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Original Article |

Smaller Neocortical Gray Matter and Larger Sulcal Cerebrospinal Fluid Volumes in Neuroleptic-Naive Women With Schizotypal Personality Disorder FREE

Min-Seong Koo, MD; Chandlee C. Dickey, MD; Hae-Jeong Park, PhD; Marek Kubicki, MD; Na Young Ji, MD; Sylvain Bouix, PhD; Kilian M. Pohl, PhD; James J. Levitt, MD; Motoaki Nakamura, MD; Martha E. Shenton, PhD; Robert W. McCarley, MD
[+] Author Affiliations

Author Affiliations: Clinical Neuroscience Division, Laboratory of Neuroscience, Department of Psychiatry, Veterans Affairs Boston Healthcare System, Brockton Division, Harvard Medical School, Brockton, Mass (Drs Koo, Dickey, Park, Kubicki, Levitt, Nakamura, Shenton, and McCarley); Departments of Psychiatry and Neurology (Dr Dickey) and Psychiatry Neuroimaging Laboratory, Department of Psychiatry, and Surgical Planning Laboratory, Magnetic Resonance Imaging Division, Department of Radiology (Drs Kubicki, Bouix, and Shenton), Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; Department of Radiology, Yonsei University, Seoul, Korea (Dr Park); Department of Psychiatry, University of North Carolina Hospital, Chapel Hill (Dr Ji); and Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Boston (Dr Pohl).


Arch Gen Psychiatry. 2006;63(10):1090-1100. doi:10.1001/archpsyc.63.10.1090.
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Context  Structural brain abnormalities, including larger cerebrospinal fluid (CSF) volumes, have been observed in men diagnosed as having schizotypal personality disorder (SPD).

Objectives  To determine whether women with SPD have abnormalities similar to those of men with SPD and to elucidate specific SPD regional volume deficits and symptom correlations.

Design  Naturalistic study.

Setting and Participants  Thirty neuroleptic-naive women with SPD and 29 female control subjects, both recruited from the community. Participants were group matched for age, parental socioeconomic status, handedness, and IQ.

Interventions  A new segmentation method was applied to magnetic resonance images to automatically parcel the images into CSF, gray matter, and white matter. The neocortex was manually separated from subcortical and other nonneocortical structures. Voxel-based morphometry was applied to determine global and regional volume deficits.

Main Outcome Measures  Left and right neocortical gray matter, white matter, and CSF relative volumes as well as clinical symptoms from the Structured Interview for Schizotypy and the Schizotypal Personality Questionnaire–Brief Version.

Results  Smaller left (3.84%) and right (3.83%) neocortical gray matter relative volumes associated with larger left (9.66%) and right (9.61%) sulcal CSF relative volumes were found in women with SPD compared with controls. Voxel-based morphometry showed that the neocortical deficits in SPD were especially prominent in the left superior and middle temporal gyri, left inferior parietal region with postcentral gyrus, and right superior frontal and inferior parietal gyri. In the SPD group, larger lateral ventricle volumes correlated with more severe symptoms on the Structured Interview for Schizotypy and the Schizotypal Personality Questionnaire–Brief Version.

Conclusions  The smaller neocortical gray matter volume and larger sulcal CSF volume provide evidence of the brain basis of this personality disorder and emphasize the communality of brain abnormalities in the schizophrenia spectrum.

Figures in this Article

Schizotypal personality disorder (SPD) is genetically related to schizophrenia1,2 and shows similar psychophysiologic, neurochemical, and cognitive functional abnormalities.3,4 Moreover, data from neuroimaging studies confirm pathological similarities between SPD and schizophrenia,4,5 such as in the superior temporal gyrus,610 basal ganglia,11,12 and thalamus.13 Finally, smaller volumes have been reported in the frontal lobe in schizophrenia1417 and in individuals with schizotypal features,18 although not all studies agree.1,2,4

These findings suggest focal, regional volume deficits in schizophrenia spectrum disorders that are not confined to a single area but are more widespread, although some areas may be more affected than others.19 Some structural neuroimaging studies2024 in schizophrenia show smaller overall cortical gray matter volume relative to controls, with accompanying larger cerebrospinal fluid (CSF) or ventricle volumes,20,21,24 whereas some studies show negative findings, including a postmortem study25 and some imaging studies.26,27 Studies with nonpsychotic first-degree relatives of patients with schizophrenia have also reported smaller cortical gray matter and larger sulcal CSF20,28 or ventricle20,29,30 volumes compared with control subjects. To reconcile these different findings, it seems essential that studies control for potential confounders that likely affect cerebral cortical volume, such as demographic variables3133 (including age, sex, and handedness), and especially factors associated with chronic serious mental illness, such as recurrent hospitalizations and neuroleptic medication use.3438

With respect to the control of potential confounding variables, SPD is a schizophrenia spectrum disorder that is genetically related to schizophrenia,2 but because the subjects are not psychotic, they usually do not receive neuroleptic medications or require recurrent hospitalizations. Consequently, individuals with SPD may afford a clearer representation of the underlying brain abnormalities in schizophrenia spectrum disorders.

In a previous study39 of men with SPD, the Clinical Neuroscience Laboratory (VA Boston Healthcare System and Harvard Medical School) reported a significantly larger CSF volume not attributable to ventricular volume (eg, sulcal CSF) and a trend-level smaller cortical gray matter volume. Because sex may affect regional cerebral cortical volumes differently in healthy individuals40 and in individuals with schizophrenia4143 or SPD,9 and the clinical course of SPD may be milder in women, the present study examines brain volumes in neuroleptic-naive women with SPD compared with female controls using a newly developed and sensitive magnetic resonance imaging (MRI) segmentation method.44,45 Moreover, in the present study we focus on neocortical rather than total cortical gray matter to allow more precise delineation of brain abnormalities44,45 and to determine whether the strong evidence for neocortical abnormalities in schizophrenia20,21,46 was also observed in SPD, a schizophrenia spectrum disorder.

We hypothesized that neuroleptic-naive women with SPD would show smaller neocortical gray matter volume but larger sulcal CSF and lateral ventricle volumes than female control subjects group matched for age, sex, handedness, parental socioeconomic status, and IQ. Clinical correlates of neocortical gray matter, sulcal CSF, and lateral ventricle volumes in women with SPD were also examined. We further used voxel-based morphometry (VBM) to evaluate whether there were specific regional neocortical gray matter differences in subjects with SPD and controls.

PARTICIPANTS

From January 1, 1997, through December 31, 2005, 30 neuroleptic-naive women diagnosed as having SPD and 29 female control subjects were recruited from the community through advertisements on the transit system, in newspapers, and on fliers. Subjects with SPD from the community were recruited via the following advertisement: “Sixth Sense/Very Shy: A study at Harvard Medical School seeks right-handed people who believe they have ESP, telepathy, or a “sixth sense”; often mistake noises for voices; sense the presence of others when alone; have extreme social anxiety (or discomfort) in social situations involving unfamiliar people; and have few friends.”

Recruitment of female participants began several years after that of male participants, accounting for the timing of this article. Of the 962 individuals who responded to the SPD advertisement, 421 female participants underwent an extensive telephone screening process that used the following inclusion criteria: (1) age between 18 and 55 years; (2) right-handed; (3) English as the primary language; (4) no history of neurologic disorder with loss of consciousness longer than 2 minutes; (5) no history of electroconvulsive therapy, drug or alcohol dependence in the past 5 years, or abuse in the past year; and (6) no history of using neuroleptics ever or psychotropic medications in the past year. The SPD advertisement tapped the DSM-IV diagnostic criteria for SPD,6 which include (1) ideas of reference, (2) odd beliefs and superstitions or “sixth sense,” (3) abnormal perceptual experiences, (4) odd and vague speech, (5) suspiciousness, (6) constricted affect, (7) odd and peculiar appearance or behavior, (8) no close friends, and (9) extreme social anxiety.

Of the 421 subjects, 92 met the telephone inclusion criteria, including positive responses to at least 3 of the previously mentioned SPD criteria on screening questions. The Structured Clinical Interview for DSM-IV–Patient Edition (SCID)47 and its personality disorder version (SCID-II)48 were then used to make DSM-IV diagnoses and to exclude Axis I psychotic and bipolar disorders from both groups and Axis I and II diagnoses from controls. A recently published article3 describes in detail the clinical and demographic characteristics of subjects with SPD so recruited.

Interviews were conducted by either a licensed psychiatrist or a licensed psychologist. Interrater reliability for the diagnosis of SPD was high (κ = 0.89; n = 25).6 Women with SPD in the present study were included after diagnosis reliability testing using the same interviewers as in the present study. Interviewers were trained to detect nuances of behavior and history and to ask follow-up questions to establish the correct diagnosis. In the rare instances in which the first interviewer was uncertain about the diagnosis, a second licensed psychiatrist or psychologist interviewed the subject, and a consensus was obtained. All 30 subjects with SPD who underwent MRI and other parts of the protocol met the full DSM-IV SPD diagnostic criteria (having ≥5 of the 9 characteristics). Subjects with SPD also met the criteria for other comorbid personality and Axis I disorders, including paranoid (n = 9), borderline (n = 7), and narcissistic (n = 3) personality disorders; depression (n = 6); dysthymia (n = 2); panic disorder (n = 2); and phobic disorder (n = 1).

Female controls were recruited from the community via a different advertisement and similarly underwent the SCID and SCID II. Controls had the additional inclusion requirement of no family history of psychotic or bipolar illness and no personal history of an Axis I or personality disorder diagnosis. Controls were group matched for demographic variables, including age and parental socioeconomic status, with subjects with SPD. The project was approved by our institutional review boards at Harvard Medical School and at VA Boston Healthcare System, and after a full description of the study to the participants, written informed consent was obtained.

