Scholarly article on topic 'The evolution of illness phases in schizophrenia: A non-parametric item response analysis of the Positive and Negative Syndrome Scale'

The evolution of illness phases in schizophrenia: A non-parametric item response analysis of the Positive and Negative Syndrome Scale Academic research paper on "Psychology"

CC BY-NC-ND
0
0
Share paper
Academic journal
Schizophrenia Research: Cognition
OECD Field of science
Keywords
{"Schizophrenia subgroup" / Psychopathology / "Item response analysis"}

Abstract of research paper on Psychology, author of scientific article — Anzalee Khan, Jean Pierre Lindenmayer, Mark Opler, Mary E. Kelley, Leonard White, et al.

Abstract Background The Positive and Negative Syndrome Scale (PANSS) assesses multiple domains of schizophrenia. Evaluation of each of these domains was conducted to assess differences in the characteristics of psychopathology and their relative predominance in sub-populations. Method Subjects (N=1,832) with DSM-IV schizophrenia were represented in three sub-populations: First Episodes, n=305, Chronic Inpatients, n=694, and Ambulatory Outpatients, n=833. Nonparametric Item Response Analysis (IRT) was performed with Option Characteristic Curves (OCC), Item Characteristic Curves (ICC), slopes and item biserial correlation. Items were characterized as Very Good, Good, or Weak based on specified operational criteria for item selection. Results First episode patients were represented by negative, disorganized hostility and anxiety. Some negative domain items (Poor Rapport, Passive/Apathetic Social Withdrawal) and most positive domain items were scored as Weak. For chronic inpatients, all items of the anxiety domain and some items of the positive domain (Suspiciousness/Persecution, Stereotyped Thinking, Somatic Concerns) were Weak; for all other domains, items were Very Good or Good. For ambulatory outpatients, most items in the anxiety and hostility domain were scored as Weak. The majority of PANSS items were either Very Good or Good at assessing the overall illness severity: chronic inpatients (73.33%, 22 items), first episodes (60.00%, 18 items), and only 46.67% (14 items) in the ambulatory group. Conclusion Findings confirm differences in symptom presentation and predominance of particular domains in subpopulations of schizophrenia. Identifying symptom domains characteristic of subpopulations may be more useful in assessing efficacy endpoints than total or subscale scores.

Academic research paper on topic "The evolution of illness phases in schizophrenia: A non-parametric item response analysis of the Positive and Negative Syndrome Scale"

ARTICLE IN PRESS

Schizophrenia Research: Cognition xxx (2014) xxx-xxx

The evolution of illness phases in schizophrenia: A non-parametric item response analysis of the Positive and Negative Syndrome Scale

Anzalee Khan aÄ*, Jean Pierre Lindenmayer a,c, Mark Opler b,c, Mary E. Kelley d, Leonard White e, Michael Comptonf, Zimeng Gao b, Philip D. Harvey g,h

a Nathan S. Kline Institute for Psychiatric Research, Psychopharmacology Research, Orangeburg, NY, USA b ProPhase LLC, New York, NY, USA

c New York University School of Medicine, New York, NY, USA d Emory University, Department of Biostatistics and Bioinformatics, Atlanta, GA, USA e Mount Sinai School of Medicine, New York, NY, USA f George Washington University, Washington, DC, USA g University of Miami School of Medicine, Miami, FL, USA h Miami VA Healthcare System, Miami, FL, USA

ARTICLE INFO

Article history: Received 5 July 2013

Received in revised form 20 January 2014 Accepted 24 January 2014 Available online xxxx

Keywords:

Schizophrenia subgroup Psychopathology Item response analysis

ABSTRACT

Background: The Positive and Negative Syndrome Scale (PANSS) assesses multiple domains of schizophrenia. Evaluation of each of these domains was conducted to assess differences in the characteristics of psychopa-thology and their relative predominance in sub-populations.

Method: Subjects (N = 1,832) with DSM-N schizophrenia were represented in three sub-populations: First Episodes, n = 305, Chronic Inpatients, n = 694, and Ambulatory Outpatients, n = 833. Nonparametric Item Response Analysis (IRT) was performed with Option Characteristic Curves (OCC), Item Characteristic Curves (ICC), slopes and item biserial correlation. Items were characterized as Very Good, Good, or Weak based on specified operational criteria for item selection.

Results: First episode patients were represented by negative, disorganized hostility and anxiety. Some negative domain items (Poor Rapport, Passive/Apathetic Social Withdrawal) and most positive domain items were scored as Weak. For chronic inpatients, all items of the anxiety domain and some items of the positive domain (Suspiciousness/Persecution, Stereotyped Thinking, Somatic Concerns) were Weak; for all other domains, items were Very Good or Good. For ambulatory outpatients, most items in the anxiety and hostility domain were scored as Weak. The majority of PANSS items were either Very Good or Good at assessing the overall illness severity: chronic inpatients (73.33%, 22 items), first episodes (60.00%, 18 items), and only 46.67% (14 items) in the ambulatory group.

Conclusion: Findings confirm differences in symptom presentation and predominance of particular domains in subpopulations of schizophrenia. Identifying symptom domains characteristic of subpopulations may be more useful in assessing efficacy endpoints than total or subscale scores.

© 2014 Elsevier Inc. All rights reserved.

1. Introduction

Schizophrenia has marked heterogeneity in symptoms. The current symptom domains contained in the Diagnostic and Statistical Manual for Mental Disorders (DSM-V) are psychosis, negative symptoms, disorganization, abnormal motor behavior and social/occupational dysfunction (American Psychiatric Association, 2013). Although not part of the formal diagnostic criteria for the illness, mood symptoms including depression and anxiety are common in many patients (Green et al., 2003; Moller, 2005), hostility and

* Corresponding author at: Psychopharmacology Research Program, Manhattan Psychiatric Center, 1 Wards Island Complex, 15th Floor, Wards Island, NY 10035. E-mail address: akhan@nki.rfmh.org (A. Khan).

http://dx.doi.org/10.1016/j.scog.2014.01.002 2215-0013/© 2014 Elsevier Inc. All rights reserved.

belligerence are present in some cases (Chen et al., 2001), and cognitive impairments are present in nearly all patients (Green et al., 2004; Keefe, 2008). Symptoms as domains or dimensions have been examined in detail with factor analytic procedures (e.g., White et al., 1997a, 1997b), including factor analyses of the current dataset (Kelley et al., 2013), and the domains examined by the PANSS have been widely validated.

Different subsets of patients, defined by their stage or course of illness or their overall outcome, have different predominant symptoms (Bengston, 2006). For example, at an acute phase, patients with schizophrenia routinely come to clinical attention because of the emergence of psychosis, often accompanied by social withdrawal. Since these experiences are new and unsettling, anxiety and depression would be expected to be substantially present as well. A clear case of a subgroup defined by long term outcome is

ARTICLE IN PRESS

2 A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx

difficult to discharge patients, who have been found to have elevated levels of hostility, aggression, and positive psychotic symptoms (Bartels et al., 1991; White et al., 1997b). High levels of disorganization and communication disorders are also associated with this particular poor outcome subgroup (Davidson et al., 1995). Conversely, successful adaption to living in the community may be contingent on lower levels of disorganization, aggressiveness, and flagrant psychosis and patients with sustained community tenure are also likely not to manifest substantial aggressive and hostile behavior, which would bring them into contact with the legal system or induce readmissions.

The long term course of schizophrenia suggests longitudinal changes in patients with different outcomes developing (e.g., Chronic inpatients vs. stable outpatients) and finding similarities within a disorder may help in the expansion of models to explain stages or the course of the disorder. While the Positive and Negative Syndrome Scale (PANSS) assesses multiple dimensions of schizophrenia, evaluation of each of its individual domains has not been systematically targeted at differences in the characteristics of psychopathology in subpopulations. There is considerable interest in identifying the course and treatment needs across different stages of illness. One symptom domain that seems likely to be present across all of the different subgroups of patients is negative symptoms (see prevalence review in Buchanan, 2007). These symptoms are temporally stable in follow-up studies (Putnam et al., 1996) and are associated with impairments in functional outcomes in both community dwelling and institutionalized patients (see Chemerinski et al., 2006; and Harvey et al., 2006 for a review). They are found to be present in many patients when other symptoms are in relative remission (particularly in cases of the deficit syndrome). Negative symptoms are also present at the time of the first episode (Lindenmayer et al., 1986; Milev et al., 2005) and have been reported to be moderate or greater in severity in a substantial proportion of community dwelling patients (Kurtz, 2005). Studies of older patients have reported even higher levels of negative symptoms (Harris, 1991; Roseman et al., 2008), although the longitudinal detection of change over the lifespan is challenging. In a cross-sectional study comparing symptom severity in chronic patients across 8 decades (Davidson et al., 1995), negative symptoms were more severe in older patients and manifested a greater age-associated difference than positive symptoms. That said, studies of older patients discharged from long-stay psychiatric care found greater improvements in negative symptoms than cognitive deficits postdischarge (Leff and Trieman, 2000), implicating environmental factors to an extent.

In this paper, we present the results of an analysis of assessment data from a large collated sample of people with schizophrenia, including data from studies of first episode patients, community dwelling patients, and long-stay patients from two New York State Psychiatric facilities. These patients were all examined with a clinical psychiatric rating instrument, the Positive and Negative Syndrome Scale (PANSS) and for this paper we examined several features of their clinical symptoms. Our hypotheses were that various domains

of symptoms would be differentially prominent in different subgroups, as described above. Prominence was defined in terms of symptom severity. Using Item Response Theory (IRT) models, we examined the extent to which an individual item contributed to the overall severity scores for each domain and the extent to which items were consistently sensitive to differing levels of severity for each separate subgroup.

