NEUROCHEMISTRY OF SCHIZOPHRENIA: GLUTAMATERGIC ABNORMALITIES

Multiple neurotransmitters have been implicated in schizo-phrenia. Dopamine is the neurotransmitter most often hy-pothesized to be associated with the pathophysiology of schizophrenia for two reasons. First, dopaminergic agonists can cause or exacerbate psychotic symptoms. Second, the correlation between antipsychotic efficacy and D2 dopa-mine-receptor blockade is excellent. For these reasons, a number of postmortem studies have focused on the dopami-nergic system in schizophrenic brain. Although the results of these studies have generally been negative, the few positive findings have rarely been replicated, with the notable excep-tion of increased striatal D2-receptor expression, which may be secondary to prior neuroleptic treatment. These studies of dopaminergic abnormalities in postmortem brain in schizophrenia have been recently reviewed (1,2). Given the lack of findings associated with the dopamine system in the brain in schizophrenia, the elucidation of other potential neurotransmitter substrates of this illness has been an area of recent investigation. Glutamatergic dysfunc-tion has been hypothesized to occur in schizophrenia, and this has been one of the most active areas of neurotransmit-ter research in this illness during the past few years. In this chapter, the glutamate hypothesis of schizophrenia is re-viewed, the complexity of the molecules associated with the glutamate synapse is outlined, and postmortem neurochem-ical data suggesting glutamatergic abnormalities in schizo-phrenia are presented. GLUTAMATE AND SCHIZOPHRENIA Several lines of evidence have implicated glutamatergic dys-function in schizophrenia. Dissociative anesthetics, espe