Gustav Degreef

Reduced temporal limbic structure volumes on magnetic resonance images in first episode schizophrenia.

Pathomorphology of the limbic system has been described in post-mortem studies of schizophrenia. To determine whether this could be detected in living patients and was not secondary to the treatment or the chronicity of the disease itself, we measured the volumes of the hippocampus-amygdala complex and adjoining temporal horns of 34 patients in their first episode of schizophrenia and 25 normal volunteers using T1 weighted contiguous coronal magnetic resonance images of 3.1 mm width. The results demonstrate abnormal medial temporal lobe morphology in a subgroup of patients at the onset of their illness. There were clear laterality effects and sex differences: hippocampal tissue was significantly smaller only in the left hemisphere of male patients, whereas enlargement of the whole temporal horn or its anterior portion was present on the left side in both sexes. Dysfunction of the limbic mesiotemporal structures might explain some of the clinical features of the disease.

Hippocampus-Amygdala Volumes and Psychopathology in Chronic Schizophrenia

Volumes of the mesiotemporal structures (hippocampus-amygdala complex) were measured in 19 men who were chronic multiepisode schizophrenics and 18 age-matched healthy controls using T1-weighted contiguous coronal magnetic resonance images of 3.1-mm width. Using the level of the mammillary bodies as an anatomical landmark, the whole hippocampus-amygdala complex was divided into an anterior section (mainly containing amygdaloid tissue) and a posterior section (mainly containing the hippocampal formation). Total mesiotemporal tissue volume was reduced significantly in the patient group compared to controls (-11%), with significant reductions in both left (-20%) and right (-15%) hippocampal sections. Reduced limbic tissue volume was associated with increased severity of psychopathology. Severity of positive psychotic symptoms (Brief Psychiatric Rating Scale [BPRS] psychosis factor) was correlated significantly with right and left total mesiotemporal volumes (Spearman rhos = -0.61 p < 0.01). Negative symptom scores (BPRS anergia factor, Scale for Assessment of Negative Symptoms [SANS] global items) were not significantly correlated with any mesiotemporal tissue volumes. The data corroborate and extend previous findings of temporolimbic structure volume reduction in schizophrenia, and suggest that the positive psychotic symptoms of schizophrenia are associated with anatomic anomalies in mesiotemporal structure.

Increased prevalence of the cavum septum pellucidum in magnetic resonance scans and post-mortem brains of schizophrenic patients

A cavum septum pellucidum (CSP) has been regarded as an incidental finding of little clinical importance. However, an association between this developmental anomaly and a diagnosis of psychosis has previously been reported. We determined the prevalence of the CSP in parallel studies of brain scans obtained with magnetic resonance (MR) imaging and in the post-mortem brains of schizophrenic patients compared with normal controls. We found a significantly increased prevalence of the CSP in both the MR scans and post-mortem brains of schizophrenic patients compared with controls. In the MR study, 17 of 81 (21%) schizophrenic patients but only 1 of 46 (2%) control subjects had a CSP. In the post-mortem study, 17 of 28 (61%) schizophrenic patients and 12 of 39 (31%) normal controls had a CSP. The increased prevalence of a CSP in schizophrenic patients further indicates that anomalous development of the limbic system is an important aspect of this disorder.

Increased prevalence of cavum septum pellucidum in schizophrenia

A previous report that the presence of a cavum septum pellucidum was significantly more common in schizophrenic patients than in control subjects (DeGreef et al., 1992) stimulated the present study of an independent but similar population of first admission schizophrenic patients. A high prevalence of this developmental anomaly (44.8%) was found in the patients (n = 85), although it could also be detected in 29.8% of similarly aged control subjects (n = 47). This finding was not associated with corpus callosum, ventricular, or temporal lobe size or asymmetries.

