saccadic abnormalities among schizophrenics, their first-degree relatives, and relationship to...
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T2 RELAXATION TIME OF BASAL GANGLIA IN TARDIVE DYSKINESIA
Giovanna Calabrese*, Paolo Santino, Cristina Colombo, Roberto Cavallaro, Silvio Scarone, Giuseppe Scotti
San Raffaele Hospital, Via Prinetti 29, 20127 Milan, Italy
It has been proposed that tardive dyskinesia (TD), a movement
disorder associated with long-term exposure to neuroleptic treat-
ment, is due to iron and other metals accumulation in the basal
ganglia, which in turn causes increased production of free radi-
cals, MRI measurements of T2 relaxation time is an in-viva in-
dicator of iron accumulation. Bartzokis G. et al. (1990) reported
T2 shortening in the basal ganglia as a predictor of high risk for
TD in schizophrenic patients.
To test this hypotheses we will measure T2 relaxation time in
basal ganglia in patients with TD, compared to patients without
TD matched for age and drug treatment (dosage and duration of
neuroleptic treatment) and age matched normal subjects. TD
symptoms will be scored using the Rockland Simpson Scale for
TD (RSS), abbreviated version. For T2 measurements we will
use a composite non-selective 180” Cart-Purcell-Meiboom-Gill
spin-echo technique with 8 TEs: 20, 35, 50, 65 up to 205 msec
with increments of 15 msec. The sequence to be used has been
tested on a set of 9 vials containing 4 different concentrations of
MnCl? (0.67, 1.00, 1.45 and 2.65 mM), giving a relaxation curve
with the expected exponential decay. The test-retest analysis gave
a significance of 0,025 (MANOVA repeated measure analysis).
At the moment 1 patient and 1 normal control subject, both 30
years old, have been evaluated. The patient received 80 mg chlor-
promazine equivalent for 12 months, the RSS score was of 19.
T2 values in both the left and right putamen and lateral nucleus
of globus pallidus were lower in the patients compared to the con-
trol.
TEMPORAL LOBE PATHOLOGY IN SCHIZOPHRENIA AND ITS RELATION TO BRAIN SHIFTS IN MAGNETIC RESONANCE IMAGING
Manual F. Casanova*, Nathan M. DeVaughn
Psychiatry Service 116-D. VAMC Augusta, GA 30904.6285, USA
Computerized image analysis techniques have facilitated the
semiautomated processing of volumetric information. Studies ap-
plying this technique to schizophrenia have reported the presence
of bilateral temporal lobe volume reductions. Further attempts at
localizing the origin of this abnormality have made area compar-
sons at levels that have been matched anatomically to structures outside of the temporal lobes. This strategy does not appear to
be sound given the fact that shrinkage of the temporal lobe may disturb its normal anatomical relations to the rest of the brain. In
this study, we examined the shape reconstructed magnetic reso-
nance images of 15 patients with schizophrenia (DSM IIIR) and
an equal number of controls. Three levels were selected based
on anatomical structures located within the temporal lobe, i.e.,
amygdala, the slice where the c-shaped hippocampus was first rec-
ognized, and the planum temporale. Our results show there is a
small shift regarding the structures of the temporal lobe when
compared to the rest of the brain. The study also demonstrates
the presence of temporal lobe pathology in patients with schizo-
phrenia.
PROSPECTIVE MRI STUDY OF CAUDATE PATHOMORPHOLOGY IN FIRST EPISODE SCHIZOPHRENIA
M.H. Chakos*, J.A. Lieberman, R.M. Bilder, G. Lemer,
B. Bogetts, M. Ashtari
Hillside Hospital. Psychiatry Research, P.O.Box 38, Glen Oaks,
NY 11004, USA
In a prospective study of first-episode schizophrenics, we ex-
amined caudate pathomorphology and its clinical correlates. Us-
ing MRI, first-episode patients (N=35) and age and gender
matched controls (N= 11) had brain scans at baseline and 18
months follow-up. Patients also had baseline and monthly evalu-
ations for psychopathology, EPS and TD. Patients were treated
with a standardized algorithm involving sequential trials of three
neuroleptic drugs until response criteria were met. Caudate vol-
ume change scores were significantly different for patients and
controls (p=.OOl). For patients, smaller baseline caudates were
associated with larger caudate at follow-up (r=-.48), whereas for
controls there was no association of baseline caudate volumes and
change scores (r=.OO24). The group by time interaction (P=.OOO)
remained significant using height, weight. age, gender, cortex vol-
ume and body and frontal horn of the lateral ventricles as
covariates. Larger caudates were associated with longer time to
remission, larger cumulative neuroleptic dose, and younger age at
baseline scan. These findings suggest that caudate volumes en-
large in early treatment of first-episode schizophrenic patients and
that this enlargement may be a result of treatment with antipsy-
chotic medication.
SACCADIC ABNORMALITIES AMONG SCHIZOPHRENICS, THEIR FIRST-DEGREE RELATIVES, AND RELATIONSHIP TO
STRUCTURAL BRAIN IMAGING
Brett A. Clementz*, Jennifer E. McDowell, Terry L.
