196

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