Working memory in schizotypal personality disorder: fMRI activation and deactivation differences.

BACKGROUND: Schizotypal personality disorder (SPD) is considered a schizophrenia spectrum disorder, sharing with schizophrenia cognitive, neuropsychological, epidemiological, and biological characteristics. Working memory may be one area of shared deficit, although to date, this is only the second study to investigate working memory in SPD using fMRI. METHODS: In a block-design fMRI study, fifteen antipsychotic-naïve SPD and sixteen healthy control subjects performed blocks of a 2back visual working memory task and 0back continuous performance task while undergoing whole-brain fMRI at 3T. Whole-brain analyses were performed for the 0back>rest (fixation baseline) and the 2back>0back contrasts (isolating the working memory component from the visual perception and attention component). Parameter estimates were extracted to determine whether observed differences were due to task-induced activation and/or deactivation. RESULTS: Activation differences emerged between the two groups, without differences in task performance. In the 0back task, SPD showed decreased task-induced activation of the left postcentral gyrus. In the 2back>0back contrast, HC showed greater task-induced activation of the left posterior cingulate gyrus, superior temporal gyrus, insula, and middle frontal gyrus. These differences were due to SPD subjects' decreased task-induced activation in the left posterior cingulate gyrus, and task-induced deactivation in the remaining regions. CONCLUSIONS: These findings suggest that compared to HC subjects, individuals with SPD may achieve comparable working memory performance. However, differences emerge at the level of functional neural activation, attributable to different task-induced activation and deactivation patterns. Such differential recruitment of neural resources may be beneficial, contributing to SPD subjects' ability to perform these tasks comparably to HC subjects.

Globally and locally reduced MRI gray matter volumes in neuroleptic-naive men with schizotypal personality disorder: association with negative symptoms.

IMPORTANCE: Some, but not all, previous magnetic resonance imaging studies have indicated smaller cortical and local gray matter volumes (GMVs) in men with schizotypal personality disorder (SPD) compared with healthy control (HC) subjects. Thus, there is need for a whole-brain comparison to resolve inconsistencies and provide hitherto generally absent data on the association between GMV and symptoms. OBJECTIVE: To use voxel-based morphometry to evaluate a large sample of neuroleptic-naive men with SPD compared with group-matched HC subjects on local and global GMV and to identify associations with symptoms, especially negative symptoms. Also, to determine whether age-related GMV reductions are greater in men with SPD than HC subjects, providing presumptive evidence on possible progression. DESIGN, SETTING, AND PARTICIPANTS: This naturalistic study involved 54 neuroleptic-naive men with SPD and 54 male HC subjects aged 18 to 55 years recruited from the community and scanned on the same 1.5-T GE magnetic resonance imaging scanner. Participants were group matched on age, socioeconomic status, handedness, and IQ. MAIN OUTCOME MEASURES: Cross-sectional voxel-based morphometry, GMV in subjects with SPD and HC participants, and the relationship to clinical symptoms. RESULTS: A voxelwise analysis showed participants with SPD had significantly smaller GMV in the left superior temporal gyrus and widespread frontal, frontolimbic, and parietal regions compared with HC subjects. Most of these regional volumes were strikingly and significantly correlated with negative symptoms: the more the volume reduction, the more negative symptoms. Global cortical GMV and most regional GMV showed significant negative relationships with age in both those with SPD and HC subjects, without any group by age interactions. CONCLUSIONS AND RELEVANCE: Men with SPD showed global and widespread smaller regional GMV. The regional structural abnormalities were correlated with the severity of a participant's negative symptoms. While the pattern of GMV loss is similar to that in schizophrenia, the similar patterns of HC-SPD age-related GMV reduction suggest that SPD showed no progressive GMV loss, pointing to an important difference in the biological mechanisms of SPD and schizophrenia.

Prosodic abnormalities in schizotypal personality disorder.

