حافظه کاری فضایی - دیداری در بیماران اختلال شخصیت

Abstract Background: Cognitive processing deficits have been identified as an abnormality that schizotypal personality disorder (SPD) individuals share with schizophrenic patients. It has been hypothesized that impaired working memory may be a critical component of several of the more complex cognitive deficits found in schizophrenia spectrum patients. Method: 18 DSM-III-R SPD patients, and 17 normal comparison subjects were compared on a pen and paper visuospatial working memory task. Moreover, we identified a second psychiatric comparison group comprised of nine patients with other, non-odd cluster personality disorder diagnoses who met no more than one of the SPD criteria and were also tested on the same task. Each person was given 14 immediate recall trials and 10 trials using a 10 s delay. Results: SPD patients performed significantly worse than normal control subjects on the working memory task. SPD patients also performed significantly worse compared to the non-schizophrenia-related personality disorder psychiatric comparison group. Conclusions: Like schizophrenic patients, SPD patients demonstrate working memory impairment compared to normal controls. This impairment may be specific to the schizophrenia-related personality disorders.

1. Introduction Cognitive deficits have been identified as one of the central abnormalities found in schizophrenic patients. In fact, cognitive impairment in schizophrenia may be a better predictor of daily functioning than symptom severity (Gold and Harvey, 1993 and Green, 1996). However, the susceptibility to schizophrenia occurs in a spectrum and the prototypic spectrum disorder is schizotypal personality disorder (SPD), which shares common genetic and biologic substrates with schizophrenia (Battaglia et al., 1995, Gunderson et al., 1983, Kendler and Diehl, 1993, Siever and Davis, 1991, Siever et al., 1990 and Siever et al., 1993b). It is critical to identify whether any particular cognitive deficits in schizophrenia are related to these common substrates of the spectrum (in which both schizophrenic and SPD patients would be expected to show impairment) or are associated specifically with chronic schizophrenia, with its accompanying psychosis and prior long term treatment (in which case, these deficits would be found in chronic schizophrenic patients but not in SPD patients). Since schizotypal subjects do not suffer from the chronic psychosis associated with schizophrenia, their performance on cognitive tasks is less likely to be confounded by poor motivation, long-term neuroleptic effects, or chronic hospitalization. Studies to date have shown impairments in sustained attention, verbal learning, executive functioning, and performance on eye tracking tasks in schizophrenic patients, SPD patients, schizotypal volunteers and relatives of schizophrenic patients (Braff, 1981, Cannon et al., 1994, Gold and Harvey, 1993, Javitt et al., 1995, Javitt et al., 1997, Keefe et al., 1994, Keefe et al., 1997, Lees Roitman et al., 1997, Park and Holzman, 1993, Siever et al., 1993a, Trestman et al., 1995 and Weinberger et al., 1988). While schizophrenic patients are likely to show marked deficits in most areas of cognitive processing, schizotypal patients show largely intact general intelligence with more circumscribed cognitive deficits (Trestman et al., 1995). The differential deficits shown by SPD patients make them an ideal population in which to study the cognitive impairments thought to characterize the schizophrenia spectrum. Schizophrenic subjects show particularly impaired performance on a range of tasks sensitive to frontal lobe dysfunction; the task that has been frequently used to assess prefrontal impairment is the Wisconsin Card Sorting Test (WCST), which measures the ability to identify and maintain a shifting cognitive set in response to verbal feedback (Weinberger et al., 1988). Clinical and non-clinical schizotypal subjects, like schizophrenic patients, are significantly more impaired on this task than normal comparison samples, although they do not show deficits in general IQ or spatial orientation measures (Battaglia et al., 1994, Lenzenweger and Korfine, 1994 and Trestman et al., 1995). In addition, SPD patients are impaired on other tasks that are thought to involve prefrontal cortical functioning such as the Verbal Fluency Test and the Stroop Color–Word Interference Test (Trestman et al., 1995). Impaired working memory is hypothesized to be a central component of several of these more complex cognitive deficits