Copyright ª Blackwell Munksgaard 2007 Bipolar Disorders 2007: 9: 71–92

BIPOLAR DISORDERS

Original Article

Neuropsychological symptom dimensions in bipolar disorder and schizophrenia
Czobor P, Jaeger J, Berns SM, Gonzalez C, Loftus S. Neuropsychological symptom dimensions in bipolar disorder and schizophrenia. Bipolar Disord 2007: 9: 71–92. ª Blackwell Munksgaard, 2007 Background: While neurocognitive (NC) impairments have been well documented in schizophrenia (SZ), there is limited data as to whether similar impairments are present in other persistent mental illnesses. Recent data indicate that NC impairments may be manifested in bipolar disorder (BPD) and that they persist across disease states, including euthymia. An important question is whether a comparable structure of NC impairments is present in the 2 diagnostic groups. Objective: In a previous factor analytic study, we identified 6 factors to describe the basic underlying structure of neuropsychological (NP) functioning in SZ: Attention, Working Memory, Learning, Verbal Knowledge, Non-Verbal Functions, Ideational Fluency. The goal of this study was to investigate whether this factor structure is generalizable for BPD. Methods: The BPD sample included patients (n ¼ 155) from an ongoing longitudinal study evaluating BPD at the time of hospitalization for relapse and at multiple time points over the following 2 years. The SZ sample included patients (n ¼ 250) from a 3-year study. For the current examination the baseline NP evaluations were selected for both samples. Results: Exploratory and confirmatory factor analyses in the BPD sample yielded factors similar to those identified in the SZ sample. The coefficients of congruence ranged between 0.66–0.90 for the individual factors, indicating a good overall correspondence between the factor structures in the 2 diagnostic groups. Analysis of covariance (ANCOVA) analysis with education level, full scale-IQ, gender and ethnicity as covariates indicated that SZ patients had markedly worse performance on the Attention and Non-Verbal Functioning factors compared to the BPD patients. Conclusions: Together, these data suggest that while the same underlying factor structure describes NP functioning in both groups, the profile of impairments appears to vary with the diagnosis.

´l Czobora,b, Judith Jaegerc,d, Pa Stefanie M Bernsc, Cristina Gonzalezc and Shay Loftusc
DOV Pharmaceutical Inc., Hackensack, NJ, Nathan Kline Institute for Psychiatric Research, Orangeburg, cThe Center for Neuropsychiatric Outcome and Rehabilitation Research, The Zucker Hillside Hospital, North Shore Long Island Jewish Health System, Glen Oaks, dDepartment of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, NY, USA
b a

Key words: bipolar disorder – commonality in factor structure – neuropsychological symptom dimensions – schizophrenia Received 1 July 2005, revised and accepted for publication 17 August 2006 Corresponding author: Judith Jaeger, PhD, MPA, AstraZeneca Pharmaceutical Company, FOC W2-651, 1800 Concovel Plaza, Wilmington, DE 19803, USA. Fax: +1 302 886 4803. e-mail: jaeger.ju@gmail.com

Controversy exists over whether bipolar disorder (BPD) and schizophrenia (SZ) are best characterized as separate disorders or along a continuum (1). The classical position assumes a categorical view based on Kraepelin’s proposition from more

The authors of this paper do not have any commercial associations that might pose a conflict of interest in connection with this manuscript.

than a century ago (2); it considers differences between psychotic symptoms across diagnoses as qualitatively different. Current diagnostic systems such as DSM (3) and ICD-10 (4) operationalized this view, and try to separate bipolar illness (excluding recurrent major depression, which Kraepelin had grouped with manic depression) and SZ in a categorical fashion by requiring the presence or absence of certain symptoms for the purpose of diagnosis. However, since symptoms

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may overlap, sometimes for extended periods, the differential diagnosis of BPD and SZ frequently poses a problem in clinical practice. In response to this, an alternative, dimensional view is often invoked in contrast to the prevailing categorical approach, which posits that BPD and SZ do not represent a discrete illness entity. For example, Crow proposed that psychosis might vary along a continuum, extending from unipolar affective disorder through bipolar affective disorder and schizoaffective disorder to typical SZ (1, 5). Recently, the dimensional view has gained favor in a rapidly growing literature emphasizing shared abnormalities that cut across the current diagnostic divide. For example, shared morphometric findings, such as enlarged ventricles (6), and white matter volume reductions in the left frontal and temporoparietal regions were found in both disorders (7). Furthermore, common cellular and molecular patterns were observed, including a decrease in cell density in the GABAergic interneurons in SZ as well as in BPD (8). At the intracellular level, both diagnostic groups showed abnormalities in intracellular molecules (e.g., PSD95) that provide a physical link between multiple neurotransmitter systems (including the glutamatergic and dopaminergic systems) which are potentially involved in the neurobiology of SZ and affective disorders (9). Since these studies do not systematically exclude cases that are diagnostically challenging (e.g., share substantial features of both disorders) findings of shared pathophysiology may be confounded by the incorrect classification of cases. Recent studies have also reported apparent overlap in the genetic susceptibility between BPD and SZ. For example, family studies show a substantial degree of familial co-aggregation between bipolar illness and SZ (10). Moreover, systematic whole genome linkage studies raised the possibility of some common chromosomal regions shared by BPD and SZ, although various metaanalyses yielded inconsistent results with regard to the strength of the evidence for each of the potential candidate regions (11–13). Additionally, in candidate gene studies, specific genes have been identified in which variation appears to confer the risk to both BPD and SZ (with the strongest evidence shown for G72/G30, in the 13q candidate region, but common susceptibility was raised for example for BDNF, COMT, DISC1, neuregulin 1, and dysbindin) (11, 14). In addition, results from the first diagnostically unrestricted twin study indicate that the common shared additive genetic variance is substantially higher for mania and SZ (49% and 68%, respectively) than the diagnosis-

specific additive genetic variance (19% for mania and 33% for SZ) (15). Similar to studies examining pathophysiology, studies of genetic susceptibility for the most part suffer from design challenges that bias against findings that would distinguish the groups as Kraepelin had proposed (e.g., the difficulty of blinding the co-twin’s diagnosis during the diagnostic process, the practice of including cases with overlapping features which increases the chance of diagnostic error and the exclusion of recurrent major depression from the bipolar group). To address the question of disease boundaries, there is growing interest in identifying more precisely defined quantitative traits, which would represent more direct ÔdownstreamÕ biological consequences of genes than the symptoms. Such traits, or endophenotypes could serve as an alternative (or complement) to the categorical disease phenotypes, and potentially underlie a more accurate diagnostic classification. Based on their heritability and the fact that they can be measured objectively and reliably, certain domains of neurocognitive (NC) performance have been considered as candidate endophenotypes in major mental disorders including BPD and SZ. In the case of SZ, general NC deficits and deficits in various specific tasks indexing broader cognitive domains have been demonstrated, particularly in tasks of Attention, Long-Term Memory, Working Memory, and Executive Functioning (16). With regard to BPD, in the earlier literature, a common misconception was that, in contrast to SZ, bipolar affective disorder is not associated with general cognitive impairment independent of illness episodes, or in the premorbid state (6). However, newer literature challenged this view, and converging evidence suggests that persons with BPD exhibit persistent cognitive impairment across a range of tasks of Attention, Memory and Executive Function during remission (17–21). Furthermore, cognitive dysfunctions seem to be present in BPD patients not only during acute symptom exacerbation but both in prodromic and residual phases (14). Some of the authors concluded that particularly poor performance on tests of Verbal Memory was consistently found as a characteristic of BPD (17, 22). Glahn et al. (23) recently suggested that Verbal Learning and Memory and Executive Function/Working Memory may represent the most salient endophenotypic components of neurocognition in BPD because these domains appear heritable, co-segregated within families, associated with the disease, and impaired during periods of symptom remission.

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and limits the interpretability of the findings since the various components of the NC profiles across diagnoses were assembled from data derived from different studies. In general. The 11 domains comprised: Verbal Fluency. Working Memory. Since component measures were arbitrarily selected. In particular. This review concluded that BPD patients exhibit extensive cognitive abnormalities with a pattern of deficits that is not unique to this disease. and as stated by Horn and McArdle (26. IQ. we derived 6 clearly identifiable factors that had good psychometric properties with excellent construct. Abstraction. and that among 5 NC domains including Visuospatial/ Constructional. and Vigilance showed the largest impairments in both groups. effect size ¼ 0. The difference in terms of attention functioning did not reach significance (effect size ¼ 0. Another recently published meta-analytic review of the literature (16). (25) showed that patients with SZ were more impaired than patients with BPD in terms of general functioning [medium effect size (0. Attention. Language. with a higher level of impairment in patients with SZ in this study (22). and Executive Functions (Cognitive Flexibility. However. A potential research strategy to overcome this problem and to compare patterns of NC deficits in BPD and SZ is to administer a comprehensive neuropsychological (NP) battery consisting of several measures tapping into each of several putative NC domains. see above). Verbal Working Memory. focused on a different number of domains. (22) focused specifically on a comparison of profiles of NC abnormalities between BP and SZ in 8 domains. no previous studies compared the NC factor structure derived from the same instrument in both bipolar and schizophrenic patients.55) for the total score]. Verbal/Declarative Memory. This makes the comparisons difficult. Attention (Sustained. To our knowledge. the domainsÕ (construct) validity may not generalize to different samples. which included IQ. The metaanalysis (24) showed significantly worse performance in the patients with SZ in 9 out of 11 cognitive domains. Similar to the above 2 meta-analyses. Surprisingly. However. Hobart et al. and applied different definitions. Ôthe basis for drawing scientific inference is severely lackingÕ. or within the same sample over time. Mental Speed. this investigation compared NC performance in patients with BPD and SZ in 11 NC domains. The only areas in which performance of the 2 patient groups were not statistically significant were delayed Visual Memory and Fine Motor Skills. those studies that investigated multiple areas simultaneously. 24. Selective). this study concluded that while the level of impairments was higher in patients with SZ. Perceptual-Motor Functions. on the basis of the analysis of a comprehensive NC test battery. it is difficult to evaluate the validity of these results since it is conceivable that the group differences were confounded by the extent to which the NC domains represented different underlying constructs (factors) across diagnoses. as far as we know. and Sustained Attention/Vigilance. p. no empirical evidence has been shown to demonstrate that the various definitions of the underlying NC domains were valid in a particular diagnostic group. Verbal Memory Delayed. the profile shape did not differ between BPD and SZ. The majority of studies used only a relatively small set of tasks. Perceptual-Motor Functions. whereas the study by Seidman et al. respectively. The 2 large recent meta-analyses published only a few months apart from each other (16. In our previous factor analysis of patients with SZ. Concept Formation. Obtaining such evidence is a logical prerequisite of further group comparisons. A recently conducted meta-analysis of all comparative studies indicated that patients with BPD generally perform better than patients with SZ. Visual Memory Delayed. Memory. Mental Control.65) obtained a significant difference between the groups.33). Visuo-Spatial Ability. Abstraction/Executive. 117) without such evidence. considered 11 and 4 domains. Factor analysis provides 1 way to obtain this evidence based on the analysis of interrelationships among various NC measures. 73 . including Verbal Ability. Overall. the above literature that compared NC in patients with BPD and SZ had certain limitations. and generalizable across diagnoses. RBANS).Neuropsychological symptom dimensions An important theoretical question regarding NC functions as potential candidate endophenotypes is their diagnostic specificity. despite the fact that a substantial research effort has been spent to demonstrate that BPD and SZ share specific domains of psychopathology in terms of factor analytic structure. Executive Control. and the composition of tasks was vastly different across studies. and Fine Motor Skills. Visual Memory Immediate. Verbal Memory Immediate. The study by Seidman et al. Using a standardized test battery (Repeatable Battery for the Assessment of Neuropsychological Status. (22) defined 8 domains for the comparison of respective NP profiles. Delayed Memory and the Immediate Memory only the latter (Immediate Memory. Memory. defined only 4 major NC domains. Verbal Fluency). but the distribution of effect sizes revealed a large degree of heterogeneity (24).