OBJECTIVE: Patients with schizophrenia speak with blunted vocal affect but little is known regarding the prosody of persons with schizotypal personality disorder (SPD). This work examined expressive prosody in SPD, its relationship to brain structure, and outlined a framework for measuring elements of prosody in clinical populations. METHODS: Twenty-eight antipsychotic-naïve SPD subjects were matched with 27 healthy comparison (HC) subjects. Subjects read aloud short sentences and responded to probes to record both predetermined and self-generated speech samples. Samples were analyzed acoustically (pause proportion, duration, attack, and pitch variability) and subjectively by raters (amount of pauses, degree of emotion portrayed, and how much they wanted to hear more from the subjects) on paragraph, sentence, word, word-fragment, and syllable levels. Alexithymia and ability to self-monitor behavior were compared between groups. The pars opercularis was manually traced on structural MRI data. RESULTS: SPD subjects' speech had significantly more pauses, was slower, had less pitch variability, and expressed less emotion than HC subjects. Pitch variability correlated with socio-economic status achievement. There was no difference between groups in left or right pars opercularis volumes. A statistically significant correlation suggested that smaller left pars opercularis volumes in SPD subjects correlated with more pauses and less emotion. SPD subjects reported more alexithymia and difficulty self-monitoring their behavior compared with controls. In SPD subjects the high alexithymia correlated with raters not wanting to hear more from them and SPD subjects' inability to modulate their social behavior correlated with their having fewer friends. Thus, the SPD subjects exhibited insight. CONCLUSIONS: SPD subjects displayed significant prosodic deficits that were measurable in speech samples as brief as a word-fragment. The determinants of these deficits are not known although these may include a dysfunctional pars opercularis. These data add to the nascent literature describing social cognition deficits in SPD.

Facial emotion recognition and facial affect display in schizotypal personality disorder.

BACKGROUND: Patients with schizophrenia have deficits in facial affect expression and detection that hinder social interactions. The goal of this study was to examine whether or not epidemiologically-related antipsychotic-naïve schizotypal personality disorder (SPD) subjects would have similar deficits as patients with schizophrenia. METHODS: Matched SPD and healthy comparison (HC) subjects were asked to identify the eight classic emotions (SPD N=55, HC N=67) and to discriminate gender. Subjects (SPD N=22, HC N=17) were also photographed while displaying the same emotional expressions. Raters scored the subjects' facial expressions along several dimensions. RESULTS: SPD subjects compared with HC were slower and less accurate in identifying facial expressions. This may have been driven by deficits in identifying gender. Although raters were able to identify correctly SPD and HC subjects' expressions equally well, raters found SPD subjects' facial expressions to be more odd, more ambiguous, and the subjects less attractive in general compared with HC subjects. Raters were less confident in their ability to correctly interpret SPD subjects' facial expressions and raters were less comfortable with the idea of spending time with the SPD subjects compared with HC subjects. CONCLUSIONS: SPD subjects face two hurdles in terms of daily social interactions. They have problems both in correctly interpreting others' facial expressions and in generating socially attractive and unambiguous facial expressions.

Factors in sensory processing of prosody in schizotypal personality disorder: an fMRI experiment.

INTRODUCTION: Persons diagnosed with schizophrenia demonstrate deficits in prosody recognition. To examine prosody along the schizophrenia spectrum, antipsychotic-naïve schizotypal personality disorder (SPD) subjects and healthy control subjects were compared. It was hypothesized that SPD subjects would perform more poorly; with cognitive and demographic factors contributing to the poor performance. The superior temporal gyrus (STG) was selected as the region-of-interest (ROI) given its known abnormalities in SPD and its important role in the processing of prosody. METHODS: SPD and healthy comparison (HC) subjects were matched on age, IQ, and parental social-economic status (PSES). Cognitive measures included the Speech Sound Perception Test (SSPT) to examine phonological processing (SPD=68, HC=74) and the Verbal Fluency task to examine executive functioning (SPD=129, HC=138). The main experiment was a novel fMRI task of prosody identification using semantically neutral sentences spoken with emotional prosody (SPD=16, HC=13). Finally, volumetric measurement of the superior temporal sulcus (STS), a key region for processing prosody, and partially overlapping with the STG, was performed (SPD=30, HC=30). RESULTS: Phonological processing and executive functioning were both impaired in SPD subjects compared with HC subjects. Contrary to the prediction, SPD subjects, as a group, were similar to HC subjects in terms of correctly indentifying the emotion conveyed and reaction time. Within the SPD group, prosody identification accuracy was influenced by executive functioning, IQ and perhaps PSES, relationships not found with HC subjects. Phonological perception aided prosody identification in both diagnostic groups. As expected, both groups activated the STG while performing the prosody identification task. However, SPD subjects may have been less "efficient" in their recruitment of STG neurons. Finally, SPD subjects demonstrated a trend toward smaller STS volumes on the left, particularly the lower bank. CONCLUSIONS: These data suggest that subtle differences between SPD and controls in phonological processing, executive functioning, IQ, and possibly PSES, contributed to difficulty in processing prosody for some SPD subjects.

