Supplemental Materials
Relationship of CNTRACS and MATRICS Tasks to Symptoms in Schizophrenia
Another important question is the degree to which tasks from the MATRICS and CNTRACS batteries relate to clinical symptom severity. One concern in using cognitive tasks in treatment trials has been the issue of “psuedospecificity” (Breier, 2005), or the degree to which changes in psychotic symptoms may lead to the appearance of changes in cognitive function. Fortunately, there is a good deal of evidence to suggest that the severity of higher cognitive deficits in schizophrenia is not related to the severity of psychotic symptoms such as hallucinations and delusions (Ventura et al., 2010), although, consistent with Bayesian models of psychosis (Clark, 2013; Corlett et al., 2010), visual processing tasks that measure the influence of stored knowledge on perception have shown strong relationships with positive symptoms (e.g., patients who fail to see common illusions, and therefore see test objects veridically, tend to be those with higher levels of positive symptoms, with both phenomena through to reflect the same core abnormality; Keane et al., 2013). However, it has recently been shown that the working memory and processing speed tasks in the MATRICS battery, as well as the composite score, significantly correlated with negative symptoms. Further, disorganized symptoms correlated with the overall composite score, processing speed, verbal learning, visual learning and social cognition (August et al. 2012). The CNTRACS task of goal maintenance (AX- CPT/DPX) has also shown a significant relationship with disorganized symptoms (Gold et al. 2012), as has an earlier version of the JOVI when used in inpatient samples (Silverstein et al., 2000; Uhlhaas et al., 2005, Uhlhaas et al., 2006). Given that these previous studies on the relationships to symptom severity in the MATRICS versus CNTRACS batteries were conducted in different samples, one of the goals of the current study was to compare performance on the CNTRACS tasks and a subset of the MATRICS tasks to clinical symptoms in the same participants.
Are clinical symptoms related to cognition or function?
Correlations between the cognitive tasks and symptom measures were non-significant after correcting for multiple comparisons (Supplemental Table). This was true even when looking at the common factor score. At a nominal p-value of .05, the AX-CPT, the DPX, and the HVLT-R were correlated with mania, and the HVLT-R was also correlated with disorganized symptoms. Interestingly, however, the measures of function were significantly correlated with symptoms. The MSIF and UPSA-B correlated significantly with all measures of clinical symptoms (positive, disorganized, negative, manic, and depressed). The SLOF Patient report was significantly correlated with positive, disorganized, and depressed symptoms, but the SLOF Informant report only showed a significant relationship with manic symptoms. To better understand the contribution of clinical and cognitive measures to functional outcome, we also performed partial correlations. After controlling for all clinical symptoms, the RISE, AX-CPT, DPX, and BACSsc all remained significantly correlated with the UPSA-B, and the HVLT-R remained significantly correlated with the MSIF and SLOF Patient report. After controlling for performance on all cognitive paradigms, disorganized, negative, and depressed symptoms remained significantly correlated with the UPSA-B. In addition, positive, disorganized, negative, and depressed symptoms remained significantly correlated with the MSIF, and positive and disorganized symptoms remained significantly correlated with the SLOF Patient report. Thus, symptoms and cognitive function seem to make independent contributions to performance of life skills.
Associations with Clinical Symptoms
None of the tasks significantly correlated with clinical symptom severity after correcting for multiple comparisons. For positive symptoms, these results are consistent with a large body of literature (Addington et al. 1991; Nieuwenstein et al. 2001). However, the lack of association with negative or disorganization symptoms is somewhat surprising. As noted in the main text, this was a fairly highly functioning sample with relatively low levels of symptoms, and the low scores and limited variance might have reduced our sensitivity to detect such correlations. That said, the majority of functioning measures were associated with symptom levels across domains, indicating that reduced variance was not the only explanation for non-significant relationships between cognition and symptoms. Further, most of the function and symptom measures remained significantly correlated after controlling for variance associated with the cognitive tasks, and most of the cognitive tasks remained significantly correlated with the UPSA-B after controlling for clinical symptoms. Previous work has shown this pattern in a large group of schizophrenia patients, whose changes in neuropsychological performance were seemingly independent from changes in clinical symptoms (Harvey et al. 2006). Our findings are consistent with this prior work, and suggest that cognitive function and clinical symptoms make independent contributions to levels of function.
