Scielo RSS <![CDATA[Salud mental]]> http://www.scielo.org.mx/rss.php?pid=0185-332520060001&lang=es vol. 29 num. 1 lang. es <![CDATA[SciELO Logo]]> http://www.scielo.org.mx/img/en/fbpelogp.gif http://www.scielo.org.mx <![CDATA[El papel actual de los procedimientos neuroquirúrgicos en padecimientos mentales]]> http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0185-33252006000100001&lng=es&nrm=iso&tlng=es <![CDATA[Introducción a la neurocirugía psiquiátrica]]> http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0185-33252006000100003&lng=es&nrm=iso&tlng=es Resumen: La neurocirugía para tratar los trastornos psiquiátricos tiene sus primeros antecedentes modernos a mediados del siglo XIX con los trabajos de Buckhart, quien resecó parcialmente la corteza frontal de pacientes psiquiátricos. Aunque los resultados fueron alentadores en cuatro de seis casos, la muerte de uno y crisis convulsivas en otros dos frenaron el desarrollo de este procedimiento. En 1936, Egas Moniz y Almeida Lima efectuaron una sección de las fibras frontales en pacientes psiquiátricos con diversos diagnósticos, procedimiento que denominaron lobotomía prefrontal. El éxito de este tratamiento llevó a Moniz a obtener un premio Nobel en 1949. A su vez, esto alentó a Fulton y a Jacobsen a promover este tipo de procedimientos, denominados entonces "psicocirugía", en Estados Unidos. Desafortunadamente, la ausencia de un entendimiento adecuado de la fisiopatología y la sobreindicación de los procedimientos provocó que entre 1935 y 1950 se operaran alrededor de 20,000 pacientes en condiciones cuestionables y con importantes complicaciones. La aparición de los fármacos antipsicóticos y la falta de regulación y entendimiento de la neurocirugía psiquiátrica evitan nuevamente que este tratamiento se realice de manera científica y controlada. Aun así, Spiegel y Wacis iniciaron en 1946 la era de la neurocirugía estereotáctica que reduce el riesgo de complicaciones de la neurocirugía funcional. Cuatro procedimientos fueron aceptados entonces por la OMS para el tratamiento seguro y efectivo de enfermedades psiquiátricas. Estas cirugías incluyen la cingulotomía, la capsulotomía anterior, la tractotomía subcaudada y la leucotomía límbica (combinación de cingulotomía y tractotomía). Por otro lado, los trastornos psiquiátricos que han mostrado mejoría sustancial después de alguno de estos procedimientos neuroquirúrgicos son el trastorno depresivo mayor, el trastorno obsesivo-compulsivo, el trastorno bipolar, algunos trastornos de ansiedad, la adicción a sustancias y los trastornos impulsivos-agresivos. Es importante señalar que los criterios de inclusión a protocolos neuroquirúrgicos asistenciales o de investigación para mejorar los síntomas psiquiátricos han sido bien establecidos, y la selección de pacientes y los grupos neuroquirúrgicos deben ser supervisados por un comité de ética bien acreditado. Actualmente, las indicaciones para proponer como candidato a neurocirugía a un paciente son: Una enfermedad psiquiátrica diagnosticada de acuerdo con los criterios del DSM IV-R; evidencia de refractariedad (mejoría inferior a 50% de los síntomas) con los tratamientos convencionales; ésta debe ser avalada por dos psiquiatras. El padecimiento debe tener una duración de al menos cinco años. Además, un comité ético revisor de los protocolos quirúrgicos y de investigación debe evaluar a cada candidato al procedimiento o protocolo y cerciorarse de que el paciente o las personas responsables de él entiendan los criterios médicos y psiquiátricos para participar en el proceso; el comité supervisa también el proceso de consentimiento. Los procedimientos neuroquirúrgicos sólo podrán ser indicados en pacientes psiquiátricos con capacidad y ellos mismos aprobarán y firmarán un consentimiento informado. Las clínicas de neurocirugía psiquiátrica deberán trabajar estrechamente y contar con los siguientes especialistas: Un equipo de neurocirujanos estereotácticos con experiencia probada en neurocirugía psiquiátrica, neuromodulación, radiocirugía e investigación. Un equipo de psiquiatras con amplia experiencia en condiciones psiquiátricas y de investigación. Preferiblemente, ambos grupos deberán tener experiencia en neurocirugía psiquiátrica o contar con la asesoría de una clínica de neurocirugía psiquiátrica. La neurocirugía psiquiátrica deberá realizarse sólo para restaurar la función normal y aliviar al paciente de su angustia y sufrimiento. Los procedimientos deberán practicarse para mejorar la vida de los pacientes y nunca por motivos políticos, cuestiones legales o propósitos sociales. Finalmente, la neuromodulación ha demostrado ser una técnica útil y segura para el alivio de trastornos psiquiátricos debido a que sus efectos son reversibles y ajustables a cada paciente. Por lo mismo, en la actualidad se ha aplicado con éxito en el tratamiento de la depresión mayor, el trastorno obsesivo compulsivo y la enfermedad de Gilles de la Tourette.<hr/>Abstract: Recent background in neurosurgery for psychiatric disorders can be placed in the mid XIXth century. Buckhartd made partial resection of frontal cortex in 6 psychiatric patients, with successful results in 4 of them, but important side effects prevented the development of this scientific approach. In 1936 Egas Moniz and Almeida Lima performed a new neuro-psychiatric technique for treatment of several psychiatric disorders, named prefrontal lobotomy. Results of this treatment won Moniz a Nobel Prize in 1949, and encouraged Freeman and Watts to further develop this kind of surgery in United States of America. Unfortunately, the knowledge about pathophysiology was not sufficient to make a precise indication of surgery in this patients. Between 1935 and 1950, nearly 20,000 surgeries were performed in doubtful conditions, showing important side effects. On the other hand, the emergency of new drugs for the treatment of psychiatric disorders along with the absence of regulation stopped development of "psychosurgery". However, in 1946 Spiegel and Wacis started stereotactic age of neurosurgery, thus reducing risk and complication of this procedures. Nowadays, World Health Organization accepted four neurosurgery procedures for psychiatric disorders: cingulotomy, anterior capsulotomy, subcaudate tractotomy and limbic leucotomy (a combination of cingulotomy and subcaudate tractotomy). Best results for this kind of surgery are shown for affective disorders (major depression disorder, bipolar disorder, anxiety disorders) and obsessive compulsive disorder. Besides, in clinical research protocols the inclusion criteria for neurosurgical procedures in psychiatry have been well defined. Both patients' selection and medical team must be monitored by ethics committee. Currently, the requirements to consider a patient as a candidate for psychiatric neurosurgery are: Clear psychiatric diagnosis in accordance to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM.IV-TR). Evidence of refractivity (improved of symptoms inferior to 50%) to conventional treatments provided by two different psychiatrists. A minimum of 5 years of evolution in symptoms. The ethics committee must monitor surgical and research protocols in a case by case basis. The Committee will made sure that patient and relatives understand medic and psychiatric inclusion criteria. Neurosurgical procedures will only be indicated when the patient is able to understand and accept any details presented to him or her in a formal Consent Form. Neurosurgery psychiatric clinical teams should be integrated by: Stereotactic neurosurgeons whose have experience in psychiatric neurosurgery, neuromodulation, radiosurgery and clinical issues. A psychiatric team with ample experience in psychiatric conditions and research protocols. In case both teams of specialists are not experienced enough in the field of psychiatric neurosurgery, they must look for technical advice from other neurosurgical psychiatric centers. Psychiatric neurosurgery can only be performed to recover healthy conditions and relief suffering. These interventions must always be performed with the sole objective of improving patients