An Assessment of Five (PANSS, SAPS, SANS, NSA-16, CGI-SCH) commonly used Symptoms Rating Scales in Schizophrenia and Comparison to Newer Scales (CAINS, BNSS)

Scales measuring positive and negative symptoms in schizophrenia remain the primary mo Scales measuring positive and negative symptoms in schizophrenia remain the primary mode of assessing and diagnosing schizophrenia by clinicians and researchers. The scales are mainly used to monitor the severity of positive and negative symptoms and track treatment response in schizophrenics. Although these scales are widely used, quality as well as general utility of each scale varies. The quality is determined by the validity and reliability of the scales. The utility of the scale is determined by the time of administration and the settings for which the scales can be administered in research or clinical settings. There are relatively fewer articles on the utility of newer scales like CAINS (Clinical Assessment Interview for Negative Symptoms) and the BNSS (Brief Negative Symptom Scale) that compare them to the older scales PANSS (Positive and Negative Symptoms Scale), SAPS (Scale for the Assessment of Positive Symptoms) SANS (the Scale for the Assessment of Negative Symptoms), NSA-16 (Negative Symptom Assessment-16) and CGI-SCH (Clinical Global Impression Schizophrenia. The older scales were developed more than 30 years ago. Since then, our understanding of negative symptoms has evolved and currently there are newer rating scales evaluating the validity of negative symptoms. The older scales do not incorporate the latest research on negative symptoms. CAINS and BNSS are attractive for both their reliability and their concise accessible format, however, a scale that is simpler, accessible, user-friendly, that incorporates a multidimensional model of schizophrenia, addresses the psychosocial and cognitive component has yet to be developed.

Introduction schizophrenia", "negative symptoms scale in schizophrenia", "positive and negative syndrome scale in schizophrenia", "screening for schizophrenia", and "utility of scales in schizophrenia". Research articles that were generated using the above mentioned search terms met our inclusion criteria if at least one of the negative or positive symptoms scales (PANSS, SANS, SAPS, NAS-16 and CGI-SCH CAINS, BNSS) were mentioned within the title and/or abstract. We excluded editorials.

The Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms (SANS and SAPS)
The (SANS) and (SAPS) were developed in 1980 to fill a conspicuous gap in tools that could effectively measure the severity of negative and positive symptoms [2]. A standardized scale measuring either positive or negative symptoms did not exist at the time, and negative symptoms were often overlooked, in both clinical as well as in research settings, while positive symptoms were sometimes overemphasized. With Crow's work on the importance of negative symptoms, new interest in screening patients with negative symptoms, as well as the inter-correlation of negative symptoms, arose [3]. Partly in response to this paradigm shift, the Scale for the Assessment of Negative Symptoms (SANS) was developed [4]. SAPS were subsequently released a year later, enabling the clinician to evaluate positive symptoms using a similar structure and format to SANS [5]. Specific symptoms in both scales were chosen on the basis of both clinical experience and empirical statistical evaluation of data interrelationships and correlations [6].
SANS and SAPS are both utilized frequently in clinical and research settings. The question of reliability and validity has been raised since its inception, and various studies have been conducted on the validity of the scales. Earlier studies have mostly focused on interrater reliability, which has been shown to be consistent, even in multiple cross-cultural settings [2]. Other studies have focused on the temporal stability of the two scales, particularly in regards to the effect of treatment [7]. One study conducted by Malia et al. demonstrated that while SAPS and SANS both show moderate temporal stability over a 12-month time frame, subscale scores of apathy and bizarre behavior were not shown to have much stability [8].

Nature of scoring
SANS measures negative symptoms on a 25 item, 6-point scale. Items are listed under the five domains of affective blunting, alogia, avolition/apathy, anhedonia/asociality, and attention. While, SAPS measures positive symptoms on a 34 item, 6-point scale. Items are listed under hallucinations, delusions, bizarre behavior, and positive formal thought disorder. Items on both scales are clearly defined.

Criticisms
While SAPS and SANS are commonly utilized throughout research to assess symptoms of schizophrenia, one pertinent criticism of these two scales strikes at the positive/negative symptoms model of schizophrenia that has been popular since the 1980s-some authors have suggested that the bi-dimensional relationship between SAPS and SANS may be confounding the ability of those who use the scales to move beyond a dualistic model of negative and positive symptoms, which in itself may be a construct that is not necessarily helpful. Advocating for a re-conceptualization of the structure of schizophrenia, Klimidis, et al. and Minas, et al. proposed a multidimensional structure composed of at least three categories, including hallucinations/delusions, positive thought disorder, and negative symptoms, rather than merely dividing schizophrenic symptoms into positive and negative symptoms [9,10]. A separate study conducted on the inter-correlations between symptoms utilizing SAPS and SANS produced a three dimensional model composed of psychotic, disorganized, and negative factors [11]. Proponents of a more complex paradigm of schizophrenic symptomatology argue that schizophrenia cannot be separated or divided as neatly as SAPS and SANS. Based on Crow's "two syndromes," newer models that take more dimensions and incorporate the diverse elements of schizophrenic symptoms into their structures may need to be developed.