We hypothesized primarily that negative symptoms would be found to be consistently validly measured and similarly prominent in all three subgroups. We also hypothesized that institutionalized patients would have more severe and validly measured symptoms of hostility and disorganization, and psychosis, compared to the other two groups. First episode patients were hypothesized to have greater severity and measurement validity for anxiety/depression and psychosis. Community dwelling patients were hypothesized to be less impaired in other symptom domains (such as Anxiety and Disorganized domains), with resulting alterations in the patterns of domain structure and IRT findings.

2. Methods

2.1. Data source

This study uses data from 5 different observational studies (see Table 1) aimed at cognition, functioning, and the course of illness in people with schizophrenia. Subjects (N = 1,832) were all diagnosed with DSM-IV schizophrenia or schizoaffective disorder, and were combined into three groups: First Episodes, n = 305, Chronic Inpatients, n = 694, and Ambulatory Outpatients, n = 833. Studies were carried out in accordance with the latest version of the Declaration of Helsinki. Study procedures were reviewed by appropriate ethics committees and informed consent (with specific exceptions as seen below) was obtained after the procedures were fully explained.

The First Episode group was defined as: consenting 18-45-year-old patients who met DSM-IV criteria for schizophrenia, or schizoaffective disorder for no more than 1 year prior to the assessment and during which period they had no more than two psychiatric hospitalizations for psychosis; and who did not have another axis I diagnosis, including substance dependence or abuse (Compton et al., 2009; Compton et al., 2011). Diagnoses were determined using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I; First et al., 1998). Patients with first episode were not determined by age but rather the course of symptom presentation and to ensure that all courses during first episode (illness onset, episode onset, end of episode, relapse of episode) were covered. The Chronic Inpatient group was defined as: 18-85-year-old patients who met the DSM-IV criteria for schizophrenia or schizoaffective disorder and staying in a chronic psychiatric ward for > 6 months. This group was examined with a waiver of signed informed consent because all patients in the hospital received the assessment and information was

Table 1

Clinical description of data used in the investigation.

Chronic Patient Sample

First Episode Sample

Series

Setting

Mean (sd) % Male

Kay & Sevy,

Inpatient

33.1 (10.2) 77

Caton et al., 1994,1995 Urban Community 400

38.8 (10.6) 50

Bell et al., 1994

Veterans Hospital

Rehabilitation

40.2 (8.6) 95

Davidson et al.,

Geriatric

inpatient

75.7 (7.0) 44

Bowie et al., 2008

Outpatient 238

56.6 (9.7) 73

Harvey et al., 2010

Outpatient 195

44.0 (5.2) 69

48.9 (15.1) 64

23.6 (4.9) 73

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx

then obtained from medical records. The Ambulatory group was defined as: consenting 18-80-year-old outpatients who met the DSM-IV criteria for schizophrenia, or schizoaffective disorder, who were living in the community in a residence less restrictive than a nursing home, and receiving maintenance drug treatment, at least with an an-tipsychotic agent as the main drug treatment.

2.2. instrument

The PANSS (Kay et al., 1987) is a 30-item rating instrument evaluating the presence/absence and severity of Positive, Negative and General Psychopathology of Schizophrenia. All 30 items are rated on a 7-point scale (1 = absent; 7 = extreme). The PANSS is administered by a clinician trained in psychiatric interview techniques, with experience working with populations with Schizophrenia (e.g. psychiatrists, mental health professionals) and takes approximately 45 minutes to complete. PANSS interviews were conducted by trained interviewers who had at least 1 year experience using the PANSS. The PANSS-derived Marder domain score was used. The study by Marder et al. (1997) factor analyzed the PANSS scores and produced five dimensions: negative symptoms, positive symptoms, disorganized thought, uncontrolled hostility/excitement, and anxiety/depression. All assessments were performed with raters who were trained prior to rating, with the training described in the individual publications. See Table 1 for a description of the samples of patients in the study.

2.3. Data analysis

2.3.1. Assessment of unidimensionality of the PANSS-derived domains

One important assumption of non-parametric IRT is that the construct being measured (i.e., the domains of psychopathology) is unidimensional, meaning that the covariance among the items can be explained by a single underlying dimension. The percentage of the total variance explained by the first component is regarded as an index of unidimensionality. A Principle Components Analysis (PCA) without any rotation was conducted to assess unidimensionality as follows: (1) a PCA was conducted on each of the five domains of the PANSS for each group (First Episode, Chronic Inpatients, Ambulatory); (2) the variance explained by the first component produced by the PCA was examined; (3) if the variance explained by the first component was >20.00%, unidimensionality was assumed (see Reckase (1979) for methods of assessing unidimensionality using PCA). Suitability of the data for factor analysis was tested by Bartlett's Test of Sphericity (Bartlett, 1954), which should be significant, and the Kaiser-Meyer-Olkin (KMO) measure of sampling adequacy, which should be >0.50 (Kaiser, 1970, 1974). It is important to have unidimensionality to ensure that all items in the domain are adding to the overall construct being measured. Multi-dimensionality would indicate that items within the domain are measuring more than one construct. However, it should be noted, a set of items may have multiple eigenvalues greater than 1 and still be sufficiently unidimensional for analysis with IRT (Orlando and Thissen, 2000).

2.3.2. Non-parametric item response analysis

Nonparametric IRT models (Petersen, 2004; Sijtsma & Molenaar, 2000) provide a broad-spectrum and flexible data analytic framework for investigating a set of polytomously scored items and for determining ordinal scales for measurement that include items that have changeable locations and sufficient discrimination power (Sijtsma et al., 2008). A nonparametric approach to modeling responses for the PANSS items would allow for no a priori expectation about the form of rating distributions, and items with non-monotonic item response functions can be identified. The IRT examines the probability of choosing each response (PANSS item score) in relation to severity of

Fig. 1. Example of an 'ideal' option characteristic curve (OCC). Note: Symptom severity refers to the total PANSS score of the domain being measured.

PANSS-derived domains (positive, negative, disorganized thought, hostility/excitement, anxiety/depression) and to examine the ability of each domain items to differ with levels of severity. A nonparametric kernel smoothing method and software (TestGraf), developed by Ramsay (2000) to estimate Option Characteristic Curves (OCC) was used. The smoothing parameter was selected conditional on the balance desired between bias and the variance of estimation, two components of the mean square error of the estimator in Item Characteristic Curves (ICC) estimation (Hardle, 1990; Ramsay, 2000). These methods have been used previously in studies on the performance of PANSS items (Khan et al., 2011; Santor et al., 2000). TestGraf software (Ramsay, 2000) was used to fit the model. TestGraf produces OCCs, ICC, an Item Information Function (IIF), and a Test Information Function (TIF) to assess the measurement precision of each item in each domain across the range of severity.

Option Characteristic Curves (OCC) are graphical representations of the probability of rating the different scores on the PANSS for a given item across the range of domain severity (or the latent variable, theta©). Therefore, the probability of choosing a particular response is plotted against the range of symptom severity. If the probability of rating an item changes as a function of symptom severity, the option is useful; that is, it discriminates differences in domain specific symptom severity. For OCC, individuals were ranked according to a maximum likelihood estimation of their expected total scores on the derived symptom domain. Fig. 1 presents a graphical description of the OCC of an 'ideal' item.

To validate that items of the symptom domain are either Very Good or Good at assessing the overall severity, Item Characteristic Curves (ICC) were examined. ICCs are graphical illustrations of the expected total domain score on an item as a function of overall symptom severity. Fig. 2 displays an example of an item with an ideal ICC. Both OCCs and ICCs were using a Gaussian kernel smoothing technique of the

Fig. 2. Example of an 'ideal' item characteristic curve (ICC). Note: Expected score refers to the total PANSS score on the domain being measured. Item Score refers to the 7 PANSS option scores.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx

Table 2

Distribution of baseline score for PANSS-derived domains.

Marder Domain

Std. Error

Std. Deviation

Variance

Anxiety First episode 305 10.8375 .31372

Chronic inpatient 694 8.2320 .14288

Ambulatory chronic outpatients 831 8.4481 .12880

Disorganized First episode 305 18.5750 .45094

Chronic inpatient 694 21.2017 .29482

Ambulatory chronic outpatients 831 13.5665 .17686

Hostility First episode 305 9.8063 .34958

Chronic inpatient 694 8.8012 .15308

Ambulatory chronic outpatients 831 6.1368 .10120

Negative First episode 305 21.3125 .53854

Chronic inpatient 694 20.8040 .31043

Ambulatory chronic outpatients 831 14.7192 .22224

Positive First episode 305 28.7063 .45855

Chronic inpatient 694 23.2579 .27161

Ambulatory chronic outpatients 831 18.2759 .25294

7.77 5.06 4.42 4.03 2.90 6.81 8.18 6.36 5.80 7.16 7.24

15.75 14.17 13.59

32.54 60.32 25.62

19.55 16.26

8.39 46.41 66.88 40.45 33.64 51.20 52.40

4.21 4,19

4.22 7,38 7,46 7,32 4,22 4,27 4,24

7.42 7,46 7,37 14,47

8.43 8,42

expected total score on an item based on the distribution of overall PANSS-derived scores. Items' OCCs and ICCs were then examined, and items with Weak discrimination were identified.

2.3.3. ¡RT based item selection

To assess measurement precision dependent on the latent trait (i.e.,0, PANSS-derived domains), the Item Information Function (IIF) was plotted, indicating the range over the total severity of symptoms (0) and to assess the amount of information about the specific domain (e.g. positive domain) that is provided by each item. The sum of the llFs is provided as the Test Information Function (TIF), represented as 1(0), indicating the amount of information in the scale about the specific symptom at various severity levels. Items were characterized as Very Good, Good, or Weak based on the following operational criteria (adapted from Khan et al., 2011) and examination of the Item biserial correlation.

Criterion 1: The extent to which OCCs increase rapidly with changes in overall symptom severity. Basis of rating: Examination of the OCCs.

