Emily L. Canfield

A longitudinal study of the corpus callosum in chronic schizophrenia

BACKGROUND Decreased callosal size and anisotropy have been described in schizophrenia patients but their longitudinal progression remains poorly understood. METHODS We performed diffusion-tensor and structural magnetic resonance imaging at baseline and at follow-up four years later in 49 chronic schizophrenia patients and 16 healthy comparison subjects. Schizophrenia patients were subdivided into good-outcome (n=23) and poor-outcome (n=26) groups. Baseline-to-follow-up changes in size, shape, position and fractional anisotropy of the corpus callosum, divided into five sagittal sections and five rostro-caudal segments, were assessed. RESULTS At baseline scan and in comparison to healthy subjects, schizophrenia patients displayed 1) smaller callosal size, 2) lower average anisotropy in all sagittal sections except the midline, and 3) more dorsal average coordinate position. During the four years after the baseline scan, patients with schizophrenia exhibited a more pronounced decline in absolute size of the corpus callosum than healthy comparison subjects. As compared with the good-outcome group, the corpus callosum in poor-outcome patients at baseline was of smaller size and lower average anisotropy, more elongated and posteriorly positioned. During the follow-up interval, poor-outcome patients displayed a more pronounced decline in size but less pronounced decline in anisotropy of the corpus callosum than patients with good outcomes. CONCLUSIONS Differences in callosal size between schizophrenia patients and healthy subjects seen at baseline continue to widen in the chronic phase of the illness, especially in patients with poor functional outcome. Baseline differences in callosal anisotropy among patients with different outcomes, however, diminish over time.

Poor outcome in chronic schizophrenia is associated with progressive loss of volume of the putamen

BACKGROUND We have previously demonstrated that putaminal but not caudate volumes are associated with poor outcome in patients with chronic schizophrenia. Present longitudinal study was designed to investigate progressive differences in striatal volumes among chronic schizophrenia patients with different outcomes and healthy subjects. METHODS Structural MRI scans were acquired at baseline and at follow-up four years later to evaluate volumetric changes in 26 poor-outcome schizophrenia patients, 23 good-outcome patients and 16 healthy subjects. RESULTS Schizophrenia patients with different outcomes entered the study with similar volumes of the caudate nucleus and putamen. The rate of decline in volumes of the putamen was greater in patients with poor outcome than in the good-outcome group, so that their putaminal but not caudate volumes were significantly smaller at the time of follow-up. There were no differences in baseline and follow-up volumes of the putamen or in the rate of their progression among patients with schizophrenia and healthy comparison subjects. The caudate volumes were lower in schizophrenia patients than healthy subjects at baseline and follow-up, but showed no differential patterns of progression between the groups. CONCLUSIONS Volumes of the putamen may represent a longitudinal marker of treatment responsiveness and outcome in patients with chronic schizophrenia.

Longitudinal Assessment of Gray and White Matter in Chronic Schizophrenia: A Combined Diffusion-Tensor and Structural Magnetic Resonance Imaging Study

Previous studies have reported continued focal gray matter loss after the clinical onset of schizophrenia. Longitudinal assessments in chronic illness, of white matter in particular, have been less conclusive. We used diffusion-tensor and structural magnetic resonance imaging in 16 healthy subjects and 49 chronic schizophrenia patients, subdivided into good-outcome (n=23) and poor-outcome (n=26) groups, scanned twice 4 years apart. Fractional anisotropy, gray matter and white matter volumes were parcellated into the Brodmann’s areas and entered into multiway ANCOVAs. At baseline, schizophrenia patients had 1) lower anisotropy in frontoparietal white matter, 2) larger posterior frontal white matter volumes, and 3) smaller frontal, temporal, and parietal gray matter volumes. On follow-up, healthy subjects showed a more pronounced 1) decline in anisotropy, 2) expansion of regional white matter volumes, and 3) reduction in regional gray matter volumes than schizophrenia patients. Good-outcome patients showed a more pronounced decline in white matter anisotropy and a less pronounced increase in white matter volumes than poor-outcome patients. Poor-outcome patients displayed a greater gray matter loss throughout the brain than good-outcome patients. In the chronic phase of the illness, longitudinal changes in both gray and white matter are in the direction of an effacement of between-group differences among schizophrenia patients and healthy subjects. Similarly, preexisting white matter differences between good-outcome and poor-outcome patients diminish over time. In contrast, gray matter volumes in poor-outcome patients continue to decline more rapidly than in patients with good outcome. These patterns are consistent with earlier onset of aging-associated changes in schizophrenia.

Smaller superior temporal gyrus volume specificity in schizotypal personality disorder

BACKGROUND Superior temporal gyrus (STG/BA22) volume is reduced in schizophrenia and to a milder degree in schizotypal personality disorder (SPD), representing a less severe disorder in the schizophrenia spectrum. SPD and Borderline personality disorder (BPD) are severe personality disorders characterized by social and cognitive dysfunction. However, while SPD is characterized by social withdrawal/anhedonia, BPD is marked by hyper-reactivity to interpersonal stimuli and hyper-emotionality. This is the first morphometric study to directly compare SPD and BPD patients in temporal lobe volume. METHODS We compared three age-, sex-, and education-matched groups: 27 unmedicated SPD individuals with no BPD traits, 52 unmedicated BPD individuals with no SPD traits, and 45 healthy controls. We examined gray matter volume of frontal and temporal lobe Brodmann areas (BAs), and dorsal/ventral amygdala from 3-T magnetic resonance imaging. RESULTS In the STG, an auditory association area reported to be dysfunctional in SPD and BPD, the SPD patients had significantly smaller volume than healthy controls and BPD patients. No group differences were found between BPD patients and controls. Smaller BA22 volume was associated with greater symptom severity in SPD patients. Reduced STG volume may be an important endophenotype for schizophrenia-spectrum disorders. SPD is distinct from BPD in terms of STG volume abnormalities which may reflect different underlying pathophysiological mechanisms and could help discriminate between them.

