El circuito cerebral de la recompensa en los trastornos afectivos / Brain Reward Circuitry in Affective Disorders

Los síntomas conductuales de la depresión son numerosos y variados, cubriendo los dominios emocionales, motivacionales, cognitivos y fisiológicos. Estudios recientes en modelos animales de depresión y en pacientes depresivos utilizando técnicas neuropsicológicas combinadas con imagenología funcional muestran que grandes subgrupos de estos pacientes presentan deficiencias en el procesamiento de las recompensas a los estímulos emocionales positivos, que son nucleares en depresión. La proteína Rac 1, un regulador crítico de la actina del citoesqueleto, se reduce en el NAcc tanto en depresión como en modelos animales de adicción, lo que lleva al crecimiento de espinas dendríticas inmaduras en las MSNs del NAcc y esto es consecuencia de modificaciones epigenéticas selectivas en esta región, del gen que codifica Rac 1, tanto en modelos de estrés en roedores como en humanos depresivos (estudios post-mortem). El gran desarrollo de algunos de los modelos experimentales de depresión que cuentan con evidencias moleculares, sistémicas y conductuales no se han traducido en nuevos medicamentos pero al avanzar en la comprensión patofisiológica del trastorno y sus correlatos neuroimagenológicos, permitirán, junto a las modernas técnicas de investigación, buscar marcadores biológicos de los endofenotipos diferentes que se combinan para generar un trastorno que posee múltiples subtipos que los agrupan en clusters diferentes

The behavioral symptoms of depression are numerous and varied, and encompass the emotional, motivational and physiologic domains. Recent studies in animal models of depression and depressive patients, which used neuropsychological techniques combined with functional imaging, show that large subgroups of these patients display deficiencies in the processing of rewards to positive emotional stimuli, which are nuclear in depression. Rac 1 protein, a critical regulator of cytoskeleton actin, is reduced in the NAcc, both in depression as well as in animal models of addiction, which leads to the growth of immature dendritic spines in the MSNs of the NAcc, and this is the result of selective epigenetic alterations in this region, of the gene that codifies Rac1, both in models of stress in rodents as well as in depressive human beings (post-mortem studies). The great development of some of the experimental models of depression that provide molecular, systemic and behavioral evidences have not translated into new medications, but the progressive pathophysiological understanding of the disorder and its neuroimaging correlates will enable, together with the modern investigations techniques, to search for biological markers of the different endophenotypes that combine to generate a disorder which has multiple subtypes that gather in different clusters

Tratamento homeopático dos distúrbios emocionais e comportamentais da infância e da adolescência / Homeopathic treatment of emotional and behavioral disturbances of the childhood and the adolescence

Objetivo: discutir a racionalidade científica do modelo homeopático e sua aplicação no tratamento dos distúrbios emocionais e comportamentais da infância e adolescência...

Objective: to discuss the scientific rationality of the homeopathic model and it's application in the treatment of the emotional and behavioral disturbances of childhood and the adolescence...

Olanzapine in the treatment of behavioral problems associated with autism: an open-label trial in Kuwait

To study the efficacy and safety of olanzapine for the treatment of children with autism associated with disruptive behavior problems. A prospective open-label trial was conducted on 40 male children [mean age 12.2 +/- 2.2 years, range 7-17 years] meeting Diagnostic Statistical Manual IV criteria for autism. After a washout period from previous medications [2-14 days], patients received olanzapine [5-10 mg/day] for a 13-week treatment period. The primary efficacy measures were Aberrant Behavior Checklist [ABC] and Clinical Global Impressions-Severity [CGI-S] done at baseline and end of treatment. At the beginning and end of treatment, patients underwent laboratory and physical investigations: ECG, chest X-ray, urinalysis, serum chemistry, blood glucose and lipid profile, hematology and hepatitis B serology. Paired comparison of baseline and 13-week endpoint scores showed significant reductions in ABC subscale scores for irritability [p < 0.0001], lethargy [p < 0.0001], stereotyped behavior [p < 0.005], hyperactivity [p < 0.0001] and inappropriate speech [p < 0.005]. Of 40 patients, 12 [30%] were considered as 'improved' on CGI-S scores compared to baseline, a statistically significant difference [p < 0.05]. No liver enzyme elevation or any other serum biochemical changes resulted from treatment, which was not associated with significant body weight changes or any other treatment-emergent side effects. The study shows that olanzapine treatment can be beneficial in alleviating some behavioral symptoms [irritability, hyperactivity/noncompliance and lethargy/withdrawal] associated with autism. The short period of this trial limits inferences about adverse effects such as body weight increase and tardive dyskinesia. Further long-term placebo-controlled studies of olanzapine are required

