos depende en parte de la variabilidad en la secuencia genómica en las personas. El genotipo, un ambiente dado, un perfil epigenético específico y factores estocásticos afectan el fenotipo, el cual incluye estructuras corporales, procesos fisiológicos y conducta. Los fenotipos psiquiátricos generalmente se limitan al funcionamiento y a los síntomas clínicos, debido a que el acceso al Sistema Nervioso Central es complicado y en la mayoría de los casos no hay pruebas biológicas que necesariamente contribuyan al diagnóstico. Por esta razón, en la actualidad se buscan alternativas para facilitar la identificación de factores de riesgo de tipo genético. La identificación de marcadores biológicos, cognitivos o conductuales medibles, fenotipos intermedios o endofenotipos podría ser una de estas nuevas opciones. Estos marcadores podrían ser más simples que el diagnóstico psiquiátrico general, y de manera ideal tendrían un significado biológico preciso y una acción más directa en los genes. El empleo de endofenotipos ha sido útil en otras ramas de la medicina. Hasta ahora se han propuesto diversos criterios y especificaciones para los endofenotipos. En esta revisión se describirán posibles tipos de endofenotipos o biomarcadores, así como fenotipos relacionados con la respuesta farmacológica en algunos trastornos psiquiátricos.

Alfabetización en salud mental en el trastorno bipolar: Asociación con la percepción de agresividad y el género en estudiantes de medicina / Mental health literacy in bipolar disorder: Association with perception of aggressiveness and gender of medical students

Introduction Developing mental health literacy in students and health professionals in general implies gaining abilities in recognizing and treating mental illnesses. In bipolar disorder, this is an important issue due that it helps reducing stigma and the treatment gap found in patients with this diagnosis. Objective To determine the associations between some variables of mental health literacy (illness, recognition, attributable causes and suggested treatment) about bipolar disorder with gender and perception of aggressiveness/dangerousness in a group of medical students. Material and methods One-hundred and three medical students from a public university in Mexico City completed the Aggressiveness Public Concept Questionnaire to assess mental health literacy and aggressiveness/dangerous-ness perception. Results 59.6% of students did not recognize the presence of a mental illness. As described symptoms were not considered as a manifestation of a mental disorder, 83.7% considered non-psychiatric interventions as the most adequate alternative for the management of the behaviors exposed in the vignette. 87.7% considered that the person described in the vignette was aggressive and 33.7% perceived the subject as dangerous. Discussion Campaigns of mental health literacy for medical students must be directed to improve recognition of the essential features of bipolar disorder, therapeutic options as well as the real prevalence and methods of prevention of aggressiveness of these patients.

Introducción La alfabetización en salud sental (ASM) por parte de estudiantes y profesionales de la salud implica su capacidad para reconocer la enfermedad mental y su adecuado manejo, y constituye un elemento esencial para reducir el estigma y la brecha de tratamiento de los pacientes con trastorno bipolar (TBP). Objetivo Determinar la asociación entre algunas variables de la ASM (reconocimiento, causas atribuibles y tratamiento sugerido) para el TBP con el género y la percepción de agresividad en un grupo de estudiantes de medicina. Material y métodos Ciento tres estudiantes de pregrado de la carrera de Medicina de una Universidad pública de la Ciudad de México completaron el Cuestionario de Concepto Público de Agresividad (CPA) para valorar la ASM y la percepción de agresividad/peligrosidad. Resultados El 59.6% de los estudiantes no reconocieron la presencia de una enfermedad mental. Al no considerar los síntomas como la manifestación de una enfermedad mental, el 83.7% sugirió intervenciones no psiquiátricas/no restrictivas para el manejo adecuado de las conductas expuestas en la viñeta clínica. El 87.7% de los estudiantes consideró que la persona descrita era agresiva y el 33.7% la percibió como peligrosa. Discusión Las campañas de ASM para estudiantes de medicina deben abocarse a incrementar el conocimiento de las características esenciales del TBP, las opciones de tratamiento así como la prevalencia real y métodos de prevención de la agresividad en estos pacientes.