Ratings for Criterion 1: The probability (y-axis of OCC curve) of selecting an option increases with increasing levels of severity, e.g., the probability of option 2 being selected doubles from 0.5 to 0.25 when severity increases from a score of 12-18 (based on Fig. 1).

Criterion 2. The region in which each option is more likely to be selected is ordered, left to right, in accordance with their option scores on the OCC graphs. Basis for rating: Examination of the OCCs.

Ratings for Criterion 2: The severity regions and corresponding severity scores, e.g., the region in which option 2 is most likely to be selected, falls between the regions in which option 1 and option 3 are most likely to be selected.

Criterion 3. Options for an item span the full continuum of severity from the lowest score to the highest score. Basis of rating: Examination of the OCCs.

Ratings for Criterion 3: For a particular item, all seven options span the entire range of severity (e.g., from 5 to 45 in Fig. 1).

Criterion 4. There is a range of severity in which items are expected to be scored. This is represented by the number of scores (1-7) for which the item was more likely to be scored than all other options. Basis of rating: Examination of the 1CCs.

Ratings for Criterion 4: Items for which > 5 of the 7 choices are considered acceptable.

Criterion 5. The steeper a slope of the 1CC, the more discriminant the item is. Slopes were computed in TestGraf for ICC graphs of each item from the median option score (i.e., four (Moderate) on the PANSS). Basis of rating: Slope of the ICCs. Ratings for Criterion 5: Slope is expected to be > 0.40.

Criterion 6. Biserial correlations were examined. Biserial correlations are classical test theory estimates of item discriminating. In TestGraf, the biserial correlation is the correlation between an item and overall symptom psychopathology. The possible range of values

for the biserial correlation is +1 to — 1. A correlation is "medium" at 0.30-0.49 and "large" at (0.50-1.00). Ratings for Criterion 6: A biserial correlation of >0.50 (i.e., large).

Similar to Khan and colleagues (2011) and adding an examination of the biserial correlation, items were scored as Very Good if all of the six criteria were fulfilled. Items were scored as Good if at least > 4 of the 6 criteria were met. Items were scored as Weak, if they fulfilled < 3 of the 6 criteria. Items judged as Weak were considered as contributing least to the domain symptomatology of the specific schizophrenia subgroup examined. All items were reviewed and scored by two psychometricians, independently, and discrepancies in ratings were reviewed in a consensus meeting.

3. Results

Data analysis included PANSS item scores from 1,840 patients (2 patients were removed from the Ambulatory group due to missing PANSS item data). Scores for each PANSS-derived Marder domain score is provided in Table 2.

3.1. Unidimensionality of domains

Principle Components Analysis, with no rotation, was performed for each schizophrenia group. For all three groups, all five PANSS-derived domains had >20.00% variance explained in the first

Table 3

Eigenvalues of PANSS-derived domains (without rotation).

First episode KMO Bartlett's # % variance Unidimensionality

test of Components of first assumed sphericity loading component

Anxiety 0.514 p < 0.001 2 35.749% Yes

Disorganized 0.621 p < 0.001 3 32.538% Yes

Hostility 0.500 p < 0.001 2 32.401% Yes

Negative 0.600 p < 0.001 3 26.975% Yes

Positive 0.660 p < 0.001 2 28.343% Yes

Chronic

inpatients

Anxiety 0.646 p < 0.001 1 48.941% Yes

Disorganized 0.673 p < 0.001 2 33.284% Yes

Hostility 0.530 p < 0.001 2 41.231% Yes

Negative 0.642 p < 0.001 3 32.257% Yes

Positive 0.721 p < 0.001 2 34.643% Yes

Ambulatory

Anxiety 0.638 p < 0.001 1 44.365% Yes

Disorganized 0.663 p < 0.001 2 30.197% Yes

Hostility 0.547 p < 0.001 2 36.823% Yes

Negative 0.671 p < 0.001 2 34.141% Yes

Positive 0.709 p < 0.001 3 33.886% Yes

KMO: Kaiser-Meyer-Olkin measure of sampling adequacy. Bartlett's Test of Sphericity significant (p < .001).

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx

Table 4

Item selection for First Episode patients derived from the Item Response Analysis of the PANSS.

Criteria met (Yes/No)

Based on OCCs

Based on ICCs

Biserial r

Overall rating

Anxiety G2. Anxiety G3. Guilt Feelings G4. Tension G5. Depression Disorganized P2. Conceptual Disorganization N5. Difficulty in Abstract Thinking G5. Mannerisms and Posturing G10. Disorientation G11. Poor Attention G13. Disturbance of Volition G15. Preoccupation Hostility P4. Excitement P7. Hostility G8. Uncooperativeness G14. Poor Impulse Control Negative

N1. Blunted Affect N2. Emotional Withdrawal N3. Poor Rapport N4. Passive/Apathetic Social Withdrawal N6. Lack of Spontaneity and Flow of Conversation G7. Motor Retardation G16. Active Social Avoidance Positive P1. Delusions P3. Hallucinatory Behavior P5. Grandiosity P6. Suspiciousness/ Persecution

N7. Stereotyped Thinking G1. Somatic Concerns G9. Unusual Thought Content

G12. Lack of Judgment and Insight

Yes Yes No Yes

Yes Yes Yes Yes

Yes Yes Yes Yes

Yes Yes No No

Yes Yes

No Yes

No No No

Yes Yes No Yes

No Yes Yes Yes

Yes Yes No Yes

Yes Yes No No

Yes Yes

No Yes

No No Yes

Yes Yes Yes Yes

Yes Yes Yes Yes

Yes Yes Yes Yes

Yes Yes Yes Yes

Yes Yes

Yes Yes

Yes Yes

Yes Yes Yes

Yes No No Yes

No Yes Yes Yes

No Yes No Yes

Yes Yes Yes Yes

Yes Yes

No No No

No Yes Yes Yes

No Yes Yes Yes

Yes Yes No Yes

Yes Yes No No

Yes Yes

Yes Yes

No No Yes

0.795 (Yes) 0.651 (Yes) 0.645 (Yes) 0.769 (Yes)

0.660 (Yes)

0.606 (Yes)

0.61S (Yes)

0.479 (No) 0.733 (Yes) 0.649 (Yes) 0.716 (Yes)

0.69S (Yes) 0.S20 (Yes) 0.774 (Yes) 0.799 (Yes)

0.660 (Yes) 0.606 (Yes) 0.61S (Yes) 0.479 (No)

0.733 (Yes)

0.649 (Yes) 0.716 (Yes)

0.433 (No) 0.501 (Yes)

0.471 (No) 0.560 (Yes)

0.532 (Yes) 0.125 (No) 0.596 (Yes)

0.317 (No)

Good Good Weak Very good

Very good

Very good

Weak Very good Very good Very good

Good Very good Weak Very good

Very good Very good Weak Weak

Very good

Very good Very good

Weak Good

Weak Weak

Weak Weak Good

Biserial r = Biserial correlation.

component and Bartlett's Test of Sphericity was significant for each component in each group (all p values < .001). See Table 3 for the variance accounted for in each of the first principal component for each domain in each of the three groups.

3.2. PANSS-derived domain performance 3.2.1. First episodes

3.2.1.1. Option Characteristics Curves. OCCs are used to rate criterion 1-3. Figs. 3,4, and 5 shows OCCs for items for First Episode patients on Anxiety and Hostility domains, Negative and Disorganized domains, and the Positive domain, respectively. In general, the OCCs for option 1 (absent) were clearly less likely to be rated than were other options at higher severity scores. Option 7 (extreme) was also used infrequently; the range of discrimination was above the 95th percentile for all items. Items not meeting Criteria 1 are presented in Table 4.

All items met Criterion 2, except, Anxiety domain (Tension), Hostility domain (Uncooperativeness), Negative domain (Poor Rapport, Passive/ Apathetic Social Withdrawal), Disorganized domain (Disorientation,

Mannerisms and Posturing), Positive domain (Delusions, Stereotyped Thinking, Somatic Concerns, Grandiosity, Suspiciousness and Persecution, Lack of Judgment and Insight), which did not receive a score of "Yes."

3.2.1.2. Item characteristic curves. ICCs were used to rate Criterion 4. Figs. 3,4, and 5 shows ICCs for items for First Episode patients on Anxiety and Hostility domains, Negative and Disorganized domains, and the Positive domain, respectively. Table 4 presents items for which Criterion 4 was not met.

For Criterion 5 and 6, the slopes and biserial correlations of all items are presented in Table 4.

3.2.2. Chronic inpatients

3.2.2.1. Option characteristics curves. Figs. 6, 7, and 8 shows OCCs for items for Chronic inpatients on Anxiety and Hostility domains, Negative and Disorganized domains, and the Positive domain, respectively. Similar to First Episode patients, the OCC for option 1 (absent) were clearly less likely to be rated than were other options at higher severity scores. Option 7 (extreme) was also used infrequently; the

ARTICLE IN PRESS

6 A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx

Table 5

1tem selection for Chronic inpatients derived from the 1tem Response Analysis of the PANSS.