Dichotic listening in schizotypal personality disorder: evidence for gender and laterality effects.

Verbal dichotic listening performance was examined in 42 right-handed men and women with DSM-IV-defined schizotypal personality disorder (SPD) and 68 right-handed controls. As expected, both male and female control groups showed a right ear advantage on a verbal dichotic listening task. Although SPD subjects in general had lower accuracy scores than comparison subjects, only male SPD subjects showed an abnormal left ear advantage that was specifically due to deficient right ear performance. The results suggest that left hemisphere temporal lobe structures may be particularly involved in male, but not female, SPD.

Shape abnormalities of caudate nucleus in schizotypal personality disorder.

BACKGROUND: Previously, we reported abnormal volume and global shape in the caudate nucleus in schizotypal personality disorder (SPD). Here, we use a new shape measure which importantly permits local in addition to global shape analysis, as well as local correlations with behavioral measures. METHODS: Thirty-two female and 15 male SPDs, and 29 female and 14 male normal controls (NCLs), underwent brain magnetic resonance imaging (MRI). We assessed caudate shape measures using spherical harmonic-point distribution model (SPHARM-PDM) methodology. RESULTS: We found more pronounced global shape differences in the right caudate in male and female SPD, compared with NCLs. Local shape differences, principally in the caudate head, survived statistical correction on the right. Also, we performed correlations between local surface deformations with clinical measures and found significant correlations between local shape deflated deformations in the anterior medial surface of the caudate with verbal learning capacity in female SPD. CONCLUSIONS: Using SPHARM-PDM methodology, we found both global and local caudate shape abnormalities in male and female SPD, particularly right-sided, and largely restricted to limbic and cognitive anterior caudate. The most important and novel findings were bilateral statistically significant correlations between local surface deflations in the anterior medial surface of the head of the caudate and verbal learning capacity in female SPD. By extension, these local caudate correlation findings implicate the ventromedial prefrontal cortex (vmPFC), which innervates that area of the caudate, and demonstrate the utility of local shape analysis to investigate the relationship between specific subcortical and cortical brain structures in neuropsychiatric conditions.

A preliminary study of emotion processing interference in schizophrenia and schizoaffective disorder.

The impact of emotional arousal may be an equal or more important factor than valence in determining whether emotion interferes with language output in individuals with schizophrenia. An affective reactivity task, comprising conditions separated by emotional valence (positive, negative) and arousal (low, high), was administered to 22 individuals with schizophrenia or schizoaffective disorder and 13 non-patient controls. Individuals with schizophrenia or schizoaffective disorder demonstrated variable reactivity to both valence arousal. Results suggest that high arousal content can be especially impairing to certain individuals, and it is those individuals with schizophrenia and schizoaffective disorder who demonstrate more depressive symptomatology that show the greatest affective reactivity to negatively valenced, high arousing information. Clarifying aberrant emotion processing in schizophrenia is crucial to understanding precursors to symptom exacerbation and to the consideration of optimal treatment strategies.

MRI abnormalities of the hippocampus and cavum septi pellucidi in females with schizotypal personality disorder.

OBJECTIVE: This study examined MRI hippocampal volume and cavum septi pellucidi (CSP) in female subjects with schizotypal personality disorder (SPD) and comparison subjects. METHOD: MRI was performed on 20 SPD and 29 comparison subjects with delineation of left and right hippocampi. Number of slices containing the CSP was counted. Subjects were given a working memory task, the Delayed Alternation task and other measures of working memory including the Wechsler Memory Test-Revised and the California Verbal Learning Test. Clinical measures were derived from the SCID-II. RESULTS: SPD females evinced bilaterally smaller hippocampal volumes compared with non-psychiatric female subjects (15.1% on left, 15.7% on right). Additionally, SPD subjects showed statistically significantly more slices containing CSP, and a trend level difference when large CSP was defined as four or more slices (20% vs. 6.9%). SPD subjects demonstrated more errors, more perseverations, and a trend toward more failure to maintain set on the Delayed Alternating task, which were associated with smaller left hippocampal volumes. There was no difference between groups in logical memory, verbal learning or semantic clustering nor a significant correlation between these measures and hippocampal volumes. Clinically, in SPD subjects, right hippocampal volumes correlated negatively with odd appearance/behavior and positively with suspiciousness/paranoia, and odd speech was positively correlated with the number of slices containing a CSP in exploratory analyses. CONCLUSIONS: Female SPD subjects showed bilaterally smaller hippocampal volumes and larger CSP than comparison subjects, similar to what has been shown in schizophrenia. Moreover, these abnormalities have clinically significant associations which may help to explain some of the manifestations of the disorder.

