Dopamine/dopaminergic system schizophrenia

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. 

One of the few studies directly identifying an abnormality in dopamine neurotransmitter in schizophrenia demonstrated a lateralised, left hemisphere, elevation in the amygdala (Reynolds, 1983), which added to the evidence for the view of schizophrenia as a left temporal lobe disorder. This elevation is not, however, interpreted as a primary pathology it seems likely that it reflects a dysfunction or dehcit in the neuronal systems controlling dopaminergic activity, and a correlation with diminished levels of a marker for GABA support this interpretation (Reynolds et ah, 1990). 

We will first review the dopaminergic system in the cortex from the anatomical and functional point of view, followed by a review of the evidence for a cortical deficit with special emphasis on the imaging data of cortical I ) receptors as a probe of dopaminergic function in schizophrenia and in related conditions used to model the cortical dopamine deficit. 

According to Carpenter, Conley, and Buchanan (1998), stimulants such as cocaine and amphetamines activate the dopaminergic system in the brain, which explains why the abuse of stimulants can induce a paranoid psychosis that mimics the positive symptoms representative of schizophrenia. In turn, if a person who is diagnosed with schizophrenia is given stimulants of this type, the psychosis may be exacerbated. It follows, therefore, that the typical antipsychotic medications act by blocking the dopamine receptors. 

It is thought that there is an abnormality of dopamine receptors or increased release of dopamine in the mesolimbic and mesocortical pathways in schizophrenics. However, no reproducible changes in dopaminergic systems have been found in schizophrenia and the abnormality may be in another system that is somehow linked to dopaminergic neurones. More recently, it has been suggested that schizophrenia may be a developmental disorder of the prefrontal cortex where there is actually a deficiency of dopamine, which leaves dopamine activity in the mesolimbic pathway unbalanced. 

Dopamine is a major catecholamine neurotransmitter in the central nervous system (37) that is involved in the neuroregulation of locomotor activity, emotion, and neuroendocrine secretion (38,39). Clinically, dopaminergic drugs are used to treat Parkinson s disease and schizophrenia by activating or blocking dopamine receptors, respectively (40). 

Neuroleptic drugs are used in the treatment of psychosis, such as schizophrenia they are generally antagonist ligands of dopamine at the central nervous system level. " Indications and therapeutic effects of the various families of neuroleptics result from two factors. The first one is the specifity of the ligand toward the different types of dopaminergic receptors, which are unequally distributed in the... 

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