CLINICAL MEASURES

Clinical symptoms were measured using the Structured Interview for Schizotypy (SIS)49,50 and the Schizotypal Personality Questionnaire–Brief Version (SPQ-B).51 Use of the SIS began in the middle of female recruitment; therefore, only 15 of the 30 women with SPD completed the SIS. Data were acquired on 9 factors from the SIS (magical thinking, ideas of reference, illusions, suspiciousness, psychotic-like phenomena, restricted emotion, social isolation/introversion, schizotypal social anxiety, and anger to slights) and 3 factors from the SPQ-B (cognitive-perceptual, interpersonal, and disorganized).

MRI ACQUISITION, POSTPROCESSING, AND AUTOMATED SEGMENTATION METHOD

All the participants underwent MRI using a 1.5-T system (1.5T Signa; GE Medical Systems, Milwaukee, Wis). The acquisition protocol involved 2 MRI pulse sequences, as described elsewhere.12 Several steps were taken to process the images on computer workstations (Sun Microsystems, Mountain View, Calif). First, a preprocessing filter was used to reduce noise. Next, T2 information from the double-echo spin-echo axial slices was coregistered with data from the spoiled gradient recalled (SPGR) images by reformatting the axial voxels into the voxel dimensions corresponding to those in the coronal SPGR images.52 Third, a recently developed segmentation method45 was applied to the MRIs to partition the images into the 3 major tissue classes: gray matter, white matter, and CSF. The method is based on use of an expectation maximization algorithm, which simultaneously estimates the inhomogeneities in the images and segments the images into the 3 major tissue classes. The algorithm analyzes SPGR and T2-weighted MRIs45 and uses spatial priors53 to increase the accuracy of the approach. Spatial priors capture the probability of a certain tissue class being present at a certain location in the 3-dimensional volume. Compared with other state-of-the-art algorithms,44 this method produces highly accurate segmentations of the 3 major tissue classes because it combines previous information, image inhomogeneity correction, and dual-channel analysis. The final step measured the volume of the different tissue classes using medical imaging software (3D-Slicer; an Open Source development project begun at the MIT Artificial Intelligence Laboratory and the Surgical Planning Laboratory at Brigham and Women's Hospital).54 The voxel volumes of gray and white matter and CSF were summed, yielding the total intracranial contents (ICC).

NEOCORTEX SEPARATION METHOD FROM THE SEGMENTED BRAIN

To exclude nonneocortical tissues from the whole segmented brain, the exclusion region of interest (ROI) was manually drawn on each coronal slice of the nonrealigned SPGR image to remove the basal ganglia, thalamus, brainstem, cerebellum, and medial temporal structures (amygdala-hippocampus complex).7,12,39,55 First, the exclusion ROI was drawn on the coronal slices from anterior to posterior starting with the first slice in which the basal ganglia appeared. The whole basal ganglia were drawn, and as soon as the temporal stem appeared, the medial temporal structures (hippocampus and amygdala) were also added to the exclusion ROI. Progressing posteriorly, the brainstem, the third and fourth ventricles, and the entire infratentorial structure (eg, the cerebellum) were added to the exclusion ROI. Then, the expectation maximization atlas segmentation, the exclusion ROI, and the ICC mask were merged into a single image, resulting in neocortical gray matter, white matter, and CSF. This ROI delineation included all 6 layers of the neocortex and excluded the major portion of nonneocortical cortex, including limbic cortical areas (except for the piriform cortex) and most of the paralimbic cortex, except for portions of the cingulate, insula, and temporal pole (see the publication by Mesulam56 for an anatomical description). For simplicity, we labeled this ROI as neocortical gray matter because the included regions of non–6-layer cortex compose less than 5% of the neocortical gray matter volume.

The merged image was then realigned and resampled with the reference line connecting 2 points of the anterior and posterior commissures, resulting in reformatted images 0.9375 mm thick. Figure 1A illustrates an SPGR image of a woman with SPD, and Figure 1B illustrates the segmentation results on the image in Figure 1A. Figure 1C illustrates the results of applying the exclusion ROI to the segmented image so as to include only neocortical structures. Finally, the realigned neocortical brain images were overlaid on the corresponding realigned SPGR images for further manual division of the left and right neocortices. Also, lateral ventricle volume was delineated (Figure 1C) to examine whether any CSF volume change found would be attributable to lateral ventricle or sulcal CSF. The lateral ventricles were manually separated from sulcal CSF space on each slice. Then sulcal CSF was measured from the CSF volumes by excluding the ventricle volumes. Interrater reliabilities (based on intraclass correlation coefficients) among 3 raters (M.K., M.N., and Adam Cohen, BA) on 5 MRIs for separation of the neocortex from other tissue were high on the left (r = 0.999) and right (r = 0.998) neocortices and also on left (r = 0.987) and right (r = 0.989) lateral ventricles and on ICC (r = 0.999).

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Figure 1.

Spoiled gradient recalled images. A, Gray scale image of a woman with schizotypal personality disorder. B, The same image with automatically segmented tissue types overlaid. Cerebrospinal fluid is color coded as turquoise, gray matter as red-brown, and white matter as pink. C, The same image with the neocortex and ventricle extracted by manual exclusion of nonneocortical structures from the automatically segmented image. Cerebrospinal fluid is color coded as green, gray matter as brown, and white matter as yellow on the right; color codes on the left are as in part B. The lateral ventricle is color coded as dark blue on the right and as dark green on the left. The region of interest definition illustrated in part C was used for the statistical analysis.

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VBM ANALYSIS

Voxel-based analysis of gray matter volume differences between women with SPD and controls was conducted using optimized VBM57 and SPM2 software (Institute of Neurology, University College London, London, England).58 Because the structural SPGR images used in this study differed from the SPM T1 template, we created a study-specific template by averaging all spatially normalized SPGR images into the Montreal Neurological Institute (McGill University, Montreal, Quebec) T1 template using a nonlinear spatial transformation function.

Spatial normalization was conducted by applying nonlinear spatial transformations (derived from all SPGR images to the new group template) to segmented gray matter images (see the “Methods” section for a description of segmentation). Spatially normalized gray matter maps that were resampled to a voxel size of 1×1×1 mm3 were modulated by the jacobian determinant of spatial normalization transformation to preserve volume changes minimized during the nonlinear transformation. These modulated segmentations were smoothed using an isotropic gaussian kernel with 8-mm full-width half-maximum to accommodate misregistration errors and subtle anatomical variations. Significant differences in the adjusted regional volume were obtained using t statistics at every voxel in the gray matter from subjects with SPD and controls. Clusters consisting of a minimum of 1000 contiguous voxels with the threshold of uncorrected P<.005 were considered significantly different between groups.

STATISTICAL ANALYSIS

Statistical analyses for MRI structural measures were performed on relative brain volumes to correct for variations in head size. Relative volumes were obtained by dividing absolute volumes by ICC and multiplying by 100. (Using absolute, rather than relative, volumes or covarying by ICC [also by ICC and age] in these analyses did not affect the statistical conclusions.)

The effects of group (subjects with SPD vs controls) difference were examined using repeated-measures analyses of variance with group as the between-group factor and laterality (left vs right) as the within-group factor. Planned contrasts consisting of unpaired t tests for normally distributed groups (neocortical gray matter, white matter, and sulcal CSF volumes) were subsequently performed. For nonnormally distributed volumes (lateral ventricle volumes, Shapiro-Wilks test: left [W30 = 0.78; P=.01 in women with SPD; W29 = 0.85; P=.01 in controls] and right [W30 = 0.69; P=.01 in women with SPD; W29 = 0.96; P = .27 in controls]), the Mann-Whitney test was applied.

To evaluate the association between relative volumes of gray matter and CSF, Pearson product moment correlations were performed. Spearman correlations were derived for correlations with lateral ventricle volumes because of the nonnormality of this sample.

There were no significant group differences in demographic characteristics, including age, IQ, parental socioeconomic status, and handedness (Table 1). The groups differed in participant socioeconomic status (t57 = −2.6; P = .01), consistent with other SPD studies.3 There was no significant difference between the 2 groups in ICC (t57 = −1.1; P = .26) (Table 2).

Table Graphic Jump LocationTable 1. Demographic Characteristics of the 59 Study Participants*
Table Graphic Jump LocationTable 2. Volumes of Neocortical Gray Matter, White Matter, and Cerebrospinal Fluid
NEOCORTEX AND CSF VOLUME MEASURES

A repeated-measures analysis of variance of neocortical gray matter relative volumes revealed a significant main effect of group (SPD vs control) (F1,57 = 6.13; P = .02) (Table 2). There was no significant main effect of laterality (left vs right hemisphere) (F1,57 = 0.03; P = .87) and no interaction between group and laterality (F1,57<0.001; P>.99). Planned follow-up contrasts applying t tests showed that left (t57 = −2.39; P = .02; effect size = −0.62; 3.84% smaller) and right (t57 = −2.53, P = .01; effect size = −0.66; 3.83% smaller) neocortical gray matter relative volumes were significantly smaller in subjects with SPD than in controls (Figure 2 and Table 2). There was no difference in asymmetry between groups (t57 = 0.03; P = .82). In contrast to gray matter, white matter relative volumes revealed no significant differences between groups (Table 2).

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Figure 2.

Neocortical gray matter relative volumes for women with schizotypal personality disorder (SPD) and female control subjects. Horizontal lines indicate means, and t values are from t test comparing groups.

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A repeated-measures analysis of variance of relative volume of sulcal CSF revealed a significant main effect for group (F1,57 = 7.98; P = .01) and no significant effect for laterality, with no interaction between laterality and group (Table 2). Planned follow-up t tests showed that the sulcal CSF relative volumes were larger in subjects with SPD than in controls on the left (t57 = 2.53; P = .01; effect size = 0.66; 9.66% larger) and right (t57 = 2.79; P = .007; effect size = 0.73; 9.61% larger) (Figure 3 and Table 2).

