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Abstract prepared for Soc. For Biological Psychiatry Symposium William T. Greenough, James E. Black, Anna Y. Klintsova, Ian Kodish, Natalya Uranova, Ivetta S. Zimina, Olga V. Vihreva, Valentina I. Rachmanova, Diana D. Orlovskaya "Neuropil hypoplasticity in Schizophrenic brains preserved with a short postmortem autolysis time". Depts Psychiat, Psychol, Beckman Inst, Univ Illinois UrbanaChampaign; LDS Hospital, Salt Lake City, UT and Lab Clin Neuropath, Ment Hlth Res Ctr, Russian Acad Med Sci, Moscow, RU We have examined the neuropil structure of prefrontal area 10 in chronic schizophrenics compared with matched controls to assess cellular correlates of reported “reduced neuropil,” using parallel light microscope examination of Golgi-impregnated material and electron microscopy. In postmortem brain of schizophrenia patients (n=20) as compared to controls (n=16) there was a decreased number-weighted volume of postsynaptic spines in upper layers of prefrontal area 10 (21% in layer I and 35% in layer II) as well as of presynaptic axon terminals and of mitochondria in presynaptic axon terminals in contrast to visual area 17 where no significant changes of spine size were found. Post-synaptic density length was also decreased. Golgi studies similarly indicate reduced dendritic field size in layer II-III and layer V pyramidal neurons and in other cell types in prefrontal cortex, with generally less pronounced effects in area 17. Preliminary Golgi data also indicate reductions in the basilar dendritic spine density of prefrontal layer II-III pyramidal neurons. Since a majority of the axospinous synapses in upper layers of the prefrontal cortex belong to pyramidal neurons of layers III and V, the data support the hypothesis that reduced spine size and number and reduced size of pyramidal neurons in the prefrontal cortex of schizophrenics (Rajkowska et al., Arch. Gen. Psychiat, 1998) contribute to a general reduction in neuropil volume (Selemon and GoldmanRakic, Biol. Psychiat. 1999). In further possible support of this, we found reduced numerical density of synapses in layer I of schizophrenic prefrontal cortex. In addition, we found a reduced volume fraction of astrocytic processes in layer I and a parallel, although nonsignificant, decrease in layer II, including astrocytic processes that are in close apposition to synapses, in the same cases where significant changes in synapse size and density were detected. These data clearly support the reduced neuropil hypothesis and provide evidence that both synaptic size and synaptically-associated astrocytic processes are reduced in upper layers of the prefrontal cortex. The data are consistent with the disconnection hypothesis that posits reduced and dysfunctional effective connectivity in schizophrenia (Friston, Acta Psychiat Scand, 1999). Supported by the J. S. McDonnell Foundation and NARSAD.