Download AbstSchizBiolPsychiat.greno

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.