Consideraciones metodológicas y éticas para la conducción de ensayos clínicos controlados aleatorizados (ECCA) sobre intervenciones para las adicciones / Methodological and ethical aspects in conducting randomized controlled clinical trials (RCT) for addictive disorder's interventions

According to epidemiologic reports, the harmful use of alcohol and illicit drugs has increased among the Mexican population. This use is associated to several risks and issues that affect public health and the public well-being of the country. In this article it is acknowledged the need for development of treatment models and interventions whose therapeutic value is demonstrated by scientific evidence, that respond to the attention needs of the population affected by substance use in our country and that can be generalized in community clinical practice. In clinical research, randomized controlled clinical trials (RCT's) are the "gold standard" to demonstrate the effect of a therapeutic intervention. A randomized controlled clinical trial is a prospective study in which the effect, value and safety of one or various experimental interventions are tested against a "control" intervention in human subjects. Acknowledging that in Mexico there is a lack of research on addiction treatment that is compliant with all the requirements to be considered as an RCT, this article presents some methodological and ethical considerations that are neccesary for their design and conduction. These considerations include from the establishment of a relevant research question and objectives, adequate study design, development of strategies for data management, statistical analysis, monitoring of interventions, safety monitoring and research quality assurance and protection of human subjects.

Según reportes epidemiológicos, el consumo nocivo de alcohol y drogas ilegales dentro de la población mexicana ha ido en aumento, lo que se asocia a varios riesgos o problemáticas que afectan la salud y bienestar públicos del país. Se reconoce la necesidad de desarrollar modelos de tratamiento e intervenciones cuyo valor terapéutico esté respaldado por la evidencia científica, que respondan a las necesidades de atención de la población afectada por el consumo de sustancias en nuestro país y que puedan generalizarse en la práctica clínica comunitaria. Dentro de la investigación clínica, el "estándar de oro" para demostrar el efecto de una intervención terapéutica son los ensayos clínicos controlados aleatorizados (ECCA). Un ECCA es un estudio prospectivo en el cual se prueba el efecto, valor y seguridad de una o varias intervenciones experimentales contra una intervención "control" en sujetos humanos. Reconociendo que en México hay una falta de investigaciones sobre tratamientos para las adicciones que cumplan con todos los requisitos para ser considerados ECCA, en este artículo se presentan distintas consideraciones metodológicas y éticas que deben tomarse en cuenta para su diseño y conducción en la materia; abarcando aspectos que parten desde el establecimiento de una pregunta y objetivos relevantes hasta el diseño adecuado del estudio y el desarrollo de estrategias para la administración de datos, análisis estadístico, monitoreo de las intervenciones, monitoreo de seguridad y aseguramiento de la calidad de la investigación y protección de los sujetos humanos que participan.

La melatonina como un factor promotor de la diferenciación neuronal: implicaciones en el tratamiento de las demencias / Melatonin as a neuronal differentiation factor: therapeutic implications for dementia

Dementias are progressive and neurodegenerative neuropsychiatry disorders, with a high worldwide prevalence. These disorders affect memory and behavior, causing impairment in the performance of daily activities and general disability in the elders. Cognitive impairment in these patients is related to anatomical and structural alterations at cellular and sub-cellular levels in the Central Nervous System. In particular, amyloid plaques and neurofibrillar tangles have been defined as histopathological hallmarks of Alzheimer's disease. Likewise, oxidative stress and neuroinflammation are implicated in the etiology and progression of the disease. Neuronal precursors from human olfactory neuroepithelium have been recently characterized as an experimental model to identify neuropsychiatric disease biomarkers. Moreover, this model not only allows the study of neuropsychiatric physiopathology, but also the process of neurodevelopment at cellular, molecular and pharmacological levels. This review gathers the evidence to support the potential therapeutic use of melatonin for dementias, based on its antioxidant properties, its anti-inflammatory effect in the brain, and its ability to inhibit both tau hyper-phosphorylation and amyloid plaque formation. Furthermore, since melatonin stimulates neurogenesis, and promotes neuronal differentiation by inducing the early stages of neuritogenesis and dendrite formation, it has been suggested that melatonin could be useful to counteract the cognitive impairment in dementia patients.