Criteria met (Yes/No) Overall rating

Based on OCCs Based on ICCs Biserial r

1 2 3 4 5 6

Anxiety

G2. Anxiety Yes Yes Yes No No 0.852 (Yes) Good

G3. Guilt Feelings No No Yes No No 0.706 (Yes) Weak

G4. Tension No No Yes No No 0.714 (Yes) Weak

G5. Depression No No Yes No No 0.761 (Yes) Weak

Disorganized

P2. Conceptual Yes Yes Yes Yes Yes 0.642 (Yes) Very good

Disorganization

N5. Difficulty in Yes Yes Yes Yes Yes 0.689 (Yes) Very good

Abstract Thinking

G5. Mannerisms and Yes Yes Yes Yes Yes 0.645 (Yes) Very good

Posturing

G10. Disorientation Yes Yes Yes Yes Yes 0.788 (Yes) Very good

G11. Poor Attention Yes Yes Yes Yes Yes 0.781 (Yes) Very good

G13. Disturbance of Volition Yes Yes Yes Yes Yes 0.649 (Yes) Very good

G15. Preoccupation Yes Yes Yes Yes Yes 0.640 (Yes) Very good

Hostility

P4. Excitement Yes Yes Yes No No 0.691 (Yes) Good

P7. Hostility Yes Yes Yes Yes Yes 0.813 (Yes) Very good

G8. Uncooperativeness Yes Yes Yes Yes Yes 0.740 (Yes) Very good

G14. Poor Impulse Control Yes Yes Yes No No 0.812 (Yes) Good

Negative

N1. Blunted Affect Yes Yes Yes Yes Yes 0.724 (Yes) Very good

N2. Emotional Yes Yes Yes Yes Yes 0.864 (Yes) Very good

Withdrawal

N3. Poor Rapport Yes Yes Yes Yes Yes 0.772 (Yes) Very good

N4. Passive/Apathetic Yes Yes Yes Yes Yes 0.859 (Yes) Very good

Social Withdrawal

N6. Lack of Spontaneity Yes Yes Yes Yes Yes 0.853 (Yes) Very good

and Flow of Conversation

G7. Motor Retardation Yes Yes Yes Yes No 0.639 (Yes) Good

G16. Active Social Yes Yes Yes Yes Yes 0.509 (Yes) Very good

Avoidance

Positive

P1. Delusions Yes No Yes Yes Yes 0.513 (Yes) Good

P3. Hallucinatory Behavior No No Yes Yes No 0.585 (Yes) Weak

P5. Grandiosity Yes No Yes Yes Yes 0.608 (Yes) Good

P6. Suspiciousness/ No Yes Yes No No 0.426 (No) Weak

Persecution

N7. Stereotyped Thinking No No Yes No No 0.516 (Yes) Weak

G1. Somatic Concerns No No Yes No No 0.338 (No) Weak

G9. Unusual Thought Yes Yes Yes Yes Yes 0.761 (Yes) Very good

Content

G12. Lack of Judgment No No Yes Yes Yes 0.337 (No) Weak

and Insight

Biserial r = Biserial correlation.

range of discrimination was above the 95th percentile for all items. 1tems that did not meet Criterion 1 and 3 are presented in Table 5.

For Criterion 2, all items, except Anxiety domain (Tension, Guilt Feelings, Depression), and items from the Positive domain (Delusions, Stereotyped Thinking, Hallucinatory Behavior, Somatic Concerns, Grandiosity, Suspiciousness and Persecution, Lack of Judgment and Insight), did not meet the requirements for a score of "Yes."

3.2.2.2. Item Characteristic Curves. Figs. 6, 7, and 8 shows ICCs for items for Chronic inpatients on Anxiety and Hostility domains, Negative and Disorganized domains, and the Positive domain, respectively. For Criterion 4, at least five options were selected (see y-axis to the highest point on the ICC), for all items except the following: all items of the Anxiety domain (Anxiety, Tension, Guilt Feelings, Depression), two items of the Hostility domain (Excitement, Poor Impulse Control), and three items of the Positive domain (Stereotyped Thinking, Suspi-ciousness and Persecution, Somatic Concerns).

For Criterion 5 and 6, the slopes and biserial correlations of all items are presented in Table 5.

3.2.3. Ambulatory outpatients

3.2.3.1. Option Characteristics Curves. Figs. 9,10, and 11 show OCCs for items for Ambulatory outpatients on Anxiety and Hostility domains, Negative and Disorganized domains, and the Positive domain, respectively. Similar to First Episode and Chronic inpatients, the OCC for option 1 (absent) were clearly less likely to be rated than were other options at higher severity scores. Option 7 (extreme) was also used infrequently; the range of discrimination was above the 95th percentile for all items. 1tems that did not meet Criterion 1,2 and 3 are presented in Table 6 (See Table 7).

3.2.3.2. Item Characteristic Curves. Figs. 9,10, and 11 show ICCs for items for Ambulatory outpatients on Anxiety and Hostility domains, Negative and Disorganized domains, and the Positive domain, respectively. For Criterion 4, all items of the Anxiety domain, all items of the Hostility domain, four items of the Disorganized domain (Difficulty in Abstract Thinking, Disorientation, Mannerisms and Posturing, Poor Attention, Preoccupation) and four items of the Positive domain (Grandiosity, Suspiciousness and Persecution, Unusual Thought Content and Active Social Avoidance) were met.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx 7

Table 6

Item selection for Ambulatory outpatients derived from the Item Response Analysis of the PANSS.

Criteria met (Yes/No) Overall rating

Based on OCCs Based on ICCs Biserial r

1 2 3 4 5 6

Anxiety

G2. Anxiety No No Yes No No 0.701 (Yes) Weak

G3. Guilt Feelings Yes Yes Yes No No 0.700 (Yes) Weak

G4. Tension No No Yes No No 0.715 (Yes) Weak

G5. Depression No No Yes No No 0.698 (Yes) Weak

Disorganized

P2. Conceptual Yes Yes Yes Yes Yes 0.861 (Yes) Very good

Disorganization

N5. Difficulty in No No Yes No Yes 0.688 (Yes) Weak

Abstract Thinking

G5. Mannerisms No No Yes No No 0.600 (Yes) Weak

and Posturing

G10. Disorientation No Yes Yes No No 0.536 (Yes) Weak

G11. Poor Attention No No Yes No No 0.539 (Yes) Weak

G13. Disturbance Yes Yes Yes Yes Yes 0.623 (Yes) Very good

of Volition

G15. Preoccupation No No Yes No No 0.498 (No) Weak

Hostility

P4. Excitement No No Yes No No 0.601 (Yes) Weak

P7. Hostility No No Yes No No 0.606 (Yes) Weak

G8. Uncooperativeness No No Yes No No 0.568 (Yes) Weak

G14. Poor Impulse No No Yes No No 0.369 (No) Weak

Control

Negative

N1. Blunted Affect No No Yes Yes Yes 0.513 (Yes) Good

N2. Emotional Yes Yes Yes Yes Yes 0.777 (Yes) Very good

Withdrawal

N3. Poor Rapport Yes Yes Yes Yes Yes 0.714 (Yes) Very good

N4. Passive/Apathetic Yes Yes Yes Yes Yes 0.723 (Yes) Very good

Social Withdrawal

N6. Lack of Spontaneity Yes Yes Yes Yes Yes 0.700 (Yes) Very good

and Flow of

Conversation

G7. Motor Retardation Yes Yes Yes Yes Yes 0.745 (Yes) Very good

G16. Active Social Yes Yes Yes No Yes 0.689 (Yes) Good

Avoidance

Positive

P1. Delusions Yes No Yes Yes Yes 0.756 (Yes) Good

P3. Hallucinatory Yes Yes Yes Yes Yes 0.751 (Yes) Very good

Behavior

P5. Grandiosity No Yes Yes No No 0.608 (Yes) Weak

P6. Suspiciousness/ No No Yes No No 0.512 (Yes) Weak

Persecution

N7. Stereotyped Thinking Yes No Yes Yes Yes 0.569 (Yes) Good

G1. Somatic Concerns Yes Yes Yes Yes Yes 0.541 (Yes) Very good

G9. Unusual Thought No No Yes No No 0.335 (No) Weak

Content

G12. Lack of Judgment Yes Yes Yes Yes Yes 0.506 (Yes) Very good

and Insight

Biserial r = Biserial correlation.

For Criterion 5 and 6, the slopes and biserial correlations of all items are presented in Table 6.

4. Discussion

This study aimed at using Item Response Analysis to identify which symptoms of the PANSS were Very Good, Good or Weak at assessing illness severity and at representing domains in three cross-sectionally different subgroups of patients: First Episode patients, Chronic Inpatients and Ambulatory Outpatients. The findings confirm differences in symptom presentation and specific predominance of particular domains in each subgroup.

First episode patients were well represented by most negative symptoms, most disorganized symptoms, most hostility symptoms (except G8: Uncooperativeness), and all anxiety symptoms, (except G4: Tension). As hypothesized, depression and anxiety symptoms are well represented in first episode patients as are most negative

symptoms. This observation indicates that negative symptoms are already present at the early stage of the disorder. Similarly, in a longitudinal study of symptoms, Arndt and colleagues (1995) found that the negative symptoms were already prominent at the time of the pa-dents' first episode and remained relatively stable throughout the 2 years in which the patients were followed. However, two key negative symptoms, N3: Poor Rapport and N4: Passive/Apathetic Social Withdrawal are not well characterized in first episode patients in our sample, possibly because these symptoms are not yet fully developed, particularly in the area of diminished relatedness. In contrast, the item N1: Blunted Affect is scored as a Very Good negative symptom item pointing to its early presentation in the disorder manifesting a marked deficit in expressiveness. Studies of firstepisode patients demonstrate that flat affect is indeed present at the onset of illness (Shtasel et al., 1992) and are debilitating and resistant to intervention (Carpenter, 2004). Surprisingly, PANSS symptoms of disorganization are also well represented at the early stage of the

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx

Table 7

Comparison of First Episode, Chronic 1npatients and Ambulatory Outpatients and item functioning for each PANSS domain.

