Perspectiva neurobiológica de la esquizofrenia
-
-
[1] Instituto Nacional de Psiquiatría
Instituto Nacional de Psiquiatría
México
-
- Localización: Salud mental, ISSN 0185-3325, Vol. 24, Nº. 6, 2001, págs. 36-42
- Idioma: español
- Enlaces
-
Resumen
- español
En esta revisión se examinan los diversos sistemas bioquímicos relacionados con la esquizofrenia, así como sus interacciones a fin de explicar su fisiopatología, ya que hasta ahora se ha intentado partir de una sola teoría bioquímica para explicar la génesis de la esquizofrenia.
La dopamina es uno de los principales neurotransmisores involucrados en la génesis de la esquizofrenia. El planteamiento actual del funcionamiento dopaminérgico radica en la presencia de un estado hipodopaminérgico en la corteza prefrontal y un estado hiperdopaminérgico, principalmente en los ganglios basales La serotonina inhibe la liberación de dopamina en la sustancia nigra, en el estriado y en la corteza prefrontal, lo que podría explicar la presencia de síntomas extrapiramidales al utilizar agonistas serotoninérgicos. Los antagonistas serotoninérgicos facilitan la liberación prefrontal de dopamina, con lo cual se reducen los síntomas negativos.
La interacción entre los sistemas dopaminérgicos y glutamatérgicos ha mostrado una función excitadora e inhibidora sobre la liberación dopaminérgica, lo que la relaciona con los síntomas de la esquizofrenia.
La disfunción del receptor NMDA podría ser un factor importante en la génesis de la esquizofrenia. Los antagonistas del receptor NMDA ocasionan degeneración de las regiones corticolímbicas e inducen estados psicóticos en el humano adulto: asimismo pueden inducir neurotoxicidad y degeneración neuronal. Estos últimos se bloquean mediante antagonistas dopaminérgicos.
Se propone que las alteraciones en diversos sistemas de neurotransmisión observados en la esquizofrenia son secundarias a la pérdida neuronal o debidas a un neurodesarrollo anormal. Sin embargo, es posible que la disfunción dopaminérgica o de otros sistemas sea la causa primaria de la esquizofrenia, lo que condiciona un neurodesarrollo anormal.
- English
This review examines several biochemical systems related to schizophrenia and their interaction with their physiopathology.
Until now, the explanation has been based in just one biochemical theory to explain the etiology of schizophrenia.
Dopamine has been one of the primary neurotransmitters involved in the etiology of schizophrenia. The actual statement of dopaminergic functioning lays over the presence of a hypodopaminergic functioning in the prefrontal cortex and a hyperdopaminergic state, principally in basal ganglia. On the other hand, an increase in prefrontal dopaminergic activity reduces dopaminergic concentration in the striatum.
Serotonin inhibits dopamine release on the nigral substance, the striatum and prefrontal cortex; this could explain the presence of extrapyramidal symptoms when using of serotoninergic agonists. Serotoninergic antagonists facilitate prefrontal dopamine release and improve negative symptoms.
This mechanism explains the effects of atypical antipsychotics over negative symptoms.
Antagonists of 5-HT3 do not induce changes over primary dopaminergic activity, but they diminishe dopamine release mediated by stress, so that these substances can have a prophylactic effect over relapses induced by stress in schizophrenic patients.
The interaction between dopaminergic and glutamatergic systems had shown an excitatory-inhibitory function over dopaminergic release, which is related to schizophrenic symptoms.
NMDA receptor disfunction may be a primary factor in the etiology of schizophrenia. NMDA receptor antagonists cause corticolimbic degeneration and induce psychotic states in the human, thus inducing neurotoxicity and neuronal degeneration, both of which are blocked by dopaminergic antagonists.
It has been proposed that NMDA receptors estimulate GABAergic cells which establishe the synapsis with excitatory neurons mediated by aminoacids, so that the loss of inhibition caused by NMDA antagonists may be responsible of the induced psychotic state and neuronal degeneration.
In the thalamus, the hypofunction of the nucleus reticularis may be originated by the absence of GABAergic cells and by a hypoglutamatergic state.
Glutamatergic agonists have proved to be effective in treatment-resistant patients because dopamine blocks glutamatergic release. The persistence of psychosis may be explained if this occurs in key synapses and in the context of a diminished NMDA function.
It is important to consider that all neurotransmitter systems interacted with one another, so that the deficits found in each one cause a common change with an increase in the glutamatergic-talamic-cortical activity.
The etiology of the fronto-temporal disfunction in early stages of neurodevelopment is multifactorial where genetic and environmental factors interven and produce abnormal neuronal migration conditioning abnormal morphologic brain changes in cortical fronto-temporo-limbic regions. On the other hand, it is suggested that psychotic symptoms initiate on adolescence due to a development disfunction of the neural network of these cortical regions.
Likewise, it is proposed that disfunctions in several neurotransmitter systems in schizophrenia are secondary to neural loss or abnormal neurodevelopment. Nevertheless, it is likely that dopaminergic or other system disfunctions are the primary cause of schizophrenia which conditions an abnormal neurodevelopment.
- español
