Dopamine hypothesis of schizophrenia

Carlsson, A. (1988). The current status of the dopamine hypothesis of schizophrenia. Neuropsychopharmacology, 1(3), 179-86. 

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. 

Seeman P. (1987). Dopamine receptors and the dopamine hypothesis of schizophrenia. Synapse. 

In 1976, Ian Creese, David R. Burt, and Solomon H. Snyder of Johns Hopkins University in Baltimore, Maryland, reported that the most effective schizophrenia medications are the ones that have the strongest affinity for dopamine receptors. Researchers also discovered drugs that increased the amount of dopamine inadvertently caused schizophrenic symptoms in patients. These findings led to the dopamine hypothesis of schizophrenia—too much dopamine causes schizophrenia. 

Dutch researcher Jacques van Rossum proposes the dopamine hypothesis of schizophrenia, which attributes the symptoms of the disease to an excess of dopamine. 

After dopamine was identified as a neurotransmitter in 1959, it was shown that its effects on electrical activity in central synapses and on production of the second messenger cAMP by adenylyl cyclase could be blocked by antipsychotic drugs such as chlorpromazine, haloperidol, and thiothixene. This evidence led to the conclusion in the early 1960s that these drugs should be considered dopamine-receptor antagonists and was responsible for the dopamine hypothesis of schizophrenia described earlier in this chapter. The antipsychotic action is now thought to be produced (at least in part) by their ability to block dopamine in the mesolimbic and mesocortical systems. 

These findings have been incorporated into the dopamine hypothesis of schizophrenia. However, additional factors complicate interpretation of dopamine receptor data. For example, dopamine receptors exist in both high- and low-affinity forms, and it is not known whether schizophrenia or the antipsychotic drugs alter the proportions of receptors in these two forms. The fact that aripiprazole shows partial agonism at D2 and 5-HT1A receptors in preclinical studies suggests that the proportions of several receptors in their various affinity states may prove clinically important. 

This chapter has provided a clinical description of psychosis, with special emphasis on the psychotic illness schizophrenia. We have explained the dopamine hypothesis of schizophrenia, which is the major hypothesis for explaining the mechanism for the positive symptoms of psychosis (delusions and hallucinations). 

In its original form, the dopamine hypothesis of schizophrenia postulated that the positive symptoms of the illness arose as a consequence of the... 

It may be concluded that despite the importance of the dopamine hypothesis of schizophrenia in serving to unify the mechanism of action of both typical and atypical neuroleptics, it is apparent that some serotonin receptor subtypes, and glutamate receptors of the NMDA subtype, may also play a crucial role. 

Jentsch JD, Roth RH. 1999. The neuropsychopharmacology of phencyclidine From NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia. Neuropsychopharmacology 20 201-225. 

Toda M, Abi-Dargham A. 2007. Dopamine hypothesis of schizophrenia Making sense of it all. Curr Psychiatry Rep... 

Baumeister AA, Francis JL. 2002. Historical development of the dopamine hypothesis of schizophrenia. J Hist Neurosci 11 265-277. 

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