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Figure 3.

Sulcal cerebrospinal fluid (CSF) (A) and lateral ventricle (B) relative volumes for women with schizotypal personality disorder (SPD) and female control subjects. Horizontal lines indicate means, and t (or U) values are from the t (or Mann-Whitney) test comparing groups.

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To determine whether the difference in sulcal CSF volume was paralleled by SPD-control differences in the lateral ventricles, nonparametric (Mann-Whitney) tests for lateral ventricle relative volumes were also performed and showed no significant difference on either the left (U = −1.5; P = .10) or right (U = −0.6; P = .55) ventricle (Table 2). The scatterplots of the lateral ventricles showed 1 SPD outlier each on the left and right, but even with this outlier removed, the SPD-control group differences were not significant.

To determine whether smaller neocortical gray matter volumes were associated with larger volumes of the surrounding sulcal CSF, we performed a correlation analysis, finding that total neocortical gray matter relative volumes were significantly negatively correlated with the relative volumes of the total sulcal CSF surrounding the neocortex in the SPD group (r = −0.36; P = .048) (Figure 4). In contrast, the control group showed no such significant correlation between total sulcal CSF and total neocortical gray matter relative volumes (r = 0.18; P = .36). A comparison of SPD and control correlation coefficients using the Fisher z transformation showed that these r values were significantly different (z = −2.03; P = .02). We also performed a similar correlation in the SPD group between relative volumes of the lateral ventricles and neocortical gray matter, finding that there was no significant correlation (r = −0.08; P = .68).

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Figure 4.

Inverse correlation between relative volumes of neocortical gray matter and surrounding sulcal cerebrospinal fluid (CSF) in women with schizotypal personality disorder. r = Pearson correlation coefficient. The least squares line was added for ease of interpretation.

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We did not find any differences in neocortical gray matter, sulcal CSF, or lateral ventricle volumes between subjects with SPD without depression and those who were comorbid for depression. In addition, 6 subjects with SPD had first-degree relatives with psychosis, although there was no significant volume difference in neocortical gray matter, white matter, and sulcal CSF between groups with and without a family history.

GRAY MATTER REGIONS SHOWING MORE PRONOUNCED VOLUME DEFICITS IN WOMEN WITH SPD VS CONTROLS: VBM ANALYSIS

Optimized VBM analysis showed greater deficits in subjects with SPD compared with controls on the left side in the superior (Brodmann area [BA] 22) and middle (BA 21) temporal gyri and the inferior parietal (BA 40) region with postcentral gyrus (BA 13) and on the right side in the superior frontal (BA 6) and inferior parietal (BA 40) gyri (Figure 5 and Table 3). In contrast, no area showed a deficit in controls compared with subjects with SPD.

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Figure 5.

Regions of reduced regional gray matter volume in subjects with schizotypal personality disorder compared with control subjects analyzed using optimized voxel-based morphometry. The left superior and middle temporal gyri, the tempoparietal region, and the right superior frontal gyrus with the inferior parietal region showed deficits in subjects with schizotypal personality disorder (see Table 3 for specific coordinates). The scale shows the color codes of z values (standard normal deviates) corresponding to the t statistics of the volume deficits for subjects with schizotypal personality disorder.

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Table Graphic Jump LocationTable 3. Areas of Reduced Regional Gray Matter Volume in Subjects With Schizotypal Personality Disorder Compared With Control Subjects
CORRELATIONS OF RELATIVE VOLUMES WITH CLINICAL SYMPTOMS

In subjects with SPD, more severe SIS symptoms were associated with larger lateral ventricle relative volumes but not with neocortical gray matter or sulcal CSF relative volumes (Figure 6). Specifically, we found that schizotypal social anxiety scores (n = 15; ρ = 0.70; P = .003; effect size = 1.83), anger to slights scores (n = 15; ρ = 0.61; P = .02; effect size = 1.43), and restricted emotion scores (n = 15; ρ = 0.60; P = .02; effect size = 1.40) were significantly positively correlated with total relative volumes of the lateral ventricles. Because there were 9 SIS factors and Bonferroni correction would have meant that only the single P = .003 (which was below .0056 [.05/9]) for social anxiety would have been significant, correlation analyses with the SPQ-B were performed to determine whether the association between more severe symptoms and larger lateral ventricles could also be found in this different schizotypal symptom scale (Figure 6). On the SPQ-B, lateral ventricle volumes were significantly positively correlated with cognitive-perceptual factor scores (n = 21; ρ = 0.62; P = .003) and interpersonal factor scores (n = 21; ρ = 0.59; P = .005).

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Figure 6.

Positive correlations between lateral ventricle relative volumes and symptom scores on the Structured Interview for Schizotypy (SIS) (A, B, and C) and on the Schizotypal Personality Questionnaire–Brief Version (SPQ-B) (D and E). The Spearman ρ was used because of the smaller sample size and nonnormality of ventricles. Least squares lines were added for ease of interpretation.

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There are 4 major findings in this study. First, left and right neocortical gray matter relative volumes in neuroleptic-naive women with SPD were significantly smaller than those in demographically matched controls by 3.84% and 3.83%, respectively, but no difference was found in white matter volumes in subjects with SPD compared with controls. Second, left and right sulcal CSF relative volumes surrounding the neocortex in women with SPD were significantly larger than those in controls by 9.66% and 9.61%, respectively. In addition, the larger sulcal CSF relative volumes were associated with smaller neocortical gray matter relative volumes in this sample of women with SPD but not in controls. Third, VBM analyses showed that the neocortical deficits in SPD were most prominent in the left superior and middle temporal gyri, left inferior parietal region with postcentral gyrus, and right superior frontal and inferior parietal gyri. Fourth, although we found no group difference in lateral ventricle volume, we did find that larger lateral ventricle relative volumes correlated with more severe symptoms (social anxiety, anger to slights, and restricted emotion scores on the SIS and interpersonal and cognitive-perceptual scores on the SPQ-B) in women with SPD.

These findings are especially noteworthy because, to our knowledge, this is the first study to report statistically significantly smaller neocortical gray matter volume in association with larger sulcal CSF relative volume in a neuroleptic-naive group of women with SPD. These results are highly consistent with previous findings39 in a smaller sample of 16 men with SPD compared with 14 male controls of larger CSF volumes, not attributable to enlarged lateral ventricle volumes, together with trend level smaller total cortical gray matter volumes. This study used a similar, although not identical, exclusion of subcortical structures and found that SPD cortical gray matter volumes were 7.1% smaller (trend level significance, P = .07; effect size = 0.78) and CSF volumes not attributable to the lateral ventricle were larger (P = .01; effect size = 0.54).39 The present data for women with SPD (Table 2) show similar effect sizes for neocortical gray matter (effect size = 0.62 on the left and 0.66 on the right) and sulcal CSF volume (effect size = 0.66 on the left and 0.73 on the right). It is likely that the present statistically significant results in neocortical gray matter are due to the larger sample size (30 women with SPD and 29 female controls). The slightly larger effect size and greater percentage reduction in neocortical gray matter volumes in men vs women with SPD may reflect sex differences.

We think it is likely that the larger sulcal CSF volume reported herein was due to the smaller volume of underlying gray matter, as evinced by their significant correlation. Also note that the lateral ventricle volume difference measured herein (0.48 mL on the left and 0.27 mL on the right) was too small to account for the difference in cortical gray matter volume (15 mL on the left and 14.9 mL on the right).

Findings of smaller total neocortical gray matter volume in women with SPD in the present study and previous findings in men with SPD together suggest that cortical brain abnormalities in SPD are widespread but are greater in some regions than others. For example, in women with SPD, our laboratory found a 21% smaller Heschl gyrus volume,8 a much larger difference than the 3.8% smaller neocortical gray matter volume reported herein. In addition, in men with SPD, our laboratory reported 9% reductions in left superior temporal gray matter volumes.6 The left temporal neocortical deficits are consistent with a previous study of subjects with SPD10 and our study of first-episode schizophrenia59 and hence are consistent with a model of temporal neocortical abnormalities across the schizophrenia spectrum. The frontal region, on the other hand, was reported to be preserved in SPD.60 With respect to this discrepancy, we echo the previous conclusion61 that SPM findings need to be confirmed with specific ROI analysis and note that the right superior frontal gyrus deficit and bilateral inferior parietal regions have not yet been examined using ROI analysis in SPD.

These findings of smaller neocortical gray matter volume and larger CSF volume in subjects with SPD are similar to those of neuroimaging studies of patients with schizophrenia2024,62 and their nonpsychotic siblings20,30 and support the hypothesis of a shared genetic diathesis between SPD and schizophrenia.63 The present SPD findings in neuroleptic-naive individuals seem particularly important for understanding the underlying brain morphologic features in schizophrenia spectrum disorders, given the potential confounding effects of neuroleptic medications on ROI volumes.37

A variety of possible causes for the deficits in gray matter volume have been reported, with deficits in neural development appearing especially important.5 In general, MRI abnormalities in SPD seem less severe than those in schizophrenia,4,5 including cavum septi pellucidum abnormalities, which are developmental in origin.64 As a measure of relative severity, it will be important to evaluate patients with schizophrenia using the same global ROI measures as in this study, particularly given that preliminary neocortical gray matter data from this group suggest a 5.6% control-schizophrenia difference compared with the 3.8% control-SPD difference.65 A growing number of studies in schizophrenia indicate significant postonset progression of MRI gray matter volume loss that parallels worsening symptoms and functional measures.66,67 In contrast, this progression of severity seems to be absent clinically in SPD,3 and there is no evidence of progression of MRI abnormalities in SPD, although there has been no systematic longitudinal study.4,5

Approximately 75% of neuroimaging studies assessing ventricular volumes have reported enlarged lateral ventricles in patients with schizophrenia.68 Because lateral ventricular enlargement may indicate tissue loss in surrounding brain regions,69 these findings have generated great interest. The present study showed no significant difference in lateral ventricle volumes between subjects with SPD and controls, which is consistent with other findings in the literature for subjects with SPD.39,70,71

The present results, however, showed that specific psychopathologic symptoms in SPD, as measured with the SIS and SPQ-B, were not associated with measures of gray matter volumes but were associated with lateral ventricle volumes. Two domains, although controversial,63 have been suggested for the characterization of SPD symptoms, and both were correlated with ventricular volumes in the present study: the cognitive-perceptual72 (or positive63) domain and the social-interpersonal72 (or negative49) domain. However, not all laboratories have found such correlations. For example, Siever et al,70 in a computed tomography study, reported that in subjects with SPD, there were no significant correlations between clinical symptoms and ventricle volumes. There were, however, methodological differences between that study and the present study. Siever et al70 included clinic-based men who were not neuroleptic naive. In the schizophrenia literature, ventricular volumes have been found to correlate with the severity of symptoms. For example, Shenton et al68 reported that thought disorder correlated with left to right ventricle-brain ratio. In a recent longitudinal study, Lieberman et al36 found that a greater improvement in negative symptoms was correlated with a lower increase in lateral ventricle volumes.