First episode Chronic Ambulatory

patients inpatients outpatients

Overall rating Overall rating Overall rating

Anxiety

G2. Anxiety Good Good Weak

G3. Guilt Feelings Good Weak Weak

G4. Tension Weak Weak Weak

G5. Depression Very Good Weak Weak

Disorganized

P2. Conceptual Disorganization Very Good Very Good Very good

N5. Difficulty in Abstract Very Good Very Good Weak

Thinking

G5. Mannerisms and Posturing Weak Very Good Weak

G10. Disorientation Weak Very Good Weak

G11. Poor Attention Very Good Very Good Weak

G13. Disturbance of Volition Very Good Very Good Very good

G15. Preoccupation Very Good Very Good Weak

Hostility

P4. Excitement Good Good Weak

P7. Hostility Very Good Very Good Weak

G8. Uncooperativeness Weak Very Good Weak

G14. Poor Impulse Control Very Good Good Weak

Negative

N1. Blunted Affect Very Good Very Good Good

N2. Emotional Withdrawal Very Good Very Good Very good

N3. Poor Rapport Weak Very Good Very good

N4. Passive/Apathetic Weak Very Good Very good

Social Withdrawal

N6. Lack of Spontaneity and Very Good Very Good Very good

Flow of Conversation

G7. Motor Retardation Very Good Good Very good

G16. Active Social Avoidance Very Good Very Good Good

Positive

P1. Delusions Weak Good Good

P3. Hallucinatory Behavior Good Weak Very good

P5. Grandiosity Weak Good Weak

P6. Suspiciousness/Persecution Weak Weak Weak

N7. Stereotyped Thinking Weak Weak Good

G1. Somatic Concerns Weak Weak Very good

G9. Unusual Thought Content Good Very Good Weak

G12. Lack of Judgment Weak Weak Very good

and Insight

disorder pointing to the centrality of cognitive symptoms at all stages, except for the items G10: Disorientation and G5: Mannerisms/Posturing. It should be noted that G5: Mannerisms and Posturing is considered a difficult item to score based on previous 1RT analysis (Santor et al., 2000) and is more likely to be endorsed by raters at higher severity levels. Further, both G10: Disorientation and G5: Mannerisms and Posturing are perhaps rare in first episode patients and are more characteristic of chronic patients. Unexpectedly, positive symptoms were not well represented in this first episode group, particularly the symptoms of P1: Delusions, P6: Suspiciousness and Persecution and G12: Lack of Judgment and 1nsight. The only strong PANSS positive items for the first episode group are P3: Hallucinatory Behavior and G9: Unusual Thought Content. Both these items represent the developing psychotic process, while the weaker positive items do not describe this early stage of the disorder. Other studies have shown that positive symptoms were found to be prominent at the onset of the illness and declined over the course of the follow-up period (Arndt et al. 1995). As hypothesized, the hostility domain is well represented by both G14: Poor Impulse Control and P7: Hostility in these first episode patients.

For chronic inpatients we found that the disorganized and negative symptom domains were the most robust domains, showing Very Good psychometric properties for all items of the disorganized domain, and for 6 of the 7 items of the negative symptom domain. The positive dimensions formed the third most robust

domain. This confirms findings in the majority of chronic schizophrenia samples where the negative, disorganized and positive components accounted for most of the variance in factor analyses studies (Emsley et al., 2003; Fresan et al., 2005). Similar results were also obtained for the hostility domain, where all symptoms are scored as Good or Very Good and reflect the fact that these patients are in an inpatient setting. Not surprisingly, the domain of anxiety is not well represented, with all PANSS items being scored as Weak for this subgroup. This may reflect the loss of an affective range and emotional responsiveness as the disorder progresses. As observed in our findings and other studies (Emsley et al, 1999; Koreen et al, 1993), anxiety and depressive symptoms are more common in first episode schizophrenia, than in patients with chronic schizophrenia. Alternatively, this group most likely is also treated with more rigorous antipsychotic regimens and may be therefore more subject to extrapyramidal side effects further reducing their range of emotional depth. Surprisingly, the domain of positive symptoms receives an uneven representation in this chronic inpatient group, with two key positive items being scored as Weak: P3: Hallucinatory Behavior and G12: Lack of Judgment and Insight with only G9: Unusual Thought Content assessed as a Very Good item.

The ambulatory subgroup shows a symptom profile which reflects this group's greater stability and community dwelling. The domains of anxiety, disorganization and hostility are not well represented by the corresponding PANSS items supporting the possibility that the PANSS does not measure these three domains very sensitively in ambulatory outpatients. This finding may also be related to the fact that the PANSS was originally developed based on a chronic inpatient sample (Kay et al., 1987), more akin to the present chronic inpatient sample. An exception is the item of P2: Conceptual Disorganization, which is rated as Very Good and confirms the validity and importance of cognitive deficits in the symptomatic presentation of the disorder for all three subgroups. In contrast to the domains of anxiety, disorganization and hostility, the negative symptom domain is well represented in this subgroup by the PANSS as all items are scored as Very Good, further confirming the validity of the negative domain and its corresponding items. These results are consistent with those obtained in previous studies indicating the most frequently present negative symptoms in outpatients with schizophrenia are N4: Passive Apathetic Social Withdrawal, N2: Emotional Withdrawal, N3: Poor Rapport and N1: Blunted Affect (Bobes et al., 2010; Lewis and Lieberman, 2008).

The ambulatory subgroup is also found to have the positive domain well represented by three strong items, P3: Hallucinatory Behavior, G1: Somatic Concern and G12: Lack of Judgment and 1nsight, while the other items are not as strongly represented. The fact that pharmacological treatments are most effective for positive symptoms (Feldman et al., 2003; Miller 2004), and possible psychosocial interventions the outpatient subgroup may have been exposed to, could explain the higher severity of negative symptomatology.

Our results confirm that a majority of PANSS items are either Very Good or Good at assessing the overall illness severity and psy-chometrically robust for two of the three subgroups: chronic inpa-tients (73.33%; 22 out of 30 items) and first episodes (60.00%, 18 out of 30 items). For the ambulatory group, only 46.67% (14 out of 30 items) were identified as Very Good or Good. One may expect a higher number of Very Good items representative of chronic inpatients as the PANSS scale was originally designed for inpatients in a New York State psychiatric center (Kay et al., 1987) and was also initially validated on similar inpatient samples (see Kay et al., 2000 for a review). As expected, our present nonparametric 1RT showed that the Negative Symptom items (particularly, N1: Blunted Affect, N2: Emotional Withdrawal, N6: Lack of Spontaneity and Flow of Conversation, G7: Motor Retardation and G16: Active Social Avoidance) showed good discriminative properties across all three

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx

subpopulations, and most negative items reflected the entire range of severity (i.e., increases in symptom intensity correspond to increases in illness severity), and that these items most closely approximate the "ideal" item illustrated in Fig. 1. In contrast, items of the Positive Symptoms domain, P1: Delusions, P3: Hallucinatory Behavior, P7: Hostility, G1: Somatic Concern and G12: Lack of Judgment and Insight, showed good approximation to the "ideal" item presented in Fig. 1 only for the ambulatory outpatients. Other than P3: Hallucinatory Behavior and G9: Unusual Thought Content, most of the positive domain were not representative of first episode patients. This was also found for the chronic inpatient group where most positive symptoms with the exception of G9: Unusual Thought Content was not well represented. These cross-sectional findings of variance in sensitivity and possible validity of PANSS measured symptoms may suggest the need for some revision of PANSS items or a more selective use of PANSS symptoms dependent on the patient population at hand. For example, it appears that positive symptoms in first episode patients are not be measured with the positive PANSS domain as are depression and anxiety symptoms in chronic inpatients. The PANSS may be least adapted to reliably assess the range of symptoms in ambulatory outpatients where we found that the domains of anxiety, disorganization and hostility were not well represented.

4.1. Limitations

The current study of symptom variations among three subgroups of schizophrenia patients is subject to limitations. First, the sample was selected according to a criterion for participation in a clinical trial, and may not accurately represent patients encountered in clinical practice. Because of the differences in investigators and study inclusion criteria, study participants may have differed widely by demographic characteristics, and the level of PANSS training may have differed across studies. Second, Cella and Chang (2000) warned of the possible limitations of using IRT methods to evaluate healthcare measures since IRT methods were originally developed for, and used with a fairly homogeneous educational assessment population. When applying these methods to more heterogeneous clinical populations there may be limitations to obtain item-free estimates of sample latent traits. Thirdly, some studies have suggested that a follow-up of two or more years may be more appropriate when exploring symptoms in first episode patients (Mane et al., 2009; Milev et al., 2005). Our study only looked at baseline data and this may have been a limitation in terms of understanding whether symptom presentations observed in this IRT will persist at follow-up for each subgroup. A 12- or 24-week follow up may help us better delineate the course of the three subgroups. Fourthly, it should be noted that subjects in the first episode group did not have any other Axis I disorders, while subjects in the other subgroups were not screened out for other Axis I disorders. The presence of other Axis I disorders can provide present a confounding variable as the other disorders may present with additional symptoms. Finally, for IRT, and item score patterns, false positives may arise, for example, from attributing a pattern with relatively many scores of 1 (i.e., Absent) as a "Weak" item. It may be noted that, in general, several different causes might lead to the same kind of pattern. False positives may be reduced with the use of a two-stage procedure suggested by Marco (1977), which was not incorporated in the present study. Use of this procedure involves first estimating item parameters, calculating bias indices, identifying and deleting biased items, then estimating abilities using the remaining unbiased items. However, this procedure would be applicable in previous PANSS analysis for reducing the number of PANSS items (e.g., Khan et al., 2011). Although, the available dataset for this study was adequate for conducting an IRT, the symptom structures presented in this study should not be considered a gold standard for identifying

psychopathology in each subgroup. Other studies will be needed to determine if these symptom structures are replicated across different samples and show medication group difference through sensitivity to therapeutic change.

5. Conclusions

This study used an Item Response Analysis to identify psycho-metrically valid and sensitive symptoms of the five PANSS domains in three cross-sectionally different subgroups of patients: first episodes, chronic inpatients and ambulatory outpatients. The emerging dimensional approach to classification and treatment of psychiatric disorders calls for a better understanding of symptom-related variations at different stages of schizophrenia and for proper validation of psychometric scales used for the evaluation of symptom dimensions. This examination of the psychometric suitability of the PANSS items and its five symptom domains has shown that PANSS domains have different predominance patterns in three patient subgroups. First episode psychosis patients are characterized by strong domains of anxiety, disorganization and negative symptoms. The chronic inpatient group is well represented by the disorganization, hostility and negative domains. Finally, patients in the ambulatory group show only a predominance of the negative domain with some representation of the positive domain. While this examination of PANSS items of the five psychopathology domains cannot replace the examination of the longitudinal trajectory of these domains across the illness course, the three patient groups do represent distinct stages of the disorder and allow for the examination of variances in symptom presentation overtime and possible underlying mechanisms contributing to symptom expression.

