De la estabilización sintomática a la recuperación funcional en el tratamiento farmacológico de la Esquizofrenia y la Depresión Unipolar / From symptomatic stability to functional recovery in the pharmacological treatment of schizophrenia and unipolar depression

Este trabajo revisa en qué medida el tratamiento farmacológico incide en el curso crónico de la esquizofrenia y de la depresión unipolar. Se propone contestar tres preguntas: ¿produce la curación del trastorno?; ¿incide significativamente en su evolución sintomática?; ¿limita o modifica sustancial mente la discapacidad resultante? A partir de analizar conceptualmente la bibliografía disponible, se concluye que los antipsicóticos mejoran el curso sintomático de la esquizofrenia, aunque su eficacia es limitada, y que no tienen incidencia en la discapacidad que acompaña al trastorno. Con respecto a la depresión se observa que un porcentaje importante de pacientes permanece sintomático a pesar de recibir tratamientos adecuados. No hay datos acerca de la eficacia de la farmacoterapia en la potencial discapacidad resultante de la depresión unipolar.

This work summarizes the efficacy of pharmacotherapy does it cure these diseases? Does it exert any significant effect on the symptomatic presentation of the disorders? Which is its action on the social dysfunction provoked by schizophrenia or depression?A conceptual analysis of available bibliography was performed. It could be concluded that antipsychotics improve the symptomatic course of schizophrenia, although their efficacy is limited, and that these drugs does not act on the social dysfunction provoked by the disease. With respect to depression, it could be concluded that a significant proportion of patients remain symptomatic despite receiving adequate treatments. No data about efficacy of pharmacotherapy on the dysfunction resultant from unipolar depression is available.

Papel de los aminoácidos excitatorios en la neuropatología / Role of excitatory amino acids in neuropathology

Excitatory amino acids (EAA) became known as neurotransmitters of the central nervous system (CNS) in the last decade. The most studied EAA are glutamate and aspartate. Both are synthesized by the same mechanism as gama-aminobutyric acid. (Fig. 1). Glutamate is widely distributed in the CNS and the spinal cord, being the areas of higher concentration the cerebral cortex, the hypocampus and the cerebellum. There have been identified two type of receptors for glutamate: ionotropic and metabotropic. The former includes three different types: NMDA, AMPA and KA. NMDA receptor is coupled to a Na+, and Ca2+, channel being the second ion the most important one. This receptor has several sites of binding for various substances. Along with the site for N-methyl-D-aspartate, which binds glutamate and/or aspartate, there have been identified a site for the binding of glycine (which is different from the strychnine sensitive one), a site for poliamines such as spermine and spermidine, and a site for the binding of Zn2+ (Table 1). AMPA receptor is associated to a Ca2+ -Na+, channel, being in this case the Na+ the most important ion. There are two metabotropic type receptors: L-AP4 and trans-ACPD. Both are coupled to a G protein and agonists exert their action increasing phospholipase C activity which in turn induces an increment of IP3 and diacyl-glicerol, and a consecutive releasing of Ca2+, from intracellular stores. EAA play a role in some physiological processes. One of them is long-term potentiation (LTP), an electrochemical phenomenon involved in memory consolidation. Antagonists of NMDA and AMPA receptor prevent the development of LTP, and conversely, the agonist of glycine site of NMDA receptor --D-cycloserine -- facilitates memory consolidation. Since 1957, EAA are considered neurotoxic substances and there are many indirect evidences to support this statement. Pathogenesis of neuronal damage elicited by EAA involves the events shown in Fig. 3. Prevention of the cascade of events that provokes neurotoxicity may be achieved by NMDA antagonists, but once it has begun it may be only aborted substracting the Ca2+ from the medium, using nifedipine or blocking AMPA receptor with an antagonist (CNQX). EAA have been shown to play a toxic role in neuronal damage induced by ischemia. Research using various experimental models demonstrated that NMDA receptor antagonists (i.e. MK 801) blocks postischemic damage. Interventions at various levels of the pathogenic cascade shown in Fig. 4 provoke the same results. There is enough evidence to suspect that NMDA and AMPA receptors are altered in epilepsy. NMDA antagonists (i.e. MK801 or AP5) prevent the development of epileptic seizures induced by kindling; CNQX, an AMPA antagonist, blocks the increase in electrical activity induced by K+, in slices of hypocampus; felbamate, an antiepileptic drug, blocks the glycine site (not strychnine sensitive) decreasing NMDA receptor activity. Several neurodegenerative disorders have been associated with exogenous administration or accidental intake of EAA. (i.e. neurolatirism, Guam disease). Similarities between these diseases and lateral amiotrophic sclerosis indicate that in the latter EAA may play a pathogenic role. Finally, the psychotomimetic effect of phencyclidine (an antagonist of NMDA receptor) suggests that in schizophrenia, together with dopaminergic neurotransmission impairment, some dysfunction of glutamate pathways may be present.