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Órgano Oficial del Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz

2001, Number 6

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Salud Mental 2001; 24 (6)

Perspectiva neurobiológica de la esquizofrenia

Graff-Guerrero A, Apiquian R, Fresán A, García-Anaya M

Language: Spanish
References: 48
Page: 36-42
PDF size: 216.65 Kb.


ABSTRACT

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 symptom s. 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.


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