Lateralized P3 deficit in schizotypal personality disorder.

BACKGROUND: Reduced, left-lateralized P3 amplitude has been reported in several studies focusing on electrophysiologic function in schizophrenia. Also, several lines of evidence suggest a similarity between schizophrenia and schizotypal personality disorder (SPD). This study was undertaken to determine the replicability of our previous finding of a left-lateralized P3 amplitude deficit in SPD. METHODS: We recorded event-related potentials in 21 SPD and 18 normal control subjects in an auditory "oddball" P3 paradigm. RESULTS: In the SPD subjects, but not in the control subjects, there was lower P3 amplitude at T3 compared with T4. CONCLUSIONS: These results are similar to the ones in our previous work and further support the presence of a left-lateralized P3 deficit in SPD.

Visual perception and working memory in schizotypal personality disorder.

OBJECTIVE: Patients affected by schizophrenia show deficits in both visual perception and working memory. The authors tested early-stage vision and working memory in subjects with schizotypal personality disorder, which has been biologically associated with schizophrenia. METHOD: Eleven subjects who met DSM-III-R criteria for schizotypal personality disorder and 12 normal comparison subjects were evaluated. Performance thresholds were obtained for tests of visual discrimination and working memory. Both form and trajectory processing were evaluated for each task. RESULTS: Subjects with schizotypal personality disorder showed intact discrimination of form and trajectory but were impaired on working memory tasks. CONCLUSIONS: These data suggest that subjects with schizotypal personality disorder, unlike patients affected by schizophrenia, have relatively intact visual perception. Subjects with schizotypal personality disorder do show specific deficits on tasks of comparable difficulty when working memory demands are imposed. Schizotypal personality disorder may be associated with a more specific visual processing deficit than schizophrenia, possibly reflecting disruption of frontal lobe systems subserving visual working memory operations.

Verbal and nonverbal neuropsychological test performance in subjects with schizotypal personality disorder.

OBJECTIVE: The authors contrasted verbal and nonverbal measures of attention and memory in patients with DSM-IV-defined schizotypal personality disorder in order to expand on their previous findings of verbal learning deficits in these patients and to understand better the neuropsychological profile of schizotypal personality disorder. METHOD: Cognitive test performance was examined in 16 right-handed men who met diagnostic criteria for schizotypal personality disorder and 16 matched male comparison subjects. Neuropsychological measures included verbal and nonverbal tests of persistence, supraspan learning, and short- and long-term memory retention. Neuropsychological profiles were constructed by standardizing test scores based on the means and standard deviations of the comparison subject group. RESULTS: Subjects with schizotypal personality disorder showed a mild to moderate general reduction in performance on all measures. Verbal measures of persistence, short-term retention, and learning were more severely impaired than their nonverbal analogs. Performance on measures of memory retention was independent of modality. CONCLUSIONS: The results are consistent with previous reports that have suggested a mild, general decrement in cognitive performance and proportionately greater involvement of the left hemisphere in patients with schizotypal personality disorder. The findings provide further support for a specific deficit in the early processing stages of verbal learning.

Large CSF volume not attributable to ventricular volume in schizotypal personality disorder.

OBJECTIVE: The purpose of this study was to determine whether schizotypal personality disorder, which has the same genetic diathesis as schizophrenia, manifests abnormalities in whole-brain and CSF volumes. METHOD: Sixteen right-handed and neuroleptic-naive men with schizotypal personality disorder were recruited from the community and were age-matched to 14 healthy comparison subjects. Magnetic resonance images were obtained from the subjects and automatically parcellated into CSF, gray matter, and white matter. Subsequent manual editing separated cortical from noncortical gray matter. Lateral ventricles and temporal horns were also delineated. RESULTS: The men with schizotypal personality disorder had larger CSF volumes than the comparison subjects; the difference was not attributable to larger lateral ventricles. The cortical gray matter was somewhat smaller in the men with schizotypal personality disorder, but the difference was not statistically significant. CONCLUSIONS: Consistent with many studies of schizophrenia, this examination of schizotypal personality disorder indicated abnormalities in brain CSF volumes.

Electrophysiological correlates of language processing in schizotypal personality disorder.