Managing psychiatric emergencies

Behavioral emergencies are common; goals of the intervention are rapid evaluation, containment and referral to appropriate follow up. Clinicians will be likely called on to assess and manage agitation, acute psychosis and suicidality alone or in combination. Reaching an accurate diagnosis must be emphasized. Physician should be aware of the differences among the major psychiatric disorders, also to look for medical reasons in patients with psychiatric presentations. Mechanisms that lead to agitation also predispose to impulsivity, aggression and psychosis. This patient population needs careful and special approach in order to evaluate, treat and refer. Suicide is a serious, growing and complex public health problem and its rate continue to rise. This article will discuss how to assess acute psychosis, agitation, impulsivity, aggression and suicidality

Dolor y malestar: un ejemplo experimental de interacción neuro-inmune / Pain and sickness: an experimental example of neuro-immune interaction

Bajo la definición de malestar general se agrupan una constelación de signos y síntomas tales como fiebre, disminución de la actividad, pérdida del apetito, disminución de la libido, trastornos del sueño y modificaciones en el umbral del dolor, entre otros. Estas manifestaciones son necesarias para hacer frente a procesos infecciosos y son iniciadas por el sistema inmunitario y controladas por el sistema nervioso, por lo que representan un ejemplo ideal de interacción entre ambos componentes. En el presente estudio se analizaron los cambios conductuales inducidos en el umbral del dolor luego de la administración i.p. de lipopolisacárido (LPS), una endotoxina que forma parte de la pared de bacterias gram negativas. Adicionalmente, se determinaron los cambios que ocurren en los patrones de descarga de dos poblaciones de neuronas de la formación reticular bulbar, las células “off” y “on”, luego de la administración de la endotoxina. Estas células aparentemente constituyen los brazos ejecutores del sistema de modulación endógena del dolor. Los resultados obtenidos indican que dependiendo de la dosis de LPS empleada (100 o 200 μg/kg) se pueden activar diferentes mecanismos de modulación, que a su vez parecen depender de las dos poblaciones de neuronas bulbares. La dosis de 100 μg/kg de LPS produjo antinocicepción, la cual estuvo asociada a incrementos en la actividad de las células “off” y a la disminución de la actividad de las “on”. La dosis de 200 μg/kg de LPS produjo hiperalgesia, la cual se acompañó de una disminución de la actividad de las celulas off”y un aumento en la actividad de las células on.

The definition of sickness/illness behavior involves a constellation of signs and symptoms such as fever, decrease of physical activity, anorexia, decrease of libido, insomnia and changes of the pain threshold, among others. These manifestations are necessary to face infectious processes and are apparently initiated and controlled by the immune and the nervous system, so that they represent an ideal example of interaction between both components. In the present study the behavioral changes in the pain threshold induced by the i.p. administration of lipopolysaccharide, an endotoxin derived from gram-negative bacterial cell walls, were analyzed. Additionally, changes in the discharge pattern of two neuronal populations of the medullary reticular formation, the off- and on-cells, which apparently act as the executory arm of the endogenous pain modulatory system were determined after endotoxin administration. The results indicate that depending on the LPS dose (100 or 200 μg/kg) different modulatory mechanisms might be activated, which in turn seem to be the consequence of the activation of the two different classes of medullary neurons. Antinociception was produced after administration of 100 μg/kg of LPS. That was associated to an increase of the off-cell firing and a reduction of the on-cell activity. Hyperalgesia was produced after administration of 200 μg/kg of LPS. That effect was accompanied by an inhibition of the off-cell activity and an increase of the on-cell firing. These findings suggest that changes of the pain threshold that occur during sickness/illness involve the differential participation of the two control options of the endogenous pain modulatory system and of specialized mechanisms of communication between the immune and the nervous system.