Psychopathology and cognition in divergent functional outcomes in schizophrenia
Introduction
Over the last decade the persisting functional disabilities and dependencies observed in many schizophrenia patients have been seen increasingly as consequences of cognitive impairment. Considerably less importance has been assigned to psychopathology, especially psychotic (positive) symptoms, in terms of accounting for functional outcome variance. Green (2007), for example, has stated that, in contrast with cognition, psychotic symptoms are weak determinants of community functioning. This view of cognitive impairment and symptoms is influential and grounded in several lines of evidence. First, the cognition–functional outcome relationship has been confirmed in numerous studies, proving fairly consistent across community and psychosocial functioning and some aspects of vocational skill acquisition (Green et al., 2000, Matza et al., 2006, Green et al., 2004, Green, 2006). At the same time, it has been noted that poor functional outcome often persists despite significant symptomatic improvement (San et al., 2007, Lindstrom et al., 2007). Anti-psychotic medication is relatively successful in reducing symptom severity, but at best marginally successful in improving cognition (Mishara and Goldberg, 2004, Goldberg et al., 2007, Remillard et al., 2008). Moreover, scores on standard cognitive measures and symptom severity scales are only weakly related or even independent, implying a partial dissociation of these two facets of schizophrenic illness (Lucas et al., 2004, Rocca et al., 2006). Thus psychopathology defines the clinical presentation and diagnosis of schizophrenia, but cognitive performance mediates functional status. It follows that treatment success is no longer reducible to symptom control and improving cognitive performance has emerged as a principal target for the next generation of medications (Marder, 2006).
Nonetheless, evidence contradicting this account of functional status has also emerged. In addition to data supporting associations between negative and disorganization symptoms and functional variables (Milev et al., 2005, Kurtz et al., 2005), there are recent reports that positive symptoms predict community outcome (Wittorf et al., 2008). Furthermore, longer treatment duration with antipsychotic medication associates not only with symptomatic improvements, but also with functional improvement (Dunayevich et al., 2007). Similarly, patients meeting criteria for symptom remission following treatment demonstrate significantly enhanced independence in community living relative to patients not attaining remission (Helldin et al., 2007). Accordingly, there are grounds for reconsidering the role of psychopathology in the prediction and, potentially, determination of functional outcome.
It is noteworthy that most studies supporting the validity of cognitive test variables—and the relative invalidity of psychotic symptoms—as predictors of functional outcome use correlational methods and focus on accounting for significant amounts of outcome variance. While this approach has value, it is often difficult to determine whether an adequate range of functional outcomes or symptom severity is being sampled. In theory, restricted variance in predictor or criterion will limit validity. In practice, this restriction often occurs with respect to both symptoms and outcome. For example, Twamley et al. (2002) found no relationship between positive symptoms and level of residential independence in patients with schizophrenia. However, extremely low mean symptom scores suggest that the study sample comprised primarily remitted patients. In other cases, interpretation of data obtained from continuous outcome scales may be problematic because of floor or ceiling effects. Thus Bowie et al. (2006) reported descriptive statistics from the Specific Level of Function Scale consistent with restricted variance and probable ceiling effects on 4 out of 6 subscales. Even with more adequate score distributions, the meaning of multivariate outcome prediction may be unclear. A clinical sample of patients with mild-to-moderate functional disability may yield adequate variance for statistical purposes, but the resulting validities may not apply to patients with severe or no disability. These limitations are seldom noted or discussed, possibly encouraging unwarranted generalization of prediction validities across the complete range of clinical states and outcome in schizophrenia.
In the present study, we were influenced by the remission criterion approach and applied a similar rationale to the study of functional outcome. Given a sufficiently broad range of clinical settings for recruitment, clear and meaningful criteria can be applied to select patients with both highly favourable and unfavourable functional outcomes (Emsley et al., 2008, Mattsson et al., 2008). Hence we recruited patients with schizophrenia and schizoaffective disorder from a variety of settings including those with demanding rehabilitation programs as well as from settings that require minimal involvement. The reasoning underpinning this approach was that it should yield adequate numbers of patients with extreme functional outcomes, both favorable and unfavorable, who could then be evaluated with measures of symptom severity and cognition. The basic question motivating our research was: does the comparison of schizophrenia patients with markedly divergent functional status support or contradict the importance assigned to cognitive performance relative to symptom severity, with special reference to positive symptoms?
Section snippets
Participants
Patients were recruited from ambulatory outpatient settings that required active program attendance and comprised vocational and/or social rehabilitation. Settings included the Hamilton Program for Schizophrenia, the Community Schizophrenia Service (St. Joseph's Healthcare Hamilton), the Cleghorn Program (St. Joseph's Healthcare Hamilton), the Canadian Mental Health Association (Toronto branch) and the Challenging Directions program (Whitby Mental Health Center). Male and female subjects who
Results
Mean Global Support MSIF scores in patients (3.81, S.D. = 1.42) and healthy comparison samples (1.15, S.D. = .36) differed significantly (t(228) = 22.03, P < .001) and corresponded to an effect size (Cohen's d) of 2.24. This confirmed the validity of the MSIF as a highly discriminating measure of community independence. Group assignment criteria applied to the pool of 156 patients yielded 28 HF and 24 HU assignments. Accordingly, 18% of the clinical sample demonstrated community independence levels
Discussion
The results of this investigation of highly divergent functional outcomes in schizophrenia suggest that researchers have underestimated the importance of psychopathology including positive symptoms for understanding and, possibly, influencing community independence. We studied patients with levels of independence approaching normal functionality as well as those receiving very comprehensive oversight and support across life settings. Psychopathology on its own accounted for almost half of the
Role of funding source
Funding for this study was provided by the Ontario Mental Health Foundation (OMHF) and by the Community Schizophrenia Vocational Rehabilitation Foundation (CSVR). The OMHF and CSVR Foundation had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
Contributors
W. Heinrichs designed the study and wrote the protocol. N. Ammari wrote the protocol. A. Miles and S. McDermid Vaz collected the data. W. Heinrichs and B. Chopov conducted the analyses. All authors contributed to and approved the final manuscript.
Conflicts of interest
There are no conflicts of interest with respect to this manuscript.
Acknowledgements
We express our appreciation to Susan Strong, MHSc, Peter Prendergast, MB, Suzanne Archie MD, Diana Smith, B.A., Andrew Miki, MA, Elizabeth Faraone, B.Sc., Frances Carullo, B.A. Ashley Oman, B.A., Joel Goldberg, Ph.D. and the staff of the Community Schizophrenia Service, the Cleghorn Program, St. Joseph's Healthcare Hamilton, The Hamilton Program for Schizophrenia, The Canadian Mental Health Association Toronto Branch, Challenging Directions and the Whitby Mental Health Center for their
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