OBJECTIVE: This study examined whether the electrophysiological correlates of language processing found previously to be abnormal in schizophrenia are also abnormal in schizotypal individuals. The authors used the N400 component to evaluate language dysfunction in schizotypal individuals. METHOD: Event-related potentials were recorded in 16 comparison subjects and 17 schizotypal individuals (who met full DSM-III-R criteria) to sentences presented both visually and aurally; half of the sentences ended with an expected word completion (congruent condition), and the other half ended with an unexpected word completion (incongruent condition). RESULTS: In the congruent condition, the N400 amplitude was more negative in individuals with schizotypal personality disorder than in comparison subjects in both the visual and auditory modalities. In addition, in the visual modality, the N400 latency was prolonged in the individuals with schizotypal personality disorder. CONCLUSIONS: The N400 was found to be abnormal in the individuals with schizotypal personality disorder relative to comparison subjects. The abnormality was similar to the abnormality the authors' laboratory reported earlier in schizophrenic subjects, in which the N400 amplitude was found to be more negative in both congruent and incongruent sentence completions. The N400 abnormality is consistent with the inefficient use of context.

Schizotypal personality disorder and MRI abnormalities of temporal lobe gray matter.

BACKGROUND: Structural MRI data indicate schizophrenics have reduced left-sided temporal lobe gray matter volumes, especially in the superior temporal gyrus (STG) and medial temporal lobe. Our data further suggest a specificity to schizophrenia spectrum disorders of STG volume reduction. Interpretation of research studies involving schizophrenics may be complicated by the effects of exposure to neuroleptics and chronic illness. Sharing the same genetic diathesis of schizophrenics, subjects with schizotypal personality disorder (SPD) offer a unique opportunity to evaluate commonalities between schizophrenia and SPD, particularly as SPD subjects are characterized by cognitive and perceptual distortions, an inability to tolerate close friendships, and odd behavior, but they are not psychotic and so have generally not been prescribed neuroleptics nor hospitalized. Evaluation of brain structure in SPD may thus offer insight into the "endophenotype" common to both disorders. In addition, differences between groups may suggest which are the brain structures of schizophrenics that contribute to the development of psychosis. METHODS: To test the hypothesis of whether SPD subjects might show similar STG abnormalities, STG and medial temporal lobe regions of interest (ROI) were manually drawn on high resolution coronal MRI 1.5 mm thick slices. Images were derived from 16 right-handed male SPD subjects, without regard to family history, and 14 healthy, right-handed, comparison males who did not differ from the SPD group on parental socio-economic status, age, or verbal IQ. RESULTS: As predicted, SPD subjects showed a reduction in left STG gray matter volume compared with age and gender matched comparison subjects. SPD subjects also showed reduced parahippocampal left/right asymmetry and a high degree of disordered thinking. Comparisons with chronic schizophrenics previously studied by us showed the SPD group had a similarity of left STG gray matter volume reduction, but fewer medial temporal lobe abnormalities. CONCLUSIONS: These abnormalities strengthen the hypothesis of a temporal lobe abnormality in SPD, and the similarity of STG findings in schizophrenia and SPD suggest that STG abnormalities may be part of the spectrum "endophenotype." It is also possible that presence of medial temporal lobe abnormalities may help to differentiate who will develop schizophrenia and who will develop the less severe schizophrenia spectrum disorder, SPD.

Neuropsychological dysfunction in schizotypal personality disorder: a profile analysis.

In order to examine the neuropsychological profile of schizotypal personality disorder (SPD), we studied a wide array of cognitive functions in 10 right-handed men who met DSM-III-R criteria for SPD and 10 matched normal controls. Cognitive functions included abstraction, verbal and spatial intelligence, memory and learning, language, attention, and motor skills. Neuropsychological profiles were constructed by standardizing test scores based on the means and standard deviations of the normal control group. SPD subjects showed significant decrements in performance on the California Verbal Learning Test, a word-list learning measure which requires semantic clustering for more efficient performance, and on the Wisconsin Card Sort Test, a measure requiring concept formation, abstraction, and mental flexibility. These results suggest possible areas of specific neuropsychological dysfunction in SPD, and are consistent with current hypotheses of left-temporal and prefrontal brain dysfunction in schizophrenia.

Topographic abnormalities of P3 in schizotypal personality disorder.

