Abstract: Objective: To evaluate the sensitivity and specificity of the Two Whooley questions and the Arroll question, using the SCID, The Structured Clinical Interview (SCID-I) as the gold standard for detecting perinatal depression. Materials and methods: We interviewed 210 women during pregnancy and 6 months postpartum. Results: The criterion with the greatest sensitivity was responding positively to either Whooley question (pregnancy= 94.7 %; postpartum=100.0%), while the most specific criterion was responding positively to the two Whooley questions plus the Arroll question (Pregnancy=90.0% Postpartum = 85.7%). Conclusion: The Whooley and Arroll questions have adequate psychometric properties to detect possible cases of depression during the perinatal period. They can be applied during prenatal check-ups and postpartum consultations. Timely detection of women at risk of perinatal depression can contribute to their treatment for reducing their adverse consequences in mothers and infants.

Resumen: Objetivo: Evaluar la sensibilidad y la especificidad de la Escala de las dos preguntas de Whooley y la pregunta de Arroll para detectar riesgo de depresión perinatal, usando la SCID como estándar de oro. Material y métodos: Se entrevistó a 210 mujeres durante el embarazo y 6 meses después del parto. Resultados: El criterio con mayor sensibilidad fue responder positivamente a cualquiera de las Preguntas de Whooley (embarazo = 94.7%; posparto = 100.0%) y, el más específico, responder positivamente a las preguntas de Whooley más la de Arroll (embarazo = 90.0% , Posparto = 85.7%). Conclusiones: Las preguntas de Whooley y Arroll tienen propiedades psicométricas adecuadas para detectar posibles casos de depresión durante el periodo perinatal. Pueden aplicarse durante las citas de control prenatal y consultas en el postparto. Detectar de manera oportuna a mujeres en riesgo de depresión perinatal puede ayudar a su atención para reducir sus consecuencias adversas en madres e infantes.

Abstract: Objective: To evaluate the sensitivity and specificity of the Two Whooley questions and the Arroll question, using the SCID, The Structured Clinical Interview (SCID-I) as the gold standard for detecting perinatal depression. Materials and methods: We interviewed 210 women during pregnancy and 6 months postpartum. Results: The criterion with the greatest sensitivity was responding positively to either Whooley question (pregnancy= 94.7 %; postpartum=100.0%), while the most specific criterion was responding positively to the two Whooley questions plus the Arroll question (Pregnancy=90.0% Postpartum = 85.7%). Conclusion: The Whooley and Arroll questions have adequate psychometric properties to detect possible cases of depression during the perinatal period. They can be applied during prenatal check-ups and postpartum consultations. Timely detection of women at risk of perinatal depression can contribute to their treatment for reducing their adverse consequences in mothers and infants.

Resumen: Objetivo: Evaluar la sensibilidad y la especificidad de la Escala de las dos preguntas de Whooley y la pregunta de Arroll para detectar riesgo de depresión perinatal, usando la SCID como estándar de oro. Material y métodos: Se entrevistó a 210 mujeres durante el embarazo y 6 meses después del parto. Resultados: El criterio con mayor sensibilidad fue responder positivamente a cualquiera de las Preguntas de Whooley (embarazo = 94.7%; posparto = 100.0%) y, el más específico, responder positivamente a las preguntas de Whooley más la de Arroll (embarazo = 90.0% , Posparto = 85.7%). Conclusiones: Las preguntas de Whooley y Arroll tienen propiedades psicométricas adecuadas para detectar posibles casos de depresión durante el periodo perinatal. Pueden aplicarse durante las citas de control prenatal y consultas en el postparto. Detectar de manera oportuna a mujeres en riesgo de depresión perinatal puede ayudar a su atención para reducir sus consecuencias adversas en madres e infantes.

Excessive daytime sleepiness (EDS) is a highly disabling sleep disorder related to alterations in behavioral performance, work injuries and vehicle accidents. A high prevalence of EDS (from 16% to 32%) in the general population has been reported. The Functional Outcomes Sleep Questionnaire (FOSQ) is an instrument that measures the impact of EDS in a patient's functional state in different sleep disorders. This questionnaire has been validated in different countries (Norway, Turkey, Spain). Therefore, the objective of this study was to obtain the cultural validation, the internal consistency, construct validity and factor congruence of the adapted questionnaire for the inhabitants of Mexico City (FOSQ-México). In the first part of the study we translated the questionnaire using the standard methodological process. The FOSQ cultural adaptation was made by the Natural Modified Semantic Networks technique in a sample of 78 participants. In the second part, the adapted FOSQ was applied to 152 participants to test items discrimination, internal consistency, factor analysis by principal-components and factorial congruence with the original version. The principal-components analysis of the FOSQ yielded six meaningful factors that explained 67.2% of the total variance, an average a coefficient between 0.85 to 0.94 for the six factors. The factorial congruence coefficients ranged from 0.360 to 0.969 between the original and the FOSQ-México version. This study demonstrated that the FOSQ version for inhabitants of Mexico City is reliable, valid and conceptually equivalent to the American version.

La Somnolencia Diurna Excesiva (SDE) es uno de los problemas de sueño más incapacitantes ya que se relaciona con déficits en la ejecución conductual, accidentes laborales y vehiculares. Se estima una prevalencia en la población general de entre 16% y 32%. El Functional Outcomes Sleep Questionnaire (FOSQ) es el cuestionario más utilizado para medir el impacto de la SDE en el estado funcional de pacientes con diferentes trastornos del dormir, el cual se ha validado en distintos países. Por lo tanto, el objetivo de este estudio fue adaptar culturalmente el FOSQ y obtener la confiabilidad, la validez de constructo y los coeficientes de congruencia factorial para la versión FOSQ-México. En una primera fase se tradujo el cuestionario utilizando el procedimiento metodológico estándar. También se hizo la adaptación cultural de los reactivos mediante la técnica de Redes Semánticas Naturales Modificadas en una muestra de 78 participantes. En una segunda fase, el cuestionario adaptado se aplicó a 152 participantes para determinar la discriminación entre reactivos, la consistencia interna, el análisis factorial con rotación ortogonal con un método de componentes principales y comprobar la congruencia factorial. Los resultados indicaron que los 30 reactivos del FOSQ se agruparon en seis factores que explican el 67.2% de la varianza total, con un coeficiente a total de 0.94 y de 0.85 promedio para los factores. Se obtuvieron coeficientes de congruencia factorial de 0.360 a 0.969 entre la versión original y el FOSQ-México. Se demostró que la versión adaptada del FOSQ para habitantes de la Ciudad de México es confiable, válida y equivalente conceptualmente con la versión norteamericana.