Las demencias son enfermedades neuropsiquiátricas, progresivas, neurodegenerativas y con una alta prevalencia a nivel mundial. Ocupan uno de los primeros lugares como enfermedades que causan incapacidad en los adultos mayores. En estos pacientes el Sistema Nervioso Central presenta alteraciones anatómico-estructurales a nivel celular y subcelular que se asocian con deficiencias cognitivas. En particular, en la enfermedad de Alzheimer se han caracterizado marcadores histopatológicos como las placas amiloides y las marañas neurofibrilares. Se sabe que el estrés oxidativo y la neuroinflamación participan en la etiología y el desarrollo de la enfermedad. Recientemente se caracterizó a los precursores neuronales del neuroepitelio olfatorio humano como un modelo experimental adecuado para identificar biomarcadores de rasgo y para estudiar la fisiopatología de diversas enfermedades neuropsiquiátricas, así como el proceso del neurodesarrollo, a nivel celular, molecular y farmacológico. En este trabajo se presenta la evidencia que sustenta que la melatonina puede ser útil en el tratamiento de las demencias, por su capacidad antioxidante, por su efecto anti-inflamatorio, así como por el efecto inhibidor de la hiperfosforilación de la proteina tau y de la formación de placas amiloides. Además, al estimular la formación de nuevas neuronas, la neuritogénesis en sus etapas tempranas y la formación de dendritas, la melatonina podría contribuir a contrarrestar la pérdida de las funciones cognitivas que se observa en estos padecimientos.

Asociación de los trastornos externalizados y la edad de inicio en pacientes con trastorno bipolar tipo I y II ¿Son los síntomas de los trastornos externalizados predictores de una edad de inicio más temprano? / Association between externalizing disorders and age of onset in patients with bipolar disorder type I and II. Are the externalizing disorders symptoms predictors of an earlier onset?

Background Early onset mania (MIMT), compared with adolescent onset mania (MIA), has a different clinical presentation of classic mania adult onset (MIEA). Patients with MIA have a course more like the MIEA. Externalizing disorders (ADHD, ODD, and TC) have been associated with an earlier age of onset of bipolar disorder and as a marker of poor prognosis. Our goal is to determine the frequency of symptoms related to disruptive behavior disorders in patients with bipolar disorder start very early, early and adult evaluated retrospectively. Methods The total sample (N=64) of adolescent and adult patients was obtained from the National Institute of Psychiatry (INPRF) clinics. The diagnosis was confirmed by the research team. Patients signed the informed asentment and consentment. We applied the K SADS PL Mexico, MINI and MINI KID. We used the EEPE-AA for externalizing disorders. Results There were significant differences in scores compared by EEPE AA EIED groups in the Inattention subscale for GIMT. The presence of ADHD, ODD, TC and Suicide Risk in the time of evaluation was significantly associated with an earlier onset. Discussion and conclusion Our data supports the clinical utility and importance of separating the TBP by age of onset. The detection of externalizing disorders may speak of an early onset of the disorder and may also have implications for prognosis and psychopharmacological treatment, since the TBP-onset childhood to adulthood remains similar and difficult to manage. This suggests that we must have a longitudinal view of this disorder.

