Despite the limitations of the
dopamine hypothesis, compelling evidence remains that implicates dysfunction of CNS
dopamine systems in the pathophysiology of
schizophrenia. The longitudinal measurement of levels of plasma HVA has proved a useful tool in studying
neuroleptic effects and has highlighted time-dependent effects as a potentially important facet of the mechanism of
antipsychotic action of these drugs. Despite the good clinical correlates of plasma HVA levels, caution is needed in interpreting plasma levels of HVA with regard to CNS
dopamine activity. The peripheral nervous system significantly contributes to levels of HVA that circulate in plasma. This issue is underscored by the fact that CSF HVA shows different
neuroleptic response patterns than that seen in plasma. The administration of a peripherally acting
MAO inhibitor to enhance the CNS "signal" in circulating levels of HVA does not resolve the "problem" of different CSF-plasma HVA
neuroleptic response patterns. The possibility that mesocortical
dopamine activity is reflected by CSF HVA is suggested by indirect evidence from clinical and preclinical studies. Future studies in which attempts are made at using both plasma and CSF HVA to enhance neurochemical and clinical correlates may help to advance our understanding of the contributions of specific CNS
dopamine systems to
schizophrenia.