The relationship among porosity, size and particle distribution (1-2 mm and 2-3.36 mm) with water retention for different mixtures of materials: coir (Fc), stone (P) or volcanic stone (T), combined in variables proportions (0:100, 25:75, 50:50, 75:25 and 100:0 v/v) was studied. The effect of the combination Fc:P with a particle size (1-2 mm) on response variables in lettuce seedlings var. Summertime was analyzed. The water retention curve was determined. The types of pores and the particle distribution pattern of the mixtures was analyzed though thin sections. Porosity was quantified using an image analyzer. Results showed that Fc:T and Fc:P mixtures (75:25 v/v), showed the highest volumetric (98 %) and gravimetric (230 %) water retention capacity, as well as an anisotropic or heterogeneous pore system (macro and micro), and a band distribution, that allowed percolation and optimal water retention for the development of lettuce seedlings, represented in the best response variables and quality of root ball. In contrast, the rest of the mixture with an isotropic or homogeneous pore system, either simple or compound packing pores, and a basic random distribution of particles, generating more percolation or more water retention, that limited the growth of seedlings. Micromorphology can be useful for understanding the physical properties of the substrates by directly determining the type, size and continuity of pores, characteristics that affect water-air availability.

Se estudió la relación entre la porosidad, el tamaño y distribución de partícula (1-2 mm y 2-3.36 mm) con la retención de humedad para diferentes mezclas de materiales: fibra de coco (Fc): piedra (P) o tezontle (T), combinados en proporciones variables (0:100, 25:75, 50:50, 75:25 y 100:0 v/v). Además, se analizó el efecto de la combinación Fc:P con un tamaño de partícula (1-2 mm) sobre variables respuesta en plántulas de lechuga var. Summertime. Se determinó la curva de retención de humedad. Los tipos de poros y el patrón de distribución de las partículas de las mezclas, se analizaron a través de secciones delgadas y la porosidad se cuantificó con un analizador de imágenes. Los resultados mostraron que las mezclas Fc:T y Fc:P (75:25 v/v), presentaron la mayor capacidad de retención de humedad gravimétrica (230 %) y volumétrica (98 %). Además, un sistema de poros heterogéneo o anisotrópico (macro y micro), y una distribución en bandas, que permitieron percolación y retención de humedad óptima para el desarrollo de las plántulas de lechuga, expresada en las mejores variables respuesta y calidad del cepellón. En contraste, el resto de las mezclas con un sistema de poros homogéneo o isotrópico, ya sea de poros de empaquetamiento simple o compuesto, y una distribución básica aleatoria de partículas, generaron más percolación o más retención de humedad, que limitaron el crecimiento de las plántulas. La micromorfología puede ser útil para comprender las propiedades físicas de los sustratos al determinar directamente el tipo, tamaño y continuidad de los poros, características que afectan la disponibilidad de agua-aire.

The aim of this work was to describe the prevalence of signs and symptoms of temporomandibular disorders (TMD) in children of the State of Puebla, Mexico. A descriptive observational study was performed. After calculating sample size, children who met the following selection criteria were included: registered at an official elementary school, either sex, ages between 8 and 12 years, who accept to participate in the study and whose parents have signed the informed consent forms. The Research Diagnostic Criteria for Temporomandibular Disorders were used by calibrated researchers (Kappa.90) under the same conditions. Descriptive statistics were applied by using SPSSv15 software. The study included 235 children, 129 (54.9%) female and 106 (45.1%) male, of average age 9.31+1.2 years. Prevalence of signs and symptoms was 33.2%, and predominately muscular (82%), 48.1% showed signs of muscular pain and 19.1% joint pain. 63.4% showed signs of alteration in the mouth opening pattern, 39.1% presented joint sounds on opening or closing the mouth and 20.4% on mandibular excursions. The high prevalence of signs and symptoms related to temporomandibular disorders, in particular in children with mixed dentition, shows the importance of TMD evaluation during this period, when morphological changes associated to growth and craniofacial development prevail.

El objetivo del presente trabajo fue describir la prevalencia de signos y sintomas de los trastornos temporomandibulares (TTM) en ninos del estado de Puebla, Mexico. Se realizo un estudio observacional descriptivo. Previo calculo de tamano de muestra, se incluyeron ninos que cumplieron con criterios previos de seleccion: inscriptos en escuela primaria oficial, de cualquier sexo, en edades de 8 a 12 anos, que aceptaron participar en el estudio y cuyos padres firmaron el consentimiento informado. Se utilizaron los Criterios de Investigacion Diagnostica para los TTM, aplicados por investigador estandarizado (Kappa .90) bajo las mismas condiciones. Se calculo estadistica descriptiva con el programa SPSS v15. Se incluyeron 235 ninos, 129 (54.9%) mujeres y 106 (45.1%) varones con promedio de edad de 9.31�}1.2 anos. La prevalencia de signos y sintomas de TTM fue del 33.2% predominantemente musculares (82%), 48.1% presentaron dolor muscular y 19.1% articular. El 63.4% presento alteraciones en el patron de apertura bucal, 39.1% presento ruidos articulares en apertura o cierre y 20.4% a las excursiones mandibulares. Las altas prevalencias de los signos y sintomas relacionadas con los Trastornos Temporomandibulares, particularmente en ninos con denticion mixta, demuestran la importancia de la evaluacion de los TTM durante este periodo, donde prevalecen los cambios morfologicos asociados al crecimiento y al desarrollo craneofacial.

Introduction Depression is a public health problem that carries substantial costs for the individual and the society. In order to establish evidence-based priorities for resource allocation in mental health care, it is necessary to integrate the costs and effectiveness of interventions and specify the essential packages for their treatment. The following are pioneering studies of cost-effectiveness for the treatment of depression: 1. compared psychopharmacology options (fluoxetine, imipramine and desipramine) to found no difference between drugs in terms of clinical efficacy, effect on quality of life and costs, and 2. evaluated cost-effectiveness of collaborative program of stepped care in primary care of persistent depression, to demonstrate a substantial increase in the effectiveness and additional moderate cost increase in comparison with usual treatment. Recently, the World Health Organization convened the National Institute of Psychiatry Ramón de la Fuente, as a collaborating center, to participate in the <<Selecting interventions that are cost-effective>> labeled WHO-CHOICE (CHOosing interventions that are Cost-Effective). This paper presents the findings of the evaluation of cost-effectiveness of different clinical interventions for the treatment of depression in Mexico, considering its implementation in primary care services. Method The cost-effectiveness unit of measure gathered by WHO (and used in this work) are the years of healthy life lost because of disease, named DALYs (Disability Adjusted Life Years). DALYs result from the sum of years lost by premature mortality over the years that are lost through living in disability status. The advantages of using a measure of health at the population level as lost DALYs is that it allows comparing interventions for different diseases and addresses a relevant question from the avoidable burden health policy standpoint. Interventions evaluated included: 1. tricyclic antidepressants, 2. new antidepressants (SSRIs), 3. brief psychotherapy, 4. trycliclic antidepressants + brief psychotherapy, 5. new antidepressants + brief psychotherapy, 6. tricyclic antidepressants + brief psychotherapy + proactive case management, and 7. new antidepressants + brief psychotherapy + proactive case management. DALYs avoided as a result of each intervention or combination were calculated to determine its effectiveness. Both patients and program costs, a 3% discount by the process of converting future values to present ones, as well as an age adjustment giving less weight to year lived by the young were included. Finally, the cost of averted DALYs for each intervention was estimated to determine their cost effectiveness. Results The combined strategies of proactive case management with psychotherapy plus antidepressants can be considered as the most effective one. With the combination with tricyclic antidepressants, the number of DALYs averted was 207,1 71, and with SSRI of 21 7,568, corresponding to more than double of DALYs when tricyclic anti-depressants are used alone and almost double when using only SSRIs. The most expensive intervention was the combination of SSRIs with brief psychotherapy, with a total of $12,256 million pesos (972 million dollars), the least expensive treatment were tricyclic antidepressants, which involved $4,523 million pesos (359 million dollars). Over 99% of the costs were from patient medications, and less than 1% from program and training costs. It is clear that the greatest cost is for added proactive case management. The use of SSRI was the most cost-effective treatment (no combination) for the management of depression in Mexican primary care. The most cost-effective combination was tryciclic antidepressants plus brief psychotherapy plus proactive case management. Conclusions Although the are some studies on health economics in Mexico, most are directed to consider costs, and few ones have evaluated the cost-effectiveness relationship of diagnostic and therapeutic interventions, lees son in the mental health field. Antecedents of the present study in Mexico included a study that observed that psychiatric patients require more medical consultations, laboratory analysis, hospitalization days, surgeries and medication, in contrast with patients that never needed mental attention. Nevertheless, investigations about cost-effectiveness relationship are rare. Just one study evaluates the costs of positive changes in psychopathology with antipsychotic medication for the treatment of schizophrenic patients. In this direction, the present work is the first effort to evaluate cost-effectiveness of different communitarian interventions to treat depression in Mexico. According with our findings, also in México, the interventions available to treat depression in primary care level prevent a substantial number of DALYs: almost six times when SSRIs plus brief psychotherapy plus proactive case management are administered. The specific effect of proactive case management is preventing relapses and increasing the time free of disease, which results in greater benefit to the patient, his family and the society. Thus, interventions are cost-effective despite the proactive case management significantly increases the cost of care to these patients. In conclusion, the inclusion of psychosocial treatments is advantageous from a cost-effectiveness standpoint. Averted DALYs with these interventions are more <<economic>>. As observed in previous studies, a modest investment in improving depression produces greater gains in resource-limited environments. In Mexico, there is evidence that such interventions in primary care are effective when they are given by medical staff with a brief training, making them a promising tool for a cost-effective and evidence-based public policy.