Age and diffusion tensor anisotropy in adolescent and adult patients with schizophrenia

Findings of white matter pathology as indicated by diffusion tensor anisotropy values in schizophrenia are well established, but the differences in this measure between the onset of the disease and the chronic state are not well known. To investigate the differences between these states in the progression of the disease of schizophrenia we acquired 1.5 T diffusion tensor anisotropy images on 35 adult patients with schizophrenia and schizoaffective disorder, 23 adolescents having their first psychotic episode, and age and sex matched controls (33 adults and 15 adolescents). Regions of interest in major cortical white matter tracts chosen as salient to the prefrontal executive deficit in schizophrenia were assessed using stereotaxic coordinates from the Talairach and Tournoux atlas. Regions of each tract along anterior-posterior and/or inferior-superior directions in both hemispheres were evaluated in multiway ANOVA. Tracts between the frontal lobe and other brain regions, but not temporal, occipital and interhemispheric tracts, showed a differential aging pattern in normals and patients indicating that the white matter pathology in these regions is not stable between the onset and the chronic state in schizophrenia. This suggests that tracts involved in the connectivity of the temporal lobe white matter deficits were already well in place in adolescent patients, while frontal lobe pathology continues to develop from adolescence to adulthood.

Brodmann area analysis of white matter anisotropy and age in schizophrenia

Diffusion tensor and structural MRI images were acquired on ninety-six patients with schizophrenia (69 men and 27 women) between the ages of 18 and 79 (mean=39.83, SD=15.16 DSM-IV diagnosis of schizophrenia according to the Comprehensive Assessment of Symptoms and History). The patients reported a mean age of onset of 23 years (range=13-38, SD=6). Patients were divided into an acute subgroup (duration ≤3 years, n=25), and a chronic subgroup (duration >3 years, n=64). Ninety-three mentally normal comparison subjects were recruited; 55 men and 38 women between the ages of 18 and 82 (mean=35.77, SD=18.12). The MRI images were segmented by Brodmann area, and the fractional anisotropy (FA) for the white matter within each Brodmann area was calculated. The FA in white matter was decreased in patients with schizophrenia broadly across the entire brain, but to a greater extent in white matter underneath frontal, temporal and cingulate cortical areas. Both normals and patients with schizophrenia showed a decrease in anisotropy with age but patients with schizophrenia showed a significantly greater rate of decrease in FA in Brodmann area 10 bilaterally, 11 in the left hemisphere and 34 in the right hemisphere. When the effect of age was removed, patients ill more than three years showed lower anisotropy in frontal motor and cingulate white matter in comparison to acute patients ill three years or less, consistent with an ongoing progression of the illness.

Progressive ventricular expansion in chronic poor-outcome schizophrenia.

ObjectiveTo compare progressive changes in lateral ventricular size in chronic schizophrenia patients with good and poor outcomes. BackgroundSeveral longitudinal studies associated excessive ventricular enlargement with poor outcome early in the course of schizophrenia. Changes in its chronic phase have not been as well ascertained. MethodsWe used MRI to evaluate progression of the lateral ventricular size in 49 chronic schizophrenia patients (26 with poor outcome, 23 with good outcome) and 16 healthy comparison participants, scanned twice 4 years apart. ResultsIn comparison with healthy participants, schizophrenia patients displayed significantly enlarged body, and anterior and posterior horns of the lateral ventricles at baseline and follow-up, but no between-group differences in their longitudinal expansion were observed. Progressive enlargement of the posterior horn in the poor-outcome (Kraepelinian) group, however, was more pronounced than in schizophrenia patients with good outcome. ConclusionsExcessive ventricular enlargement in the chronic phase of schizophrenia may be specifically associated with poor functional outcome of the illness.

Larger putamen size in antipsychotic-naïve individuals with schizotypal personality disorder

OBJECTIVE To (a) compare the size of the dorsal and ventral striatum (caudate and putamen) in a large sample of antipsychotic-naïve individuals with schizotypal personality disorder (SPD) and healthy control participants; (b) examine symptom correlates of striatal size in SPD. METHODS The left and right caudate and putamen were hand-traced on structural MRI at five dorsal to ventral slice levels in 76 SPD and 148 healthy control participants. A Group×Region (caudate, putamen)×Slice (1-5: ventral, 2, 3, 4, dorsal)×Hemisphere (left, right) mixed-model MANOVA was conducted on size relative to whole brain. RESULTS Primary results showed that compared with the controls, the SPD group showed (a) larger bilateral putamen size overall and this enlargement was more pronounced at the most ventral and dorsal levels; in contrast, there were no between-group differences in caudate volume; (b) larger bilateral size of the striatum ventrally, averaged across the caudate and putamen. Among the SPD group, larger striatal size ventrally, particularly in the left hemisphere was associated with less severe paranoid symptoms. CONCLUSIONS Striatal size is abnormal in SPD and resembles that of patients with schizophrenia who respond well to antipsychotic treatment. The results suggest that striatal size may be an important endophenotype to consider when developing new pharmacological treatments and when studying factors mitigating psychosis.

MAGNETIC RESONANCE AND DIFFUSION TENSOR IMAGING STUDY OF THE CORPUS CALLOSUM IN ADOLESCENT AND ADULT SCHIZOPHRENIA

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