found in individuals with schizophrenia spectrum disorders. Working memory is defined as the function that serves for the retention of the stimulus information during the delay period between stimulus acquisition (Baddeley, 1983). Studies of non-human primates have shown that lesions in prefrontal cortex lead to severe spatial working memory deficits (Funahashi et al., 1989, Goldman-Rakic, 1994 and Goldman-Rakic and Friedman, 1991). Human analogues of the delayed response tasks which activate prefrontal cortex in monkeys have been developed and used to study working memory within the schizophrenia spectrum (Keefe et al., 1995). Unlike other tasks such as the WCST that include utilization of working memory as part of performance of a complex task component of task performance (Gold et al., 1997), the delayed response task is a much simpler and specific task involving working memory. Using such analogues, spatial working memory deficits have been identified in schizophrenic individuals who varied in their overall severity of illness (Harvey et al., 1995, Keefe et al., 1995 and Park and Holzman, 1993), relatives of schizophrenic patients (Cannon et al., 1994, Carter et al., 1996, Keefe et al., 1994, Keefe et al., 1997 and Park et al., 1995b), individuals with elevated perceptual aberration scores on the Chapman Scale (Park et al., 1995b) as well as psychometrically defined (by self-report) SPD individuals (Park and McTigue, 1997) from college samples. None of these studies addressed the specificity of this finding to SPD by examining a non-schizophrenia-related psychiatric comparison group. While most studies to date have focused on non-clinical SPD samples, who may or may not meet DSM-III-R criteria for SPD, it is also advantageous to study clinically identified SPD patients when investigating cognitive deficits. A clinical sample includes individuals with a broader range of intellectual functioning who, by definition, meet full criteria for SPD. In contrast, deficits in cognitive impairment are difficult to identify in college samples because they are already preselected on the basis of good intellectual functioning (Lencz and Raine, 1995). In such samples, SPD individuals identified on the basis of scales such as the Chapman Perceptual Aberration Scale may also include people with affective disorder symptomatology (Chapman et al., 1980). Thus, it remains to be determined whether clinically diagnosed SPD patients share a working memory impairment with schizophrenic patients. Furthermore, there have been no studies addressing the specificity of this association in a clinical population. Although there is evidence that SPD is related to schizophrenia, it appears that the schizophrenia spectrum may extend beyond the borders of the full criteria for schizotypal personality disorder (Siever and Davis, 1991). In fact, we have reported (Trestman et al., 1995) on cognitive impairment in DSM-III SPD patients where, in order to meet the disorder, four out of eight traits need to be present (in contrast to DSM-III-R where five out of nine criteria need to be present in order to meet SPD). Since it is unclear where the schizophrenia boundary lies, we wanted to identify and characterize a group of personality disorder patients that are clearly free of any schizophrenia spectrum symptomatology, to determine if these non-schizophrenia-related personality disorder patients demonstrate similar cognitive deficits or whether these deficits are more specific to SPD. This report utilizes the human analogue delayed response task developed by Keefe et al. (DOT Test — see Section 2), the performance of which has previously been reported to be impaired in schizophrenic subjects compared to controls (Keefe et al., 1995). The present study is the first to our knowledge to compare visuospatial working memory function in clinical patients diagnosed with DSM-III-R SPD with a normal comparison cohort. In addition, this study is also the first to test whether working memory impairment (in patients clinically identified and rated by DSM-III-R) is specific to the schizophrenia spectrum personality disorders compared to other, non-schizophrenia-related personality disorders. In this study, we hypothesized that SPD patients would demonstrate a working memory impairment compared to the normal comparison group. Moreover, we conducted a secondary pilot study to evaluate the specificity of the finding and we hypothesized that SPD patients would demonstrate a working memory impairment compared to the non-schizophrenia-related personality disorder cohort.

