Following the recommendation of the NIMH-MATRICS Consensus Development Conference on Negative Symptoms (1
), the CAINS is a clinical rating scale for negative symptoms with potent and clear treatment targets for the next generation of pharmacological and psychosocial treatments. The CAINS development process was unique in that it included the recommended sample types for negative symptom treatment trials (32
); included input from multiple stakeholders (industry, government, academia); followed a rigorous empirical approach; elicited and incorporated feedback at each stage, keeping results available and transparent; and developed training materials for dissemination.
Converging structural analyses replicated the two-factor structure we reported in our first study (3
). Further structural and item-level analyses indicated that three of the 16 items should be dropped, and the final CAINS contains 13 items. Given the modest association between scales and their differential validity correlations, the CAINS is optimally implemented as a two-scale measure, one tapping expression (four items) and the other assessing motivation/pleasure (nine items). These scales are consistent with the domains identified in reviews of the negative symptom on older negative measures, such as the SANS and the PANSS (34
). However, should certain indications require the use of a single score (e.g., clinical trial designs), a composite of the two subscales can be computed in much the same way that a composite is computed from the separable cognitive domains in the MATRICS Consensus Cognitive Battery. Notably, the CAINS can be administered in a timely manner while also comprehensively covering the domains.
Analyses indicated that the CAINS is stable across a 2- to 3-week period, an outcome that portends well for studies assessing change in treatment trials. As in our first study (3
), we adopted a rigorous approach to assessing interrater agreement, comparing raters from different sites, and our findings indicate high agreement for both the expression and motivation/pleasure scales. The CAINS includes interview questions built into the measure, explicit anchor descriptions, and a detailed manual, which will help preserve rater agreement at other sites. CAINS scores will be easier to compare across sites and studies given that the ratings will be made from the same standardized interview probes.
The CAINS exhibited strong convergent validity, as evidenced by linkages to other negative symptom measures; self-report measures of constructs covering social engagement, pleasure experience, and motivation; and independently assessed emotion expressions. That the correlations between the CAINS motivation/pleasure scale and SANS were not stronger reflects the fact that the CAINS taps underlying domains of motivation and pleasure and distinguishes experience and behavioral engagement. The CAINS also exhibited strong discriminant validity by its nonsignificant correlations with depression, medication side effects, IQ, and cognition. Although other studies have found modest correlations between negative symptoms and cognition (36
), these correlations may not hold longitudinally, may partly reflect inclusion of cognition in older negative symptom scales, and are perhaps accounted for by overlap between older negative symptom scales and functioning measures (31
The CAINS also demonstrated linkages to functional outcome. The CAINS motivation/pleasure scale was related to all aspects of functioning, and the expression scale was related to independent living and family functioning. Improving the lives of people with schizophrenia involves not only decreasing symptoms but also improving functioning. Evidence from recent longitudinal studies indicates that improvements in negative symptoms predict improvements in functioning, particularly among people early in the course of illness (e.g., 37
). Interestingly and unexpectedly, neither of the CAINS scales was related to functional capacity as assessed by the UPSA-Brief. Thus, with respect to functioning, the CAINS is not directly related to what the individual can
do but instead is related to what he or she actually does, and researchers interested in functioning and negative symptoms should keep this distinction in mind. Given the CAINS’s psychometric properties, it is well positioned to be included in future studies designed to assess symptom and functional recovery in schizophrenia.
Important next steps for the CAINS include assessing it for use across cultures and populations outside of academic settings (e.g., adolescents at risk for psychosis, patients early in the course of illness, inpatients, patients with more severe symptoms, patients in community clinics), as well as comparisons with a broader range of neurocognitive tests and other negative symptom scales (e.g., the Negative Symptom Assessment [38
]). Of particular importance is inclusion of the CAINS in treatment trials to ascertain its sensitivity to change. Research that seeks to delineate the neurobiological and behavioral processes that undergird these symptoms, processes that are also a current focus of the Research Domain Criteria (5
), will further help to focus the development of treatments for the motivation/pleasure and expression domains. Indeed, to move the field forward, progress must be made on complementary fronts: isolating mechanisms and processes underlying these domains and developing treatments to improve them. The CAINS provides a means for assessing these domains comprehensively, reliably, and validly such that progress on these fronts may be propelled forward more quickly and in a more focused manner.
Why might researchers and clinicians opt to use the CAINS instead of other negative symptom measures? The CAINS was developed to address conceptual and psychometric limitations of existing instruments, and our approach included an emphasis on constructs with a strong cognitive and affective neuroscience research base (approach motivation, pleasure, social engagement, and affective expression), large sample sizes, and an iterative data-analytic approach. Other strengths of the CAINS include the standardized interview prompts built into the measure; the clear, comprehensive, and discriminating anchor points for items; the instrument’s combination of brevity and comprehensiveness; and the availability of a training manual and videos (http://www.med.upenn.edu/bbl/downloads/CAINSVideos.shtml
). The CAINS’s inclusion of prospections of pleasurable experiences is another strength that has been at the center of recent views on negative symptoms (40
). Our results demonstrate that interrater agreement for the CAINS is higher than that reported for the SANS (28
), and the test-retest reliability is comparable to those of the SANS and the PANSS (28
). The CAINS demonstrates greater convergent validity than the BPRS negative symptom scale, and its convergent validity is comparable to or greater than that of the SANS. The CAINS scales are less strongly related to positive symptoms, agitation, and depression than other measures, and the CAINS demonstrates linkages to functioning comparable to the SANS.
Although clinical trials may opt to use a single composite CAINS score, it is important to emphasize that the CAINS also distinguishes two clear treatment targets with substantial grounding in neuroscience: expression and motivation/pleasure. For example, translational efforts to understand processes related to expression are pursued in human studies (41
) as well as informative mouse models that examine underlying regulatory mechanisms (42
), and contemporary models of negative symptoms emphasize linkages between motivation and pleasure (11
). Indeed, an important issue for the field to address is whether there are common or distinct mechanisms underpinning the two dimensions of negative symptoms. Current models and studies of negative symptoms suggest both distinct mechanisms (40
) as well as different types of patients who may have more severe deficits in one but not both dimensions (44
). Practically speaking, clinicians and researchers can gauge improvement in negative symptoms across these two dimensions, rather than five overlapping symptoms or a total composite that does not distinguish the two core domains of negative symptoms.