quality of life and they must never be used for political, legal or social purposes. Finally, Neuromodulation has shown to be a useful and safe tool in relief of psychiatric disorders. Neuromodulation's effects are reversible and they can adjusted to patient. Nowadays, Neuromodulation is being used in patients with major depression, obsessive compulsive disorder and Tourette's illness. <![CDATA[Evaluación neuropsicológica y neurocirugía psiquiátrica]]> http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0185-33252006000100013&lng=es&nrm=iso&tlng=es resumen está disponible en el texto completo<hr/>Abstract: Neuropsychology, as a part of cognitive neurosciences should be incorporated to the process of evaluation of any patient considered to be needing psychiatric neurosurgery, in order to obtain objective information of the processes and functions that shape each one's cognitive system and of the changes that may take place after surgery. To attain this objective, the neuropsychologist doing the evaluation should be experienced in assessing patients with psychiatric disorders, as it is necessary to have a deep knowledge not only of the clinical characteristics of these ailments but also of the information processing models that typify each entity. Thus, by making an evaluation within a conceptual and empirical frame, an adequate interpretation of the results may be attained. At the same time it is necessary to know the neurochirugical techniques being applied in each case and also to be aware of the possible side effects that may take place. The need for this type of assessments is due to two reasons: to find the possible damage that surgery may cause and to consider the improvement that follows the decrease of clinical symptoms. The previous two facts are associated to clinical improvement as both have different temporal courses. The first will produce a behavioural effect more evident during the first post operative year while at further stages, the second will be made more evident with the decrease of clinical symptoms, thus reflecting on the neuropsychological performance. Another possibility to be considered in this type of cases is that the cerebral systems related with psychopathology as well as those underlying executive and cognitive performance will be distributed differently in the brain and, therefore, with this kind of treatment they will be affected in a different way, this makes it necessary to do not only previous but subsequent evaluations in order to asses accurately the changes in the cognitive processes. Also, should there be found more severe neuropsychological alterations than those expected for a specific psychiatric disorder, there is a risk of increasing post operative changes because any adverse surgical effect may interact or be added to the cognitive failures that typify the illness and, thus, prognosis will be worsened. Regarding the most relevant research on this field, Dougherty et al. report that 20% of their 44 patients with obsessive compulsive disorder (OCD) mentioned at least one adverse effect; of these patients 5% reported a loss of memory that was corrected after six to 12 months. Among the writings that include neuropsychological evaluation as such, it was found that Nyman's group in Sweden, proposes that, independently form the neurosurgical technique used in patients with OCD, the main objective of the operation is to counteract the lack of balance between the frontal sector and the sub cortical regions, as well as that of the basal nuclei and the limbic structures. Therefore, as a proposal, they explore the functions pertaining to the frontal region because they believe that following surgery there must be failures in this area. This belief is also based on a previous research in which they found that five from ten patients presented after surgery a larger number of preservative answers in the Wisconsin Card Sorting Test (WCST), a fact that points out a dysfunction in the encephalon's anterior sector. Nevertheless, they consider that this preservative pattern of responses in the WCST is not permanent; on the contrary, there is improvement after capsulotomy, as shown when the evaluation results are compared to other patients' evaluations, previous to capsulotomy. In another study they reported different failures depending of the surgical strategy being used; thus with frontal ventromedial lesion no alterations were found although when the ventral striated was involved, there were differences as to the number of categories and the conceptual level in WCST. Besides, the group with the worst ranging was the one with large lesions at dorsal level which gave place to visual spatial perception alterations, as well as to psychomotor slowness in a sequence task, and to intrusions in an associated learning task. This finding was expected because the extent of the regions affected by the lesion corresponds to the alterations observed. No differences were reported in another research, as to the WAIS ratings or the Memory Scale of Wechsler, neither before nor after the operation. Nevertheless, the WCST showed some differences in regard to the categories established in respect to the control group, which were interpreted as a lack of abstract reasoning and cognitive flexibility. In schizophrenic patients submitted to leucotomy because of their aggressive behaviour and lack of impulse control, follow up, while comparing their cognitive performance to that of other schizophrenic subjects who had not been operated, showed that there were negative effects on different cognitive aspects, although these, as part of the dysfunction expected for schizophrenia, were not caused by surgery. Up to this moment, in Mexico there is not an evaluation protocol for patients needing psychiatric neurosurgery , and therefore, solid and objective standards should be established for this purpose. For more than a decade, the Instituto Nacional de Psiquiatría Ramón de la Fuente (INPRF), has used neuropsychologic exploration protocols which are based not only on a wide clinical experience in the field of psychiatric disorders but also on the research carried out by our institution. Besides, integration of neuropsychological studies is based on international parameters designed to apply and interpret these instruments. As well, with the same tests it is possible to distinguish between the alterations pertaining to illness and those resulting from neurosurgery. This, in turn will be considered for establishing, if required, reasoned rehabilitation techniques. This battery is composed by the following tests: Wechsler Adult Intelligence Scale (WAIS), Integrated Program for Neuropsychological Exploration Test of Barcelona (Short Version), Rey's Complex Figure (Standarization for Mexican Population, Instituto Nacional de Psiquiatría), and Verbal Learning Test Spain Complutense (TAVEC). This battery must be applied before the procedure, and follow up should be made for a period of between three, six to eight months, continuing with this evaluation protocol for at least three years. Nevertheless, flexibility may be allowed in case there should be complaints from the patient that justify making an evaluation before the given time. On the other hand, considering the position and vulnerable condition in this type of surgical procedures paradigms that evaluate different functions of the frontal sector are proposed in order to obtain specific information of their functioning before and after intervention. We propose to use the Wisconsing Card Sorting Test (WCST), the Stroop Test and the Trail Making B. In addition to the previous statements, the personality changes that may appear ought to be considered, because some personality alterations associated with hypo-frontality have been reported in patients submitted to capsulotomty, although such alterations may be due to judgement errors that are typical of cognitive damage. Finally, we consider that within the selection and interdisci-plinary handling process for patients who may need psychiatric neurosurgery, information obtained from neuropsychological evaluation is necessary. Besides, it