an interim dataset from this ongoing study was cleaned and frozen (i. with the diagnosis of SZ (n ¼ 185. 18 and 36 months (not included in this report). Subjects were enrolled within 6 months of symptom exacerbation requiring hospitalization. 26%) were enrolled in the study.. subjects from this database were included in the analyses. and 74 . and Ideational Fluency). the aim of the second (Study 2: ÔBipolar StudyÕ) was to investigate the above relationship in patients with BPD. Baseline NC testing was conducted whenever possible when patients were optimally stabilized after hospitalization for the index episode. by investigating whether the same underlying factor structure of NC functions that characterized patients with SZ would generalize to patients with BPD. Approximately 30% had moderate to high mania with no or low depressive symptoms. if they had completed the baseline NC assessment. Altogether. For the present analyses.g. and. The 2 studies represented subsequent phases of the research project. Subjects were consenting patients in a 3-year study of SZ and schizoaffective disorder [diagnosed using the Structured Clinical Interview for DSM-IV (SCID)] which involved repeated neurocognitive testing. The core results.. Approximately 5% of the sample had active mixed symptomatology at the time of testing (e. Hence. and dimensionality reduction was an important tool to achieve a reduction in Type I error arising from multiple repeated testing of individual variables. A total of 250 patients. For the present analyses. 17 items) (31). 15 items) (30) of 0–7 for questionable and 8–15 for mild mania and. divergent and predictive validity. The goal of the first (Study 1: ÔSchizophrenia StudyÕ) was to test the longitudinal relationship between NC deficits and life functioning (disability) in patients with SZ or schizoaffective disorder. Verbal Knowledge. Staff administering NC tests were previously trained and observed in test battery administration to assure uniformity. have been published (28). including details concerning the NC factors that were identified. Study 2: Bipolar sample. conversely. 0–6 for not depressed and 7–17 mildly depressed. Non-Verbal Functions. moderate or greater symptoms on both mania and depression rating scales). Subjects received a comprehensive NC test battery and Positive and Negative Symptom Scale (PANSS) (29) ratings at baseline (used for the present report) and again after 6. approximately 11% of the sample had moderate to high depression with no or mild mania at the time of neurocognitive testing.Czobor et al. 11% (n ¼ 17) of the subjects in the primary dataset (n ¼ 155) evidenced symptoms on Study 1: Schizophrenia sample. Both studies collected a large number of NC variables and aimed to conduct factor analyses for the purpose of data (dimensionality) reduction. This aim was previously accomplished in the first study in a subset comprised of the first 156 patients enrolled (see below for further details).80). The PANSS raters had demonstrated interrater reliability compared to an expert (ICC ‡ 0. The principal objective of the current study was to extend this research further. subjects were included in the analyses if they had completed the baseline NC assessment. and stability over time in a longitudinal study (factors included Attention. Using cut-off scores for the Clinician-Administered Rating Scale for Mania (CARS-M. The objective of this naturalistic longitudinal study is to evaluate approximately 200 individuals aged 18 to 54 years with BPD [diagnosed using SCID (3)] at the time of hospitalization for relapse and at multiple time points over the following 24 months. for the Hamilton Depression Rating Scale (HAM-D.e. the final dataset from this study was used. The subjects for the analyses that we report here are consenting patients from an ongoing 24-month study investigating predictive and concurrent associations between NC deficits and disability in life functioning in individuals with BPD. Baseline NC data from a total of 155 subjects were used for the purpose of the current investigation. the question of generalizability of the NC factors across diagnoses served as a principal practical motivating problem for the current investigation. 74%) or schizoaffective disorder (n ¼ 65. an essential question was whether the same factor structure that we found in the SZ sample is applicable to the bipolar sample. we found that the majority (approximately 54%) of the sample had no or mild symptoms on both scales. Working Memory. Learning. Methods The data for the research reported here were collected in 2 longitudinal clinical studies investigating predictive and concurrent associations between neurocognitive performance and disability in life (psychosocial) functioning (LF) in individuals with serious mental illnesses [see companion paper (27) in this issue for further details of this research]. Since the principal purpose of Study 2 was similar to that of Study 1. no further changes were made in the database).

In addition. the bipolar sample demonstrated a significantly higher full scale-IQ and more years of education. medication data were available for a total of 142 patients (91. The NC battery was designed to examine functional domains previously considered important by virtue of their demonstrated impairment in people with major mental 75 . The 2 groups evidenced mild levels of symptom severity as shown by the respective psychometric ratings in each group. the analysis of the medication data indicated that all patients received polypharmacy in the bipolar sample.1 (SD) (9. n (%) White Black Hispanic Other a demographic prevalence data. The distribution (%) of the most common treatments was the following: lithium (69. Diagnostic distribution: schizophrenia ¼ 74% (n ¼ 185) versus schizoaffective disorder 26% (n ¼ 65). valproic acid (60.7c 18.4c 13. In the bipolar sample.6 12. Psychometric assessments of symptom severity in each study were conducted at baseline and each of the follow-up visits including neuropsychological testing. Overall. the proportion of female patients was higher in the bipolar as compared to SZ group. b Psychopathology. In addition to the neuroleptics.4) Schizophrenia sample (n ¼ 250a.5) (10. the 2 groups were essentially identical in terms of age.05) in their ethnicity and gender distributions. in the SZ sample.8) Sample size may vary due to missing data. In secondary analyses.3%). CARS-M (30) and the HAM-D scale (31) for the bipolar patients.1) (6.4 19.7) (4. In particular. symptom severity was indexed by the total score on the positive (POS) and negative symptom (NEG) subscale of the Positive and Negative Symptom Scale (PANSS).5%). reflecting the overlapping boundaries of BPD with the SZ spectrum in terms of symptom presentation. The rating instruments in each study were specific to the population targeted in that study.8) 113 29 7 6 (72. Thought Insertion.4f) 94 (37.3%).8) (2. In Study 2.9 20.7 points in full scale-IQ). onset of illness.6f) (42. The raters for each of these rating instruments in our study had demonstrated interrater reliability compared to an expert (ICC > 0.1c 86.0%). Comparison of the 2 samples The demographic characteristics of the bipolar (n ¼ 155) and SZ (n ¼ 250) samples are shown in Table 1. and anxiolytics (18.4) (8. many patients were taking another class of psychotropic medication as well including mood stabilizers. which focused on patients with BPD. f Significant difference in proportions (p < 0.Neuropsychological symptom dimensions Delusions involving ÔReplacement of WillÕ (Delusions of Control. the overwhelming majority of the patients (93% of the sample) were taking at least 1 neuroleptic medication at baseline. antidepressants (38.2f) 88 (56. anticonvulsants (67.8) Characteristics Age Onset of illness Age first treated Education Full scale-IQ CARS-Md/PANSS POSe HAM-Dd/PANSS NEGe Gender. Neurocognitive performance.2 14. The groups.6%). and age at which they received the first psychiatric treatment.6) 99 106 28 17 (39. Thought Deletion. anxiolytics. As Table 1 shows. Descriptive and demographic characteristics in the bipolar and the schizophrenia (reference) sample Bipolar sample (n ¼ 155a) Mean 35. neuroleptics (typical and atypical neuroleptics combined: 65.5) (6. the principal measures of psychopathology were the CARS-M (30) and the HAM-D (31). The distribution of atypical and typical agents in the sample was 68% and 32%. benzodiazepines (22. the PANSS positive and negative symptom subscale for the schizophrenics (Table 1).4) (11.1 20.5) (5. however.3 19. Thought Broadcasting) and Hallucinations. In Study 1.4) (11. the principal measures of psychopathology were the PANSS and the Brief Psychiatric Rating Scale (BPRS) (32). respectively. symptom severity was indexed by the total score on the Clinician-Administered Rating Scale for Mania (CARS-M) and the Hamilton Rating Scale for Depression (HAMD. Furthermore. d In the bipolar sample.b) Mean 36.9) 156 (62. at the time of the current analyses.0c 82.0 10.3) (5.9) (6. which focused on patients with SZ and schizoaffective disorder. e In the schizophrenia sample. we investigated whether the inclusion of these subjects in the sample had an impact on the principal results. while polypharmacy was common.8) (2.05) between the two samples (chi-square test). n (%) Male Female Race. were significantly different (p < 0. as expected on the basis of Table 1.6 (SD) (10.9f) (18.5) (3. c Significant mean difference (p < 0. although the former difference was quite modest (3. In the SZ sample.0%). and antidepressants. respectively.2) (6. a significantly higher proportion of patients from the white ethnic group were present in the bipolar as compared to the SZ sample. 17-item version).6% of 155).9) (8. respectively.1 21.9) (8.05) between the two samples (ANOVA).4%). Measures 67 (43.80).