Reduction of caudate nucleus volumes in neuroleptic-naïve female subjects with schizotypal personality disorder.

BACKGROUND: The caudate nucleus might contribute to the psychopathological and cognitive deficits observed in schizotypal personality disorder (SPD), a schizophrenia spectrum disorder. Here we focused on female patients, because this group is underrepresented in studies of SPD and schizophrenia, and we might learn more about the caudate and clinical and cognitive impairments that are unique to female patients diagnosed with SPD. METHODS: Magnetic resonance imaging scans, obtained on a 1.5-T magnet with 1.5-mm contiguous slices, were used to measure the caudate in 32 neuroleptic-naïve women with SPD and in 29 female normal comparison subjects. Subjects were group-matched for age, parental socioeconomic status, and intelligence quotient. RESULTS: We found significantly reduced left and right caudate relative volume (8.3%, 7.7%) in female SPD subjects compared with normal comparison subjects. In female SPD subjects, we found significant correlations between smaller total caudate relative volume and worse performance on the Wisconsin Card Sorting test (nonperseverative errors) and on the California Verbal Learning Test (verbal memory and learning), and significant correlations between smaller total caudate relative volume and both positive and negative symptoms on the Structured Interview for Schizotypy. CONCLUSIONS: These findings demonstrate that, for female SPD subjects, smaller caudate volume is associated with poorer cognitive performance and more schizotypal symptomatology.

The five-factor model in schizotypal personality disorder.

Studies of the five-factor model of personality in schizotypal personality disorder (SPD) have produced inconsistent results, particularly with respect to openness. In the present study, the NEO-FFI was used to measure five-factor personality dimensions in 28 community volunteers with SPD and 24 psychiatrically healthy individuals. Standard multivariate statistical analyses were used to evaluate personality differences as a function of diagnosis and gender. Individuals with SPD had significantly higher levels of neuroticism and significantly lower levels of extraversion, agreeableness and conscientiousness than those without SPD. Female, but not male, SPD subjects had significantly higher openness levels than their healthy counterparts, and this gender-specific group difference persisted when SPD symptom severity was statistically controlled. These findings suggest that gender-associated differences in openness may account for prior inconsistent findings regarding this dimension, and they further underscore the importance of examining gender effects in future studies of SPD.

Fronto-temporal disconnectivity in schizotypal personality disorder: a diffusion tensor imaging study.

BACKGROUND: Using diffusion tensor imaging (DTI), we previously reported abnormalities in two critical white matter tracts in schizophrenia, the uncinate fasciculus (UF) and the cingulum bundle (CB), both related to fronto-temporal connectivity. Here, we investigate these two bundles in unmedicated subjects with schizotypal personality disorder (SPD). METHODS: Fifteen male SPD subjects and 15 male control subjects were scanned with line-scan DTI. Fractional anisotropy (FA) and mean diffusivity (D(m)) were used to quantify water diffusion, and cross-sectional area was defined with a directional threshold method. Exploratory correlation analyses were evaluated with Spearman's rho, followed by post hoc hierarchical regression analyses. RESULTS: We found bilaterally reduced FA in the UF of SPD subjects. For CB, there was no significant group difference for FA or D(m) measures. Additionally, in SPD, reduced FA in the right UF was correlated with clinical symptoms, including ideas of reference, suspiciousness, restricted affect, and social anxiety. In contrast, left UF area was correlated with measures of cognitive function, including general intelligence, verbal and visual memory, and executive performance. CONCLUSIONS: These findings in SPD suggest altered fronto-temporal connectivity through the UF, similar to findings in schizophrenia, and intact neocortical-limbic connectivity through the CB, in marked contrast with what has been reported in schizophrenia.

Clinical, cognitive, and social characteristics of a sample of neuroleptic-naive persons with schizotypal personality disorder.