The positive and negative symptom scale (PANSS)
PANSS provides objective measuring of clinical response to pharmacologic treatments and it is incredibly useful in clinical research, with some claiming it as the "gold standard measure of treatment efficacy." Longitudinal data for individual patients can be pooled together to examine the effect covariates have on the treatment arm versus the control placebo group in therapy specific studies, hence, PANSS is a reliable means of assessing patients chronologically throughout the course of their illness. A study categorized patients into four mutually exclusive groups based upon results from the PANSS. These results showed that in a treatment group primarily seen in the outpatient setting, "19% of individuals were classified as having prominent negative symptoms, 20% as having prominent positive symptoms, and 21% as having both prominent positive and prominent negative symptoms" [12]. This study reinforced that those with negative symptoms have poorer overall outcomes as measured by remission rates and that those with both positive and negative symptoms have even worse outcomes, further demonstrating that the negative symptoms directly affect severity and chronicity of schizophrenia.

Nature of scoring
PANSS is comprised of 30 distinct items organized into three independent subscales with scoring that ranges from 30 to 210 points [13]. It has been previously demonstrated that the positive, negative, and general psychopathology sub-scales show normal distribution and independence from each other. The negative symptoms subscale assesses for blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking. The positive subscale addresses delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness, and hostility. The general psychopathology subscale addresses somatic concern, anxiety, feelings of guilt, tension, mannerisms and posturing, depression, motor retardation, uncooperativeness, unusual thought content, disorientation, poor attention, lack of judgment and insight, disturbance of volition, poor impulse control, preoccupation, and active social avoidance.

Criticisms
In the midst of a body of literature with supportive data on the validity and usefulness of PANSS, some still question the scale's ability to serve as a "stand-alone" screen for schizophrenia, challenging its reputation for being the gold standard scale. There is a degree of ambiguity and redundancy for evaluation of cognitive items assessed through its subscales. The biggest pitfall of PANSS is its lack of sensitivity and specificity in predicting global cognitive functioning. Additionally, the depression sub-scale fails to differentiate between "depression, negative symptoms, and extra-pyramidal side effects" which is a crucial problem given the distinct treatments and adverse downstream sequelae if inappropriately diagnosed [13]. Evaluating the factors measured by PANSS individually in a comprehensive fashion often leads to creating lengthier scales with redundant inquiries. Conversely, however, paring down the scale to minimal inquiries is just as problematic and can result in yielding incomplete data, weaker correlations, and less reliable outcomes [13]. Also, studies that use PANSS to evaluate the efficacy of psychotropic pharmacotherapy can be biased when mean outcomes are reported, serving as a systematic flow that is unlikely to detect covariates affecting placebo response [13].
Indeed, one of the most common drawbacks of PANSS is its complexity. In addition to its length, PANSS, which utilizes an interval scale of 1 to 7 for each of its 30 items, requires converting PANSS into a ratio scale in order to score patients and track response to treatment correctly. A recent systematic review found that as many as 62% of authors utilizing PANSS may have used incorrect calculations in their research, and that very few of the articles even included calculation methods [14].
PANSS was compared with Brief Psychiatric Rating Scales (BPRS)/ older counterpart and it has shown consistently better outcome than (BPRS). In a psychiatric rehabilitation study both tools exhibited strong interrater reliability; however, result showed that PANSS was superior to the BPRS in clinical predictive power [14].

