Neuropsychological performance in schizotypal personality disorder: importance of working memory

BACKGROUND: Cognitive deficits consistently have been reported in schizophrenia patients and in patients with schizotypal personality disorder. For this study, the authors wanted to identify which of the domains of cognitive impairment represent "core" deficits of schizophrenia, comparing subjects with schizotypal personality disorder to two comparison groups: healthy volunteers and patients with personality disorders unrelated to schizophrenia. METHOD: Three groups completed a neuropsychological battery: patients with DSM-III-R schizotypal personality disorder (N=82); patients with DSM-III-R personality disorders unrelated to schizophrenia (i.e., a personality disorder other than schizotypal, schizoid, or paranoid [N=44]); and healthy volunteers (N=63). The battery included the California Verbal Learning Test, Trailmaking Test parts A and B, the Dot test of working memory, the Stroop Color and Word Test, the Paced Auditory Serial Addition Test, the WMS visual reproduction test, and the WAIS-R vocabulary and block design. RESULTS: Normative standards for performance that controlled for age, gender, and education were created from the scores of the healthy volunteers. Overall, schizotypal personality disorder patients performed significantly worse than the healthy volunteers and those with personality disorders unrelated to schizophrenia. Specifically, patients with schizotypal personality disorder demonstrated impaired performance on the Paced Auditory Serial Addition Test, WMS visual reproduction test, Dot test, and California Verbal Learning Test. In addition, in a regression analysis, performance on the Paced Auditory Serial Addition Test demonstrated the largest effect size. Indeed, it accounted for unique variance above and beyond all other cognitive measures, since controlling for Paced Auditory Serial Addition Test performance abolished group differences across all other measures. CONCLUSIONS: Patients with schizotypal personality disorder demonstrated moderate cognitive impairment compared with healthy volunteers (significant for seven out of 11 measures). These differences reached statistical significance for tasks of working memory, episodic memory, and delayed recall. Working memory performance accounted for the group differences. This study supports the view that working memory represents a core deficit of schizophrenia spectrum disorders.     

Empathic accuracy and cognition in schizotypal personality disorder

Interpersonal dysfunction contributes to significant disability in the schizophrenia spectrum. Schizotypal Personality Disorder (SPD) is a schizophrenia-related personality demonstrating social cognitive impairment in the absence of frank psychosis. Past research indicates that cognitive dysfunction or schizotypy may account for social cognitive dysfunction in this population. We tested SPD subjects and healthy controls on the Empathic Accuracy (EA) paradigm and the Reading of the Mind in the Eyes Test (RMET), assessing the impact of EA on social support. We also explored whether EA differences could be explained by intelligence, working memory, trait empathy, or attachment avoidance. SPD subjects did not differ from controls in RMET, but demonstrated lower EA during negative valence videos, associated with lower social support. Dynamic, multimodal EA paradigms may be more effective at capturing interpersonal dysfunction than static image tasks such as RMET. Schizotypal severity, trait empathy, and cognitive dysfunction did not account for empathic dysfunction in SPD, although attachment avoidance is related to empathic differences. Empathic dysfunction for negative affect contributes to decreased social support in the schizophrenia spectrum. Future research may shed further light on potential links between attachment avoidance, empathic dysfunction, and social support.     

Cognitive function and symptoms in adolescents with schizotypal personality disorder