We believe that a strength of the present study is that it represents, to our knowledge, the largest study of women with SPD evaluating total gray matter volume and total sulcal CSF volume. Furthermore, possible confounding variables, including neuroleptic treatment,3437 age,31,32 sex,31,33,73 handedness,33 and other demographic factors (eg, parental socioeconomic status), that could affect the size of the gray matter or other compartments in the brain were carefully controlled. We believe that a second positive attribute is the use of a new and sensitive expectation maximization segmentation method44,45 to evaluate the neocortex more accurately. The increased sensitivity and accuracy of this new segmentation method, together with the larger sample size, provided enough statistical power to show the association between smaller gray matter volumes and larger sulcal CSF volumes in women with SPD. However, there were several potential limitations. First, as in almost all SPD studies,3,7476 there was diagnostic comorbidity, especially with depression and with paranoid and borderline personality disorders, each of which might affect the results. Although we did not find that the subgroup with comorbid depression had different volumetric values than the nondepressed subjects with SPD, other comorbid disorders might have contributed to the results. Because alcohol consumption may be a potential confounder of MRI brain measures,77,78 even if subjects do not receive a diagnosis of alcohol dependence or abuse, we note that our clinical study of a larger female SPD cohort found no more alcohol use in SPD than the low level in controls.3

In conclusion, the findings of smaller neocortical gray matter volume and larger sulcal CSF volume in women with SPD were congruent with previous findings in men with SPD and add to a growing number of studies reporting the existence of MRI brain abnormalities in SPD. Furthermore, because similar findings have also been reported in patients with schizophrenia and their unaffected siblings, we believe that the present findings support the hypothesis that SPD is in the schizophrenia spectrum and shares a genetic diathesis with schizophrenia that is expressed in similar brain abnormalities.

Correspondence: Robert W. McCarley, MD, Department of Psychiatry, 116A, Veterans Affairs Boston Healthcare System, Brockton Division, Harvard Medical School, 940 Belmont St, Brockton, MA 02301 (robert_mccarley@hms.harvard.edu).

Submitted for Publication: September 7, 2005; final revision received January 19, 2006; accepted February 16, 2006.

Author Contributions: Dr McCarley takes responsibility for the integrity of the data and the accuracy of the data analysis.

Funding/Support: This study was supported by Merit Awards from the Department of Veterans Affairs (Drs Shenton and McCarley); a Research Enhancement Award Program (Drs Shenton and McCarley); a Middleton Award (Dr McCarley); a VA Advanced Career Development Award (Dr Dickey); a Stanley Summer Fellowship (Dr Ji); and grants K05 MH 070047 and R01 MH 50740 (Dr Shenton) and R01 MH 40799 and R01 MH 052807 (Dr McCarley) from the National Institute of Mental Health.

Previous Presentation: This study was presented in part at the International Congress of Schizophrenia Research; April 6, 2005; Savannah, Ga.

Acknowledgment: We acknowledge the comments and suggestions of Noriomi Kuroki, MD, at Tokyo University; the technical support of Lida Ungar, BA, and Adam Cohen, BA; and the administrative support of Marie Fairbanks.