will allow the neuropsychologist, as part of the team in charge of these patients, not only to make realistic and objective suggestions regarding the therapeutic strate-gies to be used in each particular case, but also, to advise their relatives. <![CDATA[<strong>Radiocirugía psiquiátrica con Gamma Knife</strong>]]> http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0185-33252006000100018&lng=es&nrm=iso&tlng=es resumen está disponible en el texto completo<hr/>Abstract: Today, psychosurgery is a minimally invasive and highly selective treatment performed only on some patients with severe, refractory treatment, affective, anxious, or obsessive-compulsive disorders. Recent advancements in technology and functional neuroanatomy as well as economic pressures to lower the cost of caring for the chronically ill may provide an opportunity for psychosurgery to become a more attractive option in the treatment of psychiatric disease. In recent years, the rapid adoption of computer-based techniques for surgical planning and visualization and image-guided surgery have made possible a number of impressive advances in functional neurosurgery. Magnetic resonance imaging (MRI) allows for the acquisition of highly detailed structural information of soft tissues in the brain. Minute pathological alterations can be visualized even before they are detected by other means. Stereotaxic atlases based on this information are now used to achieve an extraordinary precision in the placement of electrodes and probes and to plan the operation. Functional imaging is currently possible with special metabolic markers and MRI, as well as computerized techniques for the mathematical processing and visualization of images. Thus, non-invasive evaluation of brain function can be performed with extraordinary precision and sensitivity. Bloodless stereotaxic surgery without opening the skull (even the patient's head does not need to be shaved) is possible thanks to a revolutionary technique called radiosurgery. The destruction of nervous or vascular tissue inside the brain is achieved by projecting thin and powerful beams of ionizing radiation, which come from several angles around the patient's head. These beams produced by sources of radioactive cobalt (the "gamma knife" developed in the 60's by the Swedish neurosurgeon Lars Leksell). With this modality, radiation energy concentrates in a single small point inside the brain. Gamma Knife radiosurgery was first used in our country in 1996 to treat patients diagnosed with treatment-refractory psychiatric diseases. This treatment modality requires a multidisciplinary effort on the part of psychiatrists, neuropsychologists, neurologists, neurosurgeons and medical physicists. This should also be in accordance with the psychiatric neurosurgical protocol and ethics code of Medica Sur, as well as following the guidelines established by the National Nuclear Regulatory Commission and the Radiosurgery and Stereotaxic Radiotherapy Section of the Mexican College of Neurological Surgery. Ten patients have been treated with several procedures like cingulotomy, anterior capsulotomy, subcaudate tractotomy and limbic leukotomy in order to aid them in obsessive-compulsive disorder, major depression, pathological aggression, and Asperger and Tourette Syndromes. In this paper we disclose our experience with follow-ups ranging from six months to seven years in accordance with the most usual evaluation scales for mental disease and multiaxial evaluation framework of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). In our cases, the most common indications have been refractory obsessive-compulsive disorder (OCD), pathologic aggression and major depression after at least two years of treatment and with the involvement of at least two psychiatrists. According to the basal diagnosis, psychological tests are used by the neuropsychology specialist from our group and /or the neuropsychologists who have given medical treatment along with the psychiatrists. Six males and four females were treated with an age range of 13 to 52 years, and an average age of 28.2 years. The first patient had impulsive disorder and hetero-aggression, with a history of two bilateral prefrontal lobotomies with no stereotaxic planning and without a good response. The patient had gamma radiosurgery with bilateral anterior capsulotomy and continued his antipsychotic treatment. For two years, the patient had a good response and was able to go back to his wife and mother. After those two years, he developed a hypersexuality syndrome that led to a divorce from his wife and the patient was lost to clinical follow-up. The second patient was an adolescent with corpus callosum lipoma and hetero-aggression and compulsive syndrome refractory to medical treatment including carbamazepine levels above the therapeutic level. Three persons had to continuously watch him at home during 24 hours a day. He had a history of bilateral stereotaxic cingulotomy with thermocoagulation without a good response. Under general anesthesia, a gamma bilateral stereotaxic capsulotomy was performed. After 2 months of latency period and three years of follow-up, the hetero-aggression has been under control. Carbamazepine treatment is still used. The third patient had physical hetero-aggression towards his parents for more than seven years. He underwent gamma radiosurgery for bilateral capsulotomy and after a latency period of three months and a three year follow-up the patient has had no aggression episodes. The fourth patient had hetero-aggression since his teenage years, with a course of more than 6 years of this disorder and major depression with suicidal attempts. He had an electroconvulsive therapy session that led to a minor improvement lasting 2 months. Gamma radiosurgery was used for a limbic leukotomy in the cingula and the anterior arm of the internal capsules. His aggressiveness has significantly improved and his depression has been fluctuating under medical supervision. The patient has anxiety crisis that the patient's mother helps to control by giving him marijuana. The fifth patient had OCD of more than 10 years of course and a predominance of contamination fobias and bleeding hands because of frequent washing. She was treated with bilateral gamma capsulotomy and after two months of latency she stopped using gloves and after two years of follow-up the fobias have disappeared and has been able to work with no limitations in a company office. The sixth adolescent patient is the son of a neurosurgeon colleague and has symptoms of hetero and self-aggression, impulsivity and destructive behavior associated with mental retardation. The patient underwent a bilateral anterior capsulotomy under general anesthesia. The suggested treatment protocol was to combine the procedure with bilateral limbic leukotomy and hypothalamic procedure in a second surgical stage to control the self-aggression outbreaks. The patient had significant improvement of his impulsivity during the first two months and before the end of his minimum latency period of 6 to 8 months developed a zone of radionecrosis. He had an open cingulotomy after five months of radiosurgery in another hospital and his current clinical course is unknown. The seventh patient with Asperger and Tourette syndrome and impulsivity and hetero-aggression had a bilateral anterior gamma capsulotomy with significant improvement and after one year of follow-up he had a less severe clinical recurrence and underwent bilateral gamma cingulotomy to complete limbic leukotomy. He has early shown improvement but his follow-up is only two months. The eighth patient had schizophrenic disorder displayed as impulsivity crisis, obsessive ideas and hetero-aggression towards his family fluctuating with periods of depression. He had a limbic leukotomy and has good control of his aggression and is still under medical treatment as most of the patients are. The nineth patient in the series had major depression, suicidal attempts and chronic anxiety refractory to medical treatment. She was operated two years before and had a bilateral capsulotomy by thermocoagulation and because her clinical picture prevailed, she had bilateral anterior capsulotomy with gamma knife. In her six month follow-up, her anxiety has improved, and she has had no new major depression crisis and her follow-up neuropsychological tests are pending to be made in her home town. <![CDATA[La neurocirugía en los trastornos de la alimentación: ¿una alternativa posible?]]