Obstetric complications in schizophrenia, schizoaffective disorder and normal comparison subjects

Previous studies have indicated that obstetric complications (OCs) may be risk factors for schizophrenia, but findings are inconsistent, and data about other diagnostic groups are relatively scarce. We compared the obstetric histories of subjects with schizophrenia, major affective disorder and normal controls. Our subjects included 61 schizophrenia, 26 schizoaffective, 28 major affective disorder patients and 21 normal controls. OCs were rated on the McNeil-Sjöström Scale using data from mothers reports and for a subsample from hospital and birth certificate records. The frequency of OCs did not differ statistically between diagnostic groups at any stage or for the three stages combined. OCs of at least level 4 were found in 69% of schizophrenia patients, 62% of schizoaffective patients, 68% of major affective disorder patients and 71% of the normal comparison group. OCs of at least level 5 were found in 23% of schizophrenia patients, 23% of schizoaffective patients, 21% of the major affective disorder patients and 14% of the normal comparison group. Our findings indicate that the etiologic significance of OCs may not be specific to schizophrenia.

Morphologic Markers of Neurodevelopmental Paths to Schizophrenia

The most widely studied cerebral morphologic abnormalities in schizophrenia may be classified as indications of: 1. medial fronto-limbic system defects; 2. periventricular damage; and 3. cerebral specialization abnormalities. The existing literature supports the independence of these morphologic abnormalities and suggests that they may reflect different pathologic processes. We hypothesize that these pathologic dimensions may be accompanied by distinguishable developmental courses and psychopathologic evolutions. An outline of these hypothetical paths to schizophrenia is presented as a heuristic for understanding heterogeneity of the cerebral morphological, neuropsychological, and clinical features of the schizophrenic syndrome.

Neuropathological and Brain Imaging Studies in Positive and Negative Schizophrenia

Recent interest in neuroanatomical schizophrenia research has focused on three major brain regions: (1) the limbic system with its important telencephalic components comprising the medial temporal lobe structures and the cingulate gyrus; (2) the prefrontal cortex, which roughly consists of frontal cortical areas anterior to the level of the genu of the corpus callosum; and (3) the basal ganglia, most importantly the globus pallidus.

Normal eye tracking is associated with abnormal morphology of medial temporal lobe structures in schizophrenia

Eye tracking and brain morphology assessed by magnetic resonance imaging were examined in 48 patients in their first episode of schizophrenia and in 15 normal controls. Schizophrenic patients showed higher rates of eye tracking dysfunction and more abnormal brain morphology involving the lateral ventricles, medial temporal lobe (MTL) structures and the frontal-parietal cortex than controls. Enlargement of the lateral ventricles and global rating of abnormal brain morphology were significantly more prevalent in male schizophrenics than female schizophrenics. These findings indicate that abnormalities in a variety of brain regions are present in some schizophrenics during the period shortly after the first hospitalization and could not be a function of treatment or chronic illness. We found no relation between abnormal eye tracking and any single feature of abnormal brain morphology. However, normal eye tracking was significantly associated with MTL abnormalities in schizophrenics, reflecting an inverse association between quality of eye tracking and degree of abnormality in MTL structures. These results suggest that abnormal eye tracking is not mediated by the same processes that lead to structural brain anomalies in schizophrenia.

Anomalous Dominance and Persistent Tardive Dyskinesia

We examined handedness and cerebral hemispheric asymmetries on computed tomography (CT) scan in a sample of schizophrenic patients who were rated also for the presence or absence of persistent tardive dyskinesia (TD). Patients with TD showed a more standard dominance pattern, with dextral hand preference and normal occipital asymmetry. Anomalous dominance was associated with a marked underrepresentation of TD. Stepwise discriminant analyses indicated that the statistical prediction of TD was enhanced by the inclusion of dominance measures. Schizophrenic patients with strong standard dominance patterns may be more susceptible to developing TD, or conversely, anomalous dominance may confer protection against TD.

Gadolinium-DTPA enhanced gradient echo magnetic resonance scans in first episode of psychosis and chronic schizophrenic patients

Ten male schizophrenic patients underwent Gadolinium-DTPA (Gd-DTPA) enhanced magnetic resonance (MR) imaging to determine the utility of paramagnetic contrast agents in evaluating neuropathology. MR images enhanced by Gd-DTPA demonstrated no defect in the integrity of the blood-brain barrier.