Results 3.1. SPD vs. normal comparison (Table 1) SPD patients did not differ significantly from the normal comparison group on age, or WAIS-R vocabulary subtest scaled scores (used as a measure of general intelligence) or immediate recall performance. SPD patients differed in years of education and WAIS block design scores from the normal comparison group (Table 1). Table 1. SPD and normal comparison (mean+SD) SPD (n=18) Normal comparison (n=17) Age 36.9±8.3 35.2±8.0 Education (years)a 14.1±2.6 16.1±2.4 WAIS – Vocabulary 10.7±2.9 11.8±2.0 – Block designb 10.1±2.9 12.2±2.3 Immediate recall distance error (cm) 0.90±0.4 0.76±0.3 Delayed (10 s) recall distance error (cm)c 2.15±1.3 1.25±0.4 Working memory deficitd (delayed−immediate recall distance error) 1.24±1.3 0.49±0.4 a t=2.21, df 33, p<0.04. b t=2.35, df 33, p<0.03. c t=2.70, df 21.5, p<0.02. d t=2.22, df 21.6, p<0.04. Table options Patients with SPD demonstrated greater working memory deficit (defined as delay recall condition error minus immediate recall condition error) compared to normal comparison subjects (t=2.22, df 21.6, p<0.04). This result remained significant, when we co-varied for age (F[1,31]=4.0, p<0.05), years of education (F[1,31]=4.5, p<0.05), WAIS-R vocabulary (F[1,31]=4.9, p<0.04), and block design (F[1,31]=6.4, p<0.02). This working memory deficit was also uncorrelated with age, education, WAIS-R vocabulary and block design (all r<0.12, all p=ns). 3.2. SPD vs. non-schizophrenia-related personality disorder patient group (Table 2) SPD patients (n=18) did not differ significantly from the non-schizophrenia-related psychiatric control group (n=9) on age, depressive symptomatology or medication history or immediate recall performance. SPD patients were significantly lower on WAIS vocabulary and block design scores and years of education from the psychiatric comparison group ( Table 2). Table 2. Schizotypal and non-schizophrenia spectrum personality disorders (mean+SD) SPD (n=18) Non-schizophrenia spectrum PD (n=9) Age 36.9±8.3 36.5±5.7 Education (years)a 14.1±2.6 16.7±1.6 WAIS – Vocabularyb 10.7±2.9 13.7±1.5 – Block designc 10.1±2.9 12.6±2.2 Ever met criteria for major depressive disorder 13 (72%) 7 (77%) Currently meet criteria for major depressive disorder 5 (28%) 2 (22%) Ever on psychiatric medication 9 (50%) 6 (75%) Days off psychiatric medication 619.1±443.4 501.7±473.6 Immediate recall distance error (cm) 0.90±0.4 0.85±0.2 Delayed (10 s) recall distance error (cm)d 2.15±1.3 1.27±0.6 Working memory deficite (delayed−immediate recall distance error) 1.24±1.3 0.41±0.5 a t=2.68, df 25, p<0.01. b t=3.44, df 24.8, p<0.01. c t=2.21, df 25, p<0.04. d t=2.28, df 24.9, p<0.04. e t=2.25, df 24.5, p<0.04. Table options Patients with SPD demonstrated significantly greater working memory deficit compared to the psychiatric control group (t=2.25, df 24.5, p<0.04). The working memory deficit was uncorrelated with age, education, WAIS-R vocabulary and block design (all r<0.17, all p=ns). In order to assess whether the finding of greater working memory deficit in SPD patients was due to any other clinical measure, we compared this deficit between patients meeting criteria for history of major depressive disorder (MDD+, n=20) and those who did not (MDD−, n=7). Working memory deficit in patients with a history of MDD (+: 0.6±0.7) did not differ significantly from those without such history (−: 1.8±1.9; t=1.6, df=6.6, p=ns). The working memory deficit did not differ in patients currently meeting criteria for MDD (0.5±0.7, n=7) from those who did not (1.1±1.3, n=20; t=1.75, df 20.81, p=ns). Working memory performance of patients with a history of having been treated with psychiatric medications (n=15) was not significantly different from the performance of patients without such history (n=12) [+: 0.8±1.3; −: 1.0±1.0; t=0.3, df=25, p=ns].