Further details of our procedures are described elsewhere. These variables were the Visual Memory Span Forward [Wechsler Memory Scale-Revised (WMS-R). Short-Term Memory Capacity/Span. thus. a 2-stage procedure was designed to implement the PCA in a stratified way. to identify. Verbal Knowledge. the data were available from the entire SZ sample. Attention. based on the pattern of relationships among the observed variables. however. and Motor Functioning. we provide only a brief description in the Appendix. Staff administering NP tests were previously trained and observed in test battery administration to assure uniformity. However. including PCA run into serious difficulties because of the extremely high number of variables in the data relative to the number of observations. Ideational Fluency. Since there are conceptual as well as clinical reasons to presume a substantial correlation between the NC factors. Even if the geometric properties of PCA remain valid. the analysis under these conditions fails to provide a robust. We note here. Study 1 was ongoing and data were available only from a subset of 156 subjects. including factor and principal component analyses (PCA). thus. Table 2. and that the omission of these variables had essentially no impact on the internal consistency of these factors (change in Cronbach alpha was <0.e. In Stage 2. Learning. Wechsler Adult Intelligence Scale-Revised (WAIS-R) Information (included in the ÔVerbal KnowledgeÕ factor). in our previous study to identify the basic NC dimensions in patients with SZ. in general. and the PROMAX rotation (33) was applied in order to obtain a conceptually interpretable simple structure. traditional multivariate methods.Czobor et al. At the time of the previous publication. the variables in each block were subjected to factor (principal component) analysis to identify the basic underlying NC constructs (factors) that explained most of the variation within such a block of variables. the neuropsychological variables were divided into blocks based on a priori knowledge about their observed associations.. we note that 3 of the variables were not obtained in the bipolar study due to the fact that our preliminary analyses indicated that they displayed a high degree of overlap with variables in their respective factors. Ideational Fluency. generalizable solution. The PROMAX rotation is an oblique rotation technique which allows for correlation between factors. and the WAIS-R Object Assembly variables (included in the ÔNon-Verbal FunctionsÕ factor). Non-Verbal Reasoning/Problem Solving. we used all available data for the current study of the replicability of the NC factor structure across the 2 diagnostic samples. Conceptual framework of the statistical analyses NC test batteries typically yield a large number of variables. and Motor Skills (Table 2). This goal. latent set of factors (dimensions). Non-Verbal Learning. hence a fundamental goal in NC research is dimensionality reduction – to find a suitable representation of such multivariate data (i. this technique provides a more realistic representation of the data than the orthogonal solution which assumes independence. that a technique called Ôblock principal component analysisÕ (BPCA) has 76 . Working Memory. Non-Verbal Functions. the same neuropsychological test battery was administered in both studies. By the time of the current analyses. Set Shifting/Cognitive Flexibility. when applied to NC data. Working Memory. To deal with this problem. Thus. can be achieved by various multivariate techniques. Verbal Learning. included in the Attention factor based on Study 1]. Verbal Knowledge. and numerical techniques yield stable results. Executive Functions. Briefly. It includes 14 tests focused on measures of General Ability. which view the observed variables as manifestations of some underlying. the covariance matrix on which the analysis is carried out is sometimes a poor estimate of the real population covariance.05 for these factors). Neuropsychological tests used in the present study Neuropsychological tests Wechsler Adult Intelligence Scale-Revised (WAIS-R) (57) Wechsler Memory Scale Revised (WMS-R) (58) Letter Number Span (46) Complex Ideational Material (47) Concentration Endurance Test (D2) (48) Stroop Test (49) Wisconsin Card Sorting Test (128-card manual version) (50) Trail Making Test (A&B) (51) Controlled Oral Word Association Test (COWAT) (52) Animal Naming Test (51) Ruff Figural Fluency Test (53) Grooved Pegboard Test (54) Finger Tapping Test (55) Edinburgh Handedness Inventory (56) disorder and their relations to functional outcomes. in Stage 1. The specific tests used have been previously described by us and others. The 10 a priori blocks comprised Sustained Vigilance. however. a relatively low number of basic underlying dimensions that provide the most efficient description of the variation in the data). As mentioned above. The factor analysis was based on the principal component method.

The analysis was based on the likelihood ratio approach. constancy in the structure of the underlying NC constructs across diagnoses (BPD versus SZ). could not be reliably combined with any of these factors or with each another. Stroop Interference. The analyses were conducted in multiple steps. longest WAIS-R Arithmetic WAIS-R Digit Span Backward WMS-R Log Mem Immed WMS-R – Verbal Pair I WMS-R – Verbal Pair II WMS-R – Visual Pair I WMS-R – Visual Pair II WAIS-R – Vocabulary WAIS-R – Informationa WAIS-R – Comprehension WAIS-R – Similarities WAIS-R – Block Design WAIS-R – Object Assemblya WAIS-R – Picture Completion WAIS-R – Picture Arrangement WCST Number of Perseverative Errors Ruff Figural Fluency Unique Designs COWAT Animal Naming Test Perseverative Errors. Trails ¼ Trailmaking Test. relies on variable stratification. Second. using the maximum likelihood estimation. 77 . the principle of simple structure entails configurational invariance. An additional 5 NC measures. the psychometric properties (reliability and construct validity) of the NC factors derived in the bipolar sample were examined.. which states that the pattern of salient (nonzero) and non-salient (zero or near-zero) loadings defines the structure of a psychometric construct. In terms of factorial invariance. Stroop ¼ Stroop ColorWord Interference Test. indicating the need to examine them separately. Finally. COWAT ¼ Controlled Oral Word Association Test. i. Grooved Pegboard Preferred plus Non-Preferred Hand. and stability over time over an 18-month period of observation. generalizability was considered as factorial invariance. i. NonVerbal functions. Six neurocognitive factors derived from the schizophrenia sample Neurocognitive factor Attention Neurocognitive measure included in factor D2 – letters minus errors Stroop . to examine whether the items have the same relationship to the same underlying factor as posited on the basis of the earlier analyses in the SZ sample. The concept of factorial invariance was based on Thurstone’s notion of simple structure (35).e. Step 1: Homogeneity of correlation matrices. number correct LNS. a factor analysis with confirmatory Procrustes rotation was performed to examine the extent of similarity between the BPD and SZ samples with regard to each of the individual factors. LNS ¼ Letter Number Span Test. items comprising the same construct are expected to exhibit the same configuration of salient and non-salient factor loadings across the 2 diagnostic groups. confirmatory factor analyses (CFA) (33) were conducted to statistically test the configurational invariance of the hypothesized factor structure. in our previous study (28). first we D2 ¼ Concentration Endurance Test. Based on the above approach.Neuropsychological symptom dimensions been described recently in the literature (34). Trails B-Trails A/Trails A. a Variables not available in the bipolar sample included: Wechsler Memory Scale Revised (WMS-R) Visual Memory Span Forward. First. Fourth. using nested hierarchical models of the data as implemented by the SAS PROC MIXED procedure (36). we tested the null-hypothesis of no-difference in the correlation matrices between the BPD and the SZ sample. Verbal knowledge. Wechsler Adult Intelligence Scale-Revised (WAIS-R) Information. Third.color only Trails A WMS-R Visual Memory Span Forwarda WAIS-R Digit symbol D2 fluctuation WAIS-R Digit span forward LNS. In particular. in Step 5. the empirical data from the bipolar sample were subjected to unrestricted exploratory factor analysis (EFA) to examine whether model modifications were necessary in terms of the number of the factors and item composition of the underlying constructs derived in the SZ sample.e. it has been demonstrated that BPCA is as efficient as ordinary principal component analysis for dimensionality reduction (34). These include: Wisconsin Card Sorting Table 3. and Ideational Fluency (Table 3). 6 factors were extracted as having good construct. and the WAIS-R Object Assembly. Working Memory. In Step 1. Statistical analyses Working memory Learning Verbal knowledge Non-verbal functions Ideational fluency For the purpose of the current investigation. WCST ¼ Wisconsin Card Sorting Test. the homogeneity of the correlation matrices across the 2 diagnostic samples was tested. Using multivariate statistical theory. which have been widely studied in SZ. The 6 factors were Attention.. Learning.words only Stroop . Finger Tapping Preferred plus Non-Preferred Hand. divergent and predictive validity. which analogous to the 2-stage procedure employed in our study. Log Mem Immed ¼ Logical Memory (immediate recall). since the CFA addresses the configurational invariance of factors across samples but does not directly investigate the extent of similarity.

Czobor et al. or that most but not all of the factors are replicable (i. The Root Mean Square Error of Approximation (RMSEA) and the Goodness of Fit Index (GFI) were used to assess model fit for the entire CFA model. Similar to our previous study. we performed EFA to investigate whether the theoretically-postulated factor structure derived from the SZ sample represents an adequate representation of the pattern of observed associations among a group of variables in the BPD sample. Step 3: Confirmatory factor analyses. not the particular magnitude of the non-zero loadings. Therefore. we used the Kaiser–Guttman eigenvalue >1 criterion (37) and Cattell’s Scree plot (38). it is conceivable that the number of interpretable factors is different in the 2 samples. and in terms of the factor structure of the individual factors based on the distribution of salient and non-salient loadings. in view of the fact that we had a relatively small sample size. Second.e. The relationship between the observed variables and the hypothesized underlying constructs can be investigated by CFA. the threshold loading of 0. The theoretical factor-loading matrix specifies the number of components to be fitted and the factor-loading pattern of the test items. A failure to reject the null-hypothesis with regard to the homogeneity of the correlation matrices across the 2 diagnostic groups may be a reflection of low statistical power.5 was chosen to indicate saliency. Therefore. the requirement is that the same pattern of (zero and non-zero) factor loadings is found in the individual groups. Test of improvement in model fit was based on chi-square statistics. in order to establish whether a construct can be conceptualized in the same way across diagnoses. For the current study. The CFA techniques used in this investigation set a priori definitions of the factor structure (measurement model) based on the findings from the SZ sample and based on our preliminary EFA findings in the BPD sample. Values of t-statistics were used to test whether the individual items were significantly related to their specific factors. Thus. The RMSEA indicates the fit of the model to the covariance matrix (or correlation matrix. In this theoretical framework. It represents the square root of the average amount that the sample covariances differ from their estimates derived on the basis of the posited factor model. following Thurstone (35). Unlike the CFA method. in a multi-group CFA no cross-sample constraints are imposed on the magnitude of the salient factor loadings. Items were allocated to factors according to their highest loading. As described above. More specifically. Step 2: Exploratory factor analyses. partial versus full factorial invariance). For this reason. RMSEA values below 0. whereas values of <0. The PROMAX rotation was applied in order to derive a simple structure to facilitate the interpretation. whereas the CFA addresses the configurational invariance of factors across samples. Step 4: Generalizability across samples. For example. zero). In order to examine the dimensionality in an EFA. In the CFA. In the structural part of the CFA models. the non-salient loadings are (implicitly) specified to be equal (i. we used the principal component method for factor extraction.e. derived a null-model likelihood by positing an unstructured homogeneous correlation matrix for the empirical data across the 2 diagnostic groups. In model 1.1 are generally considered to indicate an adequate fit. confirmatory Procrustes rotation (39) was applied to investigate the extent of similarity (generalizability) between the SZ and the BPD samples (maximum congruence). the most basic conceptualization of a construct is the pattern of non-zero and zero loadings. estimates of loadings of the individual neuropsychological items were obtained for their hypothesized factors.05 represent a close fit.90 are considered as an indication of an adequate model fit. before we proceeded with the CFA. This confirmatory procedure rotates empirically extracted principal components to a theoretically specified target matrix of factor loadings to maximize their similarity. 2 theoretically possible alternatives were tested against each other. values above 0. For GFI. since it does not take the particular magnitude of the loadings into account. In model 2. in these preliminary analyses. we relaxed the homogeneity condition (posited a heterogeneous correlation matrix by diagnostic group) and examined whether the resulting improvement in the likelihood reached statistical significance. all factors were considered interrelated constructs and a correlation was therefore allowed between any of the 6 factors. the Procrustes 78 . it does not indicate the extent of similarity (generalizability). as in our study)... As a guideline. it is possible that the 2 groups have certain systematic differences which would not result in the rejection of the null-hypothesis in our study. we investigated whether model improvements were necessary in terms of the number of factors that need to be retained for further analyses. the basic assumption was that the 6 NC factors represent 6 distinct constructs with no relationship (correlation) between them.