Antecedentes La manía de inicio muy temprano (MIMT), comparada con la manía de inicio en la adolescencia (MIA), tiene una presentación clínica distinta a la manía clásica de inicio en la adultez (MIEA). Los pacientes con MIA tienen un curso más parecido a la MIEA. Los trastornos externalizados (TDAH, TND y TC) se han asociado con una edad de inicio más temprano del TBP y como un marcador de mal pronóstico. Nuestro objetivo es determinar la frecuencia de los síntomas relacionados con los trastornos de la conducta disruptiva en pacientes con TBP de inicio muy temprano, temprano y en el adulto evaluados de manera retrospectiva. Método La muestra total (N=64) de pacientes adolescentes y adultos se obtuvo de distintas clínicas del Instituto Nacional de Psiquiatría (INPRF). El diagnóstico fue confirmado por el equipo de investigación y se solicitó la firma del asentimiento y consentimiento informado. Se aplicaron el K SADS PL México, MINI y MINI KID. Se utilizó la EEPE-AA para los trastornos externalizados. Resultados Se encontraron diferencias significativas en las puntuaciones del EEPE AA comparadas por los grupos de EIED, en la Subescala de Inatención para el GIMT. La presencia de TDAH, TND, TC y riesgo suicida en el momento de la evaluación se relacionó significativamente con un inicio más temprano. Discusión y conclusión Nuestros datos apoyan la importancia y utilidad clínica de separar el TBP por edad de inicio y la detección de trastornos externalizados podría hablarnos de un inicio temprano del trastorno. Asimismo, tiene implicaciones en el pronóstico y tratamiento psicofarmacológico, ya que el TBP de inicio en la infancia permanece en la adultez con características similares, así como de difícil manejo. Es necesario tener una visión longitudinal de este padecimiento.

Immune variations in bipolar disorder: phasic differences.

OBJECTIVES: To characterize the immunological variations of patients with a bipolar disorder (BD) diagnosis in manic (BDm) and depressive (BDd) phases, by the quantification of the serum levels of interleukin (IL)-1beta, -2, -4, -6 and tumor necrosis factor alpha (TNF-alpha). METHODS: Twenty physically healthy patients with a BD type I diagnosis and 33 matched controls were studied, after giving informed consent. The inclusion criteria included at least three weeks without any kind of psychopharmacological treatment, Young Mania Rating Scale score > or =20 for BDm (n = 10) and Hamilton Depression Rating Scale score > or =21 for BDd patients (n = 10). Exclusion criteria included any infectious diseases, allergies or any other kind of medical illness that required treatment with immunosuppressors, as well as any other diagnosis in Axis I. Physical and laboratory examinations were performed to rule out any clinical illness. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the serum cytokines concentration. RESULTS: BD patients, when compared to controls, showed significant differences (p < or = 0.05) in the serum levels of the measured cytokines. The sub-group of BDd patients showed an increase in IL-6 and TNF-alpha, as well as a decrease in IL-2 concentration. The BDm sub-group, on the other hand, showed an increase in TNF-alpha and IL-4 values, with a low concentration of IL-1 and IL-2. The comparison between both sub-groups suggests that there is a distinctive cytokine pattern for the specific phases of the disorder: for mania, we found a high IL-4 and low IL-1beta and IL-6 concentration, while in the depressive phase, the inverse pattern was found. CONCLUSIONS: Our results show the existence of phasic differences in the serum levels of cytokines in BD.

Actitudes de mujeres estudiantes de psicología hacia las personas con esquizofrenia: Relación con la percepción de agresividad y peligrosidad / Attitudes of female students of psychology toward people with schizophrenia: Relationship with perception of aggressiveness and dangerousness