One of the implications of our results is that the study of different dimensions within subgroups of schizophrenia may help to better define symptom domains of subgroups of schizophrenia patients with a psychometrically sound rating scale instead with clinical criteria and to benefit symptom dimension identification of patients. This identification may favor the design of treatment programs, which could address specific patient needs where appropriate treatments could be available.

Funding body agreements and policies

• In the past five years none of the authors have received reimbursements, fees, funding, or salary from an organization that may in any way gain or lose financially from the publication of this manuscript, either now or in the future.

• All authors indicate that they do not hold any stocks or shares in an organization that may in any way gain or lose financially from the publication of this manuscript, either now or in the future.

• All authors indicate that they do not hold or are currently applying for any patents relating to the content of the manuscript. No author has received reimbursements, fees, funding, or salary from an organization that holds or has applied for patents relating to the content of the manuscript.

• All authors have no competing funding interests.

• Non-financial competing interests: All authors confirm that they have no non-financial competing interests (political, personal, religious, ideological, academic, intellectual, commercial or any other) to declare in relation to this manuscript.

Contributors

Dr. Harvey and Dr. Khan participated in the development of the concept for the study. Dr. Harvey, Dr. Khan, Dr. Lindenmayer, and Dr. Opler participated in the design of the study and helped to draft the manuscript. Dr. Khan performed the statistical analysis and drafted the manuscript. Dr. Kelley, Dr. White, Dr. Compton and Ms.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx

Gao participated in the design, coordination and drafted the manuscript. All authors read and approved the final manuscript.

Conflict of interest

Dr. Opler owns shares in ProPhase LLC, New York, NY. ProPhase LLC has received funding from Otsuka Pharmaceutical Company, Ltd., Pfizer Pharmaceuticals, Hoffman-LaRoche Pharmaceutical, Biomarin Pharmaceuticals 1nc., Angelini Group, Janssen Pharmaceuticals, 1nc., Shire Pharmaceuticals Public Limited Company, and Reviva Pharmaceuticals 1nc. Dr. Opler, Dr. Lindenmayer and Dr. Harvey have grants and/or funding from National Institute of Health (N1H). Dr. Opler also has funding from the Weill-Cornell Medical College - Qatar Foundation. Dr. Lindenmayer and Dr. Khan have consulted for Janssen Pharmaceuticals, 1nc. Dr. Opler and Dr. Khan have consulted for Reviva Pharmaceuticals 1nc. Dr. Lindenmayer also has grants and/or funding from Pfizer Pharmaceuticals, Eli Lilly and Company, Dainippon Sumitomo Pharma, Azur Pharma, 1nc., Amgen Biopharmaceutical Company, Hoffman-LaRoche Pharmaceutical, Otsuka Pharmaceutical Company, Ltd., EnVivo Pharmaceuticals, AstraZeneca PLC, and Neurocrine Biosciences. All other authors declare that they have no conflicts of interest. All other co-authors do not have any conflicts of interest to disclose.

Acknowledgments

The authors would like to acknowledge the staff at ProPhase LLC, New York, New York and Manhattan Psychiatric Center, New York, who contributed towards the study by making substantial contributions to formatting and data review and were involved in reviewing the manuscript for important intellectual content. No financial contributions were involved in the data exchange.

References

American Psychiatric Association, 2013. Diagnostic and statistical manual of mental

disorders (5th ed., text revision). Author, Washington, DC. Andreasen, N.C., Arndt, S., Alliger, R., Miller, D., Flaum, M., 1995. Symptoms of schizophrenia: Methods, meanings and mechanisms. Arch. Gen. Psychiatry 52, 341-351.

Arndt, S., Andreasen, N.C., Flaum, M., Miller, D., Nopoulos, P., 1995. A longitudinal study of symptom dimensions in schizophrenia: prediction and patterns of change. Arch. Gen. Psychiatry 52 (5), 352-360. Bartlett, M.S., 1954. A note on the multiplying factors for various chi square approximations. J. Roy. Stat. Society 16 (B), 296-298. Bartels, S.J., Drake, R.E., Wallach, M.A., Freeman, D.H., 1991. Characteristic hostility in

schizophrenic outpatients. Schizophr. Bull. 17 (1), 163-171. Bell, M.D., Lysaker, P.H., Beam-Goulet, J.L., Milstein, R.M., Lindenmayer, J.P., 1994. Five-component model of schizophrenia: Assessing the factorial invariance of the Positive and Negative Syndrome Scale. Psychiatry Res. 52, 295-303. Bengston, M., 2006. Types of Schizophrenia. 2006. Psych. Central. Retrieved on March

26, 2013, from http://psychcentral.com/lib/2006/types-of-schizophrenia/. Bobes, J., Arango, C., Garcia-Garcia, M., Rejas, J., 2010. Prevalence of negative symptoms in outpatients with schizophrenia spectrum disorders treated with antipsychotics in routine clinical practice: Findings from the CLAMORS study. J. Clin. Psychiatry 71 (3), 280-286.

Bowie, C.R., Leung, W.W., Reichenberg, A., McClure, M.M., Patterson, T.L., Heaton, R.K., et al., 2008. Predicting schizophrenia patients' real-world behavior with specific neu-ropsychological and functional capacity measures. Biol. Psychiatry 63, 505-511. Buchanan, R.W., 2007. Persistent negative symptoms in schizophrenia: An overview.

Schizophr. Bull. 33 (4), 1013-1022. Carpenter Jr., W.T., 2004. Clinical constructs and therapeutic discovery. Schizophr. Res. 72, 69-73.

Caton, C.L., Shrout, P.E., Eagle, P.F., Opler, L.A., Felix, A., Dominguez, B., 1994. Risk factors or homelessness among schizophrenia men: A case control study. Am. J. Public Health 84, 265-270.

Caton, C.L., Shrout, P.E., Dominguez, B., Eagle, P.F., Opler, L.A., Cournos, F., 1995. Risk factors for homelessness among women in schizophrenia. Am. J. Public Health 85,1153-1156.

Cella, D., Chang, C.H., 2000. A discussion of item response theory (1RT) and its applications in health status assessment. Med. Care 38 (9), 66-72. Chemerinski, E., Reichenberg, A., Kirkpatrick B., Bowie, C.R., Harvey, P.D., 2006. Three dimensions of clinical symptoms in elderly patients with schizophrenia: Prediction of six-year cognitive and functional status. Schizophr. Res. 85 (1-3), 12-19. Chen, C.Y., Liu, C.Y., Yang, Y.Y., 2001. Correlation of panic attacks and hostility in chronic schizophrenia. Psychiatry Clin. Neurosci. 55, 383-387.

Compton, M.T., Kelley, M.E., Ramsay, C.E., Pringle, M., Goulding, S.M., Esterberg, M.L., Stewart, T., Walker, E.F., 2009. Association of pre-onset cannabis, alcohol, and tobacco use with age at onset of prodrome and age at onset of psychosis in firstepisode patients. Am. J. Psychiatry 166 (11), 1251-1257.

Compton, M.T., Gordon, T.L., Goulding, S.M., Esterberg, M.L., Carter, T., Leiner, A.S., Weiss, P.S., Druss, B.G., Walker, E.F., Kaslow, N.J., 2011. Patient-level predictors and clinical correlates of duration of untreated psychosis among hospitalized first-episode patients. J. Clin. Psychiatry 72 (2), 225-232.

Davidson, M., Harvey, P.D., Powchik P., Parrella, M., White, L., Knobler, H.Y., Losonczy, M.F., Keefe, R.S., Katz, S., Frecska, E., 1995. Severity of symptoms in chronically institutionalized geriatric schizophrenic patients. Am. J. Psychiatry 152 (2), 197-207.

Emsley, R.A., Oosthuizen, P.P., Joubert, A.F., Hawkridge, S.M., Stein, D.J., 1999. Treatment of schizophrenia in low-income countries. Int. J. Neuropsychopharmacol. 2,321-325.

Emsley, R., Rabinowitz, J., Torreman, M., 2003. The factor structure for the Positive and Negative Syndrome Scale (PANSS) in recent-onset psychosis. Schizophr. Res. 61 (1), 47-57.

Feldman, P.D., Kaiser, C.J., Kennedy, J.S., Sutton, V.K., Tran, P.V., Tollefson, G.D., 2003. Comparison of risperidone and olanzapine in the control of negative symptoms of chronic schizophrenia and related psychotic disorders in patients aged 50 to 65 years. .J Clin. Psychiatry 64 (9), 998-1004.

First, M.B., Spitzer, R.L., Gibbon, M., Williams, J.B.W., 1998. Structured Clinical Interview for DSM-IV Axis 1 Disorders. Biometrics Research Department, New York State Psychiatric 1nstitute, New York.

Fresan, A., De la Fuente-Sandoval, C., Loyzaga, C., Garcia-Anaya, M., Meyenberg, N., Nicolini, H., Apiquian, R., 2005. A forced five-dimensional factor analysis and concurrent validity of the Positive and Negative Syndrome Scale in Mexican schizophrenia patients. Schizophr. Res. 72 (2-3), 123-129.

Green, A.1., Canuso, C., Brenner, M.J., Wijcik, J.D., 2003. Detection and management of comorbidity in schizophrenia. Psychiatr. Clin. N. Am. 26,115-139.