> http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0185-33252006000100028&lng=es&nrm=iso&tlng=es resumen está disponible en el texto completo<hr/>Abstract: Composition and quantity of food in-taken varies considerably between one meal and another, or between one day and the following. Non biological factors -such as emotional, social, day time, feasibility in the type of food, and cost- are, among others, factors that in some way affect the degree of energy in-take by food, which generally is not related with daily energy expenditure. These phenomena represent an active process of regulation that is characterized by the balance between signs that stimulate hunger, called orexigenics and those that produce satiation to stop in-take, called anorexigenics, that promotes the stability in the quantity of corporal energy manifested as fat. In this feeding regulatory process there are many molecular signs that participate and regulate the in-take of behaviour food for homeostasis. There are two hypothalamic centers related with the food in-take control: the hunger centre in the lateral hypothalamus and the satiation centre in the ventromedial nucleus. In this control many impulses participate, regulated by substances called neurotransmitters, such as: neuropeptide Y, galanine, orexines for the hunger centre and nor epinephrine, serotonin, and dopamine for the satiation centre. Insulin reaches the brain through circulation and acts reducing the contribution of energy, it was the first hormonal sign that was implicated in weight control by CNS. The second identified hormone, secreted by the adiposity, was leptin. Both hormones circulate in levels proportional to the corporal fat and get to the CNS in proportion to its plasmatic concentrations. Receptors as leptin and insulin are expressed by brain neurons involved in the contribution of energy, and the administration of any of both peptides directly to the brain, reduce the in-take of food. The lack of any of these hormones produces the opposite. Leptin has a more important role than insulin in the control of the energetic homeostasis in the CNS. For example, the lack of leptin causes severe obesity with hyperfagia that persists regardless the levels of elevated insulin. In contrast, obesity isn't induced by the lack of insulin. Insulin has a critic role to promote the storage of fat and the synthesis of leptin through the fat cellule. The neuropeptide Y, produced in the arcuate nucleus of the hypothalamus has an anabolic effect. The gene of expression and secretion of this peptide in the hypothalamus increases during depletion, in the storage of corporal fat and/or when the signs of leptin/insulin are decreased in the brain. Leptin inhibits the gene of expression of the neuropeptide Y in the arcuate nucleus and the genetic "knockout" of the NPY reduces hyperfagia and obesity in mice ob/ob, indicating that the total response to the lack of leptin requires the signs of the NPY. Other substances like the Agouti protein (AGRP), the orexines (hypocretines A and B) and the concentrations of the melancortin hormone have been added to the molecule candidate list with anabolic effects. Also in the adjoining neurons of the arcuate nucleus, are originated anorexigenic peptides like alfa-MSH (a derivated of the pro-opiomelancortin, POMC) and CART (transcript protein related with cocaine and amphetamine). Both types of neurons (NPY/AGRP and POMC/CART) coexpress the leptin receptors. In those situations in which the levels of leptin or insulin are low, the NPY/AGRP neurons activate and the POMC/CART are inhibited. This suggests that the main site of adiposity signs transformation is a neuronal response in the arched nucleus. The link between the lateral hypothalamus and the elevated centers of the brain that regulate hunger and satiation is a very important aspect of the regulation system. There have been typified two types of neuropeptides linked to neurons, that appear to be exclusively of the lateral hypothalamus area: the concentrated melanin hormone (MCH) and the orexines. At the lateral zone, there have been specified two types of hypothalamic neuropeptides, the orexines A and B, also known as hypocretines 1 and 2, which are cellular bodies of the hypothalamus, especially at the lateral hypothalamus and the perifornical area, which stimulate the appetite in an independent way to other neuropeptides known. On the other hand, the orexines A and B derive (by proteolysis) of a common precursor, and are capable of activating their two respective receptors that work in conjunction with proteins G. The central administration of orexines stimulates the in-take and production of orexines' increase with fasting. These neuropeptides match with the hypocretines described by other authors, with expression in late ral hypothalamus, arched nucleus, septal nucleus and forebrain. Monoaminergic neurotransmitters. Noradrenalin Noradrenalin is synthesized in different areas of the brain such as the dorsal nucleus of the vague and the locus coeruleus.Noradrenalin shares the same place with NPY and the injection of both inside the preventricular nucleus increase the in-take of food. The repeated injection can result in weight increase; leptin can inhibit noradrenalin secretion. Dopamine Critic dependence of the in-take of food in the CNS is given by the dopamine sign, which is implicated in the voluntary lack of the food in-take. Motor alterations associated with the lack of dopamine affect also the alimentary behavior. The dopamine effect over the alimentary behavior varies depending of the studyied area. For example the routes of dopamine in the mesolimbic area contribute to the reward of the in-take of savory food. SerotoninThe 5HT2c receptor of serotonin is implicated in the decrease of the in-take of food and the weight increase, due to its effect in the impulse of the satiation centre. To maintain the homeostasis of normal energy it is necessary that the serotonin sign be intact. New alternative hypothesis. On one hand, the knowledge of regulation of the appetite-satiety neuroendocrine cycle, and on the other, the new techniques of neuromodulation through stereotaxic surgery, allow to offer an extraordinarily interesting field of research in certain patients with feeding disorders of difficult control and with an increase in the mortality risk. The alternative of controlling specific centers of hunger/satiation regulation, is still a hypothesis, though there are some data that allow us to assume that it could be feasible and we will mention them after. Current experience. Stereotaxic (Latin: stereo, three-dimensional; taxis, positioning) is a modern technique of neurosurgery that allows the localization and precise access to intra-cerebral structures, through a small orifice in the skull. If we have identified the places that regulate the intake of food or satiety, it is feasible that through this technique we can stimulate or inhibit this function and offer the patient an alternative that in theory could be feasible. Some of its possible advantages will be that we are talking about a minimum invasive surgery, generally performed using local anesthesia; patients need a minimum hospitalization stay and surgical risks are minimized. This allows us to predict in the majority of the patients a satisfactory evolution of weight decrease. The current experience of stereotaxic used in eating disorders is null; everything about it is hypothetic. However, the use of this proceeding for other accepted indications where there is previous experience, has allowed us to obtain interesting data of the evolution of these patients that shows indirectly, that the procedure has influenced in the corporal weight. We present these