0001).5 (df ¼ 701. Exploratory factor analysis Results Demographic and basic descriptive data at baseline Descriptive neuropsychological data on all individual NC variables of interest are shown in Overall. These results in the bipolar sample were similar to what we found in the expanded sample of schizophrenic patients that we used for the purpose of the current analyses [n ¼ 250. eigenvalue > 1 for factors retained for further analyses) and on Cattell’s scree-plot criterion based on the breakpoint of the curve. Since. In order to do this. for discriminant validity. indicating that the homogeneous correlation structure provides adequate fit to the data across the 2 diagnostic groups. whereas the heterogeneous correlation model resulted in chi-square ¼ 5330.e. To examine concurrent validity we assessed the ability of the 6 NC factors to distinguish between the 2 diagnostic groups. construct validity. whose size was identical to the size of original dataset. the 6 factors explained approximately 68. then.2%). including ÔDistractibilityÕ (Item 6. was subjected to factor analysis with Procrustes rotation.5%). including the subsample of patients used for our previous 79 . Homogeneity of correlation matrices The null-hypothesis of no-difference between the correlation matrices from the BPD and the SZ sample was tested by the likelihood ratio test. indexing mania and depression.Neuropsychological symptom dimensions approach estimates loadings for all items (including items that are considered non-salient).e. we examined the degree to which the 6 NC factors overlapped with psychometric ratings of clinical symptoms. normed between +1 and )1. NC functioning and psychopathology may represent separate dimensions. Second.6%). the homogeneity condition was relaxed (i. homogeneous correlation matrix across the 2 diagnostic groups.1). The likelihood ratio chi-square statistic for the improvement in model fit did not reach statistical significance (p > 0. and Learning (9. Values of CC of 0.80 and above are considered to indicate sufficient similarity between the empirically Procrustes-rotated and theoretically postulated factors. a heterogeneous correlation matrix was posited across the 2 groups). Ideational Fluency (11. similar to our published findings in the SZ sample.0% of the total variance in the neuropsychological dataset in the bipolar sample.000 samples with replacement from the original database. Scale (factorial) reliability was examined through the internal consistency reliability. The sampling variation of the CC was estimated using the bootstrap/resampling approach (40). In particular. Attention (12. Non-Verbal Functions (11. p ¼ 0.0001).. The model fit was evaluated by the coefficient of congruence (CC) (38). For the purpose of the analyses reported here. Verbal Knowledge (12. In particular.. and we examined whether the resulting improvement in the modellikelihood over the null-model likelihood reached statistical significance.5 (df ¼ 350. discriminant validity was examined via bivariate correlations between the components of the NC factors and the overall severity score of clinical symptoms. each of these samples. External (criterion-related) validity of the NC factors derived in the bipolar sample was investigated through the convergent. Comparison of the 2 groups on the individual measures indicated a significantly better performance in the BPD as compared to the SZ sample for 15 of 30 measures (corrected for multiple testing using the Hochberg procedure). first we derived the null-model likelihood by positing an unstructured. results of the exploratory factor analysis (principal component method with PROMAX rotation) in the bipolar sample indicated 6 factors based on both the Kaiser–Guttman eigenvalue criterion (i. The distribution of the amount of variance explained across the 6 factors was: Working Memory (12. we examined the degree to which the NC factors yielded convergent information with other.0%). The null-model likelihood indicated chi-square ¼ 5130.1%). Step 5: Reliability. In particular.6%). Table 4. 2 of the items of the CARSM. we first randomly selected 1. apart from such selected items. respectively. which excludes distractibility due to intrusions of visual and/or auditory hallucinations or delusions and rates whether Ôattention is too easily drawn to unimportant or irrelevant external stimuliÕ) and ÔDisordered ThinkingÕ (Item 11) were investigated. Internal consistency for each of the 6 NC factors was determined by the use of Cronbach alpha (41). in order to establish convergent validity. external measures that they would theoretically be expected to be similar to. discriminant and concurrent validity. although the magnitude of the difference was generally modest. Together. p ¼ 0.

6 38. we added the 4 motor measures (Table 4.0 43.2 6.0–29. Table 4. the results indicated that the motor variables did not load on any of the 6 basic NC factors described above.1) (3.0–61.5 31.5%).1 10.0–12. analyses (n ¼ 156)].6) (7. respectively) and 1 for dexterity (Grooved Pegboard Preferred and Non-Preferred hand. WAIS-R ¼ Wechsler Adult Intelligence Scale-Revised.4 (96.4%).5 12.9) (9.5c 89.7) (5.0–13.2 16.0 8.7) (4.0–39.3 7. Learning (10.4 7.6 16.0–14.0–20.0 41.0) (2. LNS ¼ Letter Number Span Test.0 34. Similar to our previous analyses.5) (17.0–6.0 15. the CFA analysis set a priori definitions of the factor structure based on 80 .0 Schizophrenia sample (n ¼ 250a) Mean (SD) 321.0 4.0–19. Log Mem Immed ¼ Logical Memory (immediate recall). Verbal Knowledge (11.0 10.6 11.9) (4.0 3. the 6-factor solution in the SZ sample explained 67. 1 for motor speed (Finger Tapping Preferred and Non-Preferred hand.3 33.0–21.0) Q1–Q3b 251–395 68. In particular.2) (2.0–17.7) (16.0–20.1 125.0 12.4) (6.0 6.2) Q1–Q3b 297–429 76.5 73.4) (8.8) (8.0–19.6c 39. b Q1–Q3 ¼ Interquartile range.7) (18.Czobor et al.05.1–49.0–49.7 18.0 8.0c 47.0) (24.4) (5. last 4 rows) to the set of NC variables that we used above. Working Memory (12.1) (21.1) (4.8% of the variance. Confirmatory factor analysis As mentioned in the methods.9) (12.0 7.2c 79.0 11.0) (1.8) (12.0–20.0–10. In addition to the above EFA analyses that focused on the same set of variables that we included in our previous analyses in the SZ sample.0–136. similar to our published study.0 6.0 13.0–18.0–19.0–133.9c 66.2 7.7) (22. Instead.2c 15.0 30. the individual factors explained a similar amount of variance in the SZ as in the BPD sample.0–25.0 4.6) (1. with the exception of the ideational fluency factor which was associated with a smaller amount of explained variance in the SZ sample.0 5.0 31.0 11. WMS-R ¼ Wechsler Memory Scale-Revised.3) (13.0–5.0 49.0 6.0–73.3 12.1c 53.0 13.0) (11.4) (69.5 80.0–22. we explored whether a separate motor factor can be derived in the BPD sample.0 90.0%).9) (12.0 36. c Significant mean difference (p < 0.0–8.0 4.4) (2.0–19.6) (4. and repeated the exploratory factor analysis that we performed for the more limited set of measures that did not include the motor variables. COWAT ¼ Controlled Oral Word Association Test.0 10. Descriptive statistics for individual neurocognitive measures Bipolar sample (n ¼ 155a) Neurocognitive measure D2 – letters minus errors Stroop–words only Stroop–colors only Trail Making A Time WAIS-R Digit Symbol Raw D2 Fluctuations WMS-R Digit Span Forward LNS Total Correct LNS Longest Item Passed WAIS-R Arithmetic Raw WMS-R Digit Span Backward WMS-R Log Mem Immed Ruff Figural Fluency Unique Designs COWAT Total Correct Animal Naming Total Correct WAIS-R Vocabulary Raw WAIS-R Comprehension Raw WAIS-R Similarities Raw WAIS-R Block Design Raw WAIS-R Picture Completion Raw WAIS-R Picture Arrangement Raw WMS-R Verbal Paired Association I WMS-R Verbal Paired Association II WMS-R Visual Paired Association I WMS-R Visual Paired Association II WCST Number of Perseverative Errors Finger Tapping Preferred Finger Tapping Non-Preferred Grooved Pegboard Preferred Grooved Pegboard Non-Preferred Mean (SD) 358.0 24.8) (9.0 6.0–20.0 45. Stroop ¼ Stroop Color-Word Interference Test.0 21.7) (1.7c 44.7 (98.0 3.4) (62.9c 15.0–64.0 7.4) (4.7 16.0 5.0–8.0) (4.0 9.1 22.0 4.7 8.0 6.5–114.1) (1.5–55.1) (1.0–45.9c 16.8) (19.5–102.7c 51.8c 5.0–38.0–119.4) (2.2c 42. respectively).0–25.0 4.3) (3.0 D2 ¼ Concentration Endurance Test. with Hochberg’s adjustment for multiple testing) between the 2 samples (ANOVA).0–33.7c 43. The distribution of explained variance across the 6 factors in the SZ sample was: Attention (15.6) (7.5–82. In addition.0–53.0–8.0–91.5) (13.0) (7.0 13.0c 4.9c 5.5c 34.6 12.0 34. based on the 4 variables that we used for the analysis 2 independent small factors (containing 2 related variables only) emerged.6) (5.0c 4.7) (22.0–10.0–69.1) (53.8 33.0c 38.0–50.3 19.7 11.9) (37.4) (9.5) (5.0–6.9) (9. Non-Verbal Functions (11.0 12.0 15.9c 40.6) (4.8c 15. a single motor factor could not be derived.8) (14.0 13.4c 111.0–43.0 24. a Sample size may vary due to missing data.0–9.0–5.5c 4.1c 4.0 13.7) (10.6c 99.0 30.0–6.5 6.6c 59.7%) and Ideational Fluency (3. For the purpose of this investigation.3–46.0 116.0 77.0 9.7%).4 15.0 9.7 8.0–15.0 46.7) (5.0) (1.5) (3.5c 43.0–52.0–15.0 16. Furthermore.1c 60.5) (14.0–46.2 31.8 19.7 7.3c 16.5%).0–14.1) (4.0–7.0–11.9) (5.1c 13.8 21.5 10.

