The goal of this collaborative project is to develop and validate a state-of-the-art clinical rating scale for negative symptoms so that the next-generation of pharmacological treatments may have more potent and clear treatment targets. Analyses of this large, diverse outpatient sample, which showed considerable functional disability, indicated that the CAINS is a very promising measure for future treatment studies in schizophrenia. Converging structural analyses indicated two underlying factors reflecting experiential and expressive negative symptoms. Item-level analyses revealed good distributional properties, inter-rater agreement, initial convergent and discriminant validity, and discrimination among individuals with anchor point categories. The results guided our final revisions of the CAINS, which we describe in more detail below.
Across a convergence of multiple analytic approaches, a two-factor model more parsimoniously defined the structure of the CAINS than the five original consensus-based negative symptom sub-domains. The first factor reflects experiential aspects of negative symptoms and includes diminished motivation for and engagement in pleasurable social, vocational, and recreational activities. The second factor reflects expressive aspects of negative symptoms and includes diminished verbal and non-verbal communicative output. Results demonstrated that the CAINS factor-derived scales showed clear convergent validity with another assessment of negative symptoms and these scales were largely independent of other non-negative symptom domains including depression and positive symptoms. This two-factor conceptualization of moderately correlated experiential and expressive negative symptoms comports with recent conceptual and empirical reviews of older interview-based measures of negative symptoms (Blanchard and Cohen, 2006
, Kimhy et al., 2006
, Messinger et al., 2011
). Further research will determine if these factors reflect distinct neurobiological processes. Nevertheless, the convergence of our results with prior findings provides a compelling basis for organizing the CAINS into two core dimensions and crafting subscales to optimally assess each.
Based on the a priori empirical principles that guided the data analyses, the CAINS has been shortened and revised. Within the Experience domain, the most substantial changes involved anhedonia-related items. Structural and item-level analyses indicated that these items did not cohere well with other Experience items and showed substantial skew and restricted range in the non-pathological direction. Although we adopted a Likert scale approach to assess Anhedonia intensity to address similar problems from our feasibility study (Forbes et al., 2010
), this was not successful. It is unclear whether these relatively non-pathological intensity scores found across studies reflect the absence of a pleasure intensity deficit, consistent with other research (Cohen and Minor, 2008
, Kring and Moran, 2008
) or, instead, limited sensitivity of our interview-based assessment. Nevertheless, our findings across two studies revealed psychometric limitations to rating anhedonia intensity that substantially impede their ability to demonstrate improvement in the context of a clinical trial. Thus, anhedonia intensity items were removed from the CAINS.
Anhedonia items based on the frequency of pleasurable experiences fared relatively better in the analyses, and thus these items were retained following revisions. First, we omitted the physical pleasure frequency item because it substantially overlapped with the recreational pleasure frequency item and, relative to the other anhedonia frequency items, showed the lowest inter-rater agreement, greater skew toward non-pathological ratings, and was judged to be relatively less clinically important. Second, following from the IRT analyses, we adjusted the anchors for social and recreational pleasure frequency to more clearly demarcate among rating anchor points. Third, we added a provisional vocational frequency item to provide uniformity across the social, vocational, and recreational domains. Finally, we added three new provisional frequency items for expected pleasure to test the utility of assessing expected pleasure based on frequency, rather than intensity.
Results also guided changes involving avolition and asociality items. First, although selfcare is included in several negative symptom scales and is widely regarded as clinically important, we removed the self-care item due to its very low coherence with other Experience items and its skew toward non-pathological ratings. Second, we removed the social avolition item due to empirical and conceptual overlap with the three asociality items. We revised the asociality items such that motivation for relationships was more clearly part of each item. Finally, IRT analyses led to modifications of probe questions and anchor points to help raters distinguish among rating points for the remaining avolition and asociality items.
Regarding the Expression items, results revealed problems with redundancy and lack of coherence for some, as well as concerns about inter-rater agreement, and demarcation among rating anchor points. Because the two alogia items were highly inter-correlated, we removed the spontaneous elaboration item, primarily because raters found the quantity of speech item simpler to use. Although eye contact and spontaneous movements are included in other scales, they showed poor coherence with other Expression items and relatively low inter-rater agreement and were thus removed. To address the lower inter-rater agreement, limited range, demarcations among rating points, and user-friendliness of these items, we revised all the remaining items to refine and simplify all rating anchor points. Finally, we added a provisional item aimed at making the format of the verbal expression (i.e., prosody) rating more consistent with the remaining Expression items.
Based on these results, we now have a substantially shorter and re-organized version of the CAINS. As shown in , the scale is now organized into two subscales that differ in content and the sources of information used to rate them. The Experience subscale consists of seven items (plus four provisional items) assessing experienced motivation and pleasure, as well as behavioral engagement in social, vocational, and recreational activities. The Expression subscale consists of four items (plus one provisional item) tapping verbal and non-verbal emotion expressive behaviors. Based on the data collected to date, the CAINS approach to rating negative symptom shows promising psychometric properties, inter-rater agreement, and convergent, discriminant validity.
In the final phase of the CANSAS project, the reliability and validity of the revised CAINS will be evaluated in another large sample. Test-retest reliability will be assessed to ensure that the scale shows sufficient stability for use as an endpoint in clinical trials. The convergent and discriminant validity of the CAINS will also be comprehensively evaluated. For example, independent ratings on the widely-used Scale for the Assessment of Negative Symptoms (Andreasen, 1983
) will be conducted by raters who are blind to CAINS ratings. Participants will also be assessed on psychiatric symptoms, functional capacity, functional attainment, neurocognition, and alternative measures of emotion and motivation. The final version of the CAINS will be a major step forward in the assessment of negative symptoms, thus meeting the original charge of the consensus development conference and setting the stage for the next generation of pharmacological treatment advances. The development process of the CAINS is unique with respect to the sample size, a priori empirically driven approach, and comprehensive assessment of psychometric properties and validity.
This approach will prove fruitful for attaining the ultimate goal, which is to stimulate novel pharmacological and psychosocial treatments and new research into the underlying causes of negative symptoms. Efforts to develop neuroscience based accounts of schizophrenia (e.g., Barch and Dowd, 2010
, Gur et al., 2007
, Juckel et al., 2006
, Ochsner, 2008
) integrating psychological, neurobehavioral, neuroimaging and genomic data hinge on the integrity and reliability of clinical phenotypic data. The CAINS can contribute to treatment by providing an outcome measure for interventions aimed at ameliorating impaired emotion processing and social cognition in schizophrenia (Carter et al., 2009
, Green et al., 2008
). Functional neuroimaging studies examining the underlying neural circuitry of motivated behavior and affective processes would be complemented by the CAINS, which can help establish associations between activation abnormalities and deficits in specific symptom domains.