Introducción La depresión es un problema de salud pública que conlleva costos importantes para el individuo y la sociedad. Con la finalidad de establecer prioridades basadas en evidencias para la asignación de recursos en el cuidado de la salud mental, es necesario integrar los costos y la efectividad de las intervenciones y especificar los paquetes esenciales para su tratamiento. En esta dirección, la Organización Mundial de la Salud convocó al Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, como centro colaborador, a participar en el proyecto <<Seleccionando intervenciones que son costo-efectivas>> (WHO-CHOICE, por sus siglas en inglés: CHOosing Interventions that are Cost-Effective). El presente texto presenta los hallazgos del estudio de relación costo-efectividad de diferentes intervenciones clínicas para el tratamiento de la depresión en México, considerando su implantación en los servicios de atención primaria a la salud. Método La unidad de medición de costo-efectividad seleccionada por la OMS (y utilizada en este trabajo) son los Años de vida ajustados por discapacidad a causa de alguna enfermedad (AVISA perdidos, en inglés DALYs, Disability Adjusted Life Years), que resultan de la suma de los años que se pierden por mortalidad prematura más los años que se pierden por vivir en una situación de discapacidad. Las intervenciones evaluadas fueron: 1. antidepresivos tricíclicos; 2. antidepresivos nuevos (ISRS); 3. psicoterapia breve; 4. antidepresivos tricíclicos + psicoterapia breve; 5. antidepresivos nuevos + psicoterapia breve; 6. antidepresivos tricíclicos + psicoterapia breve + manejo proactivo de caso; y 7. antidepresivos nuevos + psicoterapia breve + manejo proactivo de caso. Para determinar su efectividad, se calcularon los AVISAs perdidos que se evitan como resultado de cada intervención. Se incluyeron los costos del paciente y los del programa, un descuento de 3% por el proceso de convertir valores futuros a presentes, así como un ajuste por edad, otorgando menos peso a los años vividos por los jóvenes. Finalmente, para determinar la relación costo-efectividad, se calculó el costo por cada AVISA evitado con cada intervención. Resultados Las estrategias combinadas de manejo proactivo de caso con psicoterapia breve más antidepresivos pueden considerarse como las más eficaces. Con la combinación con antidepresivos tricíclicos, el número de AVISAs evitados fue de 207171, y con la de ISRS fue de 217568, lo que corresponde a más del doble de AVISAs cuando se emplean únicamente antidepresivos tricíclicos, y casi al doble cuando se emplean únicamente ISRS. La intervención más costosa fue la combinación de ISRS con psicoterapia breve, con un monto total de $12,256 millones de pesos (972 millones de dólares), y la menos costosa fue el tratamiento con antidepresivos tricíclicos, que implicó $4,523 millones de pesos (359 millones de dólares). De los costos, más de 99% correspondieron a medicamentos, y menos de 1% a los costos del programa y del entrenamiento. Es evidente que el mayor costo corresponde a las intervenciones en que se agrega el manejo proactivo de caso. La intervención que tuvo la mejor relación costo-efectividad, considerando un solo tratamiento, fue el uso de ISRS. La combinación más costo-efectiva fue la de antidepresivos tricíclicos con psicoterapia breve y manejo proactivo de caso. Conclusiones Es claro que las intervenciones disponibles para el tratamiento de la depresión evitan un número considerable de AVISAs. Éste es casi seis veces mayor cuando se administran ISRS + psicoterapia + manejo proactivo de caso, lo que permite que las intervenciones resulten costo-efectivas a pesar de que el manejo proactivo de caso aumenta considerablemente los costos de atención a estos pacientes. El efecto específico del manejo proactivo de caso es que evita las recaídas y aumenta el tiempo libre de enfermedad, lo que se traduce en mayor beneficio para el paciente, su familia y la sociedad en general.