indirect results, which motivate us to continue considering its possible use in patients that show the approved profile according to an ethic committee properly authorized. In depression or bipolar disorder cases, the use of the stereotaxic surgery applying electrodes in the bottom pedunculo thalamic region (ITP), independently that they show an improve in their basal alteration, the patients show a weight increase, inferring a relationship of this area and the one of the hypothalamus for the appetite/satiation control, situation that hypothetically could benefit patients with anorexia nervosa or bulimia. In the cases with Parkinson Disease, the stereotaxic procedure has been made in the pre-lemniscal (RAPRL) or the subtalamic region (STN) in a unilateral or bilateral way, and although the response hasn't been uniform, the weight changes showed a decrease, making this a possible alternative to be used in some patients with morbid obesity according to the inclusion criteria. Final comments. The expectative of stereotaxic surgery in handling patients with difficult to control feeding disorders or with high risk of morbid-mortality, is shown as an hypothesis, that should consider the specific rules of good clinical practices and adjust to the rules of an approved ethics committee, for these procedures. <![CDATA[Estudio de la relación entre consumo de drogas y migración a la frontera norte de México y Estados Unidos]]> http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0185-33252006000100035&lng=es&nrm=iso&tlng=es resumen está disponible en el texto completo<hr/>Abstract: Since the beginning of the XX Century, migration has played an important role in the relations between Mexico and the United States. The main reasons behind most of these migration movements are to improve life conditions and already established social-familiar networks. It is estimated that approximately 390,000 Mexican people migrate each year to the United States. In 2002, Mexicans represented the biggest immigrant group, with 9.5 million people. Among the main elements that cause this migrating movement are: the increasing Mexican demographic population in prime working age, the insufficient creation of jobs, low salaries, as well as the high demand that exists for manpower in the United States, specially in the agricultural, industrial and service areas. There have been important changes in the migrating process, which modify usual behaviors, habits, values, attitudes and points of view by migrants, their families, their home town and their new environment. These changes can facilitate the development of some problems, at a public health level. Some such problems include stress, depression, risky sexual behavior, AIDS contagion, or increase in the abuse of alcohol and drugs. The Community Epidemiology Work Group and NIDA has reported that South and South East areas of the United States show a high cocaine, heroine, methamphetamine, and ecstasy abuse. Most such areas are located at the Mexican border, and this problem seems to affect both countries the same. Method. The study involved following transversal, ex post facto comparisons of migrant and no migrant users drugs. The main objectives included: a) To identifiy abuse levels of migrating drug users, and compare these results with those of Mexican resident drug abusers (non migrating); b) To identify abuse levels in migrating people before and after they moved into the United States and/ or Mexican border cities, and their degree of abuse upon returning to Mexico; c) To explore any relationships between migrating and increased drug consumption, such as heroine and methamphetamine. The participant selection procedure involved intentional, sampling by using pairs. Inclusion criteria included using ilegal drugs, being new patient in the Treatment area of Centros de Integración Juvenil (CIJ), and having migrated to any Mexican border cities and/or the United States in the last five years, and stayed for a period of three months or more. The CIJ operating units that participated in the study included those in Cancán, Celaya, Chihuahua, Ciudad Juárez, Colima, Guadalajara, Hermosillo, Laguna, La Paz, León, Los Mochis, Monterrey, Puebla, Zacatecas and Zamora. These units were selected because of their high number of patients who are methamphetamine or heroine abusers, as well as for including a considerable rate of migrating people to the United States. The groups included 92 drug abusers, of which 46 went to the mexican north border or to the United States cities, and 46 non migrants. Data was gathered through the application of a questionnaire. Main findings. Some of the results revealed that 97.8% of the participants were male, with an average age of 26 years old (SD=7.5), and 80% had studied elementary school or higher. 1. Characteristics of the migrating process. Drug abusers, who migrated to the northern Mexican border, mainly went to Baja California and Chihuahua states. The ones who went to the United Stated were living in California, Texas, Arizona and Illinois. Among the main reasons for migrating were personal development, getting a job or improving it. Migrants also stated that they were "seeking adventure", and, those who went to the United States, said that their purpose was to solve family problems, or to follow tradition. Most of them had planned to stay at their new home for just one season, although a majority stayed over one year. 2. Drug abuse. All participants had consumed alcohol and almost 90% of them had smoked tobacco at least once in their lives. The illegal substances consumed by both migrating and non migrating participants included, in decreasing frequency order: cocaine, marijuana, inhalants, methamphetamines and sedatives. Prevalence among the migrating abusers was higher. Non migrating abusers, also consumed tranquilizers, heroine and other opiates. On the other hand, migrating abusers, had consumed, at least once in a lifetime one or more of the following substances: ecstasy, crack, basuco, methamphetamine, amphetamines, LSD and PCP. Migrants showed a higher percentage of those who had used central nervous system inhibitors (except methamphetamine), and most of them had used a combination of drugs. Those migrating to the United States predominantly consumed drugs to stimulate the central nervous system or to produce hallucinations, and also used some other non specified substances. Drug preference perception. Both groups reported a preference towards marijuana and cocaine. However, migrating abusers showed an additional preference for methamphetamine use. Migrating abusers stated that the reason for consuming this drug was mainly seeking stimulation, just to feel active and euphoric. The ones who migrated to the United States mentioned that they consume methamphetamine because of labor reasons, such as to be more productive and alert. Drug abuse before, during and after migrating. Eighty percent of migrating abusers had already used drugs before leaving their home town. During the migrating process the drug abuse pattern changed by increasing the use of some other drugs. Migrating abusers mentioned that they had used cocaine at their home place, but that during the migrating process, its consumption was significantly higher. They also mentioned that they continued using cocaine when they came back home, although at a lower rate. There was no record of opiates' use such as morphine, darvon, nubain or methadone when these abusers were in their home town, before migrating. They started using these drugs when they arrived to the north of Mexico or to the United States, and they continued using them when they returned. Only some abusers had used methamphetamine, crack, heroine and PCP before migrating. However, when they arrived to their migrating place, the use of these drugs was highly increased although it was reduced considerably when they returned home. LSD was consumed only at the migrating places. The use of tranquilizers and mushrooms was slightly decreased during the migrating process, but it increased when abusers returned home. In the case of those who went to