Siever  LJSilverman  JMHorvath  TBKlar  HCoccaro  EKeefe  RSPinkham  LRinaldi  PMohs  RCDavis  KL Increased morbid risk for schizophrenia-related disorders in relatives of schizotypal personality disordered patients. Arch Gen Psychiatry 1990;47634- 640
PubMed Link to Article
Kendler  KSMcGuire  MGruenberg  AMO'Hare  ASpellman  MWalsh  D The Roscommon Family Study, I: methods, diagnosis of probands, and risk of schizophrenia in relatives. Arch Gen Psychiatry 1993;50527- 540
PubMed Link to Article
Dickey  CCMcCarley  RWNiznikiewicz  MAVoglmaier  MMSeidman  LJKim  SShenton  ME Clinical, cognitive, and social characteristics of a sample of neuroleptic-naive persons with schizotypal personality disorder. Schizophr Res 2005;78297- 308
PubMed Link to Article
Siever  LJDavis  KL The pathophysiology of schizophrenia disorders: perspectives from the spectrum. Am J Psychiatry 2004;161398- 413
PubMed Link to Article
Dickey  CCMcCarley  RWShenton  ME The brain in schizotypal personality disorder: a review of structural MRI and CT findings. Harv Rev Psychiatry 2002;101- 15
PubMed Link to Article
Dickey  CCMcCarley  RWVoglmaier  MMNiznikiewicz  MASeidman  LJHirayasu  YFischer  ITeh  EKVan Rhoads  RJakab  MKikinis  RJolesz  FAShenton  ME Schizotypal personality disorder and MRI abnormalities of temporal lobe gray matter. Biol Psychiatry 1999;451393- 1402
PubMed Link to Article
Hirayasu  YShenton  MESalisbury  DFMcCarley  RW Hippocampal and superior temporal gyrus volume in first-episode schizophrenia. Arch Gen Psychiatry 2000;57618- 619
PubMed Link to Article
Dickey  CCMcCarley  RWVoglmaier  MMFrumin  MNiznikiewicz  MAHirayasu  YFraone  SSeidman  LJShenton  ME Smaller left Heschl's gyrus volume in patients with schizotypal personality disorder. Am J Psychiatry 2002;1591521- 1527
PubMed Link to Article
Dickey  CCMcCarley  RWVoglmaier  MMNiznikiewicz  MASeidman  LJDemeo  SFrumin  MShenton  ME An MRI study of superior temporal gyrus volume in women with schizotypal personality disorder. Am J Psychiatry 2003;1602198- 2201
PubMed Link to Article
Downhill  JE  JrBuchsbaum  MSHazlett  EABarth  SLees Roitman  SNunn  MLekarev  OWei  TShihabuddin  LMitropoulou  VSilverman  JSiever  LJ Temporal lobe volume determined by magnetic resonance imaging in schizotypal personality disorder and schizophrenia. Schizophr Res 2001;48187- 199
PubMed Link to Article
Shihabuddin  LBuchsbaum  MSHazlett  EASilverman  JNew  ABrickman  AMMitropoulou  VNunn  MFleischman  MBTang  CSiever  LJ Striatal size and relative glucose metabolic rate in schizotypal personality disorder and schizophrenia. Arch Gen Psychiatry 2001;58877- 884
PubMed Link to Article
Levitt  JJMcCarley  RWDickey  CCVoglmaier  MMNiznikiewicz  MASeidman  LJHirayasu  YCiszewski  AAKikinis  RJolesz  FAShenton  ME MRI study of caudate nucleus volume and its cognitive correlates in neuroleptic-naive patients with schizotypal personality disorder. Am J Psychiatry 2002;1591190- 1197
PubMed Link to Article
Byne  WBuchsbaum  MSKemether  EHazlett  EAShinwari  AMitropoulou  VSiever  LJ Magnetic resonance imaging of the thalamic mediodorsal nucleus and pulvinar in schizophrenia and schizotypal personality disorder. Arch Gen Psychiatry 2001;58133- 140
PubMed Link to Article
Shenton  MEDickey  CCFrumin  MMcCarley  RW A review of MRI findings in schizophrenia. Schizophr Res 2001;491- 52
PubMed Link to Article
Giuliani  NRCalhoun  VDPearlson  GDFrancis  ABuchanan  RW Voxel-basedmorphometry versus region of interest: a comparison of two methods for analyzing gray matter differences in schizophrenia. Schizophr Res 2005;74135- 147
PubMed Link to Article
Ho  BCAndreasen  NCNopoulos  PArndt  SMagnotta  VFlaum  M Progressive structural brain abnormalities and their relationship to clinical outcome: a longitudinal magnetic resonance imaging study early in schizophrenia. Arch Gen Psychiatry 2003;60585- 594
PubMed Link to Article
Hirayasu  YTanaka  SShenton  MESalisbury  DFDeSantis  MALevitt  JJWible  CYurgelun-Todd  DKikinis  RJolesz  FAMcCarley  RW Prefrontal gray matter volume reduction in first episode schizophrenia. Cereb Cortex 2001;11374- 381
PubMed Link to Article
Raine  ASheard  CReynolds  GPLencz  T Pre-frontal structural and functional deficits associated with individual differences in schizotypal personality. Schizophr Res 1992;7237- 247
PubMed Link to Article
Dickey  CCMcCarley  RWVoglmaier  MMNiznikiewicz  MASeidman  LJFrumin  MToner  SDemeo  SShenton  MEA MRI study of fusiform gyrus in schizotypal personality disorder. Schizophr Res 2003;6435- 39
PubMed Link to Article
Cannon  TDvan Erp  TGHuttunen  MLonnqvist  JSalonen  OValanne  LPoutanen  VPStandertskjold-Nordenstam  CGGur  REYan  M Regional gray matter, white matter, and cerebrospinal fluid distributions in schizophrenic patients, their siblings, and controls. Arch Gen Psychiatry 1998;551084- 1091
PubMed Link to Article
Zipursky  RBLambe  EKKapur  SMikulis  DJ Cerebral gray matter volume deficits in first episode psychosis. Arch Gen Psychiatry 1998;55540- 546
PubMed Link to Article
Lim  KORosenbloom  MJFaustman  WOSullivan  EVPfefferbaum  A Cortical gray matter deficit in patients with bipolar disorder. Schizophr Res 1999;40219- 227
PubMed Link to Article
Ananth  HPopescu  ICritchley  HDGood  CDFrackowiak  RSDolan  RJ Cortical and subcortical gray matter abnormalities in schizophrenia determined through structural magnetic resonance imaging with optimized volumetric voxel-based morphometry. Am J Psychiatry 2002;1591497- 1505
PubMed Link to Article
Hulshoff Pol  HESchnack  HGBertens  MGvan Haren  NEvan der Tweel  IStaal  WGBaare  WFKahn  RS Volume changes in gray matter in patients with schizophrenia. Am J Psychiatry 2002;159244- 250
PubMed Link to Article
Highley  JRWalker  MAEsiri  MMMcDonald  BHarrison  PJCrow  TJ Schizophrenia and the frontal lobes: post-mortem stereological study of tissue volume. Br J Psychiatry 2001;178337- 343
PubMed Link to Article
Narr  KLSharma  TWoods  RPThompson  PMSowell  ERRex  DKim  SAsuncion  DJang  SMazziotta  JToga  AW Increases in regional subarachnoid CSF without apparent cortical gray matter deficits in schizophrenia: modulating effects of sex and age. Am J Psychiatry 2003;1602169- 2180
PubMed Link to Article
Schlaepfer  TEHarris  GJTien  AYPeng  LWLee  SFederman  EBChase  GABarta  PEPearlson  GD Decreased regional cortical gray matter volume in schizophrenia. Am J Psychiatry 1994;151842- 848
PubMed
Cannon  TDMednick  SAParnas  JSchulsinger  FPraestholm  JVestergaard  A Developmental brain abnormalities in the offspring of schizophrenic mothers, II: structural brain characteristics of schizophrenia and schizotypal personality disorder. Arch Gen Psychiatry 1994;51955- 962
PubMed Link to Article
Weinberger  DRDeLisi  LENeophytides  ANWyatt  RJ Familial aspects of CT scan abnormalities in chronic schizophrenic patients. Psychiatry Res 1981;465- 71
PubMed Link to Article
Silverman  JMSmith  CJGuo  SLMohs  RCSiever  LJDavis  KL Lateral ventricular enlargement in schizophrenic probands and their siblings with schizophrenia-related disorders. Biol Psychiatry 1998;4397- 106
PubMed Link to Article
Good  CDJohnsrude  IAshburner  JHenson  RNFriston  KJFrackowiak  RS Cerebral asymmetry and the effects of sex and handedness on brain structure: a voxel-based morphometric analysis of 465 normal adult human brains. Neuroimage 2001;14685- 700
PubMed Link to Article
Coffey  CELucke  JFSaxton  JARatcliff  GUnitas  LJBillig  BBryan  RN Sex differences in brain aging: a quantitative magnetic resonance imaging study. Arch Neurol 1998;55169- 179
PubMed Link to Article
Wisniewski  AB Sexually-dimorphic patterns of cortical asymmetry, and the role for sex steroid hormones in determining cortical patterns of lateralization. Psychoneuroendocrinology 1998;23519- 547
PubMed Link to Article
Madsen  ALKeidling  NKarle  AEsbjerg  SHemmingsen  R Neuroleptics in progressive structural brain abnormalities in psychiatric illness. Lancet 1998;352784- 785
PubMed Link to Article
Gur  RECowell  PTuretsky  BIGallacher  FCannon  TBilker  WGur  RC A follow-up magnetic resonance imaging study of schizophrenia: relationship of neuroanatomical changes to clinical and neurobehavioral measures. Arch Gen Psychiatry 1998;55145- 152
PubMed Link to Article
Lieberman  JATollefson  GDCharles  CZipursky  RSharma  TKahn  RSKeefe  RSGreen  AIGur  REMcEvoy  JPerkins  DHamer  RMGu  HTohen  M Antipsychotic drug effects on brain morphology in first-episode psychosis. Arch Gen Psychiatry 2005;62361- 370
PubMed Link to Article
Dazzan  PMorgan  KDOrr  KHutchinson  GChitnis  XSuckling  JFearon  PMcGuire  PKMallett  RMJones  PBLeff  JMurray  RM Different effects of typical and atypical antipsychotics on grey matter in first episode psychosis: the AESOP study. Neuropsychopharmacology 2005;30765- 774
PubMed
Kemp  JKNopoulos  BCHo  BCAndreasen  NC Longitudinal assessment of the effects of neuroleptic medications on the superior temporal plane structures in subjects with schizophrenia [abstract]. Schizophr Bull 2005;31394
Dickey  CCShenton  MEHirayasu  YFischer  IVoglmaier  MMNiznikiewicz  MASeidman  LJFraone  SMcCarley  RW Large CSF volume not attributable to ventricular volume in schizotypal personality disorder. Am J Psychiatry 2000;15748- 54
PubMed
Goldstein  JMSeidman  LJHorton  NJMakris  NKennedy  DNCaviness  VS  JrFaraone  SVTsuang  MT Normal sexual dimorphism of the adult human brain assessed by in vivo magnetic resonance imaging. Cereb Cortex 2001;11490- 497
PubMed Link to Article
Goldstein  JMLevine  RRJ Overview of sex differences in schizophrenia: where have we been and where do we go from here? In:Castle  DJMcGrath  JJKulkarni  Jeds.Women and Schizophrenia. Cambridge, Mass Cambridge University Press2000;111- 153
Goldstein  JM Sex and brain abnormalities in schizophrenia: fact or fiction? Harv Rev Psychiatry 1996;4110- 115
PubMed Link to Article
Goldstein  JMSeidman  LJGoodman  JMKoren  DLee  HWeintraub  STsuang  MT Are there sex differences in neuropsychological functions among patients with schizophrenia? Am J Psychiatry 1998;1551358- 1364
PubMed
Bouix  SUngar  LDickey  CCMcCarley  RWShenton  ME Evaluating automatic brain tissue classifiers. In: Proceedings of the Seventh International Conference on Medical Image Computing and Computer Assisted Intervention, Saint Malo, France, September 26-29, 2004  Berlin, Germany Springer2004;1038- 1039
Pohl  KBouix  SKikinis  RGrimson  WE Anatomical guided segmentation with non-stationary tissue class distributions in an expectation-maximization framework. In: Proceedings of the 2004 IEEE International Symposium on Biomedical Imaging From Nano to Macro, Arlington, Va,15- 18 April 2004 New York, NY IEEE2004;81- 84
Zipursky  RBSeeman  MVBury  ALangevin  RWortzman  GKatz  R Deficits in gray matter volume are present in schizophrenia but not bipolar disorder. Schizophr Res 1997;2685- 92
PubMed Link to Article
First  MBSpitzer  RLGibbon  MWilliams  JBW Structured Clinical Interview for DSM-IV Axis I Disorders—Patient Edition (SCID-I/P), Version 2.0.  New York New York State Psychiatric Institute, Biomedical Research Dept1995;
First  MBGibbon  MSpitzer  RLWilliams  JBBenjamin  L Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II): Interview and Questionnaire.  Washington, DC American Psychiatric Press1997;
Kendler  KSOchs  ALGorman  AMHewitt  JKRoss  DEMirsky  AF The structure of schizotypy: a pilot multitrait twin study. Psychiatry Res 1991;3619- 36
PubMed Link to Article
Kendler  KSLieberman  JAWalsh  D The Structured Interview for Schizotypy (SIS): a preliminary report. Schizophr Bull 1989;15559- 571
PubMed Link to Article
Raine  ABenishay  DLencz  TScarpa  A Abnormal orienting in schizotypal personality disorder. Schizophr Bull 1997;2375- 82
PubMed Link to Article
Wells  WM  IIIViola  PAtsumi  HNakajima  SKikinis  R Multi-modal volume registration by maximization of mutual information. Med Image Anal 1996;135- 51
PubMed Link to Article
Guimond  ARoche  AAyache  NMeunier  J Three-dimensional multimodal brain warping using the demons algorithm and adaptive intensity corrections. IEEE Trans Med Imaging 2001;2058- 69
PubMed Link to Article
Pieper  SHalle  MKikinis  R 3D slicer. In: Proceedings of the 2004 IEEE International Symposium on Biomedical Imaging From Nano to Macro, Arlington, Va,15- 18 April 2004 New York, NY IEEE2004;632- 635
Shenton  MEGerig  GMcCarley  RWSzekely  GKikinis  R Amygdala-hippocampal shape differences in schizophrenia: the application of 3D shape models to volumetric MR data. Psychiatry Res 2002;11515- 35
PubMed Link to Article
Mesulam  MM Principles of Behavioral and Cognitive Neurology.  New York, NY Oxford University Press2000;
Ashburner  JFriston  KJ Voxel-based morphometry: the methods. Neuroimage 2000;11805- 821
PubMed Link to Article
Good  CDJohnsrude  ISAshburner  JHenson  RNFriston  KJFrackowiak  RS A voxel-based morphometric study of ageing in 465 normal adult human brains. Neuroimage 2001;1421- 36
PubMed Link to Article
Kuroki  NShenton  MESalisbury  DFHirayasu  YOnitsuka  TErsner-Hershfield  HYurgelun-Todd  DKikinis  RJolesz  FAMcCarley  RW Middle and inferior temporal gyrus gray matter volume in first-episode schizophrenia: an MRI study. Am J Psychiatry In press
Buchsbaum  MSNenadic  IHazlett  EASpiegel-Cohen  JFleischman  MBAkhavan  ASilverman  JMSiever  LJ Differential metabolic rates in prefrontal and temporal Brodmann areas in schizophrenia and schizotypal personality disorder. Schizophr Res 2002;54141- 150
PubMed Link to Article
Kubicki  MShenton  MESalisbury  DFHirayasu  YKasai  KKikinis  RJolesz  FAMcCarley  RW Voxel-based morphometric analysis of gray matter in first episode schizophrenia. Neuroimage 2002;171711- 1719
PubMed Link to Article
Fannon  DChitnis  XDoku  VTennakoon  LO'Ceallaigh  SSoni  WSumich  ALowe  JSantamaria  MSharma  T Features of structural brain abnormality detected in first-episode psychosis. Am J Psychiatry 2000;1571829- 1834
PubMed Link to Article
Kendler  KSMcGuire  MGruenberg  AMWalsh  D Schizotypal symptoms and signs in the Roscommon Family Study: their factor structure and familial relationship with psychotic and affective disorders. Arch Gen Psychiatry 1995;52296- 303
PubMed Link to Article
Kwon  JSShenton  MEHirayasu  YSalisbury  DFFischer  IADickey  CCYurgelun-Todd  DTohen  MKikinis  RJolesz  FAMcCarley  RW MRI study of cavum septi pellucidi in schizophrenia, affective disorder, and schizotypal personality disorder. Am J Psychiatry 1998;155509- 515
PubMed
Nakamura  MHirayasu  YSalisbury  DFBouix  SPohl  KYoshida  TKoo  MShenton  MEMcCarley  RW Smaller neocortical gray matter volume in both first episode schizophrenia and first episode affective psychosis, determined by a new segmentation algorithm [abstract]. Biol Psychiatry 2005;5729S- 30S
Kasai  KShenton  MESalisbury  DFHirayasu  YOnitsuka  TSpencer  MHYurgelun-Todd  DAKikinis  RJolesz  FAMcCarley  RW Progressive decrease of left Heschl gyrus and planum temporale gray matter volume in first-episode schizophrenia: a longitudinal magnetic resonance imaging study. Arch Gen Psychiatry 2003;60766- 775
PubMed Link to Article
Salisbury  DFMcCarley  RW Electrophysiology of schizophrenia. In:Hirsch  SRWeinberger  DReds.Schizophrenia. 2nd Oxford, England Blackwell Science Ltd2003;298- 309
Shenton  MEKikinis  RMcCarley  RWMetcalf  DTieman  JJolesz  FA Application of automated MRI volumetric measurement techniques to the ventricular system in schizophrenics and normal controls. Schizophr Res 1991;5103- 113
PubMed Link to Article
Gaser  CNenadic  IBuchsbaum  BRHazlett  EABuchsbaum  MS Ventricular enlargement in schizophrenia related to volume reduction of the thalamus, striatum, and superior temporal cortex. Am J Psychiatry 2004;161154- 156
PubMed Link to Article
Siever  LJRotter  MLosonczy  MGuo  SLMitropoulou  VTrestman  RApter  SZemishlany  ZSilverman  JHorvath  TB Lateral ventricular enlargement in schizotypal personality disorder. Psychiatry Res 1995;57109- 118
PubMed Link to Article
Buchsbaum  MSYang  SHazlett  ESiegel  BV  JrGermans  MHaznedar  MO'Flaithbheartaigh  SWei  TSilverman  JSiever  LJ Ventricular volume and asymmetry in schizotypal personality disorder and schizophrenia assessed with magnetic resonance imaging. Schizophr Res 1997;2745- 53
PubMed Link to Article
Siever  LJGunderson  JG The search for a schizotypal personality: historical origins and current status. Compr Psychiatry 1983;24199- 212
PubMed Link to Article
Cahn  WPol  HELems  EBvan Haren  NESchnack  HGvan der Linden  JASchothorst  PFvan Engeland  HKahn  RS Brain volume changes in first-episode schizophrenia: a 1-year follow-up study. Arch Gen Psychiatry 2002;591002- 1010
PubMed Link to Article
Cadenhead  KSPerry  WShafer  KBraff  DL Cognitive functions in schizotypal personality disorder. Schizophr Res 1999;37123- 132
PubMed Link to Article
Mikhailova  ESVladimirova  TVIznak  AFTsusulkovskaya  EJSushko  NV Abnormal recognition of facial expression of emotions in depressed patients with major depression disorder and schizotypal personality disorder. Biol Psychiatry 1996;40697- 705
PubMed Link to Article
Mitropoulou  VHarvey  PDMaldari  LAMoriarty  PJNew  ASSilverman  JMSiever  LJ Neuropsychological performance in schizotypal personality disorder: evidence regarding diagnostic specificity. Biol Psychiatry 2002;521175- 1182
PubMed Link to Article
Sullivan  EVDeshmukh  ADe Rosa  ERosenbloom  MJPfefferbaum  A Striatal and forebrain nuclei volumes: contribution to motor function and working memory deficits in alcoholism. Biol Psychiatry 2005;57768- 776
PubMed Link to Article
Deshmukh  ARosenbloom  MJDe Rosa  ESullivan  EVPfefferbaum  A Regional striatal volume abnormalities in schizophrenia: effects of comorbidity for alcoholism, recency of alcoholic drinking, and antipsychotic medication type. Schizophr Res 2005;79189- 200
PubMed Link to Article

