NEURAL
BIOPSIES FROM PATIENTS WITH SCHIZOPHRENIA: TESTING THE
NEURODEVELOPMENTAL HYPOTHESIS IN VITRO
F. Féron1,2, C.
Perry3, M. Wiseman2,
A. Mackay-Sim1,2, and J. McGrath2*.
1School
of Biomolecular and Biomedical Science, Griffith University,
Brisbane, QLD 4111; 2Queensland Centre
for Schizophrenia Research, Wolston Park Hospital, Wacol, QLD
4076;3Department of Surgery, University
of Queensland Medical School, Herston, QLD 4006, Australia
AIMS: Our past research
has demonstrated that neuronal cultures can be derived from
biopsy of the adult olfactory epithelium. In the present study we
are exploring mechanisms related to neurogenesis and neuronal
differentiation from adults with schizophrenia versus well
controls.
METHODS: Olfactory
epithelium biopsies were collected under local anesthesia from 10
individuals with DSM-III-R schizophrenia (including one drug-free
patient) and 10 age and sex-matched well controls. Immunostaining
for the neuronal markers indicated that neurogenesis occurred in
the biopsies from both patients and controls since all contained
cells expressing tubulin and/or olfactory marker protein.
RESULTS: The major
findings of this study were (1) biopsies from patients with
schizophrenia showed a significantly reduced ability to attach to
the culture slide: 35% of patients biopsies attached compared to
69% of control biopsies; (2) biopsies from patients with
schizophrenia had a significantly greater proportion of the cells
were undergoing mitosis: 0.69% in the patients compared to 0.35%
in the controls and (3) the addition of dopamine in addition to
FGF2 increased significantly the proportion of apoptotic cells in
the control cultures but decreased significantly the proportion
in patient cultures. The group differences did not appear to be
related to medication.
CONCLUSIONS: This study
suggests that cell adhesion and some aspects of cell cycle
regulation are affected in schizophrenia, thus supporting the
neurodevelopmental hypotheses. Future studies will example this
tissue in order to identify the presence of candidate viruses,
and to examine the impact of viral infection on cell cycle
kinetics.
This project was supported by the
Stanley Foundation.