Cognitive deficits have been documented in schizophrenia and spectrum disorders. This study examines cognitive functioning and its relation to symptoms in adolescents with schizotypal personality disorder (SPD). Participants are 89 adolescents recruited for a study of youth at risk for Axis I disorders, especially psychosis. At intake, 34 met criteria for SPD, 38 for another Axis II disorder and/or conduct disorder (Other disorder-OD), and 17 did not currently meet criteria for any DSM-IV disorder (normal control-NC). At initial assessment, cognitive functioning was measured using subtests from the Wechsler Intelligence Scales and Wechsler Memory Scales (WMS), and symptoms were measured using the Structured Interview for Prodromal Symptoms (SIPS). At the time of this report, 50 were readministered the SIPS at 1-year follow-up (T2). The SPD group scored significantly below the NC group on the Arithmetic subtest of the Wechsler Intelligence Scales, but there was only limited evidence of group differences on the WMS. Poorer performance on the Wechsler Intelligence Scales was associated with greater severity of negative and disorganized symptoms. Deficits on the WMS were linked with more severe disorganized symptoms. The findings reported here are consistent with previous reports of limited cognitive deficits in adolescents with SPD, with the most marked deficits in mental arithmetic. The associations between symptoms and cognitive scores parallel those observed in adults with schizophrenia and spectrum disorder, and they are consistent with the notion that negative symptoms are more stable and partially reflect premorbid cognitive functions.     

The effects of guanfacine on context processing abnormalities in schizotypal personality disorder.

BACKGROUND: The signature of impaired cognition in people with schizotypal personality disorder (SPD) may be centrally related to working memory impairments. Guanfacine, an alpha2A agonist that acts post-synaptically in the prefrontal cortex (PFC), has shown potential for reducing working memory limitations in other populations. This study examined the potential of guanfacine for improving context processing, a feature of working memory, in SPD. METHODS: 29 individuals with SPD entered into a 4-week, randomized parallel-design, double-blind, placebo-controlled trial of guanfacine treatment, followed by a 4-week open-label extension. A modified version of the AX-Continuous Performance Test (AX-CPT) was administered. On this task, evidence of intact context processing includes few BX errors (false cue, correct probe) and higher levels of AY errors (correct cue, false probe). RESULTS: At the end of double-blind treatment, participants treated with guanfacine demonstrated a significant reduction in BX errors and a small but significant increase in AY errors, a pattern that was not seen in the participants treated with placebo. CONCLUSIONS: SPD participants improved in their context processing toward a normal response bias, making fewer BX and more AY errors, after being treated with guanfacine.     

The Schedule for Schizotypal Personalities (SSP): A diagnostic interview for schizotypal features

The validity and reproducibility of psychiatric diagnosis are crucial to psychiatric research. To establish confidence in assigning schizotypal features, three paradigms estimating the reliability of a new instrument, the Schedule for Schizotypal Personalities (SSP), were tested. The first paradigm considered joint, but independent evaluations made by two raters simultaneously. The second paradigm assessed evaluations on different occasions, with a mean interim time of 5.9 months (test-retest procedure). Both reliability paradigms demonstrated high levels of agreement for all of the scaled items. Ninety percent of the intraclass correlation coefficients were 0.80 or better for the joint evaluations, and 70% were 0.80 or better for the test-retest evaluation. The third paradigm measured the reliability of DSM-III Schizotypal Personality Disorder. The kappa value for measuring diagnostic agreement was 0.88. The authors recommend the use of the SSP as an interview schedule and discuss the implications of their findings for genetic and biological research of schizophrenia spectrum disorders.     

Cognitive deficits in schizophrenia and affective disorders: evidence for a final common pathway disorder

This study was designed to determine whether patients with schizophrenia and those with affective disorders display a common pattern of cognitive deficits. Cognitive performance was assessed with a neuropsychological test battery in consecutively admitted in-patients with schizophrenia (n= 100) and affective disorders (n= 100). The two groups of patients showed a similar pattern of cognitive deficits, especially in tests focusing on attentional capacities. The groups only differed significantly in their performance on the Wisconsin Card Sorting Test (WCST), with the schizophrenic patients performing less well. These results suggest that, with the exception of the deficit as measured by the WCST, similar cognitive impairments exist in schizophrenia and affective disorders, even at very early stages of the illness. Therefore, patients with schizophrenia and those with affective disorders cannot be qualitatively distinguished with sufficient reliability. We postulate that the cognitive deficit pattern represents a final common pathway disorder in the two groups of patients.     