Figures

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Figure 1.

Spoiled gradient recalled images. A, Gray scale image of a woman with schizotypal personality disorder. B, The same image with automatically segmented tissue types overlaid. Cerebrospinal fluid is color coded as turquoise, gray matter as red-brown, and white matter as pink. C, The same image with the neocortex and ventricle extracted by manual exclusion of nonneocortical structures from the automatically segmented image. Cerebrospinal fluid is color coded as green, gray matter as brown, and white matter as yellow on the right; color codes on the left are as in part B. The lateral ventricle is color coded as dark blue on the right and as dark green on the left. The region of interest definition illustrated in part C was used for the statistical analysis.

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Figure 2.

Neocortical gray matter relative volumes for women with schizotypal personality disorder (SPD) and female control subjects. Horizontal lines indicate means, and t values are from t test comparing groups.

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Figure 3.

Sulcal cerebrospinal fluid (CSF) (A) and lateral ventricle (B) relative volumes for women with schizotypal personality disorder (SPD) and female control subjects. Horizontal lines indicate means, and t (or U) values are from the t (or Mann-Whitney) test comparing groups.

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Figure 4.

Inverse correlation between relative volumes of neocortical gray matter and surrounding sulcal cerebrospinal fluid (CSF) in women with schizotypal personality disorder. r = Pearson correlation coefficient. The least squares line was added for ease of interpretation.

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Figure 5.

Regions of reduced regional gray matter volume in subjects with schizotypal personality disorder compared with control subjects analyzed using optimized voxel-based morphometry. The left superior and middle temporal gyri, the tempoparietal region, and the right superior frontal gyrus with the inferior parietal region showed deficits in subjects with schizotypal personality disorder (see Table 3 for specific coordinates). The scale shows the color codes of z values (standard normal deviates) corresponding to the t statistics of the volume deficits for subjects with schizotypal personality disorder.

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Figure 6.

Positive correlations between lateral ventricle relative volumes and symptom scores on the Structured Interview for Schizotypy (SIS) (A, B, and C) and on the Schizotypal Personality Questionnaire–Brief Version (SPQ-B) (D and E). The Spearman ρ was used because of the smaller sample size and nonnormality of ventricles. Least squares lines were added for ease of interpretation.

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Tables

Table Graphic Jump LocationTable 1. Demographic Characteristics of the 59 Study Participants*
Table Graphic Jump LocationTable 2. Volumes of Neocortical Gray Matter, White Matter, and Cerebrospinal Fluid
Table Graphic Jump LocationTable 3. Areas of Reduced Regional Gray Matter Volume in Subjects With Schizotypal Personality Disorder Compared With Control Subjects