Green, M.F., Kern, R.S., Heaton, R.K., 2004. Longitudinal studies of cognition and functional outcome in schizophrenia: implications for MATR1CS. Schizophr. Res. 72, 41 -51.

Hardle, W., 1990. Applied nonparametric regression. Chapman & Hall, London.

Harris, M.J., 1991. Deficit syndrome in older schizophrenic patients. Psychiatry Res. 39, 285-292.

Harvey, P.D., Green, M.F., Bowie, C., Loebel, A., 2006. The dimensions of clinical and cognitive change in schizophrenia: Evidence for independence of improvements. Psy-chopharmacology 187 (3), 356-363.

Harvey, P., Reichenberg, A., Bowie, C.R., Patterson, T.L., Heaton, R.K., 2010. The course of neuropsychological performance and functional capacity in older patients with schizophrenia: Influences of previous history of long term institutional stay. Biol. Psychiatry 67 (10), 933-939.

Kaiser, H.F., 1970. A second-generation Little Jiffy. Psychometrika 35,401-415.

Kaiser, H.F., 1974. An index of factorial simplicity. Psychometrika 39, 31-36.

Kay, S.R., Fiszbein, A., Opler, L.A., 1987. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr. Bull. 13 (2), 261-276.

Kay, S.R., Sevy, S., 1990. Pyramidical model of schizophrenia. Schizophr. Bull. 16 (3), 537-545.

Kay, S.R., Opler, L.A., Fiszbein, A., 2000. The Positive and Negative Syndrome Scale (PANSS) Manual. Multi-Health Systems Inc., Toronto, ON.

Keefe, R.S., 2008. Should cognitive impairment be included in the diagnostic criteria for schizophrenia. World Psychiatry 7, 22-28.

Kelley, M.E., White, L., Compton, M.T., Harvey, P.D., 2013. Subscale structure for the Positive and Negative Syndrome Scale (PANSS): A proposed solution focused on clinical validity. Psychiatry Res. 205 (1-2), 137-142.

Khan, A., Lewis, C., Lindenmayer, J.P., 2011. Use of non-parametric item response theory to develop a shortened version of the Positive and Negative Syndrome Scale (PANSS). BMC Psychiatry 16 (11), 178.

Koreen, A.R., Siris, S.G., Chakos, M., Alvir, J., Mayerhoff, D., Lieberman, J., 1993. Depression in first-episode schizophrenia. Am. J. Psychiatry 150,1643-1648.

Kurtz, M.M., 2005. Symptoms versus neurocognitive skills as correlates of everyday functioning in severe mental illness. Expert Rev. Neurother. 6,47-56.

Leff, J., Trieman, N., 2000. Long-stay patients discharged from psychiatric hospitals. Social and clinical outcomes after five years in the community. The TAPS Project 46. Br. J. Psychiatry 176, 217-223.

Lewis, S., Lieberman, J., 2008. CAT1E and CUtLASS: can we handle the truth? Br. J. Psychiatry 192 (3), 161-163.

Lindenmayer, J.P., Kay, S.R., Friedman, C., 1986. Negative and positive schizophrenic syndromes after the acute phase: A prospective follow-up. Compr Psychiatry 27, 276-286.

Mane, A., Falcon, C., Mateos, J.J., Fernandez-Egea, E., Horga, G., Lomena, F., Bargallo, N., Prats-Galino, A., Bernardo, M., Parellada, E., 2009. Progressive gray matter changes in first episode schizophrenia: A 4-year longitudinal magnetic resonance study using VBM. Schizophr. Res. 114 (1-3), 136-143.

Marco, G.L., 1977. Item characteristics curve solutions to three intractable testing problems. J. Educ. Meas. 14,139-160.

Marder, S.R., Davis, J.M., Chouinard, G., 1997. The effects of risperidone on the five dimensions of schizophrenia derived by factor analysis: combined results of the North American trials. J. Clin. Psychiatry 58 (12), 538-546.

Milev, P., Ho, B.C., Arndt, S., Andreasen, N.C., 2005. Predictive values of neurocognition and negative symptoms on functional outcome in schizophrenia: A longitudinal first-episode study with 7-year follow-up. Am. J. Psychiatry 162 (3), 495-506.

Miller, A.L., 2004. Combination treatments for schizophrenia. CNS Spectrums 9 (9), 19-23.

Moller, H.J., 2005. Occurrence and treatment of depressive comorbidity/ cosyndromality in schizophrenic psychoses: Conceptual and treatment issues. World J. Biol. Psychiatry 6, 247-263.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx 11

Orlando, M., Thissen, D., 2000. Likelihood-based item-fit indices for dichotomous item response theory models. Appl. Psychol. Measure 24, 50-64.

Petersen, M.A., 2004. Book review: Introduction to nonparametric item response theory. Qual. Life Res. 14,1201-1202.

Putnam, K.M., Harvey, P.D., Parrella, M., White, L., Kincaid, M., Powchik, P., Davidson, M., 1996. Symptom stability in geriatric chronic schizophrenic inpatients: A one-year follow-up study. Biol. Psychiatry 39 (2), 92-99.

Ramsay JO. 2000. TESTGRAF: A computer program for nonparametric analysis of testing data. Unpublished manuscript, McGill University [Available online from ftp://ego. psych.mcgill.ca/pub/ramsay/testgraf].

Reckase, M.D., 1979. Unifactor latent trait models applied to multifactor tests: Results and implications. J. Educ. Stat. 4 (3), 207-230.

Roseman, A.S., Kasckow, J., Fellows, I., Osatuke, K., Patterson, T.L., Mohamed, S., Zisook, S., 2008. Insight, quality of life, and functional capacity in middle-aged and older adults with. Int. J. Geriatr. Psychiatry 23 (7), 760-765.

Santor, D.A., Ascher-Svanum, H., Lindenmayer, J.P., Obenchain, R.L., 2000. Item response analysis of the Positive and Negative Syndrome Scale. BMC Psychiatry 15, 7-66.

Shtasel, D.L., Gur, R.E., Gallacher, F., Heimberg, C., Cannon, T.D., Gur, R.C., 1992. Phenomenology and functioning in first episode schizophrenia. Schizophr. Bull. 18, 449-462.

Sijtsma, K., Molenaar, I.W., 2000. Introduction to nonparametric item response theory. Sage, Thousand Oaks, CA.

Sijtsma, K., Emons, W.H., Bouwmeester, S., Nyklicek I., Roorda, L.D., 2008. Nonpara-metric IRT analysis of Quality-of-Life Scales and its application to the World Health Organization Quality-of-Life Scale (WHOQOL-Bref). Qual. Life Res. 17, 275-290.

White, L., Harvey, P.D., Opler, L., Lindenmayer, J.P., 1997a. Empirical assessment of the factorial structure of clinical symptoms in schizophrenia. A multisite, multimodel evaluation of the factorial structure of the Positive and Negative Syndrome Scale. The PANSS Study Group. Psychopathology 30 (5), 263-274.

White, L., Parrella, M., McCrystal-Simon, J., Harvey, P.D., Masiar, S.J., Davidson, M., 1997b. Characteristics of elderly psychiatric patients retained in a state hospital during downsizing: A prospective study with replication. Int. J. Geriatr. Psychiatry 12 (4), 474-480.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx

Fig. 3. Left to right: Option Characteristic Curves (graphs shows 7 overlapping lines). Item 1: Anxiety Domain, Anxiety; Item 2: Anxiety Domain, Guilt Feelings; Item 3: Anxiety Domain, Tension; Item 4: Anxiety Domain, Depression. Item Characteristic Curve (graph shows one line with green intersecting lines). Item 1: Anxiety Domain, Anxiety; Item 2: Anxiety Domain, Guilt Feelings; Item 3: Anxiety Domain, Tension; Item 4: Anxiety Domain, Depression.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx

Fig. 3. (continued) Left to right: Option Characteristic Curves. Item 1: Hostility Domain, Excitement; Item 2: Hostility Domain, Hostility; Item 3: Hostility Domain, Uncooperativeness; Item 4: Hostility Domain, Poor Impulse Control. Item Characteristic Curve. Item 1: Hostility Domain, Excitement; Item 2: Hostility Domain, Hostility; Item 3: Hostility Domain, Uncooperativeness; Item 4: Hostility Domain, Poor Impulse Control.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx

Fig. 4. Complete caption for this figure is provided on the next page.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx 15

Fig. 4. Left to right: Option Characteristic Curves. Item 1:. Negative Domain,: Blunted Affect; Item 2: Negative Domain, Emotional Withdrawal; 1tem3: Negative Domain, Poor Rapport; 1tem4: Negative Domain, Passive Apathetic Social Withdrawal; 1tem5: Negative Domain, Lack of Spontaneity and Flow of Conversation; 1tem6: Negative Domain, Motor Retardation; 1tem7: Negative Domain, Active Social Withdrawal. Item Characteristic Curves. Item 1: Negative Domain, Blunted Affect; Item 2: Negative Domain, Emotional Withdrawal; 1tem3: Negative Domain, Poor Rapport; Item 4: Negative Domain, Passive Apathetic Social Withdrawal; Item 5: Negative Domain, Lack of Spontaneity and Flow of Conversation; Item 6: Negative Domain, Motor Retardation; Item 7: Negative Domain, Active Social Withdrawal.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx

Fig. 4. (continued). Complete caption for this figure is provided on the next page.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx 17

Fig. 4. (continued) Left to right: Option Characteristic Curves. Item 1: Disorganized Domain, Conceptual Disorganization; Item 2: Disorganized Domain, Difficulty in Abstract Thinking; Item 3: Disorganized Domain, Mannerisms and Posturing; Item 4: Disorganized Domain, Disorientation; Item 5: Disorganized Domain, Poor Attention; Item 6: Disorganized Domain, Disturbance of Volition; Item 7: Disorganized Domain, Preoccupation. Item Characteristic Curves. Item 1: Disorganized Domain, Conceptual Disorganization; Item 2: Disorganized Domain, Difficulty in Abstract Thinking; Item 3: Disorganized Domain, Mannerisms and Posturing; Item 4: Disorganized Domain, Disorientation; Item 5: Disorganized Domain, Poor Attention; Item 6: Disorganized Domain, Disturbance of Volition; Item 7: Disorganized Domain, Preoccupation.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx

Fig. 5. Complete caption for this figure is provided on the next page.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx 19

Fig. 5. Left to right: Option Characteristics Curves. Item 1: Positive Domain, Delusions; Item 2: Positive Domain, Hallucinatory Behavior; Item 3: Positive Domain, Grandiosity; Item 4: Positive Domain, Suspiciousness/Persecution; Item 5: Positive Domain, Stereotyped Thinking; Item 6: Positive Domain, Somatic Concerns; Item 7: Positive Domain, Unusual Thought Content; Item 8: Positive Domain, Lack ofJudgment and Insight. Item Characteristics Curves. Item 1: Positive Domain, Delusions; Item 2: Positive Domain, Hallucinatory Behavior; Item 3: Positive Domain, Grandiosity; Item 4:; Positive Domain, Suspiciousness/Persecution; Item 5: Positive Domain, Stereotyped Thinking; Item 6: Positive Domain, Somatic Concerns; Item 7: Positive Domain, Unusual Thought Content; Item 8: Positive Domain, Lack ofJudgment and Insight.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx

Fig. 6. Complete caption for this figure is provided on the next page.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx 21

Fig. 6. Left to right: Option Characteristic Curves (graphs shows 7 overlapping lines). Item 1: Anxiety Domain, Anxiety; Item 2: Anxiety Domain, Guilt Feelings; Item 3: Anxiety Domain, Tension; Item 4: Anxiety Domain, Depression. Item Characteristic Curves (graphs show one line with green intersecting lines). Item 1: Anxiety Domain, Anxiety; Item 2: Anxiety Domain, Guilt Feelings; Item 3: Anxiety Domain, Tension; Item 4: Anxiety Domain, Depression.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx

Fig. 6. (continued). Complete caption for this figure is provided on the next page.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx 23

Fig. 6. (continued) Left to right: Option Characteristic Curves. Item 1: Hostility Domain, Excitement; Item 2: Hostility Domain, Hostility; Item 3: Hostility Domain, Uncooperativeness; Item 4: Hostility Domain, Poor Impulse Control. Item Characteristic Curves. Item 1. Hostility Domain, Excitement; Item 2: Hostility Domain, Hostility; Item 3: Hostility Domain, Uncooperativeness; Item 4: Hostility Domain, Poor Impulse Control.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx

Fig. 7. Complete caption for this figure is provided on the next page.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx 25

Fig. 7. Left to right: Option Characteristic Curves. Item 1: Negative Domain, Blunted Affect; Item 2: Negative Domain, Emotional Withdrawal; Item 3: Negative Domain, Poor Rapport; Item 4: Negative Domain, Passive Apathetic Social Withdrawal; Item 5: Negative Domain, Lack of Spontaneity and Flow of Conversation; Item 6: Negative Domain, Motor Retardation; Item 7: Negative Domain, Active Social Withdrawal. Item Characteristic Curves: Item 1: Negative Domain, Blunted Affect; Item 2: Negative Domain, Emotional Withdrawal; Item 3: Negative Domain, Poor Rapport; Item 4: Negative Domain, Passive Apathetic Social Withdrawal; Item 5: Negative Domain, Lack of Spontaneity and Flow of Conversation; Item 6: Negative Domain, Motor Retardation; Item 7: Negative Domain, Active Social Withdrawal.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx

Fig. 7. (continued). Complete caption for this figure is provided on the next page.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx 27

Fig. 7. (continued) Left to right: Option Characteristic Curves. Item 1: Disorganized Domain, Conceptual Disorganization; Item 2: Disorganized Domain, Difficulty in Abstract Thinking; Item3: Disorganized Domain, Mannerisms and Posturing; Item 4: Disorganized Domain, Disorientation; Item5: Disorganized Domain, Poor Attention; Item6: Disorganized Domain, Disturbance of Volition; Item 7: Disorganized Domain, Preoccupation. Item Characteristic Curves. Item 1: Disorganized Domain, Conceptual Disorganization; Item 2: Disorganized Domain, Difficulty in Abstract Thinking; Item 3: Disorganized Domain, Mannerisms and Posturing; Item 4: Disorganized Domain, Disorientation; Item 5: Disorganized Domain, Poor Attention; Item 6: Disorganized Domain, Disturbance of Volition; Item 7: Disorganized Domain, Preoccupation.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx

Fig. 8. Complete caption for this figure is provided on the next page.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx 29

Fig. 8. Left to right: Option Characteristics Curves. Item 1: Positive Domain, Delusions; Item 2: Positive Domain, Hallucinatory Behavior; Item3: Positive Domain, Grandiosity; Item 4: Positive Domain, Suspiciousness/Persecution; Item 5: Positive Domain, Stereotyped Thinking; Item 6: Positive Domain, Somatic Concerns; Item 7: Positive Domain, Unusual Thought Content; Item 8: Positive Domain, Lack of Judgment and Insight. Item Characteristics Curves. Item 1: Positive Domain, Delusions; Item 2: Positive Domain, Hallucinatory Behavior; Item 3: Positive Domain, Grandiosity; Item 4:; Positive Domain, Suspiciousness/Persecution; Item 5: Positive Domain, Stereotyped Thinking; Item 6: Positive Domain, Somatic Concerns; Item 7: Positive Domain, Unusual Thought Content; Item 8: Positive Domain, Lack of Judgment and Insight.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx

Fig. 9. Left to right: Option Characteristic Curves (graphs shows 7 overlapping lines). Item 1: Anxiety Domain, Anxiety; Item 2: Anxiety Domain, Guilt Feelings; Item 3: Anxiety Domain, Tension; Item 4: Anxiety Domain; Depression. Item Characteristic Curves (graphs show one line with green intersecting lines). Item 1: Anxiety Domain, Anxiety; Item 2: Anxiety Domain, Guilt Feelings; Item 3: Anxiety Domain, Tension; Item 4: Anxiety Domain, Depression.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx

Fig. 9. (continued) Left to right: Option Characteristic Curves. Item 1: Hostility Domain, Excitement; Item 2: Hostility Domain, Hostility; Item 3: Hostility Domain, Uncooperativeness; Item 4: Hostility Domain, Poor Impulse Control. Item Characteristic Curves: Item 1: Hostility Domain,: Excitement; Item 2: Hostility Domain, Hostility; Item 3: Hostility Domain, Uncooperativeness; Item 4: Hostility Domain, Poor Impulse Control.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx

Fig. 10. Complete caption for this figure is provided on the next page.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx 33

Fig. 10. Left to right: Option Characteristic Curves. Item 1: Negative Domain: Blunted Affect; Item 2: Negative Domain, Emotional Withdrawal; Item 3: Negative Domain, Poor Rapport; Item 4: Negative Domain, Passive Apathetic Social Withdrawal; Item 5: Negative Domain, Lack of Spontaneity and Flow of Conversation; Item 6: Negative Domain, Motor Retardation; Item 7: Negative Domain: Active Social Withdrawal. Item Characteristic Curves.: Item 1: Negative Domain, Blunted Affect; Item 2: Negative Domain, Emotional Withdrawal; Item 3: Negative Domain, Poor Rapport; Item 4: Negative Domain, Passive Apathetic Social Withdrawal; Item 5: Negative Domain, Lack of Spontaneity and Flow of Conversation; Item 6: Negative Domain, Motor Retardation; Item 7: Negative Domain, Active Social Withdrawal.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx

Fig. 10. (continued). Complete caption for this figure is provided on the next page.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx 35

Fig. 10. (continued) Left to right: Option Characteristic Curves. Item 1 : Disorganized Domain, Conceptual Disorganization; Item 2: Disorganized Domain, Difficulty in Abstract Thinking; Item 3: Disorganized Domain, Mannerisms and Posturing; Item 4: Disorganized Domain, Disorientation; Item 5: Disorganized Domain, Poor Attention; Item 6: Disorganized Domain, Disturbance of Volition; Item 7: Disorganized Domain, Preoccupation. Item Characteristic Curves. Item 1 : Disorganized Domain, Conceptual Disorganization; Item 2: Disorganized Domain, Difficulty in Abstract Thinking; Item3: Disorganized Domain, Mannerisms and Posturing; Item 4: Disorganized Domain, Disorientation; Item 5: Disorganized Domain, Poor Attention; Item 6: Disorganized Domain, Disturbance of Volition; Item 7: Disorganized Domain, Preoccupation.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx

Fig. 11. Complete caption for this figure is provided on the next page.

ARTICLE IN PRESS

A. Khan et al. / Schizophrenia Research: Cognition xxx (2014) xxx-xxx 37

Fig. 11. Option Characteristics Curves. Item 1: Positive Domain, Delusions; Item 2: Positive Domain, Hallucinatory Behavior; Item 3: Positive Domain, Grandiosity; Item 4; Positive Domain, Suspiciousness/Persecution; Item 5: Positive Domain, Stereotyped Thinking; Item 6: Positive Domain, Somatic Concerns; Item 7: Positive Domain, Unusual Thought Content; Item 8: Positive Domain, Lack of Judgment and Insight. Item Characteristics Curves. Item 1: Positive Domain, Delusions; Item 2: Positive Domain, Hallucinatory Behavior; Item 3: Positive Domain, Grandiosity; Item 4: Positive Domain, Suspiciousness/Persecution; Item 5: Positive Domain, Stereotyped Thinking; Item 6: Positive Domain: Somatic Concerns; Item 7: Positive Domain, Unusual Thought Content; Item 8: Positive Domain, Lack of Judgment and Insight.