Introduction Perception of environment and reality stems mainly from factors determined by social and cultural influences. Several socialization processes promote the development of relations that endorse or reject certain values or identities. Unfortunately, many of these relations arise from prejudiced values that generate negative attitudes such as stigmatization or discrimination toward some persons. According to psychosocial models, generation of stigma is a consequence of three aspects: lack of knowledge about the person's condition (ignorance); development of negative attitudes (prejudice) and a tendency to exclude or reject some individuals (discrimination). Particularly, in mental health problems, general public knowledge of severe mental illnesses such as schizophrenia frequently develops in accordance to myths and misconceptions. For example, schizophrenics are commonly viewed as mad and incompetent individuals that produce fear and rejection. These erroneous conceptions originate from considering that they are incapable of controlling their acts, thus giving rise to aggressive, violent or dangerous conducts. Stigmatization impacts patients increasing depressive symptoms, anxiety and social withdrawal. Stigma also has a negative impact on diagnosis and treatment; timely diagnostic interventions and specialized treatments are frequently delayed in stigmatized individuals. Although it is reasonable to anticipate that stigmatization attitudes are more common among persons with low cultural levels, many studies have demonstrated that unfortunately this problem is also present in many health professionals, including those who work with the mentally ill. For these reasons different attempts have developed to reduce stigma by means of mental health literacy interventions oriented to modify and eliminate misconceptions about mental patients and their illness. In this sense, mental health literacy is defined as any educational intervention aimed to increase recognition, management and prevention of mental illness. Many studies have demonstrated that this type of interventions have a positive impact in reducing negative attitudes toward patients, diminishing in consequence treatment gap. In accordance to this theoretical framework, the principal objective of this study was to evaluate in a group of female psychology students, their attitudes toward mental illness determining their perception of danger and aggressiveness in a schizophrenic patient. We hypothesized that perception of dangerousness and aggressiveness will correlate with more negative attitudes to mental illness. Additionally, we compared attitudes to severe mental illness according to other variables related to mental health literacy such as knowledge of etiology of illness and treatment options, among female student in their first half of their career and female student in their second half. We hypothesized that advanced student will have a higher level of mental health literacy and less negative attitudes to mental illness. Method A total of 110 female psychology students from a university in Mexico City were included in the study. Group's mean age (±SD) was 21.6 (1.7) years (range 19-33 years). All subjects gave their consent to participate in a voluntary and anonymous manner. Sixty five students (59.1%) were at the initial half-stage of their career (1st to 5th semester), and forty five (40.9%) were at their last half-stage (6th to 10th semester). The study was approved by the Institutional Research and Ethical Committees (Instituto Nacional de Psiquiatría Ramón de la Fuente), and by the university's authorities. The Opinions about Mental Illness Scale (OMI), previously translated and standardized in our country (OMI-M), was used to evaluate personal attitudes toward severe mentally ill persons. OMI-M is a 34-item self-report questionnaire which evaluates attitudes utilizing a 5-points Liker scale procedure (1 = totally disagree; 5=totally agree). Evaluation includes six factors: 1. Separatism, which emphasizes the persons' perceived differences about a mental disorder and the desire of keeping a distance to be safe; 2. Stereotyping, defined as conceiving mentally ill persons in accordance to certain behavioral and intellectual patterns; 3. Restrictiveness, which includes items that uphold an uncertain notion regarding the rights of mentally ill persons; 4. Benevolence, which evaluates compassion to the mentally ill; 5. Pessimistic prediction, referring to the perception that mentally ill persons are incapable of improving on their symptoms and how society is also not optimistic in this respect; 6. Stigmatization, build upon items that perceive mental illness as a cause of shame. The Public Aggressiveness Concept Questionnaire, a self-rated instrument was also applied in the study. This questionnaire evaluates the perception of aggressiveness after reviewing a standardized clinical vignette of a patient with an active paranoid schizophrenia. The reviewer is asked to answer questions regarding the identification of aggressive conduct in the vignette, including the presence and intensity of verbal and physical violence. In another section, the way symptoms could be controlled is evaluated. Additional questions are included in the final section of the questionnaire aimed to evaluate concepts such as if the reviewer considers that the person in the vignette has a mental illness, what causes might originate this condition, and if he or she perceives the subject as socially dangerous. Data analysis was carried utilizing the SPSS, version 17.0, statistical program. Categorical variables description was done with rates and percentages; continuous variables were analyzed with means and standard deviation.