the border, heroine abuse increased, and it decreased as abusers returned home. Only some of them used methamphetamine and ecstasy at their migrating places. On the other hand, those migrating abusers that went to the United States increased their use of methamphetamine, ecstasy, cocaine, and crack, although it decreased when they returned home. Some migrating abusers started using heroin when they arrived to the border, and only continued consuming it when they came home. <![CDATA[El sistema serotoninérgico en el paciente deprimido. Segunda parte]]> http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0185-33252006000100044&lng=es&nrm=iso&tlng=es resumen está disponible en el texto completo<hr/>Abstract: Nowadays there are increasing number of studies to support the crucial role of monoamines in depressive disorders. Among them are studies such as long-term treatment of antidepressants whose mechanism of action regulates monoamine metabolism, monoamine receptor density and post-mortem studies. An acute increase in monoamine concentration at the synaptic cleft might induce desensitization of brain auto- and hetero-receptors which explains the therapeutic antidepressive response. This has been proved by monoamine depletion studies in which an antidepressant effect or a patient relapse has been observed. Likewise, the antidepressive therapeutic response occurs earlier when auto-receptors are pharmacologically blocked at nervous and somatodendritic terminals. In the first part of this review, post-mortem studies related with the serotoninergic system were analyzed, as well as the usefulness of measuring serotonin, triptophan, and serotonin metabolite levels in different biological fluids of depressed patients. In this second part, alterations in platelet transporter and serotonin receptors are discussed as platelet is considered a neural serotoninergic model. Platelets are capable of storing and releasing serotonin in a similar manner as serotoninergic synaptosomes. Thus, platelets and serotoninergic synaptic terminals share biochemical and morphological properties. Serotonin transporter in platelets of depressed patients Due to the difficulty to obtain human brain samples and disagreements in the post-mortem studies, platelets have been suggested as a peripheral model to study neural serotonin uptake. The model is supported by the fact that platelet properties are similar to those of neuronal serotoninergic synaptic terminals. Serotonin studies in platelets have been useful in clinical aspects such as depressive disturbances. Radioligand studies in platelets from untreated depressed patients have shown a decrease in [H]-imipramine binding sites, compared to the binding in platelets from control subjects. Since that decrease has been consistently confirmed in studies on affective subjects, it has been proposed as a specific biomarker of depressed patients. Nevertheless, some researchers have not found similar results, and no explanation of the variability in the density of [H]-imipramine binding sites has been proposed. Serotonin receptor changes in depressed patients The hypothesis on receptor adaptative changes proposes that there is a depletion of monoaminergic neurotransmitters in depressed subjects which induces a compensatory regulation in the number and/or function of receptors. To explore this different techniques as the following have been developed: • Techniques to evaluate receptor density and affinity, including post-mortem radioligand binding to serotonin receptors in brain tissue and in platelets from depressed patients. • Techniques to evaluate receptor regulation and sensitivity by using neuroendocrine tests described below. Somatodendritic 5HT 1A autoreceptor dysfunction in depressive disorders Dysfunction of presynaptic somatodendritic 5HTja autoreceptors has been found in behavioral changes related to anxiety, depression and alcoholism. Neuroendocrine tests after the administration of 5-HT1a agonists have been used as an index of 5-HTta receptor function. It seems that azapirodecanediones increase plasmatic concentrations of prolactin, somatotropin, and adrenocortico-tropin; they also seem to decrease body temperature. In depressed patients, the hypothermia response, following presynaptic 5-HTta receptor stimulation, and the neuroendocrine response, following hypothalamus postsynaptic 5-HTta receptor stimulation, were both diminished. These findings suggest a desensitization or down-regulation of pre- and post-synaptic 5-HTja receptors in depressed patients. Platelet 5-HT 2A receptors in depressed patients Density and affinity Most radioligand studies have found an increase of platelet 5-HT2a receptors either in major depression patients or in attempted suicide patients. However, Rosel et al. studied platelets from depressed patients, finding an increment in the 5-HT2a platelet receptors affinity for [H]-ketanserin, but not in the receptors density. Functional capacity The evaluation of receptor function and sensitivity in platelets is performed after serotonin stimulation by using neuroendocrine tests and some other functional tests, such as platelet aggregation, morphological changes, quantification of intracellular calcium, and second messengers quantification. Despite being widely used, neuroendocrine tests are not completely reliable because they could be influenced by factors such as: stress on the hypothalamus-hypophysis axis, the lack of stereo-selective agonists and antagonists for different subtype serotonin receptors, and the effect of the drugs on other neurotransmitter systems. Other methodological aspects, such as: population heterogeneity, small samples, lack of variable control (i.e. age, sex, doses, diet, menstrual cycle), and placebo effects, are limitations to the neuroendocrine tests related to a single neurotransmitter system (serotonin). Results from platelet functional studies are contradictory as well. Platelet aggregation assays in depressed patients suggested a down-regulation of 5-HT2A receptors, compared to platelets from healthy subjects. However, some other studies have found no differences. Other platelet function responses mediated by 5-HT2A receptors, such as morphology changes, intracellular calcium, and phosphatidyl inositol hydrolysis, suggest a receptor up-regulation or hypersensitivity in depressed patients. Despite some disagreement among the results of platelet 5-HT2A receptor studies in depressed patients, most of them have reported an increase in 5-HT2A receptors density in these patients. However, suicidal behavior is clearly correlated to such an increase. Similar results have been observed in most post-mortem studies reporting an increase of 5-HT2A receptors in the prefrontal cortex. Protein synthesis and mRNA for 5-HT2A receptors are increased in prefrontal cortex and hippocampus in adolescent and adult suicide victims. These findings suggest that changes in the brain serotonergic system are related to depressive states and suicidal behavior. Human brain imaging techniques as well as molecular genetics studies may be additional tools to support the understanding of the neurobiology of depressive states, and their treatment. <![CDATA[Neurotransmisores del sistema límbico. Amígdala. Segunda parte]]> http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0185-33252006000100051&lng=es&nrm=iso&tlng=es Resumen: Los neurotransmisores de la amígdala en el sistema límbico comprenden, entre otros, a las monoaminas (noradrenalina [NA]), la acetilcolina (ACh), los corticoides y la histamina. Ciertas drogas infundidas a la amígdala podrían modular la consolidación en la memoria de la inhibición del entrenamiento dirigido a evitar situaciones de estrés. La administración de anta gonistas de los receptores de la β NA en la amígdala afecta la retención en la memoria por un lapso de un día cuando se administra inmediatamente después del entrenamiento, pero no surte ningún efecto cuando se administra a las seis horas. Infusiones intraamigdalinas de NA acompañadas de antagonistas de aquellos receptores atenuarán el trastorno mnemónico. De manera importante, se ha podido