78 7.88 13.06) (0.66 0. Table 5 displays the estimated factor loadings for Model 2 (correlated factors) based on the CFA Table 5.79 0.06) (0.06) (0.70 0.06) (0.65 0.12) (0.06) (0.56 0.40 0.95 0.31 3.02 9.74 0.69 10.11) (0.84 0.75 0.68 (0.58 9.75 0.70 5.18 12.72 and 0. loadings outside the underlying construct were not estimated (restricted to be 0).11) (0. *p < 0.58 11. Stroop ¼ Stroop Color-Word Interference Test.11) (0.07) (0.11) (0.06) (0. the estimated loading coefficients reached statistical significance for each of the indicators (observed NC variables) for each of the hypothesized factors in both samples. As Table 5 shows.19 6.03 6.97 7.79 0.064 (RMSA). Although the GFI indices failed to reach the recommended threshold.18 5.70 0. for both D2 Fluctuations and LMI).21 12.75 0.12) (0.12) (0.78 0.80 0.86 3. Results of the CFA analysis indicated that the correlated factor model (Model 2) which allowed correlations between the 6 underlying factors provided a significantly better fit to the data than the independent factor model (Model 1) (BPD sample: chi-square ¼ 164.43 13.05) (0. COWAT ¼ Controlled Oral Word Association Test.4. LNS ¼ Letter Number Span Test.11) (0.06) (0.12) (0.52 6.80 0.95 0.07) (0.06) t-statistic* 12.12) (0.06) (0.00 4.06) (0.23 0.81 0.05 for all values in the column.34 0.87 11. the RMSA values were 0.74 0.48 17.26 9.06) (0.06) (0. the CFA assumed a Ôsimple structureÕ: observed NC variables were allowed to assume a non-zero estimate only for 1 of the 6 underlying constructs.61 0.86 0. 81 . the results were similar in both samples. WMS-R ¼ Wechsler Memory Scale Revised.69 0. however.43 5. SZ sample GFI ¼ 0.95 Schizophrenia sample Loading (SE) 0.12) (0.05) (0.41 0.06) (0. We note.09) (0.0001.07) (0.52 0. p < 0. respectively.78 5.06) (0. Confirmatory factor analysis estimates of factor loadings Bipolar sample Factor Attention Neurocognitive measure D2 – letters minus errors Stroop-words only Stroop-colors only Trail Making A Time WAIS-R Digit Symbol Raw D2 Fluctuations WMS-R Digit Span Forward LNS Total Correct LNS Longest Item Passed WAIS-R Arithmetic Raw WMS-R Digit Span Backward LMI Ruff Figural Fluency Unique Designs COWAT Total Correct Animal Naming Total Correct WAIS-R Vocabulary Raw WAIS-R Comprehension Raw WAIS-R Similarities Raw WAIS-R Block Design Raw WAIS-R Picture Completion Raw WAIS-R Picture Arrangement Raw WMS-R Verbal Paired Association I WMS-R Verbal Paired Association II WMS-R Visual Paired Association I WMS-R Visual Paired Association II Loading (SE) 0. the above 2 variables were omitted from our final CFA model.51 6. respectively.68 0.12) (0.73 0. the analogous values were 0. In the BPD sample.07) (0.15 analysis conducted in the BPD and in the SZ samples.72 (0.96 14.69.094 and 0.24 11.14 10. suggesting configurational invariance across the 2 samples.74 7.11) (0. WAIS-R ¼ Wechsler Adult Intelligence Scale-Revised.93 0.69 0.41 2.18 5.11) t-statistic* 6. the GFI and the RMSA were 0. df ¼ 15.65 0.83 5.45) in both samples.11) (0.24 7.85 0.74 10.06) (0. SZ sample: chi-square ¼ 663.05) (0.72 0.85 10.31 12.11) (0.06) (0.63 11.11) (0.58 0.11) (0.74 0.87 0.75 0.95 6.58 13.37 7.98 5.84 (GFI) and 0.82). estimates of loadings of the individual NC variables were obtained for their hypothesized factors only.06) (0.19 4.36 10.74 5.59 0.12) (0.81 0.12) (0. our final factor model was based on the restricted set of variables Working memory Ideational fluency Verbal knowledge Non-verbal functions Learning D2 ¼ Concentration Endurance Test. p < 0.11) (0.06) (0.64 11.62 11.78 0. In particular.0001). In other words.76 0. In particular.32 4.11) (0.76 0. The CFA results based on this model indicated an improvement in the model fit indices. in the SZ sample.63 0.11) (0. df ¼ 15.64 0.65 0.53 5.3. respectively.074 in the BPD and the SZ samples. Since these findings suggested low indicator reliability for these variables with respect to their underlying construct (Working Memory.086 respectively.95 0. for which they were considered as indicators. Indices of overall model fit showed that GFI did not reach the recommended level in either of the 2 samples (BPD sample GFI ¼ 0.63 0.10) (0.16 18. LMI ¼ Logical Memory (immediate recall). that for 2 of the variables [Concentration Endurance Test (D2) Fluctuations and Logical memory – immediate recall (LMI)] the coefficients were low (loading estimate <0.Neuropsychological symptom dimensions our earlier findings from the SZ sample.

As mentioned before. Working Memory ¼ 0.e. Inclusion of these subjects in the analyses increased diagnostic heterogeneity and phenomenological overlap across diagnoses. in the BPD sample. and the PROMAX approach was used to allow for correlation among the 6 NC factors. the Procrustes analysis used the theoretically postulated target structure based on the factor structure derived in the final factor model from the CFA analyses. including ÔDistractibilityÕ (Item 6) and ÔDisordered ThinkingÕ (Item 11). Non-Verbal Functions.850 0. and Learning. Observed CC value 0. For convergent validity.999 0. confirmatory Procrustes rotation was applied to investigate the extent of congruence between the factor structures derived in the bipolar and the SZ sample. The analyses focused on 2 items of the CARS-M. Consistent with coefficient of congruence estimates. respectively. As shown in Table 6. there was a high level of similarity between the set of loadings derived in the BPD and the SZ samples. the values of CC remained almost unchanged between the 2 diagnostic samples (Attention ¼ 0. This method is suitable for maximizing the similarity between a matrix of factor loadings and an assumed underlying structure by means of theory-based expectations as targets. 3 indicates that this relative lack of congruence for this factor is due to the fact that. not including D2 Fluctuations and LMI) since this set provided a closer fit to the empirical data.e. no meaningful differences were observed between the 2 samples in terms of construct reliability of the 6 NC factors. Table 6 displays the estimated coefficients of congruence between the corresponding factor pairs from the BPD and the SZ samples. in additional secondary analyses. we examined the degree to which the NC factors provided convergent information with measures that they would theoretically be expected to be overlapping. only 2 of the constituting items whereas in the SZ sample all 3 of the items reached saliency (in particular. An inspection of Fig. Procrustes matching As described in the Methods. Distractibility. which may have served as a major contributing factor to the similarity of the factor structures across diagnoses. based on 1. To investigate this possibility further. As Table 7 shows.837 0. The factor loading estimates yielded by the Procrustes analysis are depicted in Figs 1–6 for each of the 6 NC factors. for all factors except for Ideational Fluency.. (i. Overall.863.883 0. in the bipolar sample. Convergent validity. Disordered Thinking) and the 6 NC factors. the loading for the Ruff Figural Fluency Unique Designs was close to zero). with the exception of the Ideational Fluency factor for which the internal consistency estimate in each sample was only of moderate magnitude.601. and recomputed the coefficient of congruence for the factor structure across diagnoses.467 0. Verbal Knowledge. was examined by logistic regression analysis. Coefficient of congruence (CC) between factors derived in the bipolar and the schizophrenia samplea 95% Confidence limitsb Factor Attention Working memory Ideational fluency Verbal knowledge Non-verbal functions Learning a loadings derived in the BPD and the SZ samples.903 Lower 0. Figs 1–6 indicate a good correspondence between the set of Table 6.813 Upper 0. the Procrustes approach estimates for each factor the loadings for all variables used in the analysis (including items that are considered non-salient for a particular factor). the factor analysis was based on the principal component method. association between the above 2 items (i. Results of the logistic regressions analyses are shown in Table 8. Unlike the CFA. validity Construct reliability.932 0. For 1 of the factors (Ideational Fluency).. Reliability. 82 .787 0.979 0. Table 7 displays the Cronbach alpha estimate (measuring internal consistency) for each factor in each of the 2 samples.962 0.821 and Learning ¼ 0.878 0.000 samples drawn randomly from the original observed dataset. the internal consistency for the individual factors was generally good. Ideational Fluency ¼ 0.675 0. For the purpose of the current study. and 11% in the ÔBipolar StudyÕ evidenced some symptoms of Delusions or Hallucinations. respectively.805. the congruence was moderate. approximately 26% of the sample in the ÔSchizophrenia StudyÕ was diagnosed with schizoaffective disorder.794 0. Similar to our previous analysis. respectively. Verbal Knowledge ¼ 0. b Bootstrap/resampling estimates. respectively.797.818 0.704 0. we excluded the aforementioned subjects. Non-Verbal Functions ¼ 0.993 Factor analysis was based on the PROMAX method using Procrustes rotation.890). respectively. Results indicated that the 6 NC factors were replicable with the more homogeneous samples. for 5 of the 6 factors including Attention.Czobor et al. Working Memory. In particular.658 0.

Paired II WAIS Vocab. a statistically significant association was observed for 5 of the 6 factors including Attention. individual neuropsychological variables entering the factor analysis were grouped according to the 6 factors identified on the basis of previous study (28). 1 for complete description and abbreviations. For discriminant validity. Stroop. Correct Arithmetic Digit Sp. Forw.50 0. Stroop ¼ Stroop Color-Word Interference Test. COWAT Total Anim. WAIS Pict. WAIS Similar.50 Factor loadings 0.-Error Digit Symbol WAIS Compr. discriminant validity was examined via bivariate correlations between the neurocognitive factors and the overall severity score of clinical symptoms. Verb. Back. 2. Working Memory. Paired I Verb. On the horizontal axis.Cp. respectively. Ruff Uniq.Arr. we investigated the degree to which the 6 NC factors overlapped with psychometric ratings.Cp. WAIS Similar.Des.Neuropsychological symptom dimensions Attention factor 1.Arr. As Table 8 indicates. Working memory: comparison of factor loadings obtained in the bipolar and schizophrenia samples. Non-Verbal Func- tions. WAIS Pict. Disordered Thinking had a more general relationship with NC functioning. Time D2 Lett. indexing mania (total score on the CARS-M scale) and depression (total score on HAM-D scale. 83 . Colors WAIS Vocab. Correct LNS. WAIS ¼ Wechsler Adult Intelligence Scale. Trails A. WAIS Pict. Verb. Naming WAIS Block D. Longest LNS. Words Stroop. Ruff Uniq. Longest Arithmetic Digit Sp. Discriminant validity. Factors from the 2 samples were matched (paired) on the basis of their congruence.-Error Trails A. Paired I Verb. Visual Paired I D2 Lett. LNS. As expected. D2 ¼ Concentration Endurance Test.00 Digit Sp. Time Digit Symbol WAIS Compr. Naming Bipolar SCH/SCA Fig. Words Stroop. Visual Paired I Visual Paired lI Bipolar SCH/SCA Fig.00 0. WAIS Block D. Attention: comparison of factor loadings obtained in the bipolar and schizophrenia samples. LNS. Forw. Stroop. 17-item version). See Fig. In particular. COWAT ¼ Controlled Oral Word Association Test. LNS ¼ Letter Number Span Test. Ideational Fluency. Back. Verbal Knowledge. The factor analysis was based on the principal component method applying Procrustes rotation.Des. 1. In particular.00 Digit Sp. Working memory factor 1. Paired II Visual Paired lI COWAT Total Anim.00 Factor loadings 0. The association did not reach significance for Learning. Colors WAIS Pict. the largest effect size was observed for the association with the Attention factor. the clinical rating of Distractibility was associated with poorer functioning on the Attention and Non-Verbal Functions factors (and to a lesser extent on Learning). as indexed by the NC factors.