Negative symptoms assessment 16 (NSA-16)
The original NSA-16 scale was developed by Alphs et al. in 1989 [15]. The newer truncated version, the Negative Symptoms Assessment-4 (NSA 4), was adapted from the prototype in 1993 as a validated tool for evaluating negative symptoms of schizophrenia [16]. The NSA-16 examines for the presence, severity, and range of negative symptoms associated with schizophrenia. It was meant to be a concise and easy-to-use instrument with strong psychometric properties in terms of validity, reliability, sensitivity to change, and good clinical utility.
The NSA-16 is a semi-structured interview containing 16 items that comprehensively assess the negative syndrome of schizophrenia and it includes the following factors: communication, emotion/affect, social involvement, motivation, and retardation [15]. These factors are assessed through a structured interview and are extensive and well-defined to help standardize assessment [16].
Axelrod BN, et al, [16] assessed the validity of this scale in a sample of 223 un-medicated schizophrenic inpatients. In this study, a five factor model was found to best characterize the structure of this rating scale. The study provided support for a multidimensional model of negative symptoms in schizophrenia and it offered a useful measure of negative symptoms assessment. Standardized measurement of negative symptoms was also achieved in international trials, further supporting the validity of NSA-16. Dawn Velligan et al examined whether changes in negative symptoms (NSA 16) were associated with changes in functional outcome. Results showed that the relationship between negative symptoms changes and changes in functional outcome is complex and that negative symptoms drove the changes in the social and occupation functional scale (SOFAS) rather than the reverse [15,17]

Nature of scoring
It is a semi-structured 16 item interview, utilizing the five factors: 1. Communication, 2. Emotion/Affect, 3. Social Involvement, 4. Motivation, 5. Retardation (18). Items are rated using a 6-point Likert scale where higher scores reflect greater impairment. Detailed anchoring criteria for the rating points are provided in the scale, along with a total score, sum of the scores on the 16 item scale, and a global negative symptom rating based on the global clinical impression of the patient's negative symptoms [19].

Criticism
The main limitation of the NSA-16 is its high reliance on functioning or behaviors, even for experiential symptoms, such as reduced social drive, whose severity is measured by type and frequency of social interactions [19]. The SANS and the NSA-16 both provide a focused assessment of negative symptoms, but they must be used in conjunction with a positive symptom rating scale [18]

Negative symptoms assessment 4 (NSA-4)
A study published in the Int. Journal of Psychiatry about the validation of a 4-item Negative Symptom Assessment (SA-4) [20]. This study revealed NSA-4 is a short practical clinical tool for the assessment of negative symptoms in schizophrenia. The psychometric properties and predictive power of a four-item version (NSA-4) were compared with the NSA-16 to determine predictive validity and construct validity. Both scales showed acceptable internal consistency (cronbach alpha 0.85 and 0.64 respectively) and test retest reliability (intra-class correlation coefficient 0.87 and 0.82). This study demonstrates that NSA-4 ofters accuracy comparable to the NSA-16 in rating negative symptoms in patients with schizophrenia [20].

CGI-SCH scale (The Clinical Global Impression-Schizophrenia Scale)
The CGI-SCH scale assesses the positive, negative, depressive, cognitive symptoms, and overall severity of schizophrenia [21]. The (CGI-SCH) scale, is a brief assessment instrument which is originally adapted from the Clinical Global Impression (CGI) scale and the CGI-Bipolar Patients (CGI-BP) scale [22,23]. It was developed to study the outcome of antipsychotic treatment in schizophrenia in an observational study (Schizophrenia Outpatient Health Outcomes (SOHO) Study [24] The CGI-SCH has shown strong validity and it has slightly higher interrater reliability than that for the PANSS [25]. A study of 114 patients measuring the diversity of symptoms present in schizophrenia found high correlation coefficients between the CGI-SCH, Global Assessment of Function (GAF) and PANSS scores and substantial reliability in all dimensions, except depressive dimension. This study concluded the CGI-SCH scale is a valid, reliable instrument to evaluate severity and treatment response in schizophrenia. Administering the instrument is simple, concise, and quick, which makes it an appropriate scale for use in observational studies and in routine clinical practice [21].

Nature of scoring
The CGI-SCH is a simpler scale as it consists of only two categories: severity of illness and degree of change. The severity of illness category evaluates the situation during the week previous to the assessment, while the degree of change category evaluates the change from the previous evaluation. Each category contains five different ratings (positive, negative, depressive, cognitive, and global) that are evaluated using a seven-point ordinal scale.

Criticisms
The CGI-SCH lacks good interrater reliability, sensitivity to change, and low correlation coefficient for depression rating [21].