INTRODUCTION: Schizotypal personality disorder (SPD) shares with schizophrenia many biological features, yet little is known about the clinical characteristics of persons diagnosed with this disorder. This report describes the clinical, cognitive and socio-occupational characteristics of a community sample of subjects diagnosed with SPD. METHOD: Sixty-four male and 40 female neuroleptic-naive DSM-IV SPD subjects and 59 male and 51 female comparison subjects were recruited from the community for a total sample of 214 subjects. Demographic and cognitive differences between groups and, within the SPD group, the effect of gender on clinical features, such as the SPD criteria, SAPS, SANS, Schizotypal Personality Questionnaire, and co-morbidity, were examined using ANOVA and Chi-square distributions. RESULTS: SPD subjects, in contrast to comparison subjects, had significantly lower socio-economic status, poorer social relationships and skills, and lower vocabulary scores. Furthermore, SPD subjects demonstrated more impairment on Vocabulary scores than on Block Design, as measured by the WAIS-R, a pattern not seen in comparison subjects. In the SPD cohort, positive symptoms predominated and nearly half were co-morbid for major depression. With respect to gender, male SPD subjects, compared with female SPD subjects, evinced significantly more negative symptoms, fewer friends, had more odd speech, and were more likely to also suffer from paranoid and narcissistic personality disorders. In contrast to male SPD subjects, female SPD subjects perceived themselves to be more disorganized. CONCLUSIONS: SPD subjects, similar to schizophrenics, are impaired socially, occupationally, and cognitively, particularly in the area of verbal measures. Moreover, male SPD subjects may be more severely affected than female SPD subjects across multiple domains of functioning.

A comparative profile analysis of neuropsychological function in men and women with schizotypal personality disorder.

The purpose of this study was to compare the cognitive profiles of men and women with clinically defined schizotypal personality disorder (SPD). We examined the neuropsychological profile of SPD in 26 right-handed females and 31 right-handed males who met DSM-IV criteria for SPD, and matched comparison subjects. Cognitive performance was assessed on measures of abstraction, verbal and spatial intelligence, learning and memory, language, attention, and motor skills. Neuropsychological profiles were constructed by standardizing test scores based on the means and standard deviations of comparison groups matched for sex, age, handedness, ethnicity and parental SES. Overall, SPD subjects showed mild, general decrements in performance in most cognitive domains. However, unlike male SPD subjects, female SPDs did not show relative deficits in verbal learning and abstraction. The results suggest a less severe pattern of cognitive deficits in women with SPD compared to men, consistent with hypotheses of gender differences in cognitive function in schizophrenia.

Shape of caudate nucleus and its cognitive correlates in neuroleptic-naive schizotypal personality disorder.

BACKGROUND: We measured the shape of the head of the caudate nucleus with a new approach based on magnetic resonance imaging (MRI) in schizotypal personality disorder (SPD) subjects in whom we previously reported decreased caudate nucleus volume. We believe MRI shape analysis complements traditional MRI volume measurements. METHODS: Magnetic resonance imaging scans were used to measure the shape of the caudate nucleus in 15 right-handed male subjects with SPD, who had no prior neuroleptic exposure, and in 14 matched normal comparison subjects. With MRI processing tools, we measured the head of the caudate nucleus using a shape index, which measured how much a given shape deviates from a sphere. RESULTS: In relation to comparison subjects, neuroleptic never-medicated SPD subjects had significantly higher (more "edgy") head of the caudate shape index scores, lateralized to the right side. Additionally, for SPD subjects, higher right and left head of the caudate SI scores correlated significantly with poorer neuropsychological performance on tasks of visuospatial memory and auditory/verbal working memory, respectively. CONCLUSIONS: These data confirm the value of measuring shape, as well as volume, of brain regions of interest and support the association of intrinsic pathology in the caudate nucleus, unrelated to neuroleptic medication, with cognitive abnormalities in the schizophrenia spectrum.

An MRI study of superior temporal gyrus volume in women with schizotypal personality disorder.

OBJECTIVE: An abnormal superior temporal gyrus has figured prominently in schizophrenia research, and left superior temporal gyrus volume has been shown to be smaller in male subjects with schizotypal personality disorder. This is the first structural magnetic resonance imaging study to examine a group of female subjects with schizotypal personality disorder. METHOD: The superior temporal gyrus was drawn on coronal images acquired from female subjects recruited from the community (schizotypal personality disorder group: N=21, comparison group: N=29). RESULTS: There were no gray matter volume differences in the left or right superior temporal gyrus between the subjects with schizotypal personality disorder and the comparison subjects. Within the schizotypal personality disorder group, however, there was an interaction between hemisphere and family history of mental illness. Moreover, subjects with schizotypal personality disorder did demonstrate formal thought disorder and a negative correlation between left superior temporal gyrus volume and odd speech. CONCLUSIONS: This study of female subjects with schizotypal personality disorder showed no superior temporal gyrus volume differences, but preliminary findings indicate that among female subjects with schizotypal personality disorder, there is a left-right difference in those who have a family history of mental illness relative to those who do not. These data also suggest an association between abnormal speech and left superior temporal gyrus volume, a finding similar to that found in schizophrenia. Results from this study thus clearly reinforce the importance of studying female subjects separately.