Jemigan, David L. Braff
Department of Psychology, University of California at San
Diego, 9500 Gilman Dr., La Jolla. CA 92093, USA
Thirty schizophrenics, 24 who had magnetic resonance images,
20 of their first-degree biological relatives, and 32 nonpsychiatric
comparison subjects were tested on measures of saccadic perforn-
ante. Subjects were presented with a fixation task, a prosaccade
task, a predictive tracking task, and an antisaccade task. The
groups did not differ on either the fixation or the prosaccade tasks.
The remaining two tasks, however, differentiated the groups. The
schizophrenics had a decreased amplitude of rightward visually-
guided saccades during the predictive tracking task. Surprisingly,
the schizophrenics were able to develop a normal-level predictive
strategy. Both the schizophrenics and their first-degree relatives
had an increased number of errors on the antisaccade task.
Among the schizophrenics, there were associations between in-
creased antisaccade errors and larger caudate volume, and between
decreased saccadic gain during the predictive tracking task and
decreased mesial temporal lobe volume. Additionally, those pa-
tients with flat and/or grossly inappropriate affect had significantly
more antisaccade errors than patients without these symptoms.
The results are generally consistent with a dysfunction of dorso-
lateral prefrontal cortex and/or caudate nucleus among schizo-
phrenics. The data also offer evidence that dysfunction in these
regions may be related to a neurobiological predisposition for this
disorder.
ANATOMICAL CHARACTERISTICS OF THE CORPUS CALLOSUM AND CLINICAL CORRELATES IN SCHIZOPHRENIA
C. Colombo*, A. Bonfanti, S. Scarone
Istituto Scientifico H S. Raffaele, Via Prinetti 2Y, 20127 Miluno.
It&
Several magnetic resonance imaging (MRI) studies of corpus
callosum (CC) size in schizophrenia claim for CC structural ab-
normalities in schizophrenia, even if other similar studies lead to
opposite results. In the present investigation 19 DSM-II-R schizo-
phrenic patients (13 M, 6 F, mean age 25.e6.4) and 15 normal
controls (9M, 6F, mean age 29.6ti.2) have been evaluated in their
clinical and CC MRI anatomical characteristics. All subjects were
scanned on a Toshiba MRI unit operating at 0.5 T. The midsag-
ittal cut was scanned with Tl-weighted Spin-Echo sequences (TR
500, TE 30). The interslice-gap was 0.5 mm., the slice thick-
ness was 5 mm. MRI images of midsagittal cut were analized
with an image analysis system. The system permitted a semiau-
tomatic definition of the boundaries of the corpus callosum and
the automatic calculation of the selected area. Neither diagnosis nor sex significantly affects CC indices. Multiple Linear Regres-
sion analysis built a significant model which relates GAF (DSM-
III-R V Axis) and CC measures in schizophrenics (R-squared= .30
F with 1,17 d.f = 7.4&p= .Ol). The same analysis relates the onset of illness and CC measures in schizophrenics (R-squared=
.24, F with 1.17 d.f =5.40, p= .03).
D, RECEPTOR OCCUPANCY WITH CLOZAPINE VS HALOPERIDOL IN SCHIZOPHRENIA BY “C-NMSP PET
197
R.R. Conley*, C.J. Gounaris, D.F. Wong, C.T. Tamminga
Maryland Psychiatric Research Center. University of Maryland.
Baltimore, MD 21228, USA
It has been suggested that differences in the in vivo occupancy
of the human striatal Dz receptor by clozapine may account for
aspects of its unique antipsychotic efficacy (Sedvall, 1991). These
differences may be subtle, and thus only detectable by receptor
imaging in a within-subject controlled study. This study analyzed
percent of D, receptor occupancy in a within-subject study design
following both clozapine and haloperidol. Eight schizophrenic
patients were scanned using “C-NMSP, in our standard technique
with the General Electric 4096+ scanner, while they were drug
free, after a six week fixed dose course of haloperidol (30 mg/
day) and after a six week clozapine course (450 mg/day). Tracer
blood levels were measured with arterialized blood. The ratio
between bound ligand in the striatum over bound ligand in the
cerebellum was calculated for the three scans (drug free, on ha-
loperidol, on clozapine) using 90 minute scan data. The percent
change in each drug period between on drug and off drug was
used to indicate the percent occupancy of the drug. All drug
doses were given exactly 2 hours prior to the tracer injection for
the PET. This report is an initial step in a projected exploration
of dopaminergic and serotinergic mechanisms which may account
for the differential efficacy of clozapine.
LIFETIME NEGATIVE AFFECT AND WIDENED THIRD VENTRICLES
K.L. Dykes*, S.A. Mednick
University of Southern California. Social Science Research
Institute, Denney Research Building Room 125. Los Angeles, CA
90089, USA
Third ventricle widening has been the most reliable finding in
the brain imaging of schizophrenics. This widening has been as-
sociated with negative symptoms among schizophrenics. Possi-
bly, widening of the third ventricle involves damage to periventricular structures, including the anterior hypothalamus and
other ANS excitatory centers. Several studies have suggested that
delivery complications are one potential source of this third ven-
tricle widening. If this is the case, those with widened third ven-
tricles associated with delivery complications might be expected
to manifest negative-symptom-like behaviour early in life. We
have examined this hypothesis in the context of the Copenhagen
High Risk Study (n=200). Delivery complications were shown
to predict third ventricle widening (as measured with CT scans