-Error Digit Sp. Analyses of the total score on the CARS-M scale indicated 2 significant.Cp. WAIS Vocab. COWAT Total Anim.-Error Stroop.017) and the Non-Verbal Knowledge factors (n ¼ 148.00 Factor loadings 0. Trails A. 3.Czobor et al. WAIS Block D.20. a significant group difference was detectable only on the Attention and Non-Verbal Functions factors.00 Ruff Uniq. Words Stroop. and the age at first treatment may have a differential impact on NC functioning in the 2 84 . Diagnostic group served as an independent variable in the ANCOVA analysis.Arr. Concurrent validity. Ideational fluency factor 1. Since age. full-scale IQ.Des. patients in the BPD sample displayed a significantly better functioning on each of the NC factors than patients in the SZ sample. Verbal knowledge: comparison of factor loadings obtained in the bipolar and schizophrenia samples.16. Paired I Verb. Verbal knowledge factor 1. Colors Digit Symbol Digit Sp. education. Words Stroop. Ideational fluency: comparison of factor loadings obtained in the bipolar and schizophrenia samples. Bipolar SCH/SCA Fig. WAIS Similar. However. Naming COWAT Total Verb. WAIS Compr. As shown in Table 9. Results of the comparisons between the 2 diagnostic groups are summarized in Table 9. WAIS Pict. but modest associations including the Working Memory (n ¼ 148. See Fig. To examine concurrent validity we assessed the ability of the 6 NC factors to distinguish between the 2 diagnostic groups. Time WAIS Vocab. Correct LNS.Arr.Cp.50 Factor loadings 0. WAIS Similar. LNS. The analyses were based on the analysis of covariance (ANCOVA) model using the NC factors as dependent variables. Anim. gender and ethnicity were used as covariates. 1 for complete description and abbreviations.00 Ruff Uniq. Forw. Results of these analyses revealed no statistically significant association between the total score on the HAM-D scale and any of the 6 NC factors. Back. r ¼ )0. WAIS Pict. Paired I Verb. Longest Digit Symbol Arithmetic Digit Sp. Forw. Colors Trails A. r ¼ )0. 4. Paired II Visual Paired I Visual Paired lI Stroop.Des. WAIS Pict. D2 Lett. Bipolar SCH/SCA Fig. with a separate analysis performed for each of the factors. p ¼ 0. Back. after adjustment for the covariates. Time D2 Lett. p ¼ 0. onset of illness. Correct Arithmetic WAIS Block D. Longest Digit Sp. See Fig. WAIS Compr.50 0. Naming Verb.00 0. WAIS Pict. LNS. respectively. Paired II Visual Paired I Visual Paired lI LNS. 1 for complete description and abbreviations.047).

Arr.. Back.50 0. taken together. the bipolar sample had a higher proportion of females and white ethnicity than the SZ sample. Stroop.00 0. Colors Ruff Uniq.Cp. 6. Forw.-Error COWAT Total Anim. Furthermore. WAIS Compr. the congruence between the factor structures remained essentially unchanged with the more homogeneous samples (i. Time Bipolar SCH/SCA Fig. Visual Paired I Visual Paired lI Bipolar SCH/SCA Fig.Des. Verb. and the CFA showed that the items loaded on the factors that were theoretically stipulated on the basis of measurement model based on our prior SZ study. Non-verbal functions: comparison of factor loadings obtained in the bipolar and schizophrenia samples. Words Stroop. as well as more years of education and higher full 85 . Naming Digit Symbol WAIS Compr. this is the first study that compared the factor structure across diagnoses including SZ and BPD. indicated that the factor structure is generalizable across the 2 diagnostic samples. LNS. Forw. See Fig. WAIS Pict. Stroop. It is noteworthy that similar factor structures emerged in spite of sample differences on some demographic characteristics and IQ.Arr. WAIS Block D. None of the analyses indicated a significant effect (i. Discussion To our knowledge.10 in all analyses for the main effect or for the interaction of the above variables with the diagnosis). 1 for complete description and abbreviations. or evidenced DSM-IV symptoms of delusions and hallucinations in Study 2). Paired II Visual Paired I Visual Paired lI Ruff Uniq. WAIS Pict. Verb. WAIS Similar.e. The results. Colors Digit Sp. Trails A. WAIS Pict. 5.Des. diagnostic groups. Time D2 Lett. LNS.Cp. after excluding subjects who had schizoaffective disorder in Study 1. Learning factor 1. Correct Arithmetic WAIS Block D. WAIS Pict. Correct LNS. 1 for complete description and abbreviations.00 Digit Sp. Specifically.00 Factor loadings 0. the coefficient of congruence between the individual factors derived from the 2 samples was high.00 Digit Sp. WAIS Similar. Anim. Words Stroop. Learning: comparison of factor loadings obtained in the bipolar and schizophrenia samples.. Paired I Verb.e. Back. Longest Arithmetic Digit Sp. In particular. Paired I Verb. p > 0.Neuropsychological symptom dimensions Non-verbal functions factor 1. Paired II WAIS Vocab. Longest D2 Lett. Trails A. See Fig.50 Factor loadings 0. these variables were introduced in order to test the possibility of a differential relationship. Naming COWAT Total WAIS Vocab.-Error Digit Symbol LNS. in additional ANCOVA analyses.

0058) (0.8 1. Internal consistency reliability (Cronbach alpha) and item composition of each neurocognitive factor Standardized alpha Neurocognitive factor Attention Neurocognitive measure included in factor D2 – letters minus errors Stroop-words only Stroop-color only Trails A WAIS-R Digit symbol WAIS-R Digit Span Forward LNS.0% and 67.8 1.9–2.0035) (0.86 Non-verbal functions 0.0–2. the distribution of the explained variance across the individual NC factors was also similar in the 2 samples.0054) (0.006) (0.3) (1.80 Learning 0.9–2.2 2. the 6 factors.2–2.8 2. explained approximately 68.6 1.0 2.1) (1. Criterion-related validity: bipolar sample (n ¼ 155)a Distractibility Characteristic Attention Working memory Ideational fluency Verbal knowledge Non-verbal functions Learning a Disordered thinking ORb 2.9–2.2–3. Table 7. WAIS-R ¼ Wechsler Adult Intelligence Scale-Revised. number correct LNS. b scale-IQ (although full scale-IQ was generally low in both samples).Czobor et al.80 0.8 6. the 2 diagnostic groups were almost identical in terms of age and age at onset of illness. respectively.4 (0. including their onset starting in early adult life (42).5 1.0 (0.2–2.040) (0.3 (1.011) (0.6 1.0–2. was essentially identical. This is consistent with the fact that SZ and bipolar illness share a number of characteristics.8–2.8) (1.046) (0. LNS ¼ Letter Number Span Test.0) (1.3) (0. in contrast to the above variables.13) (0. However.8 1.2–3.10) (0. longest WAIS-R Arithmetic WAIS-R Digit Span Backward Ruff Figural Fluency Unique Designs COWAT Animal Naming WAIS-R – Vocabulary WAIS-R – Comprehension WAIS-R – Similarities WAIS-R – Block Design WAIS-R – Object Assembly WAIS-R – Picture Completion WAIS-R – Picture Arrangement WMS-R – Verbal Pair I WMS-R – Verbal Pair II WMS-R – Visual Pair I WMS-R – Visual Pair II Bipolar sample 0. c Based on logistic regression analysis with symptom severity (Disordered Thinking. indicating the odds ratio increase for higher symptom severity for each SD unit of decrease in functioning on a particular neurocognitive factor.1) (0. Table 8.5 8.4 (1.4 1. Distractibility) as a dependent variable and neurocognitive factor as an independent variable. OR ¼ odds ratio statistics.6 7.0) Chi-square (p)c 7.4 4.82 D2 ¼ Concentration Endurance Test. Specifically.83 0. the exploratory factor analysis indicated 6 factors based on the Kaiser–Guttman eigenvalue >1 criterion and Cattell’s scree plot.65 Verbal knowledge 0.86 Working memory 0. together. Stroop ¼ Stroop Color-Word Interference Test. The factor analyses yielded a similar structure across diagnoses both in terms of the number of factors and configurational invariance (salience of the loadings).9) (1.24) ORb 1.2) Chi-square (pc) 4.87 Ideational fluency 0. In addition to the total variance explained. 86 .83 Schizophrenia sample 0.5 7.8% of the total variance in the NC dataset in the BPD sample.9 1.0 1.2–2.4 1.5) (0.65 0. WMS-R ¼ Wechsler Memory ScaleRevised.70 0.80 0.9) (0. COWAT ¼ Controlled Oral Word Association Test.087) Sample size may vary due to missing data.12) (0.4 1.3 2.9–2.0) (0. The total amount of variance explained by the 6 NC factors in the 2 samples. With respect to the number of factors.

Since these findings suggested low indicator reliability for these variables with respect to their underlying construct. the NC factors provided convergent information with measures that they would theoretically be expected to be overlapping.4%) than in the SZ sample (11. 3.1 2. means in this sample were essentially identical to zero. Overall. Neurocognitive factor scores in the bipolar and the schizophrenia samples Neurocognitive measure Bipolar sample Mean (SD) 0. More specifically.01 )0.74) (0.20) and with the Non-Verbal Knowledge 87 . Verbal Knowledge.80) Group difference F (p)a 7.82) (0. Consistent with this finding. respectively.2 (0. the internal consistency for the individual factors was generally good (typically 0.45) in both samples.0 6. the relatively lower congruence for this factor is due to the fact that in the bipolar sample only 2 of the 3 constituting items reached saliency (whereas in SZ sample all 3 of these items provided high loadings on the factor). gender and ethnicity as covariates. we think that this explanation is unlikely since the distribution of treatments in the 2 diagnostic groups showed marked differences in the current investigation.33 0. it is conceivable that the high degree of similarity across factor structures in the 2 samples was to due to medication effects. Instead.87) (0. for 2 variables (D2 Fluctuations and LMI) the coefficients were low (loading estimate <0. In addition.2 0. The fact that there was only a minimal overlap between the 6 NC factors and the overall severity on symptoms of mania and depression.01) (0. As shown in Fig. motor variables.80) (0. 1 with the Working Memory (r ¼ )0.27 0. The CARS-M total score showed only 2 statistically significant (p < 0.27 0. Consequently. indicates that these factors have good discriminant validity as compared to clinical symptoms. similar to our previous findings.14) (0. with the largest effect size observed for the association with the Attention factor.65 in each sample).006) (0. see above). the individual factors accounted for approximately 10–15% of the variance in each of the samples. Since the schizophrenia sample was used as a reference.1%). the set of 6 NC factors showed favorable psychometric properties in both samples. respectively).94) (0. respectively) and 1 for dexterity (Grooved Pegboard Preferred and Non-Preferred hand. in future studies.. Since all subjects in this study received medication (typically polypharmacy.03 )0. Working Memory. Overall. while this possibility cannot be excluded. Disordered Thinking had a more general relationship with neurocognitive functioning.75) (0. The internal consistency was similar across the samples. years of education.Neuropsychological symptom dimensions Table 9. In addition to generalizability across diagnoses. Ideational Fluency. However. a significant association was present for 5 of the 6 factors including Attention. in contrast to the high level agreement observed for all other factors.85) (0.75) (0.8 0.27 0.26 (0. With regard to external validators. 1 for motor speed (Finger Tapping Preferred and Non-Preferred hand.45 0. but clinically modest associations.03 )0.81) (0. the analyses yielded 2 independent small factors. with only minor differences between the 2 diagnostic groups.28) Attention Working Memory Ideational Fluency Verbal Knowledge Non-Verbal Functions Learning a p-values are based on the analysis of covariance model and were adjusted for full-scale IQ. Wisconsin Card Sorting). the coefficient of congruence based on the Procrustes analysis showed only a moderate agreement between the 2 samples for the Ideational Fluency factor.80 or above).7 1.79) (0.92) (0.g.02 )0.81) (0. with the exception of the Ideational Fluency which explained a substantially smaller amount of the variance in the BPD (3. the current results failed to provide empirical support for combining motor speed and dexterity measures into a single motor factor (28). these results revealed a remarkable consistency between the NC factors and the cliniciansÕ observations. the motor variables were not included in final CFA model because.01 (0. with the exception of the Ideational Fluency factor for which the internal consistency estimate in each sample was of moderate magnitude (0. NonVerbal Functions. they were omitted from our final model. Higher mean values indicate better functioning.05). whereas the CFA results indicated that the estimated loading coefficients obtained statistical significance for each of the indicators (observed NC variables) for each of the hypothesized factors that they were considered part of. a significant group difference between groups was observed on each factor without the adjustment for the covariates. the set of 6 NC factors needs to be supplemented by additional measures if these abilities are of specific interest (e.03 )0.85) Schizophrenia sample Mean (SD) )0. Logistic regression analyses indicated that the CARS-M Distractibility rating was related to poorer functioning on the Attention and Non-Verbal Functions factors. In general.

