IQ and brain size in schizophrenia.

In a previous study of normal control subjects, positive correlations were demonstrated between intelligence, as measured by the Wechsler Adult Intelligence Scale-Revised, and various measures of brain size, as assessed by magnetic resonance imaging (Andreasen et al., 1993). The goal of this study was to see if these findings generalized to schizophrenia. Corresponding analyses were performed in a group of DSM-III-R schizophrenic patients (50 men and 22 women) and compared with a subset of those normal control subjects (32 men and 27 women) who were equivalent to the patient group in their age and the educational and socioeconomic background of their families of origin. Full Scale IQ score was found to be uncorrelated with any of the regions of interest for the patient group as a whole. When subjects were divided by sex, the female patients were found to have a pattern of correlations similar to that of normal control subjects, while no such relationship was apparent among the male patients. These differences did not appear to be attributable to variability in symptom severity. Thus, there appear to be gender-related differences in brain structure/function relationships in schizophrenic patients versus normal control subjects.

Subcortical and temporal structures in affective disorder and schizophrenia: a magnetic resonance imaging study.

Volumetric measurements of subcortical and temporal structures were done on a sample of 54 schizophrenic patients, who were compared with 48 bipolar patients and 47 normal controls. We observed the male schizophrenic patients to have significant enlargement in the putamen and lesser enlargement in the caudate. We found the right temporal lobe to be larger than the left across all diagnostic groups, although bipolar females failed to have this asymmetry. We did not replicate the finding of decreased hippocampal, amygdala, or temporal lobe volume in our schizophrenic patients. Nor did we find significant differences between our bipolar patients and controls in the structures measured, with the exception of the right hippocampus. Our findings are consistent with a developmental defect in pruning of subcortical brain regions or with a compensatory synaptic increase secondary to decreased input from other brain regions such as the prefrontal cortex or anterior temporal lobe structures. Coupled with the lack of temporal lobe asymmetry in bipolar females, these findings suggest that different types of gender-specific neurodevelopmental abnormalities may occur in affective versus schizophrenic psychosis, which may reflect the effects of hormonal influences on brain development in predisposed individuals.

Problems with ratio and proportion measures of imaged cerebral structures.

Ratio measures, such as the ventricle-brain ratio (VBR) based on computed tomography or magnetic resonance imaging, are widely used in psychiatric research in studies of brain function and morphology. While imaging techniques have advanced considerably, the form of the index of a structure's size has remained the same--a proportion based on an estimate of the structure's size divided by a like estimate of the whole brain size. We demonstrate that ratio and similar indices can suffer greatly in reliability when compared with simple volume measures. This loss of reliability is related to the relation of a structure's size and whole brain size. We review various methods for measuring the size of structures and discuss their strengths and limitations in terms of reliability and validity. In many instances, other methods of "correcting" for brain size (e.g., regression or covariance) may yield measurements that are more appropriate than ratios.

The distinction of positive and negative symptoms. The failure of a two-dimensional model.

The distinction of positive and negative symptoms in describing schizophrenic patients has become popular. It presupposes that symptoms cluster in two dimensions, fitting together not only theoretically but empirically. Factor analysis of three published studies of 93, 62 and 52 schizophrenic patients and a large pooled sample showed that more than two distinct dimensions are required to categorise symptoms in schizophrenia. This result is consistent across methods and samples, and with previous literature. The added dimensionality resulted from a splitting of the positive symptom domain into more distinct factors.

Structural brain abnormalities in bipolar affective disorder. Ventricular enlargement and focal signal hyperintensities.

Structural brain abnormalities were examined in a sample of 48 patients with bipolar affective disorder who were compared with 54 schizophrenic patients and 47 normal controls. As in our previous work using computed tomographic scanning, lateral ventricular enlargement was due to a diagnostic effect. In this study, the effect was more prominent in the schizophrenic men, while a trend was seen in the bipolar men. Women in both groups did not differ significantly from normal subjects. This finding is possibly consistent with the fact that men have a higher frequency of birth anomalies such as hydrocephalus. Since one cause of such birth anomalies might be periventricular hemorrhage or infarction, we also evaluated all scans for the presence of small focal regions of signal hyperintensity. A significant increase in the number of focal signal hyperintensities was noted in the bipolar patients, in comparison with normal subjects, but not in the schizophrenics. The bipolar patients with focal signal hyperintensities had a trend toward larger ventricular size than those without. The pathophysiological significance of these findings is unclear.

Developmental abnormalities of the corpus callosum in schizophrenia.

Magnetic resonance imaging was used to evaluate neuroanatomical and neuropathologic abnormalities in a consecutive series of 140 patients with schizophrenia for comparison with normal controls. Partial agenesis of the corpus callosum, a rare neurodevelopmental abnormality, was found in two patients, one of whom also had a callosal lipoma. Evidence is presented suggesting that this finding represents an increased prevalence of partial agenesis in schizophrenia. The corpus callosum develops embryologically in intimate relationship to the hippocampal formation, fornix, septum pellucidum, and cingulate gyrus. In individuals with callosal agenesis, abnormalities also occur in the development of these limbic structures. Recent neuropathologic studies have suggested the occurrence of abnormal neurogenesis in the hippocampal formation and in the cingulate gyrus in schizophrenic patients. An increased prevalence of callosal agenesis and its related limbic abnormalities would further support investigation into neurodevelopmental abnormalities of these anatomical regions in schizophrenia.

Magnetic resonance imaging of the brain in schizophrenia. The pathophysiologic significance of structural abnormalities.

In a second large series of schizophrenic patients studied with magnetic resonance imaging at the University of Iowa, Iowa City, earlier findings of decreased frontal, cerebral, and cranial size were not replicated. In this second series, control subjects were selected to be educationally equivalent to the schizophrenic patients, a modification in design that may partially account for the failure to replicate. By means of coronal images, ventricular volume was compared in patients and controls and found to differ to a highly significant degree, with the frontal horns being possibly slightly more enlarged than the rest of the ventricular system. A prominent sex effect was also observed, with most of the increased ventricular size occurring in the male patients. Within the male patients, the thalamus was also observed to be significantly smaller, a finding that could be consistent with periventricular injury. Patients with prominent negative symptoms had significantly larger ventricular size than did those with the mixed or positive subtypes. Because of its superior resolution, magnetic resonance imaging appears to offer a more sensitive index of ventricular enlargement than that provided by computed tomography.

CT abnormalities in tardive dyskinesia.

Many investigators have suspected neuropathology in tardive dyskinesia (TD) to center in the striatum. Previous computed tomographic (CT) studies of middle-aged and older subjects using linear measurements have reported primarily negative results. The present study attempts to identify neuropathological abnormalities in the periventricular region of young chronic schizophrenics using specific area measurements of in vivo brain imaging. A ratio of frontal horn area to maximal internal skull area (FHBR) was used in an effort to gain sensitivity and give a reliable measure of caudate atrophy. The ventricle-brain ratio (VBR) measurement and a cortical atrophy rating were also done. The TD and non-TD control groups did differ in the CT variables. Negative CT results do not rule out the possibility that more subtle neuropathological abnormalities may be present. Magnetic resonance imaging, with its superior gray/white matter differentiation and its ability to detect subtle differences in tissue, may discover abnormalities in TD.