Reduced processing resource availability in schizotypal personality disorder: evidence from a dual-task CPT study

Performance on a dual-task information processing task was investigated in 23 schizotypal personality disorder patients (SPD), 29 patients with other noncluster A personality disorders (OPD) and 8 non-psychiatric healthy controls (NC). All participants were assessed using a computer-based visual continuous performance test (CPT) and an auditory CPT individually, and administered again simultaneously in a dual-task condition. The SPD group showed a greater increase in the number of errors of omission than the OPD group or normal controls on the CPT tasks in the dual-task conditions. Performance operating characteristics indicated that the SPD patients did not allocate their attention in a manner different from the healthy controls, suggesting that poorer performance was due to resource limitations in the dual task condition and not strategic failures. These results are similar to previous studies of patients with schizophrenia, where performance deficits on information processing tests have been shown to be related to resource limitations more than failures in effective allocation of attention.     

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.     

Neuropsychological functioning in bipolar disorder and schizophrenia.

BACKGROUND: Some patients with bipolar disorder (BD) demonstrate neuropsychological deficits even when stable. However, it remains unclear whether these differ qualitatively from those seen in schizophrenia (SZ). METHODS: We compared the nature and severity of cognitive deficits shown by 106 patients with SZ and 66 patients with BD to 316 healthy adults (NC). All participants completed a cognitive battery with 19 individual measures. After adjusting their test performance for age, sex, race, education, and estimated premorbid IQ, we derived regression-based T-scores for each measure and the six cognitive domains. RESULTS: Both patient groups performed significantly worse than NCs on most (BD) or all (SZ) cognitive tests and domains. The resulting effect sizes ranged from .37 to 1.32 (mean=.97) across tests for SZ patients and from .23 to .87 (mean=.59) for BD patients. The Pearson correlation of these effect sizes was .71 (p<.001). CONCLUSIONS: Patients with bipolar disorder suffer from cognitive deficits that are milder but qualitatively similar to those of patients with schizophrenia. These findings support the notion that schizophrenia and bipolar disorder show greater phenotypic similarity in terms of the nature than severity of their neuropsychological deficits.     

Neuropsychological performance in pediatric bipolar disorder.

BACKGROUND: Growing awareness of childhood bipolar disorder necessitates further cognitive neuroscience research to determine unique developmental differences between pediatric and adult onset bipolar disorder. We sought to examine whether neuropsychological function in children with bipolar disorder resembles that in adults with the illness and to extend our knowledge about cognitive function in pediatric bipolar disorder. METHODS: We administered a computerized neuropsychological test battery known as the Cambridge Neuropsychological Test Automated Battery to a sample of 21 children and adolescents with bipolar disorder and compared them with 21 age- and gender-matched controls. RESULTS: In comparison to controls, children with bipolar disorder were impaired on measures of attentional set-shifting and visuospatial memory. Post hoc analyses in pediatric bipolar disorder subjects did not show significant associations between neuropsychological performance and manic symptomatology or attention-deficit/hyperactivity disorder comorbidity. CONCLUSIONS: Cambridge Neuropsychological Test Automated Battery data presented here in pediatric bipolar disorder fit well within the broader framework of known neurocognitive deficits in adult bipolar disorder. Our pediatric bipolar disorder subjects demonstrated selective deficiencies in attentional set-shifting and visuospatial memory. Our work suggests altered ventrolateral prefrontal cortex function, especially when linked to other lesion and neuroimaging studies.     

Dissociative states in multiple personality disorder: a quantitative study

Multiple personality disorder (MPD) patients may experience themselves as several discrete alter personalities who do not share consciousness or memories with one another. In this study, we asked whether MPD patients are different from controls in their ability to learn and remember, and their ability to compartmentalize information. MPD patients were not found to differ from controls in overall memory level. Learning of information by MPD patients in disparate personality states did not result in greater compartmentalization than that of which control subjects were capable. However, there were qualitative differences between the cognitive performance of patients and that of controls attempting to role-play alter personalities. Our results suggest that simple confabulation is not an adequate model for the MPD syndrome, and we consider a possible role for state-dependent learning in the phenomenology of MPD.     