determinar que la NA produce un incremento de la consolidación de la memoria, que depende tanto del tiempo como de la dosis de aplicación cuando el fármaco se infunde a la amígdala inmediatamente después de la inhibición de este tipo de entrenamiento. La amígdala, la neocorteza y el hipocampo son regiones meta del sistema cerebral frontal basal colinérgico, que se relaciona estrechamente con diversas funciones del aprendizaje y la memo ria. Cualquier neurotransmisor con actividad fosforiladora o desfosforiladora podrá regular el estado de sensibilidad a la ACh, así como las propiedades funcionales de las neuronas amigdalinas. Es posible, entonces, que exista una modulación entre los estados de aprendizaje y de recuerdo de lo aprendido en la amígdala, la neocorteza y el hipocampo que esté regida por receptores muscarínicos acetilcolinérgicos. Por medio de receptores presinápticos de la histamina 3 (H3) y un mecanismo por el momento aún desconocido, la histamina disminuye o aumenta la transmisión sináptica excitadora en el BLA. Tal modulación histaminérgica de la actividad neuronal cumple un papel importante en los procesos fisiológicos y patofisiológicos del miedo, el aprendizaje y la memoria de la emo ción y los trastornos afectivos.<hr/>Abstract: Neurotransmitters of the amygdala in the limbic system include monoamines (noradrenaline [NA]) acetylcholine (ACh), corticoids and histamine. Drugs infused into the amygdala may modulate consolidation in memory of inhibition of training directed to avoid stressful situations. Administration of antagonists of β NA receptors to the amygdala will affect retention in memory for a whole day when given immediately after training, but will have no effect when given six hours after training a test animal. Intra-amygdalar infusions of NA which may be accompanied by antagonists of those receptors will attenuate the memory disturbance. It is worth mentioning that later studies have been able to show that NA will produce an increment of memory consolidation, which will depend on the time as well as on the dose of application, when the drug is infused to the amygdala shortly after inhibition of training directed to avoid stressful situations. The amygdala, the neocortex and the hippocampus are target regions of the frontal basal cholinergic brain system, which has different effects on cognitive functions, such as memory and learning. Any neurotransmitter with phosphorylating or dephosphorylating activity may regulate the sensitive state of ACh, as well as the functional properties of amygdalar neurons. It is possible, then, that modulation mechanisms may exist between learning and recall states in the amygdala, the neocortex and the hippocampus, which could be controlled by muscarinic acetylcholinergic receptors. Through pre-synaptic receptors of histamine 3 (H3) and a currently unknown mechanism, histamine will decrease or increase excitatory synaptic transmission in BLA. Such histaminergic modulation of neuronal activity will play an important role in fear-related physiological and patho-physiological processes, learning and memory of emotion, and affective disturbances. <![CDATA[<strong>Representación social del género masculino en un grupo de niños y jóvenes que viven en la calle, en la ciudad de México. Segunda parte</strong>]]> http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0185-33252006000100056&lng=es&nrm=iso&tlng=es Resumen: Los neurotransmisores de la amígdala en el sistema límbico comprenden, entre otros, a las monoaminas (noradrenalina [NA]), la acetilcolina (ACh), los corticoides y la histamina. Ciertas drogas infundidas a la amígdala podrían modular la consolidación en la memoria de la inhibición del entrenamiento dirigido a evitar situaciones de estrés. La administración de anta gonistas de los receptores de la β NA en la amígdala afecta la retención en la memoria por un lapso de un día cuando se administra inmediatamente después del entrenamiento, pero no surte ningún efecto cuando se administra a las seis horas. Infusiones intraamigdalinas de NA acompañadas de antagonistas de aquellos receptores atenuarán el trastorno mnemónico. De manera importante, se ha podido determinar que la NA produce un incremento de la consolidación de la memoria, que depende tanto del tiempo como de la dosis de aplicación cuando el fármaco se infunde a la amígdala inmediatamente después de la inhibición de este tipo de entrenamiento. La amígdala, la neocorteza y el hipocampo son regiones meta del sistema cerebral frontal basal colinérgico, que se relaciona estrechamente con diversas funciones del aprendizaje y la memo ria. Cualquier neurotransmisor con actividad fosforiladora o desfosforiladora podrá regular el estado de sensibilidad a la ACh, así como las propiedades funcionales de las neuronas amigdalinas. Es posible, entonces, que exista una modulación entre los estados de aprendizaje y de recuerdo de lo aprendido en la amígdala, la neocorteza y el hipocampo que esté regida por receptores muscarínicos acetilcolinérgicos. Por medio de receptores presinápticos de la histamina 3 (H3) y un mecanismo por el momento aún desconocido, la histamina disminuye o aumenta la transmisión sináptica excitadora en el BLA. Tal modulación histaminérgica de la actividad neuronal cumple un papel importante en los procesos fisiológicos y patofisiológicos del miedo, el aprendizaje y la memoria de la emo ción y los trastornos afectivos.<hr/>Abstract: Neurotransmitters of the amygdala in the limbic system include monoamines (noradrenaline [NA]) acetylcholine (ACh), corticoids and histamine. Drugs infused into the amygdala may modulate consolidation in memory of inhibition of training directed to avoid stressful situations. Administration of antagonists of β NA receptors to the amygdala will affect retention in memory for a whole day when given immediately after training, but will have no effect when given six hours after training a test animal. Intra-amygdalar infusions of NA which may be accompanied by antagonists of those receptors will attenuate the memory disturbance. It is worth mentioning that later studies have been able to show that NA will produce an increment of memory consolidation, which will depend on the time as well as on the dose of application, when the drug is infused to the amygdala shortly after inhibition of training directed to avoid stressful situations. The amygdala, the neocortex and the hippocampus are target regions of the frontal basal cholinergic brain system, which has different effects on cognitive functions, such as memory and learning. Any neurotransmitter with phosphorylating or dephosphorylating activity may regulate the sensitive state of ACh, as well as the functional properties of amygdalar neurons. It is possible, then, that modulation mechanisms may exist between learning and recall states in the amygdala, the neocortex and the hippocampus, which could be controlled by muscarinic acetylcholinergic receptors. Through pre-synaptic receptors of histamine 3 (H3) and a currently unknown mechanism, histamine will decrease or increase excitatory synaptic transmission in BLA. Such histaminergic modulation of neuronal activity will play an important role in fear-related physiological and patho-physiological processes, learning and memory of emotion, and affective disturbances. <![CDATA[Filtrado sensorial y P50: implicaciones para la neurobiología de la esquizofrenia]]> http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0185-33252006000100064&lng=es&nrm=iso&tlng=es Resumen: El estudio del filtrado sensorial mediante potenciales evocados ha marcado una línea de investigación en la esquizofrenia que plantea explicaciones alternativas a la presencia de la sintomatología, y que bien merecen atención y estudio. La P50 es un potencial evocado con respuesta de latencia media que se origina en el lóbulo temporal medio, en el hipocampo y cerca de éste. Mediante estudios con magnetoencefalografía, se ha propuesto que las células piramidales situadas en el giro temporal son la fuente más probable de la P50 en el registro electroencefalográfico, correspondiente al electrodo CZ situado