Introducción El temor y el rechazo han sido las principales actitudes negativas hacia las personas con trastornos mentales graves como la esquizofrenia. Éstas surgen de la percepción pública de que los pacientes no tienen control sobre su comportamiento y son agresivos, violentos y/o peligrosos; tienen un impacto directo en las personas que padecen esquizofrenia y sus familiares, y aun cuando podría esperarse lo contrario, diversos estudios han mostrado que los profesionales de la salud en general, y de la salud mental en lo particular, muestran actitudes negativas hacia los pacientes con esquizofrenia. Diversos estudios internacionales han demostrado que las campañas dirigidas a incrementar la alfabetización en salud mental (ASM) son efectivas para modificar las actitudes negativas hacia las personas con trastornos mentales. Sin embargo, las necesidades de ASM pueden tener variaciones locales, por lo que resulta necesario conocer las actitudes hacia la enfermedad mental y los factores asociados a las mismas en las poblaciones blanco a las que se dirigirán las campañas antiestigma en una región particular. En esta dirección, el objetivo principal del presente estudio fue comparar las actitudes de mujeres estudiantes de psicología hacia las personas con trastornos mentales graves de acuerdo a la agresividad y peligrosidad percibida de un paciente con esquizofrenia. Adicionalmente, las actitudes hacia las personas con trastornos mentales graves así como las variables relacionadas con la alfabetización en salud mental se comparan entre las mujeres que cursaban la primera mitad de la licenciatura en psicología y aquellas que cursaban la segunda mitad. Método Se incluyó un total de 110 mujeres con una edad promedio de 21.6±1.7 años, estudiantes de la licenciatura en psicología de una universidad de la zona metropolitana de la Ciudad de México que aceptaron participar en el estudio de forma voluntaria y anónima. El 59.1% (n=65) se encontraba cursando la primera mitad de la licenciatura (del 1° al 5° semestre) y el 40.9% (n=45) restante, la segunda mitad (del 6° al 10° semestre). El total de la muestra completó la Escala de Opiniones sobre la Enfermedad Mental en Población Mexicana (OMI-M) para determinar las actitudes hacia las personas con trastornos mentales graves, así como el Cuestionario de Concepto Público de Agresividad (CPA), que valora el concepto público de agresividad del paciente con esquizofrenia con base en la presentación de una viñeta clínica de un paciente con esquizofrenia paranoide. Resultados El 95.5% (n=105) de las estudiantes reconocieron la presencia de una enfermedad mental en la viñeta clínica. No obstante, tan sólo el 70.9% (n=78) consideró las intervenciones psiquiátricas como las más adecuadas para el control de los síntomas. El 59.1 % (n=65) de las estudiantes consideró que el sujeto descrito en la viñeta podría ser agresivo de alguna forma y tan sólo 12.7% (n=14) lo calificó como peligroso para la sociedad. Las estudiantes que percibieron agresivo al paciente de la viñeta mostraron mayores puntajes en las áreas de restricción, predicción pesimista y en la puntuación total del OMI-M. De forma similar, aquellas que consideraron peligroso al paciente tuvieron mayores actitudes negativas en términos de separatismo, estereotipos y puntuación total del OMI-M. No se encontraron diferencias en las variables de alfabetización en salud mental (reconocimiento de la enfermedad, causas atribuibles y tratamiento sugerido), ni en la percepción de agresión y peligrosidad, ni en cuanto a las diferentes áreas evaluadas por el OMI-M entre alumnas que cursaban la primera mitad de la licenciatura en psicología y aquellas que cursaban la segunda mitad. Discusión Un alto porcentaje de estudiantes de psicología consideró agresivo al paciente descrito en la viñeta, y tal como se esperaba, esta concepción se relacionó con mayores actitudes negativas, tales como mayor nivel de restricción y de predicción pesimista. Adicionalmente, la percepción de la persona con enfermedad mental como alguien con capacidades limitadas y comportamiento extraño parece promover la distancia social. Tanto la percepción de agresión como la de peligrosidad y las actitudes negativas asociadas en esta muestra nos hablan del poco entendimiento que pudieran tener los estudiantes de psicología en relación con las experiencias vividas por los pacientes. Aun cuando nuestros resultados no pueden ser generalizados al total de los estudiantes de psicología del país, es posible sugerir la inclusión al currículo educativo de información clara y objetiva sobre aspectos psicosociales de la enfermedad -estigma y actitudes hacia la enfermedad- y no sólo aspectos teóricos sobre la fisiopatología del trastorno y características sintomáticas del padecimiento; así como el contacto regular, tanto hospitalario como comunitario, con los pacientes.