References

Siever  LJSilverman  JMHorvath  TBKlar  HCoccaro  EKeefe  RSPinkham  LRinaldi  PMohs  RCDavis  KL Increased morbid risk for schizophrenia-related disorders in relatives of schizotypal personality disordered patients. Arch Gen Psychiatry 1990;47634- 640
PubMed Link to Article
Kendler  KSMcGuire  MGruenberg  AMO'Hare  ASpellman  MWalsh  D The Roscommon Family Study, I: methods, diagnosis of probands, and risk of schizophrenia in relatives. Arch Gen Psychiatry 1993;50527- 540
PubMed Link to Article
Dickey  CCMcCarley  RWNiznikiewicz  MAVoglmaier  MMSeidman  LJKim  SShenton  ME Clinical, cognitive, and social characteristics of a sample of neuroleptic-naive persons with schizotypal personality disorder. Schizophr Res 2005;78297- 308
PubMed Link to Article
Siever  LJDavis  KL The pathophysiology of schizophrenia disorders: perspectives from the spectrum. Am J Psychiatry 2004;161398- 413
PubMed Link to Article
Dickey  CCMcCarley  RWShenton  ME The brain in schizotypal personality disorder: a review of structural MRI and CT findings. Harv Rev Psychiatry 2002;101- 15
PubMed Link to Article
Dickey  CCMcCarley  RWVoglmaier  MMNiznikiewicz  MASeidman  LJHirayasu  YFischer  ITeh  EKVan Rhoads  RJakab  MKikinis  RJolesz  FAShenton  ME Schizotypal personality disorder and MRI abnormalities of temporal lobe gray matter. Biol Psychiatry 1999;451393- 1402
PubMed Link to Article
Hirayasu  YShenton  MESalisbury  DFMcCarley  RW Hippocampal and superior temporal gyrus volume in first-episode schizophrenia. Arch Gen Psychiatry 2000;57618- 619
PubMed Link to Article
Dickey  CCMcCarley  RWVoglmaier  MMFrumin  MNiznikiewicz  MAHirayasu  YFraone  SSeidman  LJShenton  ME Smaller left Heschl's gyrus volume in patients with schizotypal personality disorder. Am J Psychiatry 2002;1591521- 1527
PubMed Link to Article
Dickey  CCMcCarley  RWVoglmaier  MMNiznikiewicz  MASeidman  LJDemeo  SFrumin  MShenton  ME An MRI study of superior temporal gyrus volume in women with schizotypal personality disorder. Am J Psychiatry 2003;1602198- 2201
PubMed Link to Article
Downhill  JE  JrBuchsbaum  MSHazlett  EABarth  SLees Roitman  SNunn  MLekarev  OWei  TShihabuddin  LMitropoulou  VSilverman  JSiever  LJ Temporal lobe volume determined by magnetic resonance imaging in schizotypal personality disorder and schizophrenia. Schizophr Res 2001;48187- 199
PubMed Link to Article
Shihabuddin  LBuchsbaum  MSHazlett  EASilverman  JNew  ABrickman  AMMitropoulou  VNunn  MFleischman  MBTang  CSiever  LJ Striatal size and relative glucose metabolic rate in schizotypal personality disorder and schizophrenia. Arch Gen Psychiatry 2001;58877- 884
PubMed Link to Article
Levitt  JJMcCarley  RWDickey  CCVoglmaier  MMNiznikiewicz  MASeidman  LJHirayasu  YCiszewski  AAKikinis  RJolesz  FAShenton  ME MRI study of caudate nucleus volume and its cognitive correlates in neuroleptic-naive patients with schizotypal personality disorder. Am J Psychiatry 2002;1591190- 1197
PubMed Link to Article
Byne  WBuchsbaum  MSKemether  EHazlett  EAShinwari  AMitropoulou  VSiever  LJ Magnetic resonance imaging of the thalamic mediodorsal nucleus and pulvinar in schizophrenia and schizotypal personality disorder. Arch Gen Psychiatry 2001;58133- 140
PubMed Link to Article
Shenton  MEDickey  CCFrumin  MMcCarley  RW A review of MRI findings in schizophrenia. Schizophr Res 2001;491- 52
PubMed Link to Article
Giuliani  NRCalhoun  VDPearlson  GDFrancis  ABuchanan  RW Voxel-basedmorphometry versus region of interest: a comparison of two methods for analyzing gray matter differences in schizophrenia. Schizophr Res 2005;74135- 147
PubMed Link to Article
Ho  BCAndreasen  NCNopoulos  PArndt  SMagnotta  VFlaum  M Progressive structural brain abnormalities and their relationship to clinical outcome: a longitudinal magnetic resonance imaging study early in schizophrenia. Arch Gen Psychiatry 2003;60585- 594
PubMed Link to Article
Hirayasu  YTanaka  SShenton  MESalisbury  DFDeSantis  MALevitt  JJWible  CYurgelun-Todd  DKikinis  RJolesz  FAMcCarley  RW Prefrontal gray matter volume reduction in first episode schizophrenia. Cereb Cortex 2001;11374- 381
PubMed Link to Article
Raine  ASheard  CReynolds  GPLencz  T Pre-frontal structural and functional deficits associated with individual differences in schizotypal personality. Schizophr Res 1992;7237- 247
PubMed Link to Article
Dickey  CCMcCarley  RWVoglmaier  MMNiznikiewicz  MASeidman  LJFrumin  MToner  SDemeo  SShenton  MEA MRI study of fusiform gyrus in schizotypal personality disorder. Schizophr Res 2003;6435- 39
PubMed Link to Article
Cannon  TDvan Erp  TGHuttunen  MLonnqvist  JSalonen  OValanne  LPoutanen  VPStandertskjold-Nordenstam  CGGur  REYan  M Regional gray matter, white matter, and cerebrospinal fluid distributions in schizophrenic patients, their siblings, and controls. Arch Gen Psychiatry 1998;551084- 1091
PubMed Link to Article
Zipursky  RBLambe  EKKapur  SMikulis  DJ Cerebral gray matter volume deficits in first episode psychosis. Arch Gen Psychiatry 1998;55540- 546
PubMed Link to Article
Lim  KORosenbloom  MJFaustman  WOSullivan  EVPfefferbaum  A Cortical gray matter deficit in patients with bipolar disorder. Schizophr Res 1999;40219- 227
PubMed Link to Article
Ananth  HPopescu  ICritchley  HDGood  CDFrackowiak  RSDolan  RJ Cortical and subcortical gray matter abnormalities in schizophrenia determined through structural magnetic resonance imaging with optimized volumetric voxel-based morphometry. Am J Psychiatry 2002;1591497- 1505
PubMed Link to Article
Hulshoff Pol  HESchnack  HGBertens  MGvan Haren  NEvan der Tweel  IStaal  WGBaare  WFKahn  RS Volume changes in gray matter in patients with schizophrenia. Am J Psychiatry 2002;159244- 250
PubMed Link to Article
Highley  JRWalker  MAEsiri  MMMcDonald  BHarrison  PJCrow  TJ Schizophrenia and the frontal lobes: post-mortem stereological study of tissue volume. Br J Psychiatry 2001;178337- 343
PubMed Link to Article
Narr  KLSharma  TWoods  RPThompson  PMSowell  ERRex  DKim  SAsuncion  DJang  SMazziotta  JToga  AW Increases in regional subarachnoid CSF without apparent cortical gray matter deficits in schizophrenia: modulating effects of sex and age. Am J Psychiatry 2003;1602169- 2180
PubMed Link to Article
Schlaepfer  TEHarris  GJTien  AYPeng  LWLee  SFederman  EBChase  GABarta  PEPearlson  GD Decreased regional cortical gray matter volume in schizophrenia. Am J Psychiatry 1994;151842- 848
PubMed
Cannon  TDMednick  SAParnas  JSchulsinger  FPraestholm  JVestergaard  A Developmental brain abnormalities in the offspring of schizophrenic mothers, II: structural brain characteristics of schizophrenia and schizotypal personality disorder. Arch Gen Psychiatry 1994;51955- 962
PubMed Link to Article
Weinberger  DRDeLisi  LENeophytides  ANWyatt  RJ Familial aspects of CT scan abnormalities in chronic schizophrenic patients. Psychiatry Res 1981;465- 71
PubMed Link to Article
Silverman  JMSmith  CJGuo  SLMohs  RCSiever  LJDavis  KL Lateral ventricular enlargement in schizophrenic probands and their siblings with schizophrenia-related disorders. Biol Psychiatry 1998;4397- 106
PubMed Link to Article
Good  CDJohnsrude  IAshburner  JHenson  RNFriston  KJFrackowiak  RS Cerebral asymmetry and the effects of sex and handedness on brain structure: a voxel-based morphometric analysis of 465 normal adult human brains. Neuroimage 2001;14685- 700
PubMed Link to Article
Coffey  CELucke  JFSaxton  JARatcliff  GUnitas  LJBillig  BBryan  RN Sex differences in brain aging: a quantitative magnetic resonance imaging study. Arch Neurol 1998;55169- 179
PubMed Link to Article
Wisniewski  AB Sexually-dimorphic patterns of cortical asymmetry, and the role for sex steroid hormones in determining cortical patterns of lateralization. Psychoneuroendocrinology 1998;23519- 547
PubMed Link to Article
Madsen  ALKeidling  NKarle  AEsbjerg  SHemmingsen  R Neuroleptics in progressive structural brain abnormalities in psychiatric illness. Lancet 1998;352784- 785
PubMed Link to Article
Gur  RECowell  PTuretsky  BIGallacher  FCannon  TBilker  WGur  RC A follow-up magnetic resonance imaging study of schizophrenia: relationship of neuroanatomical changes to clinical and neurobehavioral measures. Arch Gen Psychiatry 1998;55145- 152
PubMed Link to Article
Lieberman  JATollefson  GDCharles  CZipursky  RSharma  TKahn  RSKeefe  RSGreen  AIGur  REMcEvoy  JPerkins  DHamer  RMGu  HTohen  M Antipsychotic drug effects on brain morphology in first-episode psychosis. Arch Gen Psychiatry 2005;62361- 370
PubMed Link to Article
Dazzan  PMorgan  KDOrr  KHutchinson  GChitnis  XSuckling  JFearon  PMcGuire  PKMallett  RMJones  PBLeff  JMurray  RM Different effects of typical and atypical antipsychotics on grey matter in first episode psychosis: the AESOP study. Neuropsychopharmacology 2005;30765- 774
PubMed
Kemp  JKNopoulos  BCHo  BCAndreasen  NC Longitudinal assessment of the effects of neuroleptic medications on the superior temporal plane structures in subjects with schizophrenia [abstract]. Schizophr Bull 2005;31394