respectively. the investigation of the generalizability of the factor structure was based on cross-sectional data. despite the large sample size. Limitations There were a number of limitations in this study. additional studies should therefore address the issue of broader diagnostic generalizability (e. such data have the potential to confound state and trait effects. the effect sizes. for factors that failed to obtain statistical significance the effect size was small (0. the overall fit indices in the CFA analysis did not demonstrate a close fit for the entire model. confounding factors such as drug and alcohol abuse.38.41 and 0. 88 .20 (Ideational Fluency) shows an 85% overlap. In particular. Finally.e. we note that this proportion (68%) is higher or comparable to those described for widely used psychometric scales.. in addition to the possibility that NC functions serve as common endophenotypic markers across diagnoses. instead of a general difference in the overall NC functioning between the 2 diagnostic groups. Thus. iatrogenic effects such as use of medication. and may be explained by shared genetic susceptibility. However. However.g.g. using data from an on-going longitudinal study of SZ. NC impairment (e. such as the BPRS (44) and PANSS (45). concurrent validity was supported by the finding that the NC factors distinguished the 2 diagnostic groups. Overall. and/or common underlying neurobiological substrates. are consistent with the view that patients with BPD suffer less severe cognitive impairments than do patients with SZ (22. we note that the theoretical factor structure that we tested in this study was derived based on both crosssectional and longitudinal approaches. the number of observations for the multivariate analyses was relatively small. after adjusting for the covariates. together. we repeated the analyses by controlling for the demographic variables. patients in the BPD sample displayed significantly better functioning on each of the NC factors than patients in the SZ sample.. Third. the analyses were conducted in bipolar patients only. respectively).g. Future studies need to investigate these possibilities further. Because it can be argued that differences in IQ and education may be a consequence of the illness and therefore the adjustment for these covariates is hard to justify in a study of NC differences. whereas the CFA showed high loadings for the individual NC variables with respect to their hypothesized factors. whereas an effect size of approximately 0. the difference in Ideational Fluency reached significance. the results showed a general difference among the 2 groups: without an adjustment for the covariates. imprecision of diagnoses]. these results. First. However.16). The results indicated that in addition to Attention and Non-Verbal Functions. the Kaiser–Guttman rule that was adopted for our study). These results are consistent with the notion that clinical symptoms and NC functioning constitute independent dimensions. Second. Furthermore. the 6 factors together explained 68% of the variance). with regard to major depressive disorder). fell in the ÔmoderateÕ range for the Attention and Non-Verbal Functions (0. factors (r ¼ )0. Effect sizes of this magnitude are associated with a large degree of overlap in terms of the underlying distributions. Specifically.theanalysisoflongitudinalchanges in NC functioning and their impact on the factor structure in the BPD sample is essential. an effect size of approximately 0. at face value. Since the factor structure may changeovertime.. we note that after an adjustment for the observed group differences in the covariates. Such a large degree of overlap can be indicative of a dimensional rather than a categorical transition between the 2 diagnoses. 43). and <0. there was no significant association between the HAM-D total score and any of the 6 NC factors. Nonetheless.7 as opposed to >1.2 for Ideational Fluency. alternative explanations are conceivable [e. but not for IQ and education. This value is also comparable with the amount of variance (74%) explained by 6 factors in the analyses of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) (25) (despite that the factors in the analyses of the RBANS were retained if their eigenvalue was >0. it should be noted that in terms of statistical effect size (Cohen’s d) the difference between the 2 diagnoses was relatively modest. While the aforementioned proportion of explained variance appears low.4 (Attention) indicates a 73% overlap for the factor score distributions between the 2 diagnostic groups. a significant difference between the 2 samples was detectable only on the Attention and Non-Verbal Functions factors. these findings indicate a specific profile of difference. The lack of close fit in the current investigation is consistent with the fact that approximately 1/3 the total variance of the observed empirical variables remained unaccounted for by the factors (i.Czobor et al. and therefore sampling variance may have affected the results.. Thus. impairment in attention) represent non-specific of brain dysfunction.15 for the 3 remaining factors after correcting for the covariates). In the current investigation.

Hughes JH et al. Bullmore ET. 89 . It may be underlied by shared genetic susceptibility. Psychiatrie. A comparative profile analysis of neuropsychological functioning in patients with schizophrenia and bipolar psychoses. 61: 974–984. 6. Glahn DC. Bearden CE. The neuropsychology and neuroanatomy of bipolar affective disorder: a critical review. The continuum of psychosis and its genetic origins. 11. Br J Psychiatry 2005. 156: 1951–1957. Cardno AG. O’Donovan MC. Effects of mood and severity on memory processes in depression and mania. Woo TU. Neuropsychobiology 2002. Leipzig: JA Barth. 25. Bartko JJ et al. A systematic review. Schizophr Res 2005. 73: 49–62. References 1. Funding Source: NIMH R01 MH 60904. WHO. Seidman LJ. Arts B. part III: bipolar disorder. DC: American Psychiatric Press. A twin study of genetic relationships between psychotic symptoms. Overall. Torrent C et al. 159: 539–545. Dr Anil Malhotra. Ms Claudia Salazar. and Estelle Douglas. 1899. one human gene. Am J Psychiatry 2002. as well as the diligence in data collection and quality management provided by Drs Sara Davis-Conway. 22. van Os J et al. Koren D et al. 2. 10. 55: 41–46. Martinez-Aran A. 42: 193–204. Washington. Clinton SM. Scott Greisberg. J Psychiatr Res 2003. Arch Gen Psychiatry 2004. McDonald C. Crow TJ. Colom F et al. Association of genetic risks for schizophrenia and bipolar disorder with 21. Bearden CE. Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia. Together. 12. 1): 16–21. the nature of these processes appears to be different in the 2 disorders. 7. Sham PC et al. Bipolar Disord 2001. Owen MJ. The group comparisons revealed differences between patients with BPD and SZ in the neurocognitive domains of Attention and Non-Verbal Functions. Mol Psychiatry 2002. Magaro PA. Craddock N. Abnormalities of the NMDA receptor and associated intracellular molecules in the thalamus in schizophrenia and bipolar disorder. however. Schizophr Res 1995. 19. A continuum of psychosis. Diagnostic and Statistical Manual for Mental Disorders. Gershon ES. Am J Psychiatry 1999. Ein Lehrbuch fu ¨ r Studirende und Aerzte. 17. the profile of impairments may vary with the diagnosis. 156: 788–797. Schizophr Res 2002. 14. 8. Segurado R. Gallagher P. The sixty-fifth Maudsley lecture. van Gorp WG. 17: 135–145. Cannon TD. Walsh JP. Tabares-Seisdedos R. II: convergent/discriminant validity and diagnostic group comparisons. Ms Priya Matneja and Ms Donna O’Shea. 1994. Am J Hum Genet 2003. The authors owe enormous gratitude to the study participants who give generously of their time and without whose efforts and patience this work would never be possible. 75: 72–84. the finding of similar factor structure is consistent with the hypothesis that the same cognitive processes are involved in both disease entities. 37: 479–486. Repeatable battery for the assessment of neuropsychological status as a screening test in schizophrenia. Salazar-Fraile J et al. Kraepelin E. Schizophrenia and bipolar disorder: differences and overlaps. Hobart MP. Genome scan meta-analysis of schizophrenia and bipolar disorder. Meador-Woodruff JH. Thompson JM. Cognitive impairment in euthymic bipolar patients with and without prior alcohol dependence. Niendam TA et al.Neuropsychological symptom dimensions Conclusion specific and generic brain structural endophenotypes. 9. Vieta E. Hoffman KM. Maier W. Pradeep Nagachandran and Sarah Uzelac and by Mr Sherif Abdelmessih. Diagnostic Criteria for Research. Theberge DC et al. Zobel A. 19: 165–170. Neurocognitive impairment in euthymic patients with bipolar affective disorder. Acknowledgements The authors are grateful for the valuable advice and support provided by Dr Samuel Gershon. Rebecca Iannuzzo. Genes for schizophrenia and bipolar disorder? Implications for psychiatric nosology. 24. 16. 7: 405–411. the results of this study indicate that while the same underlying factor structure describes NC functioning in both diagnostic groups. which may indicate that NC factors operate in a different way in the 2 illnesses. Curr Opin Psychiatry 2006. 6th edn. Geneva: World Health Organization. Owen MJ. Wagner M. Craddock N. 15. Ms Marilyn Mejia. 186: 32–40. Ms Pam DeRosse. Detera-Wadleigh SD. 4. Cognitive functioning in patients with schizophrenia and bipolar disorder: a quantitative review. 53: 31–44. Levinson DF et al. Arch Gen Psychiatry 2004. The feasibility of neuropsychological endophenotypes in the search for genes associated with bipolar affective disorder. 4th edn. 6: 171–182. 61: 649–657. A preliminary study. and not much else – the case for homogeneity. Daban C. Krabbendam L. Specificity of cognitive deficits in bipolar disorder versus schizophrenia. Johnson MH. 29: 1353–1362. The large degree of overlap between the respective distributions of NC variables across diagnoses can be interpreted as reflection of a dimensional rather than a categorical transition between the 2 diagnoses. Crow TJ. J Med Genet 2005. 18. Arch Gen Psychiatry 1998. American Psychiatric Association. 32: 9–16. O’Donovan MC. 20. The ICD10 Classification of Mental and Behavioural Disorders. 80: 137–149. Density of glutamic acid decarboxylase 67 messenger RNA-containing neurons that express the N-methyl-D-aspartate receptor subunit NR2A in the anterior cingulate cortex in schizophrenia and bipolar disorder. Psychol Bull 1987. Kremen WS. Br J Psychiatry 1990. 3: 106–150. Neuropsychopharmacology 2004. Psychother Psychosom 2006. although alternative explanations are conceivable including (but not restricted to) iatrogenic effects due to medication and confounding factors such as drug and alcohol abuse. Goldberg R. 101: 28–40. Badner JA. Martinez-Aran A. 46 (Suppl. Specific executive/attentional deficits in patients with schizophrenia or bipolar disorder who have a positive family history of psychosis. 23. Stanley Medical Research Institute. 1993. Altshuler L. 5. Schizophr Bull 2006. Balanza-Martinez V. Rijsdijk FV. Bipolar Disord 2004. 3. Neuropsychological performance in depressed and euthymic bipolar patients. 13. Sham PC et al. Benes FM. The genetics of schizophrenia and bipolar disorder: dissecting psychosis.

