Victor W. Swayze

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.

Symptom dimensions and brain morphology in schizophrenia and related psychotic disorders

The heterogeneity of symptoms in schizophrenia may reflect heterogeneity of underlying pathophysiological mechanisms. Factor analytic studies have consistently identified three symptom factors, psychotic, negative and disorganized, as independent dimensions of schizophrenic psychopathology. This study examined the relationship of these symptom dimensions with volumes of specific brain regions. One-hundred and sixty-six schizophrenia spectrum patients were clinically evaluated with the Comprehensive Assessment of Symptoms and History (CASH) and scanned with a 1.5 Tesla magnetic resonance imaging scanner. Regions of interest (ROIs) were manually traced on 5 mm and 3 mm coronal slices by a single technician, blind to all aspects of subject identity. Correlations between ROI volumes and indices of symptom severity were determined. Analyses of covariance were then used to test for specific relationships between each of the three symptom dimensions and ROI volumes. Tests were made of each dimension, controlling for all others. Overall symptom severity was significantly correlated with larger ventricle volumes (lateral, third and temporal horns) and smaller temporal lobe, hippocampal and superior temporal gyral volumes. Both psychotic and negative symptom severity predicted increased third ventricular volume. Psychotic symptom severity uniquely predicted decreased superior temporal gyral volume as well as increased temporal horn volume. Within the psychotic symptom dimension, hallucinations alone predicted left superior temporal gyral volume. No significant associations between disorganized symptoms and any ROIs were demonstrated. These results provide clues to the localization of specific brain regions underlying symptom clusters in schizophrenia, and provide further validating evidence for the construct of independent dimensions of psychopathology within schizophrenia and related psychotic disorders.

Cavum septi pellucidi in normals and patients with schizophrenia as detected by magnetic resonance imaging

Cavum septi pellucidi (CSP) is a cavity between the two leaflets of the septum pellucidum. CSP is a developmental anomaly, yet the pathologic implications, if any, of an abnormally large CSP remain unclear. The reported incidence of CSP among normal populations varies greatly from 0.15% to 85%. Several studies have suggested that there is a higher incidence of CSP in patients with schizophrenia. We conducted a thin-slice magnetic resonance imaging study to evaluate the prevalence of CSP in a sample of 75 controls and 55 patients. There was a high incidence of small CSP among both groups: 58.8% in the controls and 58.2% in the patients, suggesting that a small cavum could be considered a normal variant; however, the patient group had significantly higher incidence of large CSP (20.7%) compared to the normal group (3%). The patients with large CSP were all male.

Positive and negative symptoms of schizophrenia: past, present, and future.

The “group of schizophrenias,” normally referred to with a single nominative, is phenomenologically heterogeneous. Its symptoms represent multiple psychological domains, including perception, inferential thinking, language, attention, social interaction, emotion expression, and volition. Studies of psychopathology have simplified this complex array in several ways; one has been a subdivision into positive and negative symptoms. Reports by our group and others suggest that the symptoms of schizophrenia fall into three natural dimensions: positive symptoms subdivided into psychotic and disorganized dimensions, while a third negative dimension also emerges. Since these dimensions have impressive consistency across studies, future work must examine their relationship to clinically relevant concepts such as prognosis or etiology and examine four different aspects: longitudinal course, neural mechanisms, relationship to treatment, and interrelationships in other pathological conditions.

Reversibility of brain tissue loss in anorexia nervosa assessed with a computerized Talairach 3-D proportional grid

We describe the results of our follow-up magnetic resonance imaging (MRI) study of underweight patients with anorexia nervosa, using rigorous methodology to control for head position across time. All subjects first underwent an initial scan and rescan to verify that our computerized three-dimensional co-planar grid method for volume measurement was reliable and accurate, regardless of head positioning. After a period of several months, subjects had a follow-up scan to assess for changes that may have occurred following significant weight gain. Ventricular and total brain volume measurements from the initial scans were compared with the scans from an age- and sex-matched normal control group to determine whether we could replicate previous findings of ventricular enlargement compared with controls and whether brain volume is reduced compared with controls. Anorexic subjects had significantly larger ventricles when compared with normal controls but did not differ significantly in total brain volume. Using a repeated measures analysis of variance, a priori contrasts compared the initial/rescan pair volumes with each other and the initial/rescan pair volumes with the follow-up volume. These analyses showed that ventricular and total brain volumes derived from the initial/rescan pair were nearly identical, but that at follow-up ventricular volume decreased significantly and total brain volume increased significantly after weight gain.