Schizotypy, a schizophrenia spectrum disorder, is of interest because schizotypes share traits with schizophrenics, albeit milder, without potential confounds such as chronic neuroleptic treatment and/or hospitalization. Thus, schizotypy may be particularly useful in exploring biological correlates of an underlying schizophrenic predisposition. The P3 event-related potential, which is aberrant in schizophrenia, was measured in 11 male, right-handed, DSM-III-R-defined schizotypes and 11 matched controls while subjects covertly counted 1.5 kHz target tones (15%) in trains of 1 kHz standard tones. Like schizophrenics, schizotypes displayed an asymmetrical P3, with smaller amplitudes over the left temporal lobe. Unlike schizophrenics, schizotypes were not significantly smaller in P3 amplitude over the sagittal midline of the head, although there was a trend towards reduced amplitudes at central and posterior midline sites. Asymmetry of P3 amplitude, with left-sided deficit, may be associated with the schizophrenia diathesis, but overall P3 reductions may be more associated with chronic effects.

Brain event-related potentials to complex tones in depressed patients: relations to perceptual asymmetry and clinical features.

Brain event-related potentials (ERPs) to probe tones in a dichotic complex tone test were recorded from right-handed depressed patients (n = 44) and normal subjects (n = 19) at homologous sites over left and right hemispheres (F3, F4; C3, C4; P3, P4; O1, O2). There were no differences between groups N1 or P2 amplitude, but patients had smaller P3 amplitude than did normal subjects. Depressed patients failed to show either the left ear advantage or behavior-related hemispheric asymmetry of P3 seen for normal subjects. Depressed patients also showed less difference in hemispheric asymmetry between same and different judgments. These findings indicate that the abnormal behavioral asymmetry for dichotic pitch discrimination in depressed patients reflects a reduction in hemispheric asymmetry and is related to relatively late stages of cognitive processing.

Abnormal cerebral laterality in bipolar depression: convergence of behavioral and brain event-related potential findings.

Cerebral laterality in bipolar and unipolar major depression was compared using visual half-field and dichotic listening measures of perceptual asymmetry. The results replicate our prior finding of abnormal laterality in bipolar depressed patients on a visuospatial test. Bipolar patients (n = 11) failed to show the left visual field (right hemisphere) advantage for dot enumeration seen for both unipolar patients (n = 43) and normal controls (n = 24). Bipolar patients performed significantly poorer than unipolar patients on normal controls for left visual field, but not right visual field stimuli. An electrophysiological correlate of abnormal visual field asymmetry in bipolar depression was found in brain event-related potentials recorded during audiospatial and temporal discrimination tasks. Bipolar patients had smaller N100 amplitudes for test stimuli in the left than right hemifield, whereas unipolar patients and normals did not. The origins of left hemifield deficits in bipolar depression are discussed in terms of right-sided dysfunction of an arousal/attentional system involving temporoparietal and possibly frontal regions.

Cerebral laterality and depression: relations of perceptual asymmetry to outcome of treatment with tricyclic antidepressants.

The relationship of cerebral laterality to outcome of treatment with antidepressants was examined by comparing perceptual asymmetry in subgroups of depressed patients formed on the basis of clinical response to a tricyclic antidepressant (TCA) or a monoamine oxidase inhibitor (MAOI). Perceptual asymmetries of 63 unmedicated depressed patients were assessed for verbal and nonverbal tasks, using dichotic listening and visual half-field methods, and retests were obtained on 49 patients after about 6 weeks of treatment. There were significant differences between TCA responders and TCA nonresponders in dichotic listening and visual field asymmetries. Differences in perceptual asymmetry were specific to TCAs, in that no comparable differences existed between MAOI responders and MAOI nonresponders. Although perceptual accuracy improved following successful TCA treatment, abnormal perceptual asymmetries in TCA responders were present before and after treatment and may thereby represent state-independent characteristics.

Cerebral laterality and depression: differences in perceptual asymmetry among diagnostic subtypes.

Examined the influence of diagnostic subtype of depression on perceptual asymmetry for dichotic listening and visual tachistoscopic tasks. A total of 65 unmedicated patients with major depressive disorders and 30 normal controls were tested on a verbal and nonverbal task in each modality. Patients diagnosed according to the DSM-III with melancholia had abnormal perceptual asymmetry for dichotic nonsense syllable and complex tone tasks. In contrast, patients having a nonmelancholic "atypical depression" (reactivity of mood with preserved pleasure capacity and associated features) did not differ from normal controls on these tasks, but had an increased incidence of left handedness. Bipolar depression (history of hypomania) differed from unipolar depression in showing abnormal perceptual asymmetry for a tachistoscopic dot enumeration task. Alterations of perceptual asymmetry in melancholia and bipolar depression were consistent with hypothesized right hemisphere dysfunction.