Introduction Schizophrenia is a disorder that causes significant disability. In addition, its treatment is expensive because the increased prescription of atypical antipsychotics with associated high costs. In a recent 14-country study on disability associated with physical and mental conditions, active psychosis was ranked the third most disabling condition in general population, more than paraplegia and blindness. In the global burden of disease study, schizophrenia accounted for 1.1% of the total Disability-adjusted life years (DALYs) and 2.8% of Years of lived with disability (YLDs). The economic cost of schizophrenia for society is also high. The study of the burden of schizophrenia for society, whether expressed in epidemiological or costs terms, is an insufficient basis for setting priorities for resources allocation. Thus, increasingly sophisticated economic models have been developed. Such is the case of cost-effectiveness studies, which show the relationship between resources used (costs) and benefit achieved (effectiveness) of an intervention compared with others. In Mexico, there is only one study that evaluated the cost-effectiveness of different antipsychotics to treat schizophrenia, but it was a specific approach (not generalized), and did not include psychological interventions. The present study is part of a World Health Organization's initiative labeled WHO-CHOICE: CHOosing Interventions that are Cost-Effective. WHO-CHOICE methodology involves the evaluation of interventions based on a generalized measure: DALYs, which allows carrying out several and important comparisons. The main objective was to determine the cost-effectiveness of different interventions for the treatment of schizophrenia in Mexican communitarian settings. Method Schizophrenia was modeled as a serious chronic disorder with a high level of disability, excess mortality from natural and unnatural causes, and a low rate of remission. The incidence, prevalence, and the fatality rate were estimated based on the study of the Global Burden of Disease and a review of the epidemiological literature. As the first episode of schizophrenia is currently not preventable, the occurrence represents how the epidemiological situation would be without intervention. In relation to the referral and the fatality, we did not found evidence that these rates change by a specific effect of the treatment; thus, they were kept as constants for the scenarios with or without treatment. Community-level interventions assessed were: 1. typical traditional antipsychotics (haloperidol), 2. new atypical antipsychotics (risperidone), 3. traditional antipsychotics + psychosocial treatment (family therapy, social skills training and cognitive behavioral therapy), 4. new antipsychotics + psychosocial treatment, 5. traditional antipsychotics + psychosocial treatment + case management, and 6. new antipsychotics + psychosocial treatment + case management. The effectiveness of the treatments referred to the control of positive and negative symptoms and associated levels of disability. To calculate the improvement in disability compared with natural history (when the disease is not treated), the effect sizes reported in controlled clinical trials were converted to a weight change of disability. Efficacy and extrapyramidal effects of typical and atypical antipsychotics compared to placebo were estimated from the meta-analysis of controlled clinical trials, with the score of the BPRS severity scale and the need anti-Parkinson drugs as efficacy measures. From another meta-analysis we obtained an estimate of the magnitude of the effect by adding psychosocial interventions. As an ad hoc Cochrane systematic review that found case management did not had a significant impact on clinical or psychosocial outcomes, only a minimal addition effect size when added to the combination of pharmacologic-psychosocial treatment was observed. Costs included those of the patient, the program and the training required to implement the intervention. The provision of community-based services, daily administration of antipsychotics and anticholinergics, and laboratory tests were taken into account. For psychological interventions were envisaged from 6 to 12 sessions: in primary care from 6 to 12 visits, in outpatients services a visit per month for 20-50% of cases, and in day care communitarian attention from 1-2 times a week for 20-50% of cases. A 3% discount by the process of converting future values to present ones and an age adjustment giving less weight to year lived by young were included. Finally, the cost of DALYs averted for each intervention was estimated to determine their cost-effectiveness. Results The main findings of the study are, in relation to the costs of interventions: 1. the largest share corresponds to those generated by medication, 2. the current intervention is the cheapest, and 3. the combination of new atypical antipsychotics, psychological treatment and proactive case management is the most expensive intervention. Concerning the effectiveness of interventions, the one available today, with a coverage of 50%, prevents 68 222 DALYs. Increasing coverage to 80%, the number of DALYs averted is almost doubled with the use of typical antipsychotics. The effect of psychological interventions makes the number of DALYs averted three to four times higher. Finally, in regard to cost effectiveness, the combination of typical antipsychotics, psychosocial intervention and proactive case management was the treatment with the best relation. The cost per DALY averted was $390,892 Mexican pesos, which corresponds to one third of the cost of DALY averted in the current scenario ($1,313,120 Mexican pesos). Conclusions The resources for the attention of a public health issue involve a social investment rather than an expense budget, but they are also finite and must be chosen properly to be allocated. Cost-effectiveness studies of available interventions are an essential tool for making such important decisions. Our Mexican study of cost-effectiveness of interventions to treat schizophrenia in communitarian settings suggests, in general terms: 1. That while the current situation is the one with the lowest cost, it is the least efficient, 2. all alternatives involve an additional cost to the current situation because they assume an expansion of coverage; however, the extra cost in not excessive, and 3) that within a model of community-based care, the least expensive option is treatment with typical antipsychotics combined with psychological intervention. Thus, for a modest extra cost it is possible to yield a major impact on disability. Recently, the Mexican Federal Government has included schizophrenia in the catalog of diseases covered by the program called <<Seguro Popular>>, that provides a health insurance to general population, especially to the poorest and unemployed ones. The planned actions include four specialty consultations in an interval of two months and annual psychopharmacological treatment. Clearly the addition of haloperidol, trifluoperazine and risperidone to the list of available medications should be considered a success. However, schizophrenia also requires a proactive case monitoring of long-term for best control of symptoms and a successful rehabilitation. Moreover, consistent with our findings, case management has proven to be cost-effective when compared with routine care in the community. Among the limitations of the study it is important to note that it was based on modeled parameters obtained from the international literature. In this sense, the challenge is the data generation directly from studies in Mexico.

Introducción La esquizofrenia es un trastorno que produce una importante discapacidad, y su costo para la sociedad es muy elevado. El estudio de la carga que impone la esquizofrenia sobre la sociedad, ya sea expresada en términos epidemiológicos o de costos, es una base insuficiente para establecer las prioridades para la asignación de recursos, por lo que se han desarrollado modelos económicos cada vez más elaborados. Tal es el caso de los estudios de costo-efectividad, que muestran la relación entre los recursos empleados (costos) y los beneficios logrados (efectividad) de una intervención comparada con otra(s). El presente trabajo forma parte de la iniciativa de la Organización Mundial de la Salud (OMS) para la elección basada en evidencia de intervenciones costo-efectivas denominada WHO-CHOICE, Choosing Interventions that are Cost-Effective, que implica la determinación de una medida general que posibilita comparaciones internacionales: los años de vida vividos con discapacidad (AVISAs o DALYs, de las siglas de Disability-adjusted life years). Objetivo Fue determinar la relación costo-efectividad en México de diferentes intervenciones que han demostrado ser efectivas para el tratamiento comunitario de la esquizofrenia. Método Se evaluaron las siguientes intervenciones: 1. Antipsicóticos tradicionales típicos (haloperidol), 2. Antipsicóticos nuevos atípicos (risperidona), 3. Antipsicóticos tradicionales + tratamiento psicosocial (terapia familiar, entrenamiento en habilidades sociales y terapia cognitivo conductual), 4. Antipsicóticos nuevos + tratamiento psicosocial, 5. Antipsicóticos tradicionales + tratamiento psicosocial + manejo de caso, y 6. Antipsicóticos nuevos + tratamiento psicosocial + manejo de caso. La efectividad relativa de los tratamientos se refirió al control tanto de los síntomas positivos y negativos así como de los niveles asociados de discapacidad. Se consideraron los costos del paciente, del programa y del entrenamiento, así como un descuento de 3% por el proceso de convertir valores futuros a presentes, y un ajuste de edad, otorgando menos peso a los años vividos por los jóvenes. Finalmente, se calculó el costo por AVISA evitado por cada intervención para determinar su costo-efectividad. Resultados Los principales hallazgos del estudio son, en relación con los costos de las intervenciones: 1. que la mayor proporción corresponde a los generados por los medicamentos; 2. que la intervención actual resulta la más barata; y 3. que la combinación de antipsicótico nuevo o atípico con intervención psicosocial y manejo proactivo de caso es la más cara. En cuanto a la efectividad de las intervenciones, la disponible en la actualidad, con cobertura de 50%, evita 68 222 AVISAs. Aumentando la cobertura a 80%, el número de AVISAs evitados casi se duplica con el empleo de antipsicóticos típicos. El efecto de las intervenciones psicosociales hace que el número de AVISAs evitados sea tres a cuatro veces mayor. Finalmente, en lo que respecta a costo-efectividad, la combinación de antipsicóticos típicos, intervención psicosocial y manejo proactivo de caso fue el tratamiento con la mejor relación. El costo por AVISA evitado fue de $390,892, que corresponde a un tercio del costo de AVISA evitado en el escenario actual ($1,313,120). Conclusiones Los hallazgos del estudio sugieren, en términos generales: 1. Que aunque la situación actual es la de menor costo, es la menos eficiente; 2. Que todas las alternativas implican un costo adicional a la situación actual porque asumen una ampliación de la cobertura, sin embargo, ese costo extra no es excesivo; y 3. Que dentro de un modelo de atención basado en la comunidad, la opción menos costosa es el tratamiento con antipsicóticos típicos combinados con intervención psicosocial. Por un costo extra modesto se obtendría un impacto importante en la discapacidad. Entre las limitaciones del estudio destaca que fue producto de un modelado con parámetros obtenidos de la bibliografía internacional. En este sentido, el reto es la generación de datos derivados directamente de estudios realizados en México.

