underlie the residual ataxia of detoxified alcoholics and eye tracking impainnent of schizophrenics. The presence of both sites of vennian dysmorphology in the comorbid group puts them at risk for both types of motor compromise. Supported by MH30854, AA05965, AA10723, the Norris Foundation. and DVA
1qq ABNORMAL SIGNAL INTENSITY OF CORPUS CALLOSUM IN SCHIZOPHRENIA E.L. Dick, R. Kotwal, D.R. Rosenberg, W.W. Bagwell, T . Kisler, J. Sweeney, J.W. Pettegrew, M.S. Keshavan Department ofPsychiatry, University of Pittsburgh Medical Center, Pittsburgh. PA 15213, USA
Several studies suggest alterations in the morphology of the corpus callosum (CC) in schizophrenia. The pathophysiological significance of these changes remains unclear, though abnormal neurodevelopment may be involved. In normal humans the size of the corpus callosum increaseswith age into early adulthood. Examination of the signal intensities in MRI scans can provide dues to the nature of developmental changes in the tissue characteristics in Cc. In this study, we investigated 31 first episode schizophrenia subjectsand 62 healthy subjects(40 males and 22 females, aged 7-38) who underwent MRI scans using morphometric analyses of cc. Trained reliable raters bl~d to subject identity (DK and RK) computed the mean Signal intensities of genu, body, isthmus, and spleniumof the CC using midsagittal slices of Tl weighted scans. A homogeneous region of the vitreous humor was chosen as a control region since no parallel developmental changes are expected in this. regio~. The mean signal Intensrty of the CC was higher In the schizophrenia patients in the genu and the isthmus, but not the body of the CC (p=
MRI AND COGNITIVE CORRELATES IN SCHIZOTYPAL PERSONALITY DISORDER Chandlee C. Dickey, Martina M . Voglmaier, Martha ~. Shenton, Margaret Niznikie~icz, Larry J. Seidman, Iris A. Fischer, EngKeat Teh, Richard A. Rhoads, Robert W. McCarley Clinical Neuroscience Division ofthe Laboratory of Neuroscience. VAMC. Department ofPsychiatry. Harvard Medical School, Boston, MA, USA
Schizotypal personality disorder (SPD) and schizophrenia share the same genetic diathesis. Our lab has previously shown reduced left superior temporal gyrus (STG) gray matter volumes, impaired verbal memory, and thought disorder in schizophrenics. The purpose of this study is to examine whether these abnormalities are also seen in SPD. Sixteen right handed male subjects from the community who met SPD DSM-IV criteria were age matched with seventeen controls. Similar to schizophrenics, schizotypals showed reduced left STG gray matter volumes (p<0 .OO9) as measured by manual tracings on coronal MRI images 1.5mm thick. In addition, volumes of several left temporal gray matter ROIs correlated with cognitive measures: the anterior port ion of the left STG correlated with the Thought Disorder Index (TOI) (r=0 .63; p=0.037) and the TOI correlated with the number of positive SPD criteria (r=0.56; p=0.029) . The posterior portion of the left parahippocampus negatively correlated with the total words learned on the CVLT (r= -0.55; p=0.043). There was also a trend toward a statistically significant negative correlation between the SANS and volume of the left amygdala (-0.4912; p=0.063, two-tailed) . These preliminary findings are important as they may represent biologic indices of the schizophrenia spectrum disorders.
461 GENDER DEPENDENCE OF PREFRONTAL VOLUME IN SCHIZOPHRENIA R. Gregory Doyle B.A.. Jeanelle Sheeder B.A., Donald C. Rojas Ph .D., Peter Teale M.S.E.E., Jack Simon M .D., Ph.D., Martin Reite M.D. Neuromagnetism Laboratory, Dept. of Psychiatry, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Frontal lobe volume decreases have been described in schizophrenia. In the present study, we obtained prefrontal volumes in 48 subjects, 10 males and 11 females with DSM-lIlR paranoid schizophrenia (mean age 37), and IS male and 12 female controls (mean age 35). An subjects were right-handed. Thirteen patients were medicated with a mean chlorpromazine index of 542. MR images of the brain were obtained at 1.5T. The entire head was imaged in 124 contiguous coronal slices (1.7 mm slice thickness). A combination of semiautomated and manual ROI based segmentation procedures wereused to quantify total brain volumes (TBV) and prefrontal lobe volumes. Prefrontal lobes extended from the frontal pole to the genu of the corpus callosum, and volumes were corrected as percent of TBV. Prefrontal gray and white matter volumes were separated. Male schizophrenic patients exhibited smaller relative prefrontal lobe volume than did male controls (5.,. 9.8%, C= 10.9%); female schizophrenic patients did not exhibit a similar effect (5=10.6%, C=10.9%), (F=4.9S, df=1.43, p<0.03). These effects were true for both gray and white matter. There was also suggestive evidence of a laterality trend in prefrontal gray and while matter distribution. In controls, the gray :white matter rat io was 1.56: I for the left prefrontal
lobe, and 1.26: I for the right; in schizophrenic patients, the gray :white matter ratio was 1.53: I for the left prefrontal lobe, and 1.29: I for the right(F=3.52, df:.ol.44, p<0.067). These observations are compatible with a decrease in normal interhemispheric asymmetry in the schizophrenic patient group . Overall our findings indicate that brain volumetric studies in schizophrenia should consider the sexes independently. Supported by USPHS MH47476.
