Cognitive impairment in the schizophrenia spectrum: What is the evidence for similarity to schizophrenia?

Cognitive dysfunction is a core component of schizophrenia and is strongly related to functional outcome. Schizotypal personality disorder (SPD) appears closely linked to schizophrenia in terms of biology, phenomenology, outcome, and treatment response. Individuals with SPD demonstrate a similar pattern of cognitive deficits, albeit with less severity in most areas, to individuals with schizophrenia, with core impairments in working memory, context processing, and processing capacity. The validity of the SPD cognitive profile is thus discussed in terms of these areas of impairment that are as great as those in schizophrenia, which lends support to the relationship between schizophrenia and SPD

Amphetamine, psychosis, and cognition in the schizophrenia spectrum

We previously reported that subjects with a schizophrenia spectrum personality disorder (ie, an odd cluster personality disorder), of which the prototype is schizotypal personality disorder, show cognitive impairment in circumscribed areas (working memory) compared with healthy control subjects, and that amphetamine administration improves working memory in subjects with schizotypal personality disorder. In this larger series, we wanted to determine whether amphetamine treatment ameliorates working memory impairment using three groups: subjects with a schizophrenia spectrum personality disorder (ie, schizotypal, paranoid, or schizoid personality disorder), other (subjects with nonschizophrenia spectrum) personality disorder, and healthy volunteers. We hypothesized that amphetamine treatment would improve cognitive function in domains in which subjects with schizophrenia spectrum personality disorder show impairment compared with healthy volunteers and the other personality disorder group. Overall, amphetamine treatment did not improve performance in any task compared with placebo, and there was no group by drug interaction in the total sample. However, when the sample was restricted to the subjects who showed impairment at baseline, amphetamine treatment improved visuospatial working memory. In the total patient sample, amphetamine treatment reduced negative symptoms, whereas positive symptoms remained unchanged. Amphetamine treatment improves working memory in those subjects with cognitive impairment at baseline, most of whom meet criteria for a schizophrenia spectrum disorder

The Factor Structure of Schizotypal Symptoms in a Clinical Population

There is some support for the hypothesis that the factor structure of schizophrenia symptoms is similar to the factor structure of schizotypal symptoms in nonschizophrenia populations. However, no studies to date have examined schizotypal symptoms in patients with personality disorders. In this study, confirmatory factor analyses were conducted to test the relative fit of several models of the factorial structure of schizotypal symptoms in patients diagnosed with personality disorders. The EQS: Structural Equations Program was used to analyze DSM-III symptoms of schizotypal personality disorder (SPD) based on structured clinical interviews with 213 patients meeting a diagnosis for at least one personality disorder. A subgroup of the total sample was also evaluated for DSM-III-R criteria (n = 143) to test competing models of the DSM-III-R symptoms of SPD. A three-factor model consisting of a cognitive-perceptual, interpersonal, and paranoid factor yielded the best fit to the data relative to the other models tested. These results suggest that the three-factor model of schizophrenia symptoms may not entirely correspond to the factors underlying milder schizotypal symptoms expressed in a clinical population. It is suggested that future research focus on both the similarities and the differences between SPD and schizophrenia

Cognitive and brain function in schizotypal personality disorder

Schizotypal personality disorder, a diagnosis defined partially in terms of a genetic relatedness to schizophrenia, has begun to receive extensive investigative study. While the exact etiologic relationship between schizotypal personality disorder and schizophrenia remains to be determined, three models have been considered: (1) the two may be distinct disorders, (2) they may be essentially identical disorders but expressed with different degrees of severity, or (3) they may be related disorders with a partially overlapping etiology that might account for the many similarities yet the lack of psychosis or severe deficits in schizotypal individuals. Some of the recent research in the structural and functional neuroanatomy, neurochemistry, cognitive function, and pharmacology of schizotypal personality disorder is reviewed with citation of the most recent findings from our laboratory and others. Both schizotypal and schizophrenic subjects appear to show abnormalities in temporal lobe volume, but schizotypal subjects do not appear to show the volumetric decreases in frontal cortex that schizophrenic patients evidence. Abnormalities in thalamic nuclei parallel these findings—the pulvinar, which projects to temporal association and sensory cortices, is reduced in both disorders, but the mediodorsal nucleus, which projects extensively to the frontal cortex, is reduced in schizophrenic patients but not in schizotypal patients. Functional imaging studies suggest that there may be abnormalities in frontal activation in both disorders, but that schizotypal individuals can recruit alternative regions to accomplish tasks requiring frontal lobe activation that may help compensate. Imaging studies of the subcortex including FDG/PET imaging of metabolic activity during a verbal learning task, SPECT imaging studies which measure binding of IBZM and its displacement following amphetamine administration, and plasma HVA determinations following 2-deoxyglucose administration all suggest the possibility of relatively reduced dopaminergic subcortical activity in schizotypal individuals compared to schizophrenic patients. Cognitive function is also impaired in the areas of working memory, verbal learning, and attention in schizotypal patients, as in schizophrenic patients, and they may be particularly susceptible to cognitive tasks with high context dependence, as in schizophrenia. Preliminary trials of catecholaminergic agents suggest that these agents may be able to improve these impaired cognitive functions

Neuropsychological performance in schizotypal personality disorder: evidence regarding diagnostic specificity

Individuals with schizotypal personality disorder (SPD) share cognitive deficits with schizophrenic patients, suggesting that these deficits represent a core feature of the schizophrenia spectrum. We investigated the neuropsychological profile in SPD patients compared with two comparison groups: healthy volunteers (HV) and patients who met criteria for another non-schizophrenia spectrum personality disorder (NSS). We tested 48 DSM-III-R SPD patients, 22 NSS and 32 HV on a neuropsychologic battery that included the California Verbal Learning Test (CVLT), Trail Making A and B, the DOT test of working memory, the Stroop Color–Word Interference, the Paced Auditory Serial Addition Test (PASAT), the Wechsler Memory Scale Visual Reproduction Test (WMSV–R), and the Wechsler Adult Intelligence Scale vocabulary and block design. Normative standards for performance were created using the HV group. SPD patients performed significantly worse compared with HVs; specifically, SPD patients demonstrated impaired performance on the PASAT and the WMSV–R immediate and delayed recall compared to HV. Moreover, SPD patients were impaired in the PASAT and the WMSV–R immediate condition compared with the NSS group. The NSS patients did not differ from HV on any of the cognitive tasks. The interpersonal factor of the schizotypal symptoms inversely correlated with the PASAT score ( r = −.32, p < .006). Compared with HVs, SPD patients demonstrate modest cognitive impairment. These differences reached statistical significance for the PASAT (an auditory working memory task), and the WMSV–R immediate and delayed recall (a learning–recall test). In contrast, performance of NSS patients did not differ from that of HVs. The types of deficits observed in SPD patients are qualitatively similar to but milder than those seen in patients with schizophrenia