Summary: Introduction. When the impact of illness is evaluated by indicators like mortality, mental illness has a less significant impact than other illnesses. As a result, the impact of mental disorders was underestimated until the last two decades of the previous century This perception began to change as a result of two factors: On the one hand, the study of the Global Burden of Disease reported by Murray and Lopez, and, on the other hand, the definition of mental disorders by the American Psychiatric Association. The common element shared by these two factors is the inclusion of the concept of disability. Disability is the deterioration of the expected functioning of a subject of a particular age and sex in a social context. It is a part of the social cost of illness. Objective. To assess the disability burden associated with depression, mania, agoraphobia, social phobia, general anxiety, panic disorder, and post-traumatic stress disorder (PTSD) according to the Mexican Psychiatric Survey and to compare results with the disability produced by some chronic non-psychiatric conditions. Method. This survey is based on a stratified, multistage area, probabilistic sample of adults living in urban areas of Mexico. The instrument used was the third version of the Composite International Diagnostic Interview. We report the 12-month prevalence of psychiatric disorders as defined by DSM-IV criteria. We also evaluated non-psychiatric chronic conditions like diabetes, arthritis, hypertension, backache, and other painful illnesses, identified in general as "chronic conditions". Indicators of disability were Sheehan's scale and number of work days lost. This is an easy and fast self reporting scale, which can be used both in the clinic or research. The sub-scales can be added or averaged to obtain a total score. The scale of responses is a horizontal line with numerals from 0 to 10 and five verbal descriptions, with the description "Not at all" corresponding to a value of 0; "Mild" rangimg from 1 to 3; "Moderate" from 4 to 6; "Severe" from 7 to 9; and "Very severe" corresponding to 10. Results. Close relationships and social life were the areas most deeply affected. The disorders found to produce the highest levels of disability were depression, social phobia, and PTSD. The lowest disability levels were observed in chronic conditions. On the total score of Sheehan's scale, disorders with the highest level of disability were PTSD (mean 5.35 ± 0.307) and depression (mean 4.72 ± 0.167). Depression and panic attacks were the disorders by which most days were lost on average in the previous year (25.51, CI95: 16.53-34.5; 20, CI95: 3.02-36.97). Days lost were lower in chronic conditions than in the seven mental disorders studied (6.89, CI95: 3.04-10.74). Discussion. This is the first paper to demonstrate the impact of mental disorders in Latin America evaluating the association of disability with common mental disorders. We have shown that mental disorders, especially depression, are associated with deficits in functioning and result in the loss of work days. We have also shown that persons with common mental disorders have, on average, higher levels of disability than those observed among persons with a wide range of chronic physical conditions. These results are consistent with prior studies in North America and Europe that have found that persons with common mental disorders experience substantial disability in social role functioning.

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SUMMARY Background: Major Depressive Disorder (MDD) is a disease associated to emotional, vegetative and physical symptoms, including for the latter those pain-related symptoms. MDD has a high prevalence rate with a substantial burden of illness, and it expected that by 2020 it will become the second cause of world disability. The diagnosis of MDD is difficult due to the high prevalence of painful physical symptoms, and also due to the fact these symptoms are more evident that the embedded emotional ones. Over 76% of patients with MDD, report painful physical symptoms observed, like headache, abdominal pain, back pain and unspecific-located pain; observing these symptoms can even predict depression severity. In addition, the likelihood of psychiatric disease increases, importantly, with the number of physical symptoms observed; moreover, the remission of physical symptoms predicts the complete remission in MDD. We present an observational, prospective study to examine the clinical profile of Mexican outpatients suffering MDD and determine the relationship between depression severity, painful physical symptoms in quality of life and depression. Methods: Adult patients with current episodes of MDD, treated with antidepressants were included. MDD was defined according to the criteria of the Statistical Manual of Mental Disorders - 4th Edition (DSM-IV) or in the International Classification of Diseases and Related Health Problems, 10th Revision (ICD-10). Patients should have been free of depression symptoms prior to the current episode for at least 2 months. Duration of current episode should not exceed two years. Treatment-resistant patients and those with other psychiatric diagnosis were excluded. Treatment-resistance was defined as: a) a failure to respond to treatment when two different antidepressants were employed at therapeutic doses for at least four weeks each, b) when the subject was previously treated with IMAO inhibitors, c) when electro-convulsive therapy (ECT) was previously employed. Other exclusion criteria comprise previous or current diagnosis of schizophrenia, schizophreniform or schizoaffective disorder, bipolar disorder, dementia or mental impairment. Patients were selected in 34 centers in Mexico. Patients were classified according to the presence (SFD+) or absence (SFD-) of painful physical symptoms using the Somatic Symptom Inventory (SSI); SFD+ was defined as scores ≥ 2 for the pain-related items in the SSI (items 2, 3, 9, 14, 19, 27 and 28). Visual Analogue Scale (VAS) quantified pain severity (cervical pain, headache, back pain, shoulder pain, interference of pain in daily activities and vigil-time with pain). HAMD17 and CGI-S determined depression severity, while the Quality of Life in Depression Scale (QLDS) quantified subjective well-being. Linear regression models were employed to compare groups for VAS, HAMD17, CGI-S, and QLDS, to fit the confusions or clinical predictors when needed. Proportions between groups were established with Fisher exact test or logistic regression. Significance levels were established at 0.005 due to the observational nature of the study. In the result tables, standard deviation (SD) is reported as a variation around the mean value as Mean ± SD, and 95% confidence intervals are denoted 95% IC. Results: A total of 313 patients were enrolled in the study. All of the enrolled patients were Mexican, almost them were women and had at least a previous MDD episode. Painful physical symptoms were reported by 73.7% of patients, these patients were classified into the SFD+ group. Neither statistical nor clinical significant differences between the SFD+ and SFD- groups were found when analyzing socio-demographic variables (age, gender, ethnical origin) and disease history variables (number of previous episodes of MDD, in the last 24 months, duration of current episode). At baseline, patients had a CGI-S mean score of 4.6 and HAMD17 of 26.3. HAMD17 mean score (27.1) in SFD+ patients was significantly higher (p<0.0001) than the SFD- patients (23.8), but nonsignificant differences between groups were found for the subscales central, Maier & retard. CGI-S scores were similar between SFD+ and SFD-; 4.6 and 4.5 respectively (p>0.05). Prevalent painful physical symptoms were also the most painful, when a five-point scale was employed to measure severity, and comprised muscular pain (84.9%), cervical pain (84.2%) and headache (83.5%). SFD+ patients had higher pain severity in all VAS scales (p<0.0001), with perceived severity scores twice as large when compared to SFDgroup. In particular, the global pain VAS reported average values of 49.0 and 19.7 for the SFD+ and SFD- groups respectively. Patients came to the first psychiatric consultation treated with psychotherapy (27.9%), antidepressants (37.3%), anxiolytics (28.6%) and analgesics (9.7%); more than 50% of all patients were not taking any drugs or receiving psychotherapy for treatment of MDD at baseline. Analgesics were used only by 9.7% of patients for the treatment of painful physical symptoms in their current MDD episode. No significant differences between groups were found when comparing the use of psychotherapy, antidepressants, anxiolytics, antipsychotics, mood stabilizers or analgesics. Quality of life was poor for all patients, but significantly worse in the SFD+ group than in the SFD- group (QLDS scores of 23.2 and 20.0 respectively, p<0.001). Discussion: The diagnosis and symptoms manifestation can be influenced by local socio-cultural factors, in particular cultural differences are associated with the prevalence of painful physical symptoms, but this finding is not consistent. The results of this study can be extrapolated to the MDD Mexican population, as selection criteria comprised only operative diagnosis criteria, and not enrollment into the study took place due to the presence of painful physical symptoms. Patients included into the study presented a moderate to severe disease as measured with the HAMD17 scores. The high prevalence of painful physical symptoms in patients with depression was confirmed in this study; it has been reported the patients report pain-related symptoms as the main (even the only) symptom when consulting general practitioners. Painful physical symptoms in MDD include headache, cervical pain, back pain or neck pain; the presence of painful physical symptoms in depression is associated to higher intakes medication, but in this study more than 50% of subjects were not receiving any treatment, including psychotherapy. The treatment of MDD is by no means optimal, as only 30%- 40% of these patients reach complete remission of symptoms with their first antidepressant. Psychological symptoms respond to antidepressant treatment, but in general, this is not the case for the physical symptoms. The lack of efficacy can be explained as a failure in the treatment of these painful physical symptoms. Resolving these symptoms is even a predictor for the complete remission of MDD; the evidence might suggest that treatment of emotional and physical manifestations of depression could improve successful-treatment rates. Conclusion: As found in other reports, a high prevalence of painful physical symptoms was found in MDD patients. Increase in pain severity is associated with higher HAMD17 scores but not CGI-S scores; this discrepancy in the final rates obtained with both scales suggests that both emotional and physical dimensions of MDD should be considered when the clinical assessment is performed. We concluded that clinical judgment of Mexican psychiatrists differs between their global impression and a semi-structured interview in the same patient and therefore is fundamental that the clinical evaluation consists of both emotional and physical manifestations as important components of MDD.