References:
Addington, J., Addington, D., & Maticka-Tyndale, E. (1991). Cognitive functioning and positive and negative symptoms in schizophrenia. Schizophr Res, 5(2), 123-134.
August, S. M., Kiwanuka, J. N., McMahon, R. P., & Gold, J. M. (2012). The MATRICS Consensus Cognitive Battery (MCCB): clinical and cognitive correlates. Schizophr Res, 134(1), 76-82. doi: 10.1016/j.schres.2011.10.015
Breier, A. (2005). Developing drugs for cognitive impairment in schizophrenia.
Schizophr Bull, 31(4), 816-822.
Clark, A. (2012). Whatever next? Predictive brains, situated agents, and the future of
cognitive science. Behav. Brain Sci, 1-86.
Corlett, P. R., Taylor, J. R., Wang, X. J., Fletcher, P. C., & Krystal, J. H. (2010). Toward
a neurobiology of delusions. Prog in Neurobiol, 92(3), 345-369.
Gold, J. M., Barch, D. M., Carter, C. S., Dakin, S., Luck, S. J., MacDonald, A. W., 3rd, Ragland, J. D., Ranganath, C., Kovacs, I., Silverstein, S. M., & Strauss, M. (2012). Clinical, functional, and intertask correlations of measures developed by the Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia Consortium. Schizophr Bull, 38(1), 144-152. doi: 10.1093/schbul/sbr142
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. Psychopharmacology, 187(3), 356-363.
Keane, B. P., Silverstein, S. M., Wang, Y., & Papathomas, T. V. (2013). Reduced depth inversion illusions in schizophrenia are state-specific and occur for multiple object types and viewing conditions. J Abnorm Psychol, 122(2), 506-512. doi: 10.1037/a0032110
Nieuwenstein, M. R., Aleman, A., & de Haan, E. H. (2001). Relationship between symptom dimensions and neurocognitive functioning in schizophrenia: a meta-analysis of WCST and CPT studies. J of Psych Res, 35(2), 119-125.
Silverstein, S. M., Kovács, I., Corry, R., & Valone, C. (2000). Perceptual organization,
the disorganization syndrome, and context processing in chronic schizophrenia. Schizophr Res, 43(1), 11-20.
Uhlhaas P. J., Phillips WA, Mitchell G, Silverstein SM. (2006). Perceptual grouping in
disorganized schizophrenia. Psychiatry Res. 145(2-3):105-17.
Uhlhaas, P. J., Phillips, W. A., & Silverstein, S. M. (2005). The course and clinical correlates of dysfunctions in visual perceptual organization in schizophrenia during the remission of psychotic symptoms. Schizophr Res, 75(2-3), 183-192. doi: 10.1016/j.schres.2004.11.005
Ventura, J., Thames, A. D., Wood, R. C., Guzik, L. H., & Hellemann, G. S. (2010).
Disorganization and reality distortion in schizophrenia: a meta-analysis of the relationship between positive symptoms and neurocognitive deficits. Schizophr Res, 121(1), 1-14.
Supplemental Table: Clinical Characteristic Correlation Coefficients with Cognitive Performance and Functional Outcome in Patients
Positive Symptoms / Disorganized Symptoms / Negative Symptoms / ManicSymptoms / Depressed Symptoms
RISE IRIE / -.05 / -.05 / .01 / -.05 / .09
RISE IRAE / -.06 / -.11 / -.01 / -.05 / .06
RISE AR / .05 / -.03 / .08 / .03 / .14
AX-CPT D’-context / .01 / -.09 / -.04 / -.21* / .02
DPX D’-context / -.04 / -.13 / -.08 / -.26* / -.06
JOVI Threshold / -.10 / .07 / -.01 / .08 / .01
BACSsc / -.00 / -.15 / -.09 / -.00 / .01
HVLT-R / -.18 / -.22* / -.09 / -.20* / -.15
UPSA-B / -.22* / -.39*** / -.40*** / -.38*** / -.19*
MSIF Global / .47*** / .43*** / .37*** / .25* / .32**
SLOF Patient / -.31** / -.36*** / -.12 / -.06 / -.38***
SLOF Informant / -.15 / -.27* / -.18 / -.37** / .00
* p<.05, ** p<.01, *** p<.001