Neural Biopsies From Patients with Schizophrenia: Testing the Neurodevelopmental Hypothesis In Vitro

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.