A MRI study of fusiform gyrus in schizotypal personality disorder.

The fusiform gyrus is important for face and object recognition, is abnormal in schizophrenia, but has not been studied in schizotypal personality disorder (SPD). Thin-slice MR images showed no differences, either in right, left or total fusiform gyri volumes, between subjects with SPD (N=21) and normal controls (N=19). However, there was a correlation between severity of illusions and magical thinking suffered by the SPD subjects and smaller right fusiform gyrus volumes. This suggests that future studies may be useful in determining the functional competence of this gyrus in SPD.

Smaller left Heschl's gyrus volume in patients with schizotypal personality disorder.

OBJECTIVE: Individuals with schizophrenia spectrum disorders evince similar genetic, neurotransmitter, neuropsychological, electrophysiological, and structural abnormalities. Magnetic resonance imaging (MRI) studies have shown smaller gray matter volume in patients with schizotypal personality disorder than in matched comparison subjects in the left superior temporal gyrus, an area important for language processing. In a further exploration, the authors studied two components of the superior temporal gyrus: Heschl's gyrus and the planum temporale. METHOD: MRI scans were acquired from 21 male, neuroleptic-naive subjects recruited from the community who met DSM-IV criteria for schizotypal personality disorder and 22 male comparison subjects similar in age. Eighteen of the 21 subjects with schizotypal personality disorder had additional comorbid, nonpsychotic diagnoses. The superior temporal gyrus was manually delineated on coronal images with subsequent identification of Heschl's gyrus and the planum temporale. Exploratory correlations between region of interest volumes and neuropsychological measures were also performed. RESULTS: Left Heschl's gyrus gray matter volume was 21% smaller in the schizotypal personality disorder subjects than in the comparison subjects, a difference that was not associated with the presence of comorbid axis I disorders. There were no between-group volume differences in right Heschl's gyrus or in the right or left planum temporale. Exploratory analyses also showed a correlation between poor logical memory and smaller left Heschl's gyrus volume. CONCLUSIONS: Smaller left Heschl's gyrus gray matter volume in subjects with schizotypal personality disorder may help to explain the previously reported abnormality in the left superior temporal gyrus and may be a vulnerability marker for schizophrenia spectrum disorders.

MRI study of caudate nucleus volume and its cognitive correlates in neuroleptic-naive patients with schizotypal personality disorder.

OBJECTIVE: "Cognitive" circuits anatomically link the frontal lobe to subcortical structures; therefore, pathology in any of the core components of these circuits, such as in the caudate nucleus, may result in neurobehavioral syndromes similar to those of the frontal lobe. Neuroleptic medication, however, affects the size of the caudate nucleus. For this reason, individuals diagnosed with schizotypal personality disorder offer an ideal group for the measurement of the caudate nucleus because they may be genetically related to individuals with schizophrenia but do not require neuroleptic treatment because of their less severe symptoms. METHOD: Magnetic resonance imagining (MRI) scans obtained on a 1.5-T magnet with 1.5-mm contiguous slices were used to measure the caudate nucleus and lateral ventricles in 15 right-handed male subjects with schizotypal personality disorder who had no previous neuroleptic exposure and in 14 normal comparison subjects. Subjects were group matched for parental socioeconomic status, handedness, and gender. RESULTS: First, the authors found significantly lower left and right absolute (13.1%, 13.2%) and relative (9.1%, 9.2%) caudate nucleus volumes in never-medicated subjects with schizotypal personality disorder than in normal subjects. Second, they found significant, inverse correlations between caudate nucleus volume and the severity of perseveration in two distinct working memory tasks in these neuroleptic-naive subjects with schizotypal personality disorder. CONCLUSIONS: These data are consistent with the findings of reduced caudate nucleus volume reported in studies of neuroleptic-naive patients experiencing their first episode of schizophrenia and support the association of intrinsic pathology in the caudate nucleus with abnormalities in working memory in the schizophrenia spectrum.