Neuropsychological performance in children and adolescents with obsessive-compulsive disorder and influence of clinical variables.

BACKGROUND: Several studies have found impairment in visual memory and visual organization in adults with obsessive-compulsive disorder (OCD), but little is known about the neuropsychological profile of children and adolescents with this disorder. The influence of clinical variables such as age, severity of obsessive-compulsive symptomatology, depressive symptomatology, and pharmacological treatment on cognitive performance in these patients has not been thoroughly studied. METHODS: A neuropsychological battery designed for this study was administered to 35 patients with DSM-IV-TR diagnosis of OCD without psychiatric comorbidity aged between 7 and 18 years and 35 gender- and age-matched healthy subjects. RESULTS: Children and adolescents with OCD performed significantly worse on verbal and visual memory and velocity. When depressive symptomatology was controlled, impairment in visual memory, visual organization, and velocity again was found, but impairment in verbal memory was not. Neuropsychological impairment was not related to age, obsessive-compulsive severity, and pharmacological treatment. CONCLUSIONS: Children and adolescents with OCD without psychiatric comorbidity with acute illness show impairment in visual memory, visual organization, and velocity, similar to adults. The influence of depressive symptomatology is important in cognitive performance. No relation was found between neuropsychology and age, severity of obsessive-compulsive symptomatology, or pharmacological treatment in this study.     

The brain in schizotypal personality disorder: a review of structural MRI and CT findings.

Studies of schizotypal personality disorder (SPD) are important because the condition is genetically related to schizophrenia and because data accumulating to confirm its biological underpinnings are challenging some traditional views about the nature of per-sonality disorders. This review of 17 structural imaging studies in SPD indicates that individuals with this disorder show brain abnormalities in the superior temporal gyrus, parahippocampus, temporal horn region of the lateral ventricles, corpus callosum, thalamus, and septum pellucidum, as well as in total cerebrospinal fluid volume, similar to those seen in persons with schizophrenia. Differences between SPD and schizophrenia include lack of abnormalities in the medial temporal lobes and lateral ventricles in SPD. Whether the normal volume, and possibly normal functioning, of the medial temporal lobes in individuals with SPD may help to suppress psychosis in this disorder remains an intriguing but still unresolved question. Such speculation must be tempered due to a paucity of studies, and additional work is needed to confirm these preliminary findings. The imaging findings do suggest, however, that SPD probably represents a milder form of disease along the schizophrenia continuum. With further clarification of the neuroanatomy of SPD, researchers may be able to identify which neuroanatomical abnormalities are associated with the frank psychosis seen 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.     

Associative memory encoding and recognition in schizophrenia: an event-related fMRI study.

BACKGROUND: We used an event-related functional Magnetic Resonance Imaging (fMRI) approach to examine the neural basis of the selective associative memory deficit in schizophrenia. METHODS: Fifteen people with schizophrenia and 18 controls were scanned during a pair and item memory encoding and recognition task. During encoding, subjects studied items and pairs of visual objects. In a subsequent retrieval task, participants performed an item recognition memory test (old/new decisions) and an associative recognition test (intact/rearranged decisions). The fMRI analysis of the recognition data was restricted to correct items only and a random effects model was used. RESULTS: At the behavioral level, both groups performed equally well on item recognition, whereas people with schizophrenia demonstrated lower performance on associative recognition relative to the control group. At the brain level, the comparison between associative and item encoding revealed greater activity in the control group in the left prefrontal cortex and cingulate gyrus relative to the schizophrenia group. During recognition, greater left dorsolateral prefrontal and right inferior prefrontal activations were observed in the control group relative to the schizophrenia group. CONCLUSION: This fMRI study implicates the prefrontal cortex among other brain regions as the basis for the selective associative memory encoding and recognition deficit seen in schizophrenia.     

