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Decreased Somal Size of Deep Layer 3 Pyramidal Neurons in the Prefrontal Cortex of Subjects With Schizophrenia
Joseph N. Pierri, MS, MD;
Christine L. E. Volk, BS;
Sungyoung Auh, MS;
Allan Sampson, PhD;
David A. Lewis, MD
Arch Gen Psychiatry. 2001;58:466-473.
Background Schizophrenia is associated with deficits in working memory, a cognitive
function that depends on the connections of the prefrontal cortex (PFC) with
the thalamus and other cortical regions. Pyramidal neurons in PFC deep layer
3 play a central role in both thalamocortical and corticocortical circuitry.
Given that somal size tends to be associated with both the dendritic and axonal
architecture of a neuron, abnormalities in these circuits in schizophrenia
may be associated with a change in the somal size of deep layer 3 pyramidal
neurons.
Methods We used design-based stereology to estimate the somal volume of pyramidal
neurons in deep layer 3 of PFC area 9 in 28 subjects with schizophrenia, each
of whom was matched to 1 normal comparison subject for sex, age, and postmortem
interval.
Results The geometric mean of the somal volume estimates in the subjects with
schizophrenia was significantly (P =.02) decreased
by 9.2%. This decrease was associated with a shift in the distribution of
somal volumes toward smaller sizes. Neither antipsychotic medication treatment
history nor duration of illness was associated with somal size.
Conclusions These findings independently replicate previous reports of decreased
somal size in the PFC in schizophrenia. The reduction in size of deep layer
3 pyramidal neurons is consistent with abnormalities in thalamocortical and
corticocortical circuitry, suggesting that disruption of these circuits may
contribute to cognitive abnormalities in schizophrenia.
From the Departments of Psychiatry (Drs Pierri and Lewis and Ms Volk),
Statistics (Ms Auh and Dr Sampson), and Neuroscience (Dr Lewis), University
of Pittsburgh, Pittsburgh, Pa.
Corresponding author and reprints: David A. Lewis, MD, University
of Pittsburgh, 3811 O'Hara St, W1650 BST, Pittsburgh PA 15213 (e-mail: Lewisda{at}msx.upmc.edu).
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