and validity. 37. 1981. 7: 111–118. 45.. the verbal and visual paired associates tasks were included as putative indices of Verbal and Non-Verbal learning. Chelune GJ. 37: 36–48. Educ Psychol Meas 1960. Comprehension and Similarities. The analyses that we conducted for the purpose of this study included each of the verbal and performance subtests. Odessa. SAS System for Mixed Model. 14: 229–234. Appendix: Neuropsychological tests used in the battery Wechsler Adult Intelligence Scale-Revised (WAIS-R) (57) The goal of this scale is to provide an overall evaluation of intellectual functioning.Czobor et al. 1981. 16: 297–334. 30. 51. Gottingen: Verlag for Psychologie. 1978. 48. The assessment and analysis of handedness: the Edinburgh Inventory.. 58. 56. A leisurely look at the bootstrap. Behav Sci 1962. 44. 37: 205–215. Overall J. Inc. Arithmetic. 35. Neurocognitive test performance predicts functional recovery from acute exacerbation leading to hospitalization in bipolar disorder. WI: University of Wisconsin Medical School. 42. Heaton RK. Zhang Y. Lindenmayer JP. Hyman RB. Matthews CG. Berns SM. Carpenter C. Loftus S. Benton A. Schizophr Bull 1987. Bipolar Disord 2005. Goodglass H. 23: 56–62. NJ: Lawrence Erlbaum Associates. Madison. Henry C. PA: Lea & Febiger. Loehlin JC. Grochowski S. Cronbach L. Hamilton M. reliability. 13: 261–276. The Brief Psychiatric Rating Scale in psychopharmacology research. Goldberg TE. the subject is asked to order short sequences of randomly presented letters and numbers. 31. Wechsler Adult Intelligence Scale-Revised Manual. 1993. Psychological Measurements in Psychopharmacology. Psychometrika 1951. The ClinicianAdministered Rating Scale for Mania (CARS-M): development. A practical and theoretical guide to measurement invariance in aging research. The Scientific Use of Factor Analysis. The positive and negative syndrome scale (PANSS) for schizophrenia. Bipolar Disord 2007. Schizophr Res 1995. 38. 39. 55. 1974. Fiszbein A. 29. 1995. Allen CC. Wechsler Memory Scale Revised (WMS-R) (58) The WMS-R test investigates various aspects of memory functioning. 26. A rating scale for depression. 49. Basic neuropsychological dimensions in schizophrenia. Compr Psychiatry 1996. Schizophr Res 2003. Kaplan E. In the current study. Hamsher K. Volavka J. Stat Med 2002. Philadelphia. 54: 159–165. 54. Digit Span (forward and backward tasks). Gehan E et al. 1947. Dimensions of the Brief Psychiatric Rating Scale: an examination of stability during haloperidol treatment. 21: 3465–3474. 1983. the information needs to be maintained 90 . Czobor P. The Assessment of Aphasia and Related Disorders. Cary. verbal and non-verbal learning and attention. 57. Am Stat 1983. representing the composite of VIQ and PIQ). Graf P. Exp Aging Res 1992. Gonzalez C. Jaeger J. Auditory working memory and Wisconsin Card Sorting Test performance in schizophrenia. 65: 105–116. 28. Thurstone LL. Littel RC. 50. 27. Color-Word Stroop test performance across the adult life span. Concentration-Endurance Test Manual. and cross-validation. Hedeker DR. Block principal component analysis with application to gene microarray data classification. Czobar P. New York: Hemisphere. Altman EG. IA: University Of Iowa. Farrow CE et al. The scale is composed of 11 subtests. 36. Logical Memory I (immediate recall) was included as part of the of the Working Memory factor. Latent Variable Models. 47. McArdle JJ. Hillsdale. Gold JM. 1974: 67–78. Neuropsychologia 1971. Cattel RB. The Procrustes Program: producing direct rotation to test a hypothesized factor structure. the jackknife. New York: Plenum. Arch Clin Neuropsychol 1994. 1987. 40. 34. New York: Oxford University Press. Opler LA. 1987. which yield. Figural fluency: differential impairment in patients with left versus right frontal lobe lesions. Neuropsychological Assessment. Age at onset in bipolar affective disorders: a review. Stroup WW et al. Five factor model of schizophrenia: replication across samples. Coefficient alpha and the internal structure of tests. San Antonio: Psychological Corporation. 43. 52. respectively. 53. J Clin Exp Neuropsychol 1997. FL: Psychological Assessment Resources. 7: 258–262. 32. Paillere-Martinot ML et al. Liu A. Biol Psychiatry 1994. 6 verbal and 5 performance oriented. Instructions Manual for the Adult Neuropsychology Test Battery. Czobor P. Vocabulary. Randolph C et al. Love H. Janicak PG et al. Cattel R. Berns S. Jaeger J. Wechsler D. the Visual Memory Span subtest (tapping forward) was used for the Attention factor. the performance subtests are the Picture Completion. 20: 141–151. Wechsler Memory Scale-Revised Manual. Davidson L. Gong G. Brickenkamp R. 46. 36: 124–134. Kaiser HF. Object Assembly. the verbal IQ (VIQ). the performance IQ (PIQ). and Digit Symbol. Basel: Karger. 9: 41–55. Hurley JR. Milliken GA. 2002. NC: SAS Institute. 1964. 41. Inc. Harcourt Brace Jovanovich. In order to perform this task. Ruff RM. Wisconsin Card Sorting Test Manual. Letter Number Span (46) In the Letter-Number Span test. Block Design. Multiphasic Aphasia Examination Manual. New York: Psychological Corporation. Wechsler D. IL: University of Chicago Press. Multiple-Factor Analysis. Lezak M. 1978. In: Pichot P ed. 9: 93–102. Schizophr Res 1999. Leboyer M. Efron B. Some fairly obvious distinctions between schizophrenia and bipolar disorder. Reitan R. 19: 405–420. Oldfield RC. Talley JL et al. J Neurol Neurosurg Psychiatry 1960. The verbal subtests are the Information. Arch Gen Psychiatry 1997. Clinical Neuropsychology: Current Status and Applications. 33. Iowa City. Uttl B. 39: 127–132. and the full scale IQ (FSIQ. Horn JL. 18: 117–144. Picture Arrangement. Chicago. 9: 97–113. Kay SR. The application of electronic computers to factor analysis.

Hypothesis Testing. it is considered an index of working memory functions. Stroop Test (49) Controlled Oral Word Association Test was used for the assessment of verbal fluency within phonemic (letter) constraints. Working Memory Ideational Fluency. the time to completion in seconds in part A of the test was the principal variable of interest for this task. Wisconsin Card Sorting Test (WCST. Ruff et al. Patients were asked to use one hand to put 25 pegs in a 5 by 5 grooved pegboard. Ruff Figural Fluency Test (RFFT) (53) The Stroop Test is considered a measure of selective attention and cognitive flexibility (response inhibition).. and the sequence connection was numeric-alphabetic in an alternating sequence. and Responsiveness to Feedback. Grooved Pegboard Test (54) Fine motor skills including motor speed. the test requires subjects to inhibit automatic responses by naming the color of ink in which color words are presented. 1-min trials. the subject is asked to detect as many target letters as possible in a matrix of letters consisting of 14 lines. In the conflict condition. visualmotor coordination. the principal variable of interest for this study was the number of perseverative errors that occurred during a given trial. Abstraction. The holes of the 91 . patients were given one letter of the alphabet at a time and instructed to say aloud as many words beginning with that letter as they could within 1 min. the word ÔgreenÕ printed in red ink). for a total of 3 letters in 3 min. with a maximum of 5 min allowed per part. For this task. Animal Naming Test (51) The Animal Naming Test is part of the Boston Diagnostic Aphasia Examination. (53) suggested that the task reflects fluid and flexible thinking and the ability to create novel responses without repetition. Patients are asked to read word names or name colors as quickly as possible. Based on our previous factor analytic study (28). the task being to name the color of each block and finally a conflict condition in which color names are printed in text having a different color (e. The current investigation adopted the number of correct trials and the longest sequence as the measures of interest for the analyses.Neuropsychological symptom dimensions over a short delay and transformed. For the purpose of the present study. 128 card manual version) (50) The purpose of this test is to assess sustained attention and visual scanning ability. Figural fluency tests have been developed to provide a non-verbal analogue of the word (verbal) fluency tasks. In part A. the RFFT measures the production of novel designs under both graphical and time constraints. Subjects are instructed to name as many different animals as possible in 90 s. The time to complete each test part (A and B) was recorded for each patient. The variable of interest for the current analyses was the total number of correct responses (words provided) for the 3. and the most productive 60 s are scored. reflecting Set Shifting. Since the test requires both memory storage and processing. The number of correct responses within a 60-s trial was used as the measure of interest. Controlled Oral Word Association Test (COWAT) (52) Visual motor speed and set shifting were assessed using the Trail Making Test with 2 parts: A and B. It is a generative naming task employing semantic constraints. Concentration Endurance Test (D2) (48) the color and word reading conditions were reliable indices of the Attention factor. Based on previous literature and our prior factor analyses. the total score minus errors (letters minus errors) and the fluctuation (difference between the row with the highest rate of production and the lowest rate of production) were selected for the analyses. Our previous work showed that while the conflict condition did not reliably correlate with any of the cognitive factors. patients were asked to connect in sequential order 25 numbers randomly distributed on a test page. In part B. and single-hand dexterity were tested using the Grooved Pegboard Test. Trail Making Test (A & B) (51) This test has been extensively described in the literature and seems to be cognitively polyfactorial. the test items included both numbers and letters. The test consists of 3 conditions: presenting color names in black ink (labeled as ÔwordsÕ) and presenting a block of xÕs in colored ink. This paperand-pencil test is modeled after other cancellation tasks.g.

number of pegs dropped. 92 . 10-s trials with their dominant and nondominant hand. The EHI. Subjects tap on a lever for 5. pegboard have ÔslotsÕ and the pegs have a key on one side that must be rotated to match the hole in the board. The total number of taps for each hand was used for statistical analysis. Edinburgh Handedness Inventory (EHI) (56) The Finger Tapping Test was adopted as a measure of motor speed. was used for determining which hand would be considered preferred hand for motor tests.Czobor et al. A maximum of 5 min was allowed for testing each hand. and time to complete the test was recorded for each hand. Finger Tapping Test (55) Complex Ideational Material (47) Language comprehension was assessed with 8 yes/ no questions from the Test of Complex Ideational Material (CIM) from the Boston Diagnostic Aphasia Exam (47). The number of completed rows. a standard test of manual dexterity.

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