The CAINS and BNSS (Clinical Assessment Interview for Negative Symptoms and Brief Negative Symptom Scale)
In 2005, the National Institute of Mental Health held a consensus development conference on negative symptoms. Two next-generation negative symptom scales resulted from this meeting: BNSS and CAINS. Both measures are becoming widely used and various research studies have demonstrated good psychometric properties for each scale. The study published in a schizophrenia bulletin provides the first direct psychometric comparison of these scales [26]. In this study, 65 outpatient patients diagnosed with schizophrenia or schizoaffective disorder completed clinical interviews, questionnaires, and neuropsychological testing. Separate raters completed the BNSS and CAINS within the same week. Results indicated that both measures had good internal consistency, convergent validity, and discriminate validity. High correspondence was observed between CAINS and BNSS blunted affect and alogia items. Moderate convergence occurred for avolition and asociality items, and low convergence was seen among anhedonia items. Findings from this study suggest that both scales have good psychometric properties [26].
The CAINS is an effective and validated tool for measuring negative symptoms in schizophrenia. Using a diverse sample of 162 outpatients with schizophrenia or schizoaffective disorder, the researchers assessed the structure, interpreter agreement, testretest reliability, and convergent and discriminant validity of the 13-item tool. Results were promising. The scales demonstrated good internal consistency, test-retest stability, and interrater agreement. The CAINS also showed strong convergent validity, which was determined by linkages with other measures of negative symptoms. CAINS, though brief, is also comprehensive and employable across a wide range of research and clinical contexts [27].
A study published in Schizophrenia Research highlighted the fact that patients with schizophrenia, especially those who have persistent and clinically significant negative symptoms (PNS), have the poorest functional outcomes and quality of life [28]. The presence of negative symptoms represent an unmet therapeutic need for large numbers of patients with schizophrenia. There is not one psychosocial treatment model that has been established that could address the entire constellation of PNS. In this study, a total of 51 patients with PNS were randomized into one of two groups for a period of 9 months: 1) MOtiVation and Engagement (MOVE) or 2) Treatment as usual. MOVE was a home based multi-modal treatment that employed a number of cognitive and behavioral principles to address the broad range of factors contributing to PNS and their functional consequences. Patients were assessed at baseline and every three months with multiple measures of negative symptoms. The results from this study revealed repeated measure analyses of variance for mixed models, and indicated significant Group by Time effects for the Negative Symptom Assessment (NSA; p<0.02) and the Clinical Assessment Interview for Negative Symptoms (CAINS p<0.04). Group differences were not significant until nine months of treatment and were not significant for the Brief Negative Symptom Scale (BNSS) [28].
According to the 2005 NIMH-MATRICS consensus statement, CAINS and BNSS address the five currently recognized domains of negative symptoms, differentiate appetitive aspects of anhedonia from consummatory aspects, and address desire for social relationships. Thus far, both have exhibited promising psychometric properties [29].
The CAINS is an empirically developed and evaluated measure of negative symptoms. Findings from previous research studies indicate that the CAINS is brief yet comprehensive and employable across a wide range of research and clinical contexts. Negative symptoms are resistant to treatment and impede functional recovery in schizophrenia. Recognizing the clinical importance of negative symptoms, the top recommendation was the Consensus Development Conference on Negative Symptoms (convened by the National Institute of Mental Health (NIMH) and the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS initiative) for stimulating novel treatment development [27].

Nature of scoring
The CAINS and BNSS are two scales that explore psychometric domains, including negative symptoms, different aspects of anhedonia, and interest in social relationships with others. Both scales use 13 items to assess negative symptoms [27]. It is anticipated that prospective clinical trials enrolling those with negative symptoms will demonstrate the relative sensitivity to change and global suitability of the BNSS and CAINS vs. each other and the earlier generation scales [30]. Multiple studies have found that regardless of the scale used to assess negative symptoms, strong correlations exist between higher negative symptom scores and poorer social functioning [27,28,30] Overall CAINS and BNSS are attractive for both their reliability and their concise accessible format.

Criticisms
CAINS and BNSS continue to evaluate patients' primary diagnosis on the basis of negative symptoms, with no integration of other aspects of the patients' social and cognitive functioning. The common critique leveled at SAPS and SANS for being too restrictive can also be applied to both CAINS and BNSS, and multidimensional scales has yet to be developed. Furthermore, CAINS scales are not strongly related to depression, agitation, or positive symptoms [27].

Conclusion
The older scales were developed more than 30 years ago. Since then, our understanding of negative symptoms has been evolved and currently there are newer rating scales reviewing the validity of negative symptoms. The older scales questionnaire does not incorporate the latest research on negative symptoms established by the NIMH consensus development conference on negative symptoms (CAINS and BNSS). This is the biggest difference between the older and newer scales.
It is clear that the newer negative symptom scales represent progress in the understanding of schizophrenia psychopathology. However, they still neglect to address the psychosocial and cognitive factors that are useful outcome measures.
While there are many different scales available to assess positive and negative symptoms of schizophrenia, a scale that is simpler, accessible, user-friendly, incorporates a multidimensional model of schizophrenia, addresses the psychosocial and cognitive component, and helps us better understand the severity and psychopathology of schizophrenia has yet to be developed.