DETERMINATION OF REVERSE TRANSCRIPTASE (RT)
ACTIVITY IN CLINICAL AND POST-MORTEM SAMPLES OBTAINED FROM
INDIVIDUALS WITH SCHIZOPHRENIA AND BIPOLAR DISORDER
F. Yee*, L.
Jones-Brando, E.F. Torrey, R.H. Yolken and the Stanley
Neuropathology Consortium. Stanley Division of Developmental
Neurovirology, Johns Hopkins University School of Medicine,
Baltimore, MD
Our laboratory is interested
in studying the role of retroviruses in the etiology of
neuropsychiatric illnesses such as schizophrenia and bipolar
disorder. Retroviruses may represent an important link
between genetic and environmental factors, as this would
account for horizontal and vertical transmission, and these
viruses may be involved with the disease process in
subpopulations affected with these serious mental illnesses.
An important component of infectious retroviruses is that
they contain the reverse transcriptase (RT) enzyme, and
consequently they can be detected by assays for RT activity.
In this study, we set out to
examine the levels of RT activity in various samples, e.g.
cerebrospinal fluid (CSF) from first episode patients with
schizophrenia, post-mortem cisternal fluids and various brain
regions from individuals with schizophrenia, bipolar
disorder, depression without psychosis, as well as unaffected
individuals. Before proceeding with these experiments, it is
important to determine the baseline RT activity present in
these samples, which may be due to the presence of endogenous
retroviruses. We have modified an ultrasensitive RT assay
called product-enhanced RT (PERT; Pyra el al., PNAS
91:1544-1548, 1994), by adding a second round of polymerase
chain reaction (PCR) amplification. When the resulting PCR
products are visualized with the nucleic acid dye SYBR-Green
(Molecular Probes) and analyzed with the Fluorimager Sl
(Molecular Dynamics) we are able to detect as little as 10-7
units of Moloney murine leukemia virus-reverse transcriptase
(MMLV-RT) activity in the PERT assay. Our preliminary PERT
data indicate that there is a non-significant trend of
increased RT activity in the cerebellum of groups with
schizophrenia (n=11) and bipolar disorder (n=13) compared
with the non-psychotic depression (n=12) and unaffected
(n=11) groups.