Dickey  CCShenton  MEHirayasu  YFischer  IVoglmaier  MMNiznikiewicz  MASeidman  LJFraone  SMcCarley  RW Large CSF volume not attributable to ventricular volume in schizotypal personality disorder. Am J Psychiatry 2000;15748- 54
PubMed
Goldstein  JMSeidman  LJHorton  NJMakris  NKennedy  DNCaviness  VS  JrFaraone  SVTsuang  MT Normal sexual dimorphism of the adult human brain assessed by in vivo magnetic resonance imaging. Cereb Cortex 2001;11490- 497
PubMed Link to Article
Goldstein  JMLevine  RRJ Overview of sex differences in schizophrenia: where have we been and where do we go from here? In:Castle  DJMcGrath  JJKulkarni  Jeds.Women and Schizophrenia. Cambridge, Mass Cambridge University Press2000;111- 153
Goldstein  JM Sex and brain abnormalities in schizophrenia: fact or fiction? Harv Rev Psychiatry 1996;4110- 115
PubMed Link to Article
Goldstein  JMSeidman  LJGoodman  JMKoren  DLee  HWeintraub  STsuang  MT Are there sex differences in neuropsychological functions among patients with schizophrenia? Am J Psychiatry 1998;1551358- 1364
PubMed
Bouix  SUngar  LDickey  CCMcCarley  RWShenton  ME Evaluating automatic brain tissue classifiers. In: Proceedings of the Seventh International Conference on Medical Image Computing and Computer Assisted Intervention, Saint Malo, France, September 26-29, 2004  Berlin, Germany Springer2004;1038- 1039
Pohl  KBouix  SKikinis  RGrimson  WE Anatomical guided segmentation with non-stationary tissue class distributions in an expectation-maximization framework. In: Proceedings of the 2004 IEEE International Symposium on Biomedical Imaging From Nano to Macro, Arlington, Va,15- 18 April 2004 New York, NY IEEE2004;81- 84
Zipursky  RBSeeman  MVBury  ALangevin  RWortzman  GKatz  R Deficits in gray matter volume are present in schizophrenia but not bipolar disorder. Schizophr Res 1997;2685- 92
PubMed Link to Article
First  MBSpitzer  RLGibbon  MWilliams  JBW Structured Clinical Interview for DSM-IV Axis I Disorders—Patient Edition (SCID-I/P), Version 2.0.  New York New York State Psychiatric Institute, Biomedical Research Dept1995;
First  MBGibbon  MSpitzer  RLWilliams  JBBenjamin  L Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II): Interview and Questionnaire.  Washington, DC American Psychiatric Press1997;
Kendler  KSOchs  ALGorman  AMHewitt  JKRoss  DEMirsky  AF The structure of schizotypy: a pilot multitrait twin study. Psychiatry Res 1991;3619- 36
PubMed Link to Article
Kendler  KSLieberman  JAWalsh  D The Structured Interview for Schizotypy (SIS): a preliminary report. Schizophr Bull 1989;15559- 571
PubMed Link to Article
Raine  ABenishay  DLencz  TScarpa  A Abnormal orienting in schizotypal personality disorder. Schizophr Bull 1997;2375- 82
PubMed Link to Article
Wells  WM  IIIViola  PAtsumi  HNakajima  SKikinis  R Multi-modal volume registration by maximization of mutual information. Med Image Anal 1996;135- 51
PubMed Link to Article
Guimond  ARoche  AAyache  NMeunier  J Three-dimensional multimodal brain warping using the demons algorithm and adaptive intensity corrections. IEEE Trans Med Imaging 2001;2058- 69
PubMed Link to Article
Pieper  SHalle  MKikinis  R 3D slicer. In: Proceedings of the 2004 IEEE International Symposium on Biomedical Imaging From Nano to Macro, Arlington, Va,15- 18 April 2004 New York, NY IEEE2004;632- 635
Shenton  MEGerig  GMcCarley  RWSzekely  GKikinis  R Amygdala-hippocampal shape differences in schizophrenia: the application of 3D shape models to volumetric MR data. Psychiatry Res 2002;11515- 35
PubMed Link to Article
Mesulam  MM Principles of Behavioral and Cognitive Neurology.  New York, NY Oxford University Press2000;
Ashburner  JFriston  KJ Voxel-based morphometry: the methods. Neuroimage 2000;11805- 821
PubMed Link to Article
Good  CDJohnsrude  ISAshburner  JHenson  RNFriston  KJFrackowiak  RS A voxel-based morphometric study of ageing in 465 normal adult human brains. Neuroimage 2001;1421- 36
PubMed Link to Article
Kuroki  NShenton  MESalisbury  DFHirayasu  YOnitsuka  TErsner-Hershfield  HYurgelun-Todd  DKikinis  RJolesz  FAMcCarley  RW Middle and inferior temporal gyrus gray matter volume in first-episode schizophrenia: an MRI study. Am J Psychiatry In press
Buchsbaum  MSNenadic  IHazlett  EASpiegel-Cohen  JFleischman  MBAkhavan  ASilverman  JMSiever  LJ Differential metabolic rates in prefrontal and temporal Brodmann areas in schizophrenia and schizotypal personality disorder. Schizophr Res 2002;54141- 150
PubMed Link to Article
Kubicki  MShenton  MESalisbury  DFHirayasu  YKasai  KKikinis  RJolesz  FAMcCarley  RW Voxel-based morphometric analysis of gray matter in first episode schizophrenia. Neuroimage 2002;171711- 1719
PubMed Link to Article
Fannon  DChitnis  XDoku  VTennakoon  LO'Ceallaigh  SSoni  WSumich  ALowe  JSantamaria  MSharma  T Features of structural brain abnormality detected in first-episode psychosis. Am J Psychiatry 2000;1571829- 1834
PubMed Link to Article
Kendler  KSMcGuire  MGruenberg  AMWalsh  D Schizotypal symptoms and signs in the Roscommon Family Study: their factor structure and familial relationship with psychotic and affective disorders. Arch Gen Psychiatry 1995;52296- 303
PubMed Link to Article
Kwon  JSShenton  MEHirayasu  YSalisbury  DFFischer  IADickey  CCYurgelun-Todd  DTohen  MKikinis  RJolesz  FAMcCarley  RW MRI study of cavum septi pellucidi in schizophrenia, affective disorder, and schizotypal personality disorder. Am J Psychiatry 1998;155509- 515
PubMed
Nakamura  MHirayasu  YSalisbury  DFBouix  SPohl  KYoshida  TKoo  MShenton  MEMcCarley  RW Smaller neocortical gray matter volume in both first episode schizophrenia and first episode affective psychosis, determined by a new segmentation algorithm [abstract]. Biol Psychiatry 2005;5729S- 30S
Kasai  KShenton  MESalisbury  DFHirayasu  YOnitsuka  TSpencer  MHYurgelun-Todd  DAKikinis  RJolesz  FAMcCarley  RW Progressive decrease of left Heschl gyrus and planum temporale gray matter volume in first-episode schizophrenia: a longitudinal magnetic resonance imaging study. Arch Gen Psychiatry 2003;60766- 775
PubMed Link to Article
Salisbury  DFMcCarley  RW Electrophysiology of schizophrenia. In:Hirsch  SRWeinberger  DReds.Schizophrenia. 2nd Oxford, England Blackwell Science Ltd2003;298- 309
Shenton  MEKikinis  RMcCarley  RWMetcalf  DTieman  JJolesz  FA Application of automated MRI volumetric measurement techniques to the ventricular system in schizophrenics and normal controls. Schizophr Res 1991;5103- 113
PubMed Link to Article
Gaser  CNenadic  IBuchsbaum  BRHazlett  EABuchsbaum  MS Ventricular enlargement in schizophrenia related to volume reduction of the thalamus, striatum, and superior temporal cortex. Am J Psychiatry 2004;161154- 156
PubMed Link to Article
Siever  LJRotter  MLosonczy  MGuo  SLMitropoulou  VTrestman  RApter  SZemishlany  ZSilverman  JHorvath  TB Lateral ventricular enlargement in schizotypal personality disorder. Psychiatry Res 1995;57109- 118
PubMed Link to Article
Buchsbaum  MSYang  SHazlett  ESiegel  BV  JrGermans  MHaznedar  MO'Flaithbheartaigh  SWei  TSilverman  JSiever  LJ Ventricular volume and asymmetry in schizotypal personality disorder and schizophrenia assessed with magnetic resonance imaging. Schizophr Res 1997;2745- 53
PubMed Link to Article
Siever  LJGunderson  JG The search for a schizotypal personality: historical origins and current status. Compr Psychiatry 1983;24199- 212
PubMed Link to Article
Cahn  WPol  HELems  EBvan Haren  NESchnack  HGvan der Linden  JASchothorst  PFvan Engeland  HKahn  RS Brain volume changes in first-episode schizophrenia: a 1-year follow-up study. Arch Gen Psychiatry 2002;591002- 1010
PubMed Link to Article
Cadenhead  KSPerry  WShafer  KBraff  DL Cognitive functions in schizotypal personality disorder. Schizophr Res 1999;37123- 132
PubMed Link to Article
Mikhailova  ESVladimirova  TVIznak  AFTsusulkovskaya  EJSushko  NV Abnormal recognition of facial expression of emotions in depressed patients with major depression disorder and schizotypal personality disorder. Biol Psychiatry 1996;40697- 705
PubMed Link to Article
Mitropoulou  VHarvey  PDMaldari  LAMoriarty  PJNew  ASSilverman  JMSiever  LJ Neuropsychological performance in schizotypal personality disorder: evidence regarding diagnostic specificity. Biol Psychiatry 2002;521175- 1182
PubMed Link to Article
Sullivan  EVDeshmukh  ADe Rosa  ERosenbloom  MJPfefferbaum  A Striatal and forebrain nuclei volumes: contribution to motor function and working memory deficits in alcoholism. Biol Psychiatry 2005;57768- 776
PubMed Link to Article
Deshmukh  ARosenbloom  MJDe Rosa  ESullivan  EVPfefferbaum  A Regional striatal volume abnormalities in schizophrenia: effects of comorbidity for alcoholism, recency of alcoholic drinking, and antipsychotic medication type. Schizophr Res 2005;79189- 200
PubMed Link to Article

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