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Abstract: When we talk about drugs, we usually think about illicit substances. However some substances apparently innocuous such as caffeine and other legal ones like tobacco and alcohol, are considered as abuse substances. Nicotine has not been studied as extensively as other drugs. It is known that the pharmacological and behavioural processes that determine the addiction to nicotine are similar to those that determine the addiction to other drugs such as cocaine or heroine. The main adverse effect of nicotine is death. According to the Global Burden of Disease study of the World Health Organization, the World Bank, and Harvard University, in 2020, tobacco will be the first individual cause of death in the world even over AIDS. Nicotine dependence can appear at any age, though it generally begins during adolescence, and it acts on the brain mechanisms of reward, indirectly by endogenous opioid activity and directly by dopaminergic pathways. In the researches on drugs consumption among adolescents conducted in Mexico City during 1989, 1991 and 1993, it was observed that tobacco consumption has increased lightly but systematically, from 4.8% to 4.2%. The percentage of current users (in the last month) is 21.9%. At junior high school level it is 13.7%, and at high school level 34.4%. Attention Déficit Disorder With Hyperactivity (ADDH). Altough the relationship between ADDH and drugs consumption has been recognized none of the studies conducted in our country has included this variable. ADDH is a disorder with a frequency of 1.7% to 18.9%. The difference between the reported percentages is attributed to the fact that definitions and methods used in the studies are not the same. When the disorder is not treated, there is usually a gradual accumulation of adverse processes that increase the risk of pathology. The relationship between ADDH and drug consumption is complex. In a study of adolescents who received treatment for drug abuse, it was observed that 50% of them met the criteria for ADDH. As well, this disorder was a bad prognosis factor, either to the addiction evolution and its treatment. Another complex relationship is the one between ADDH and cigarette smoking. In a study conducted among adult smokers, the subjects with ADDH had an earlier onset of the tobacco addiction, compared to those who did not had ADDH. This finding was confirmed by Milberger, who in a four years follow up study, discovered that ADDH is a significant predictor on the early tobacco consumption. ADDH can be considered as a risk factor in developing other addictions. Although the relationship between ADDH and drug consumption has been studied, the reviewed researches show up some limitations : Only clinical samples have been studied. Most of the follow up studies have included just male individuals with ADDH. In our country the effect of the clinical variables on drugs use have not been studied. In ADDH as well as in drug consumption, it has been observed a remarkable influence of cultural variables, this emphasize the need of evaluating both problems in our country. The following study was conducted under the hypothesis that ADDH and general pathology symptoms are higher among adolescents that have consumed tobacco than those who have not. Material and methods A comparative, cross-sectional survey of adolescent with and without tobacco usage was performed. Fifteen junior high schools in Puebla City were randomly selected. First year junior high school students who agreed to answer the questionnaires were included. The studied variables were: symptoms of ADDH and general psychopathology symptoms. ADDH symptoms were dimensionally evaluated with the Conners-Wells Self Report Scale (long version). General psychopathology was rated with the SCL-90 which evaluates the intensity of symptoms in 9 subscales. Tobacco consumption was determined by the Junior High school Students Questionnaire, developed at the National Institute of Psychiatry, which was used in the Drug, Alcohol and Tobacco consumption surveys in Mexico City. Tobacco consumption was considered positive when the questions about lifetime, and last month consumption were affirmative. From the 15 junior high schools selected, a first year group was chosen at the beginning of the school term. A written authorization from the parents was requested, so the students could answer to the questionnaires. It was inferred that all of them accepted because none of the parents refused explicitely. The questionnaire about drug consumption was applied the first day. Before the application, it was explained to the adolescents, that the information would be confidentially handled; the questionnaire answers would be only known by the researchers and that the information would not be given to their parents or their teachers. The second day of evaluation, the Conners questionnaire was applied. The third day the students answered to the SCL-90. All the questionnaires were applied at the beginning of the daily activities. The 19 psychopathology subscales were compared between male and women and between the students with and without tobacco consumption in the last month and during lifetime. Although the statistical significance was determined with non parametric tests (Wilcoxon test), on the tables, means and standard deviations are shown. The analysis were done with the SAS 6.12. program. The significance level was determined at 0.05. Results From 590 students registered on the selected groups, 544 (92%) were evaluated, the rest of them did not show up during the week in which the evaluations were performed. The mean age was 12 years with a standard deviation of 1, 57.3% (n=295) were males. Twenty children (3.9%) have used tobacco during the last month. On the Conners-Wells Questionnaire, they had higher scores on all ten subscales. These differencies were statistically significant in seven subscales: Familial problems, Conduct problems, Cognitive problems, anger management problems, hyperactivity, Global index, and distractibility DSM IV. General psychopathology symptoms also were higher in those individuals who used tobacco during the last month, compared to those who did not, in seven of the nine subscales the differences were statistically significant. Regarding the experimental usage of tobacco (ever in lifetime), 84 children (15%) answered affirmatively. The scores of these children were higher than the scores of children who denied ever smoked in all subscales of the Conners-Wells Questionnaire. The differences were statistically significant in nine of the ten subscales. In the SCL-90 the scores of the children who have used tobacco during lifetime, were higher in all subscales, except in phobic anxiety. Discussion Our results confirm the proposed hypothesis that the students who consume tobacco present higher levels of psychopathology, compared to those students who have never used this substance. It is necessary to underline the fact that this is the first study in our country that correlates the tobacco consumption with psychopathology symptoms, evaluated in a structured way with valid and reliable instruments.