多发性硬化工作记忆受损特点信息处理速度障碍

目的探讨多发性硬化信息处理障碍及工作记忆受损特点。方法 34例多发性硬化(MS)患者及34例匹配健康受试者进入本研究,受试者均接受一般情况调查、临床症状评估及神经心理测试等[如听觉连续加法测试(PASAT)、符号数字转换测试(SDMT)、Stroop测试、2-Back任务等]。以单侧95%可信区间为参考,按是否低于健康组SDMT成绩5%可信区间为界,将MS组进一步划分为SDMT-障碍组/保留组,进行组间比较。结果仅MS-SDMT障碍组在PASAT、2-Back、Stroop耗时上(平均秩次分别为:PASAT-3’=6.58,PASAT-2’=7.42;2-Back=21.05;Stroop-词语耗时=21.15,Stroop-色彩耗时=18.39,Stroop-干扰耗时=17.98)与健康组(平均秩次分别为:PASAT-3’=17.98,PASAT-2’=15.66;2-Back=8.94;Stroop-词语耗时=10.58,Stroop-色彩耗时=9.16,Stroop-干扰耗时=11.24)差异存在统计学意义(P<0.05)。结论对于中央执行功能要求较低的测试,如数字广度测试、Stroop任务,MS主要累及信息处理速度,信息处理准确性相对保留;对于中央执行功能要求较高的测试,MS可能通过牺牲信息处理的准确性来弥补处理速度上更大程度的落差,因此准确性下降。     

Auditory processing abnormalities in schizotypal personality disorder: an fMRI experiment using tones of deviant pitch and duration

BACKGROUND: One of the cardinal features of schizotypal personality disorder (SPD) is language abnormalities. The focus of this study was to determine whether or not there are also processing abnormalities of pure tones differing in pitch and duration in SPD. METHODS: Thirteen neuroleptic-na?ve male subjects met full criteria for SPD and were group-matched on age and parental socio-economic status to 13 comparison subjects. Verbal learning was measured with the California Verbal Learning Test. Heschl's gyrus volumes were measured using structural MRI. Whole-brain fMRI activation patterns in an auditory task of listening to tones including pitch and duration deviants were compared between SPD and control subjects. In a second and separate ROI analysis we found that peak activation in superior temporal gyrus (STG), Brodmann Areas 41 and 42, was correlated with verbal learning and clinical measures derived from the SCID-II interview. RESULTS: In the region of the STG, SPD subjects demonstrated more activation to pitch deviants bilaterally (p<0.001); and to duration deviants in the left hemisphere (p=0.005) (two-sample t). SPD subjects also showed more bilateral parietal cortex activation to duration deviants. In no region did comparison subjects activate more than SPD subjects in either experiment. Exploratory correlations for SPD subjects suggest a relationship between peak activation on the right for deviant tones in the pitch experiment with odd speech and impaired verbal learning. There was no difference between groups on Heschl's gyrus volume. CONCLUSIONS: These data suggest that SPD subjects have inefficient or hyper-responsive processing of pure tones both in terms of pitch and duration deviance that is not attributable to smaller Heschl's gyrus volumes. Finally, these auditory processing abnormalities may have significance for the odd speech heard in some SPD subjects and downstream language and verbal learning deficits.     

Neuronal activity in the hippocampus during delayed non-match to sample performance in rats: evidence for hippocampal processing in recognition memory.

Neuronal activity in the CA1 of rats was explored with regard to functional correlates of performance in an odor-guided continuous delayed non-match to sample task. Although different CA1 cells fired in association with each identifiable trial event, these analyses focused on cells that fired selectively during the period of odor cue sampling and response generation. The firing patterns of many of these cells reflected the match or non-match comparison between current and previous odor cues independent of the particular stimuli that composed those comparisons. Such cells were more prevalent in sessions when performance was highly accurate. Hippocampal cells did not demonstrate stimulus-evoked firing that persisted through the memory delay, nor did they fire differentially to session-novel vs. repeated odor presentations. These results suggest that the hippocampus contributes to recognition memory by processing comparisons between current information and representations of previous stimuli stored in parahippocampal and neocortical structures.