en el vértex, de acuerdo con el sistema internacional 10-20. En este paradigma se presentan ensayos con dos estímulos auditivos con sonido de "clic": el primero es condicionante (E1) y el segundo, de prueba (E2), y pueden tener parámetros variables de duración, intensidad, intervalo interestímulo e intervalo interensayo. Cuando existe variación en los valores de estos parámetros, se obtiene como resultado una respuesta facilitada o suprimida al segundo estímulo. La P50 es una onda con amplitud no mayor a 50 |i.V ni menor a 0.5 |i.V. Para su análisis, se saca un promedio de entre 30 y 180 ensayos de cada estímulo y finalmente se analiza mediante la comparación del porcentaje de disminución de la amplitud de E1 y de E2, también con el resultado de la diferencia de E1 menos E2, o con el porcentaje de disminución en el área de la P50 de E2 comparada con la disminución de Et Los estudios que documentan la eficacia de los antipsicóticos para normalizar el defecto en el filtrado sensorial no brindan información concluyente. Algunos estudios han observado que los pacientes sin medicación antipsicótica no presentan supresión de la respuesta a E2, o la presentan muy disminuida. Otros estu dios han documentado la repuesta no suprimida de la P50 en un grupo de esquizofrénicos bajo tratamiento antipsicótico. En ellos se observó un aumento en las latencias y amplitudes del trazo casi idénticas que las presentadas por los controles sanos. Se ha descri to que la mejoría en el déficit sensorial que presentan los esquizofrénicos bajo tratamiento antipsicótico se debe al bloqueo de la transmisión dopaminérgica. Se ha observado que algunos de los familiares en primer grado de los pacientes con esquizofrenia muestran también alteraciones en la inhibición del segundo estímulo auditivo del paradigma P50. Asimismo, en familiares sanos no fumadores que presentaban el defecto de filtrado se ha reportado una normalización transitoria del déficit sensorial registrado después de dosificar nicotina me diante goma de mascar. De acuerdo con estos datos, se ha propuesto la importancia que tiene la nicotina para el filtrado sensorial. En el paradigma de la P50, el fenómeno de habituación se produce cuando E1 activa las interneuronas a través de los receptores nicotínicos, que provocan la liberación de GABA, con la cual las células piramidales del hipocampo no logran ser excitadas por E2 y por lo tanto no responden a éste. En la esquizofrenia, la falta de habituación puede explicarse por una disminución en el número de interneuronas inhibitorias que muestran una alta ex presión de receptores nicotínicos.<hr/>Abstract: In the search for etiologic and physiologic keys to increase the knowledge about schizophrenia, research focused in the assessment of sensory gating by the use of event-related potentials has been considered an alternative to explain the presence of cognitive and positive symptoms. The P50 is a middlelatency-evoked potential originated in the temporal lobe, in the hippocampus and close to this. Through magnetoencephalographic studies, it has been hypothesized that piramidal cells located in the temporal gyrus are the most suitable source of the P50 wave present in electroencephalographic recordings. Therefore, the main wave for the obtention of the P50 is located in the vertex, which corresponds to the CZ electrode, in agreement with the 10-20 International System. The P50 paradigm is evoked by two auditory stimuli with the sound of a click, where the first stimulus is labelled conditioning (S1) and the second one, testing (S2). Both of them may have variable values for duration, intensity, inter-stimulus interval and inter-testing interval. Any variation on these parameter values leads to a suppressed or a facilitated response of the second stimulus. The amplitude established for the P50 paradigm is smaller than 50 [íV and greater than 0.5 |iV. Once the recording is acquired, the analysis of the P50 wave must be done with an average of 30 to 180 tests of S1 and S2. Results from the average can be analyzed by: a) a comparison of the amplitude's diminution percentage of S1 and S2, b) the difference between the substraction of the S1 value minus the S2 value, or c) the mean reduction of the P50 area of S1 compared with the mean reduction of the P50 area of S2. Different pharmacological assays had shown evidence of changes in sensory gating performance by means of the mechanism of action of some antipsychotics. Although some studies had shown a normalizing effect of antipsychotics over the sensory gating deficit in schizophrenic patients, the results are not conclusive. Some studies have reported that schizophrenic patients under antipsychotic treatment suppress the S2, while patients without antipsychotic treatment showed a lack of suppression of the S2. Nevertheless, other studies had reported a minor suppression of the second stimulus in groups of schizophrenic patients under antipsychotic treatment. Moreover, other studies had observed increased latencies and almost identical amplitudes of the outline between schizophrenic patients and normal healthy controls. The dopamine hypothesis has been one of the most important physiopathologic explanations for schizophrenia and the dopaminergic transmission blockade has also been implicated in the improvement of sensory gating in schizophrenic patients under antipsychotic treatment. Furthermore, a familiar pattern of sensory gating dysfunction has been found in healthy first-degree relatives of schizophrenic patients, whose response to the P50 paradigm has shown the lack of inhibition to the second auditory stimulus. This deficit is mainly observed in the parent having a greater familiar history for schizophrenia and also in half of the patient's healthy sibs. It is important to consider that although some relatives display an abnormal performance of the P50 wave, in general their cognitive performance is higher than the one showed by the schizophrenic patient. Likewise, some healthy non-smoker relatives, whose previous recordings displayed abnormal P50 waves, showed a transitory normalization of their sensory gating after nicotine administration by means of a nicotine chewing gum. It has been postulated that nicotine has a primary effect over the sensory gating performance. Hippocampal neurons receiving the originating stimuli from the medial septal nucleus are densely concentrated with nicotinic receptors. This inervation has been described as the main filter of repetitive auditory stimuli in the hippocampus. Following the hypothesis of the influence of nicotine over the sensory gating performance, it has been proposed that the habituation phenomenon occuring in the P50 paradigm takes place when interneurons are activated by nicotinic receptors after the first auditory stimuli. This activation causes a liberation of GABA, which avoids hippocampal piramidal cells excitation by S2, and therefore they do not respond to this stimulus. In schizophrenic patients, the lack of habituation can be explained by histochemical evidencies which suggest a smaller number of inhibitory interneurons with a higher expression of OC-7 nicotinic receptors. Based on these data, the actual background of the P50 paradigm brings out the possibility of including it as an important biological marker for the early detection of schizophrenia between high-risk relatives of schizophrenic patients. Further research is required to fully understand the potential advantages offered by the P50 sensory gating study. It is important to develop pharmacological studies focused on the role of specific antipsychotics over cognitive functions in schizophrenic patients. Also, future research should be addressed to the assessment of the influence of nicotinic receptors in attentional proceses and in the etiopathology of schizophrenia in order to explore O -7 nicotinic receptor selective agonists as candidates for the treatment of cognitive and perceptual disturbances in schizophrenia. The aim of this review is to give an introduction to the auditory sensory gating studies applied to schizophrenia research by means of event-related potentials.