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Abstract: Platelets llave serotonin (5-HT) uptake and storage mechanisms similar to those from neurons. In addition, they represent nearly 99% of blood 5-HT concentration. For these characteristics, platelets are considered useful biomarkers of the serotonergic synaptic neurotransmission, particularly in psychiatric disturbances such as depression. However, most studies which have evaluated platelet 5-HT concentrations in depression have not shown similar findings. It has been suggested that changes in plasma tryptophan (TRP) concentrations might modify 5-HT concentration in the brain, as well as in platelets. Likewise, decreased plasma concentrations of TRP have been found in depressed patients, and the selective 5-HT reuptake inhibitors (SSRIs) induce changes in platelet 5-HT concentration. Considering the controversy surrounding platelet 5-HT concentrations in depressed patients, and the fact that blood 5-HT and TRP have not been studied in the Mexican population, we decided to study 5-HT and tryptophan concentrations in blood and platelets from depressed and control Mexican subjects to evaluate a possible correlation with the severity of depression. The effect of fluoxetine and citalopram treatment on blood and platelet 5-HT and TRP concentrations in depressed patients was also studied. Material and methods Depressed patients The patients of this study were carefully selected and evaluated. Scales based on semi-structured interviews were applied (MINI and SCID-II) by clinical investigators to reduce any possible bias in patient selection. The influence of the seasonal variability on the 5-HT or TRP blood concentrations was controlled by pairing depressed patients and healthy subjects according to age, gender and, in the case of women, menstrual cycle phase. Patients with a complete remission of depression symptoms (defined as a score not higher than 5 points in the Hamilton's scale, and lower than 7 points in Beck's scale) were asked for a blood sample to measure platelet and blood concentrations of 5-HT and TRP. The patients were weighted before the treatment and after their improvement. Control subjects The control group was integrated by 30 healthy subjects, 24 women and 6 men, with an average age of 32.3 ± 10.8 years. Participants were recruited from the overall Mexican population, interviewed by a psychiatrist, and evaluated with the structured interview MINI and the SCID-II, all these to discard any psychiatric diagnose. None of them had received any pharmacological treatment during the three weeks prior to the study. Control and depressed women were paired according to their menstrual cycle phase. All participants received a detailed explanation of the study, and those who voluntarily accepted the stipulations signed an informed consent document. Control and patient subjects were clinically examined and studied with routine laboratory tests (blood count, blood chemistry, urinalysis, and thyroid function test). Blood sample procedures 5-HT and TRP measurements in total blood preparation were carried out according to the method described by Anderson, and were quantified by high performance liquid chromatography (HPLC). Statistical analysis The differences were statistically determined through an analysis of variance (ANOVA), with the assistance of the SPSS 12.00 (Statistical Software by SPPS Inc.). Results Results from laboratory tests, such as blood count, blood chemistry, thyroid function (T3, T4 and TSH) and urinalysis were normal in depressed subjects, as well as in healthy volunteers. Platelet number, blood 5-HT concentration, platelet content of 5-HT, and blood tryptophan concentration showed no significant differences in depressed patients in comparison to control subjects. 5-HT values in blood and platelet were significantly lower than the initial concentrations in patients after antidepressant treatment. Discussion and conclusions Discrepancies between our study and those found in the literature can be explained with three different approaches: ethnical, physiological, and methodological, as is further discussed. The significant decrease produced by the antidepressant treatment in blood and platelet serotonin concentration may be a consequence of the action of SSRIs, due to a 5-HT diminished uptake by the platelet. Considering our results, we conclude that: Blood and platelet 5-HT concentrations were not different between depressed patients and healthy volunteers. Blood TRP concentrations were not different between depressed patients and healthy volunteers. SSRIs (fluoxetine or citalopram) used in the treatment of depressed patients induced a significant decrease in blood and platelet content of 5-HT, and had no effect in TRP concentrations. Based on these results, neither blood/platelet 5-HT nor blood tryptophan concentrations seem to be good biological markers of depressive patients status. However, 5-HT, but not tryp-tophan, might be a reference point for pharmacological treatment effect.

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Introduction. Objective: our aim was to compare degrees of depression and impulsivity in a clinical sample of adolescents with suicide attempts. Material and methods. We studied adolescents of both sexes who attempted suicide and were brought to a psychiatric hospital in Mexico City in a semester. Clinical diagnosis was included in 3 possible groups: group I (behavioral disorders), group II (affective disorders) and group III (mixed disorders). Patients also responded scales in order to measure depression and other types of psychological problems. Results. A total of 65 patients (56 girls and 9 boys), with first or repeated suicide attempts, were evaluated. Depressive type diagnosis was present in 75% and impulsiveness in 42%. Impulsivity was significantly higher in boys than in girls. Overdosing was the most employed method in the suicide attempts of female patients. Psychopathology was more severe among depressed adolescents. Conclusions. There is more depression than impulsivity among adolescents who attempt suicide. Depressed adolescents show more psychopathology and family problems than non-depressed adolescents, with statistical significance. So far, this is the largest study in a clinical sample of Mexican adolescents who attempted suicide.

Introducción. Objetivo: comparar el grado de depresión con el grado de impulsividad en una muestra clínica de adolescentes con intento de suicidio. Material y métodos. Se estudió a un grupo de adolescentes de 12 a 17 años de edad, hombres y mujeres, llevados en forma consecutiva durante un semestre al Hospital Psiquiátrico Infantil Juan N. Navarro de la Secretaría de Salud por haber realizado un intento de suicidio. Sus diagnósticos clínicos fueron catalogados en 3 grupos: grupo I (conductual), grupo II (afectivo) y grupo III (mixto). Los pacientes también respondieron a escalas que miden depresión y otros tipos de problemas psicológicos. Resultados. De 65 adolescentes (56 mujeres y 9 hombres), con intentos suicidas de primera vez o repetidos, 75% tenían diagnósticos con depresión y 42% tenían diagnósticos con impulsividad. La impulsividad se encontró significativamente más elevada en hombres que en mujeres. En éstas, el medio más empleado fue la sobredosis de medicamentos. Todos los tipos de problemas psicológicos fueron más graves entre los adolescentes que estaban deprimidos. Conclusiones. Hubo mayor frecuencia de depresión que de impulsividad en adolescentes que intentaron el suicidio. Los pacientes deprimidos mostraron más psicopatología de otro tipo que los no deprimidos, y más problemas familiares. Hasta hoy éste es el estudio con más pacientes en población clínica de adolescentes con intento suicida realizado en México.