CORTICAL SURFACE IN SCHIZOPHRENIC PATIENTS AND CONTROLS: MRI, 3-D RECONSTRUCTION AND IN VIVO MORPHOMETRY Peter Falkai', T. Schormann, H. Steinmetz',
N. Palomero-Gallagher, W.G. Honer, Karl Zilles C.&O. Voigt Institute for Brain Research , University of Duesseldorf, 1Department ofPsychiatry, University of Duesseldorf, P. O. Box 12 05 10, 40605 Duesseldorf, FRG : Department ofNeurology, University of DUsseldorf, Department ofPsych iatry, UBe. Vancouver, Canada Introduction: The objective of this study is an analysis of the 3-D conformation (shape) of the cortical surface, its intersubject variability and regional distribution pattern in schizophrenics and controls . Methods: Individual 3-D surface reconstructions of brains from MRI sequences of 26 schizophrenics (13 0, 13 A) and 26 sex- and age-matched controls were normalized to a common reference format , A mean brain surface was constructed for each group using a shape based interpolation technique. For every voxel in this mean brain surface a quantitative measure of variability was calculated from the distances to respective voxels of the individual brain surface. Distances were represented color coded. Results: In male control brains highest variability was detected bilaterally in the prefrontal Brodmann's areas 9-10, visual sensory and association areas (17-19). temporal and occipito-temporal association areas (20,22,37,38,39) and in the parahippocampal gyrus. In female controls highest variability was found in the left parieto-temporal association cortex. The male schizophrenic brains differed significantly from male controls by a lower variability in the prefrontal area II , the temporal pole region area 38 and the parahippocampal gyrus of both hemispheres, by a lower variability of areas 19, 37 and 39 in the right hemisphere and of the prefrontal areas in the left hemisphere. The female schizophrenic brains showed a nearly identical regional distribution of significant differences from the respective controls as described for males. Conclusion: The results demonstrate disease-associated differences of the 3-D conformation of the cortical surface, which show a similar regional distribution in both sexes despite obvious gender-related differences of the regional distribution pattern between male and female control brains.
MRI MEASUREMENTS IN ADOLESCENTS WITH SCHIZOPHRENIA AND BIPOLAR DISORDER Robert L. Findling, Lee Friedman, Thomas P. Swales, Donald K. Swift, Alexandria Wise, S. Charles Schulz Department ofPsychiatry. Case Western Reserve University. Cleveland. Ohio 44106. US A
Previous studies have compared the structural neuroanatomy of schizophrenic patients (SZ) early in the course of their illness with normal controls (NC) using magnetic resonance imaging (MRI). To a lesser extent, similar research has been performed in patients with bipolar disorder ( BD). The purpose of this study is to examine the specificity of structural brain imaging findings in adolescents with SZ by comparing brain size, ventricular fluid volume, sulcal fluid volume, and total fluid volume in this patient population with comparison BD and NC groups. An analysis of our first 6 subjects with BD indicates that adolescents with BD have increased sulcal fluid volume and that adolescents with SZ have reduced brain volume. Our group's current attention to BD will allow us to report on results of 15 teenagers with BD and to compare them to our previously reported SZ and NC groups. As in previous reports, adolescents with BD appear to have structural neuroanatomic differences when compared to adolescent NC and SZ groups. These data add evidence to the specificity of structural neuroanatomic findings in adolescent SZ. The implications of this research will be discussed.
4()4, A STUDY OF HEAD SIZE IN ADULT PATIENTS WITH SCHIZOPHRENIA Lee Friedman, John A. Jesberger, Thomas Swales, Rebecca Rakow, Kim Ward, Diana Pi, S. Charles Schulz, Peter F . Buckley Department ofPsychiatry, Case Western Reserve University, Cleveland OH 44106. USA Our recent meta-analysis (Ward et al., Schizophrenia Research, ill press) documents reduced intracranial size and
brain size in schizophrenia. However, we did not find evidence for decreased I!'Xtracranial size. There are relatively fewstudies of extracranial size, and the typical method for assessing extracranial size, i.e.• head circumference, is probably insensi· tive. Well-documented evidence of intracranial size reductions, in the absence of extracranial size reductions, could have relevance for the pathophysiology of schizophrenia. We have undertaken a comprehensive study of head size, including the following head measures: head circumference, head length. head width, and the coronal and sagittal arcs. Below, we present our preliminary findings on 34 control subjectsand 34 patients with schizophrenia. The patients were drawn from I stale mental hospital and the controls were recruited from the waiting room of an internal medicineclinic at a county hospital