Wednesday, April 01, 2015

Schizophrenia: The Dopamine Hypothesis

Dopamine, a major excitatory neurotransmitter, may play a key role in schizophrenia. According to the dopamine hypothesis, the symptoms of schizophrenia - particularly positive symptoms (e.g. delusions and hallucinations), are produced by over-activity of the dopamine in areas of the brain that regulate emotional expression, motivated behaviour and cognitive functioning.
 
Having "too much" of this neurotransmitter is probably too simplistic; the better term is a functional excess (Lieberman, 1990). This may be caused by a failure of any of the many processes involved in breaking down and re-creating the neurotransmitter, or disruption to the receptor system (such as the receptor functioning "too well"), or there may be problems with re-uptake into the presynaptic membrane.
 
Dopamine Pathways
People diagnosed with schizophrenia have more dopamine receptors on neuron membranes than do non-schizophrenics, and these receptors seem to be over-active to dopamine stimulation (Wong, 1986). Additional support comes from the finding that the effectiveness of antipsychotic drugs used to treat schizophrenia is positively related to their ability to reduce dopamine-produced synaptic activity (Green, 1997).
 
The hypothesis that dopamine and dopaminergic mechanisms are central to schizophrenia has been one of the most enduring ideas about the illness. It was not until the 1970's, however, that the dopamine hypothesis was finally crystallized with the finding that the clinical effectiveness of antipsychotic drugs was directly related to their affinity for dopamine receptors. To date, their have been more than 6800 articles on the topic of dopamine and schizophrenia since 1991.
 
In summary, molecular imaging studies show that presynaptic striatal dopaminergic function is elevated in patients with schizophrenia; however blockade of this heightened transmission, either by decreasing dopamine levels or blocking dopamine transmission, leads to a resolution of symptoms for most patients (Howes, 2009).  

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