Abstract: Among all neurotransmitters, serotonin or 5-hydroxi-triptamine (5-HT) is probably the most studied in neuropsychopharmacology. Interest in this neurotransmitter is due to cumulative evidences showing that neuronal serotonergic systems are altered in depressed patients, as well as in several behavior dysfunctions like aggressiveness, impulsiveness, and suicide attempts, among others. Also, specific agonists and antagonists have been synthesized, which has enabled the characterization of the serotonergic receptor subtypes. Furthermore, highly selective inhibitors ofserotonin uptake have been developed, and these are capable of working in the synaptic terminals, as well as in other cell systems, such as platelets. This has allowed for the understanding and characterization of the action mechanisms of diverse psychoactive drugs interacting with the serotonergic system. Platelets have been proposed as an outlying model resembling that of serotonergic neurons due to the similarities they present in the uptake, storage, and serotonin release mechanisms, as well as the presence in platelet membranes of serotonin 5-HT2A receptors. The platelets have a serotonergic system consisting of four main components: 1. an uptake mechanism, 2. intracellular storage organelles, 3. serotonergic receptors in the plasmatic membrane, and 4. a mitochondrial enzyme, the monoamine oxidase (MAO), which metabolizes serotonin. All these elements show physiologic similarities with the neuronal serotonergic system. Serotonergic similarities in neurons and platelets In the Central Nervous System (SNC) serotonin acts mainly as an inhibitory neurotransmitter. The precursor for its synthesis is the aminoacid tryptophan. This is taken from the blood to the cerebral interstice, where it is taken up by the nervous terminals and converted into 5-hidroxytryptophan (5-HTP) by the enzyme tryptophan hydroxilase. The conversion to 5-HTP is a key regulatory step in serotonin synthesis, and is converted quickly in 5-HT by the action of the aromatic L-acid descarboxilase. However, platelets do not synthesize 5-HT, since they do not possess tryptophan hydroxilase. Thus they only display uptake, storage, and serotonin release functions. Serotonin actions The neurotransmitter functions of neuronal serotonin, generally inhibitory, depend on the serotonergic receptor characteristics it interacts with. Its action mechanism can be mediated through second messengers (metabotrophic receptors) or through a direct action over ionic channels (ionotrophic receptors). In the platelets, serotonin is stored in a slow replacement depot, where it can be released from by exocythotic mechanisms. Serotonin participates in the platelet activation that allows for their aggregation to each other for blood clotting process. Serotonin uptake To stop the serotonin neurotransmitter function, neuronal serotonin is taken up from the synaptic cleft by transporter proteins. The serotonin neuronal uptake is impelled by a proton gradient that requires ATP. The 5-HT uptake can follow two paths: the 5-HT can be metabolized by the MAO into 5-hydroxy-indolacetic acid, or it can be reintroduced into release vesicles in order to be reutilized as a neurotransmitter. The serotonin uptake by platelets occurs either by passive diffusion or by active transport mechanisms. Under physiological conditions, the active uptake mechanism is the most effective. This uptake is mediated by proteins similar to the ones required for the neuronal serotonin uptake in the brain. It requires energy and the presence of Na+ and Cl-. The platelet uptake system has a relatively high affinity (Kd) for 5-HT, being similar in magnitude from platelets to neurons. The platelet storage of 5-HT is located mainly in the dense bodies and in the storage granules. Serotonin transporters in platelets and synaptic terminals The main form of ending a serotonergic transmission pulse is by taking up 5-HT molecules from the synaptic cleft directed to reduce the serotonin concentration, which then stops the serotonergic neurotransmission. The uptake process involves a molecular recognition of 5-HT by the transporter, its binding, and passing through the membrane to be released within the cellular. Serotonin molecules bound to its transporter protein cross through the membrane using Na+ as a driving force. The return ofthe transporter to its original position requires K+ as the driving force to step this protein toward its original position. When a selective serotonin reuptake inhibitor is administered, the 5-HT concentration increases in the synaptic cleft, which enhances serotonin neurotransmission. This increase induces a down regulation cascade of both: serotonin autoreceptors (presynaptic) and postsynaptic receptors, that may finally reestablish the resting state of the neuron. It has been confirmed that the protein for neuronal as well as platelet serotonin uptake transport are synthesized by the same gene. Experimental evidence has shown that the platelet transporter presents the same functional and pharmacological characteristics than the neuronal transporter. Serotonergicreceptors Seven types of pre and post synaptic serotonin receptors, which have also several subtypes, have been characterized. Pre and post synaptic 5-HT 1 receptors . The 5-HT1 receptors are involved in both pre and post synaptic serotonergic neurotransmission. The presynaptic 5-HT1A receptors are autoreceptors. Due to their localization in the cellular body and in the dendrites, they have been named somatodendritic autoreceptors, which control the serotonin release. The postsynaptic receptors may play a role in hypothalamic thermoregulation. The presynaptic 5-HT1D receptors are autoreceptors that perform a regulation by blocking the 5-HT release. These receptors are not synthesized in platelets. Postsynaptic 5-HT 2 receptors . The 5-HT2 receptor subtypes are 5-HT2A,BandC. When postsynaptic 5-HT2Areceptors are bound to serotonin, they drive the transduction of neuronal impulses through the production of second messengers within the postsynaptic neuron. These second messengers induce the synthesis of intracellular proteins denominated transcription factors, which may regulate the expression of several neuronal genes. Platelet 5-HT2A receptors correspond to the neuronal 5-HT2A metabothropic receptors and induce alterations in platelet density and affinity. 5-HT 3 receptors . These receptors were originally described in the periphery, specifically as part of the enteric nervous system. In the CNS 5-HT3 receptors are densely present in the solitary tract nucleus and in the area postrema. These receptors are the onlymonoaminergic receptors consistingofionic channels operated by aminergic neurotransmitters. The stimulation of 5-HT3 receptors is responsible of several secondary effects of the selective inhibitors of serotonin reuptake (SISR). These effects are not mediated only in the CNS, but also in sites outside the brain, such as the intestine, which possess this type of receptors also. These receptors are not located in the platelets. 5HT 4-7 serotonergic receptors . These receptors are distributed throughout the body, where they stimulate the alimentary tract secretions and facilitate peristaltic reflexes. Their localization in serotonergic areas in the brain and platelets has not been established. Notwhithstanding their limitations, the characteristics reviewed support the conclusion that platelets can be used as partial models to study the neuronal serotonin 5-HT2 binding and uptake functions. As Alfred Pletscher stated: "although the incomplete of the pattern demands care in its application, they could have the advantage of the relative simplicity".

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