158. Decreased vesicular monoamine transporter density in schizophrenic prefrontal cortex

A recent report has suggested decreased dopaminergic innervation to the schizophrenic prefrontal cortex, based on diminished immunocytochemical labeling of tyrosine hydroxylase-positive axons in this cortical region (Akil et al, Am J Psychiatry 156:1580–1589, 1999). To further investigate possible alterations in presynaptic aspects of dopaminergic neurotransmission in schizophrenic prefrontal cortex, we have examined the binding of the vesicular monoamine transporter (VMAT2) ligand [3H]dihydotetrabenazine by quantitative autoradiography in sections of prefrontal cortex from a group of older subjects with schizophrenia and a comparison group of non-psychiatrically ill individuals. VMAT binding was readily identifiable in prefrontal cortex, although it was present in a homogeneous pattern with no lamina-specific pattern of distribution. Dramatic reductions (30–50%) were found in multiple divisions of the prefrontal cortex in the subjects with schizophrenia. Given past reports of no changes in the level of expression of this molecule after pharmacological treatment with antipsychotic agents, it in unlikely that this effect is secondary to antipsychotic exposure, but rather is associated with the illness itself. These results suggest that there are decreased numbers of dopamine-containing secretory vesicles in presynaptic nerve terminals in the schizophrenic prefrontal cortex, and are consistent with the hypothesis of decreased dopamine afferent innervation to this cortical region. This study adds to the growing evidence for alterations of patterns of dopaminergic innervation to cortical regions in schizophrenia, and suggests that there may be presynaptic abnormalities of dopaminergic neurotransmission in this illness.