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A MORPHOMETRIC ANALYSIS OF PREFRONTAL AREAS 9 AND 46 IN THE SCHIZOPHRENIC AND NORMAL HUMAN BRAIN

L.D. Selemon*, G. Rajkowska, P.S. Goldman-R&c

Section of Neuroanatomy, Yale University, New Haven, CT

06510, USA

Several prominent symptoms of schizophrenia, e.g., flattened

effect, anhedonia, thought disorder, are widely considered to stem

from dysfunction of the frontal lobes. In the present study. a di-

rect 3-D counting method (Williams and Rakic, 1988) has been

applied to prefrontal areas 9 and 46 to determine whether

cytometric anomalies mediate these frontal deficits. Morphometric

data have so far been collected from 7 schizophrenic and 8 nor-

mal brains. The major finding of the study is abnormally high

neuronal density in both areas of the diseased brains and in ad-

dition higher glial density in area 46 Significant differences in

neuronal density are found in layers 3 and 5 in area 9 and in lay-

ers 2 and 3 in area 46. Separate analysis of pyramidal and

nonpyramidal cell density indicates that pyramidal cell density is

selectively elevated in the schizophrenic brain, Our findings com-

pliment neuroimaging studies that have shown a reduction of gray

matter in the schizophrenic cortex (Weinberger et al., 1979;

Zipursky 1992; Pettegrew, 1991) and provide a cytologic (basis for

previously described metabolic and functional deficits in the pre-

frontal cortex of schizophrenics (Franzen and Ingvar, 1975;

Weinberger et al., 1986).

Supported by CNS grant 44866.

DOPAMINE SYNAPTIC ORGANIZATION IN MONKEY PREFRONTAL CORTEX CHARACTERIZED BY SERIAL SECTION ELECTRON MICROSCOPY

J.F. Smiley*, P.S. Goldman-Rakic

Section of Neurobiology, Yale School of Medicine, 333 Cedar

St., New Haven. CT 06510, USA

Dopamine synapses and processes receiving them were

characterized by serial section electron microscopy in monkey

prefrontal cortex. Dopamine immunoreactivity was visualized with

a silver precipitation technique recently developed by us that al-

lowed clear resolution of internal structures and cell membranes

of labelled axons. In all cortical layers, dopamine synapses could

be verified on about 40% of dopamine varicosities. However, be

cause dopamine synapses were often quite small and symmetric,

it is certain that many synapses were overlooked even in serial sections, and it is possible that all dopamine varicosities form

synapses. Postsynaptic processes at dopamine synapses were dif-

ferent in upper and lower cortical layers. In lower layers (IV-

VI) postsynaptic processes were about evenly divided between

dendritic spines and dendritic shafts, and most of the latter were

confirmed as spiny. In upper layers almost one thiid of dopamine synapses were found on non-spiny dendrites, which were easily

differentiated from spiny dendrites by their varicose appearance

and high density of synaptic input. The remaining synapses were

onto dendritic spines and dendritic shafts which were often con-

firmed spiny. These results indicate that the majority of dopamine

synapses in all layers are onto apparent pyramidal cell dendrites,

which form the overwhelming majority of spines in the cortex.

However, there is also a significant fraction of dopamine synapses

on nonspiny dendrites, presumably belonging to GABAergic

intemeurons, and these are more common in upper cortical lay-

ers.

Supported by NIMH grant MH44866

CHARACTERISTICS OF SCHIZOPHRENIC PATIENTS WITH ANTIBODIES TO THE 60 KDA HEAT SHOCK PROTEIN

D.H. Strauss*, S.A. Sadiq, A. Hasan, J. Underdahl, S.A. Yale, K. Kilidireas, N. Latov, J.M. German

Department of Clinical Psychobiology, Schizophrenia Research

Unit, New York State Psychiatric Institute, New York, NY 10032,

USA

We recently reported that 14 of 32 otherwise healthy patients

with schizophrenia had circulating antibodies to the 60 kDa hu-

man heat-shock protein (Hsp). A subsample of I1 Hsp antibody-

positive and 16 Hsp antibody-negative patients were studied for

evidence of other autoimmune phenomena, including elevations in

serum interleukin 2 receptor levels (sIL2r), and numbers of the

CD5+ B Cell. Antibody-positive and -negative patients were also

compared on premorbid adjustment, age of onset and first hospi-

talization, number of hospitalizations, duration of illness, psycho-

pathology ratings at index hospitalization, and positive and

negative symptom scores. Levels of sIL2r and numbers of CD5+

B cells did not differ significantly in these two groups. A trend

toward later age of onset and age at first treatment in the anti-

body-positive group was noted but was not significant. Hsp an-

tibody-positive and -negative patients did not differ in duration of

illness, number of hospitalizations, PANSS composite scores, or

positive and negative symptoms. Although antibody-positive and

-negative patients in this sample were uniform across the symp-

tom and course variables examined, larger clinical and longitudi-

nal studies of patients with antibodies to Hsp and other

autoimmune phenomena might help define a clinical autoimmune

subtype and provide information as to the nature and timing of a

putative autoimmune insult.

NEURODEVELOPMENTAL ASPECTS OF SCHIZOPHRENIA

E.F. Walker

Department of Psychology, Emory University, Atlanta, GA

30322, USA

The findings from both high-risk and follow-back research in-

dicate that adult-onset schizophrenia is preceded by childhood behavioural dysfunction. In order to further explore the precursors