Dopaminergic hypothesis

Dopaminergic hypothesis. Psychosis may result from hyper- or hypoactivity of dopaminergic processes in specific brain regions. This may include the presence of a dopamine (DA) receptor defect. 

Ramaprasad S, Newton JEO, Cardwell D, et al In vivo li NMR imaging and localized spectroscopy of rat brain. Magn Reson Med 25 308-318, 1992 Rampello L, Nicoletti G, Raffaele R Dopaminergic hypothesis for retarded depression a symptom profile for predicting therapeutic responses. Acta Psychiatr Scand 84 552-554, 1991... 

Since the discovery of the role of dopamine (DA) as a neurotransmitter in 1958, and the observations that antipsychotic drugs arepostsynaptic DA-receptor antagonists, interest in a dopaminergic hypothesis for the pathophysiology of schizophrenia has existed. However, these theories may be more appropriately oriented toward the treatment of psychosis with antipsychotics. 

Schizophrenia is a chronic, complex psychiatric disorder affecting approximately 1% of the population worldwide. The chronic nature of the illness, in addition to the early age of onset, results in direct and indirect health care expenditures in the U.S., which amount to approximately 30 to 64 billion dollars per year [4]. It is perhaps the most devastating of psychiatric disorders, with approximately 10% of patients committing suicide. The dopamine hypothesis of schizophrenia postulates that overactivity at dopaminergic synapses in the central nervous system (CNS), particularly the mesolimbic system, causes the psychotic symptoms (hallucinations and delusions) of schizophrenia. Roth and Meltzer [5] have provided a review of the literature and have concluded a role for serotonin as well in the pathophysiology and treatment of schizophrenia. The basic premise of their work stems from the known interaction between the serotonergic and dopaminergic systems. 

The D2 antagonist activity of current antipsychotics led to the "dopamine hypothesis," which states that the pathophysiology of schizophrenia is due to excessive dopaminergic neurotransmission and dysfunctional D2 signaling [6]. This hypothesis has prevailed for nearly 60 years however, it falls short as a complete explanation due to the deficiencies current antipsychotics exhibit against negative and cognitive symptoms. 

If the hypothesis of a relationship between dopaminergic activity and mental speed is correct, dopaminergic agents should improve cognitive speed. The hypothesis received partial support from studies showing that levodopa may improve arousal, awakening and mood, at least in the initial phase of treatment (Dubois Pillon, 1992). However, Pillon et al. (1989) did not find such... 

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