MRI abnormalities in tardive dyskinesia

Most investigators studying tardive dyskinesia (TD) hypothesize that the condition is due to a neurochemical abnormality of the striatum. Recently, numerous CT studies have been done to verify brain abnormalities in patients with TD; the findings have, however, been conflicting. The present study was designed to detect possible neuropathological abnormalities in the basal ganglia in a young sample of schizophrenic patients with TD as compared with schizophrenic patients without TD and normal controls. Magnetic resonance imaging (MRI) was used to measure the volumes of the caudate, putamen, globus pallidus, lateral ventricle, and intracranium. The volumes of the caudate nuclei of the patients with TD were significantly smaller than the volumes of the caudate nuclei of the patients without TD and normal controls. This abnormality in the caudate may be related to some previous conditions, which may prove a substrate that is necessary for TD to establish itself in association with neuroleptic use. Further studies are necessary to confirm our findings and to determine the pathophysiologic nature of these structural alterations and the role played by neuroleptics, whether primary or secondary.

Implications of Starvation-Induced Change in Right Dorsal Anterior Cingulate Volume in Anorexia Nervosa

OBJECTIVE Converging evidence suggests a role for the anterior cingulate cortex (ACC) in the pathophysiology of anorexia nervosa (AN). This study sought to determine whether ACC volume was affected by starvation in active AN and, if so, whether this had any clinical significance. METHOD Eighteen patients with active AN and age- and gender-matched normal controls underwent magnetic resonance imaging (MRI). Sixteen patients (89%) with AN had intelligence quotients (IQ) testing at intake, 14 (78%) had repeat MRIs after weight normalization, and 10 (56%) had outcome data at 1-year posthospitalization. RESULTS Right dorsal ACC volume was significantly reduced in active AN patients versus controls and was correlated with lower performance IQ. While ACC normalization occurred with weight restoration, smaller change in right dorsal ACC volume prospectively predicted relapse after treatment. CONCLUSION Reduced right dorsal ACC volume during active AN relates to deficits in perceptual organization and conceptual reasoning. The degree of right dorsal ACC normalization during treatment is related to outcome.

Intelligence and regional brain volumes in normal controls

Abstract The relationship between brain size and intelligence was examined in a large sample of healthy normal volunteers (N = 90). In addition to confirmation of the small but significant relationship between IQ and whole brain volume (r = 0.25, p

Positive and Negative Symptoms: Assessment and Validity

During the past decade, the study of the assessment and validity of negative symptoms has been restored to its rightful place in the realm of psychopathology. During the 1970s and early 1980s, negative symptoms were scarcely allowed in live in the servant’s quarters. Instead, they were neglected and ignored, while positive symptoms were raised to a position of pride and popularity because of their presumed superior reliability. Positive symptoms were, therefore, made the foundation of the definition of schizophrenia in the Research Diagnostic Criteria (Spitzer et al. 1978) and Diagnostic and Statistical Manual (DSM)-III (American Psychiatric Association 1980) and DSM-III-R (American Psychiatric Association 1987), and they were also given great prominence in the Present State Examination (Wing et al. 1974) and CATEGO (Wing et al. 1974). This state of affairs was in direct contradiction to the work of the historic scholars of psychopathology, Kraepelin (1919) and Bleuler (1916), who both saw negative symptoms as the core feature of schizophrenia. During the past decade, however, clinicians and investigators have returned again to this earlier perspective. Many now agree that negative symptoms (either referred to by that name or by other terms such as the apathy syndrome, the defect state, or the residual state) are the most important and the most handicapping symptoms that patients suffering from schizophrenia experience.

Evaluating and Validating Two Methods for Estimating Brain Structure Volumes: Tessellation and Simple Pixel Counting

Developments in imaging technology have made three-dimensional visualization of internal brain structures possible with excellent resolution. Since improved visualization implies improved measurement, these advances hold promise to more accurately measure the volumes of internal structures. As new technologies and techniques emerge, evaluating the relative benefits of measurement methods becomes necessary. We compared and evaluated two methods of estimating volumes from images of brain structures. One method counted pixels within a region of interest, while the other method tessellated the surface between tracings on adjacent slices. Our study assessed both measurement error for true phantom volumes and method disparity for in vivo structures in a randomly selected sample of subjects (n = 100). For our comparisons, we focused on the temporal lobe, ventricular system, and hippocampus. Bias, independence of measurement errors and maximal discrimination of individual differences are properties that are relevant to validating and evaluating measurements of cerebral structure. Pixel counting proved to be the more robust of the two methods, being less sensitive to nuisance-interactions between size of object, shape, and slice thickness. Clinical and research applications of imaging techniques may have distinctive but overlapping needs when evaluating and validating new developments in imaging.