We examined models that included neurocognition, positive symptoms, and negative symptoms as predictors of community-based functional outcomes and social skills in schizophrenia. Our meta-analyses showed there was strong cross-sectional evidence indicating that negative symptoms are related to community-based functional outcome and skill assessment. Using meta-analytic techniques, such as the Sobel test of mediation, yielded fairly strong evidence indicating that the relationship between neurocognition and functional outcome is at least partially mediated by negative symptoms. In this model, neurocognition is still a primary causal variable that influences outcome. However, we found that the total effects of neurocognition on outcome were at least partially mediated via an indirect path through negative symptoms. Therefore, neurocognition is proposed to have both direct and indirect effects on functional outcome.
Previous research has linked neurocognition to symptoms and symptoms to functional outcome, but in separate studies. In fact, there is a consistent and moderately strong relationship between neurocognition and negative symptoms. Harvey et al. (2006)
suggested that cognitive deficits and negative symptoms share many features in common and are correlated, at least cross-sectionally. They point out that cognitive deficits and negative symptoms can have a similar type of onset, course, and are correlated with other aspects of schizophrenia, e.g., functional outcome. However, as far as we are aware, no prior meta-analysis has empirically tested a mediation model using the Sobel test to examine whether negative symptoms mediate between neurocognition and functional domains. The current results indicate that the relationship of negative symptoms to community-based functioning is relatively strong, but the relationship of positive symptoms to community-based functioning is relatively weak. Thus, positive symptoms (non-disorganizing type), such as hallucinations and delusions, do not consistently interfere with a person's ability to socialize or to perform at work. Patients might learn to compensate for positive symptom deficits in various ways, e.g., ignoring beliefs about aliens while working in retail clothing store. However, the data suggest that negative symptoms might be more closely linked to impairments in daily performance or skill acquisition. This relationship seems to hold for both inpatients and outpatients with schizophrenia.
Heterogeneity in the measurement of neurocognition was very evident in the studies included in this meta-analysis. Some neurocognitive tests were used very frequently, e.g., WCST. The constructs of executive functions, working memory, and attentional processes appeared to be oversampled as compared to constructs such as visual and spatial learning and memory. In addition, even within one domain of neurocognition, such as working memory, several tests were used, e.g., digit span measured auditory processing of working memory while spatial span tests measured visual working memory. In some cases, the same tests were classified in different studies as assessing different domains, probably because the tests demanded several different cognitive processes. For the current meta-analysis, we used the MATRICS classification scheme and definitions of domains (Nuechterlein et al., 2004
) to place measures in domains based on the predominant cognitive process required.
There are several limitations to this study that warrant mention, some of which are common to all meta-analytic investigations (for a discussion, see: Rosenthal, 1991
; Lipsey and Wilson, 2001
). First, the study sample was not randomly selected. Additionally, neurocognition is not a homogenous concept and its measurement was influenced by how common a particular set of neurocognitive tests appear in the published literature. Therefore, the p
-values that were averaged across studies are certainly not precise. The relationships in the studies in this meta-analysis are cross-sectional rather than longitudinal in design. For all of these reasons, and more, one cannot use meta-analysis or any correlational data, to infer causality. Further, the selection of which variables to place as predictors and which to test as a mediator was somewhat arbitrary. A theory driven approach was used to decide the direction that neurocognition is likely an underlying “causal” factor for the severity of negative symptoms. We do not believe that there is strong evidence suggesting that negative symptoms cause neurocognitive deficits. Similarly, the severity of symptoms most likely contributes to poor outcomes, but poor outcomes could conceivably contribute to a worsening of symptoms. In addition, we note the possibility of measurement overlap resulting in an inflated correlation between negative symptoms and outcome. With the SANS, there are definitions and anchor points for rating domains such as avolition at work or school that overlap with definitions of functional outcome. Despite the fact that each of these study limitations suggest that caution should be used in interpreting the results of the current study, our findings still provide some direction for future research on potential contributors to outcome. While we believe that this study can inform future outcomes research, we want to emphasize that a meta-analysis cannot replace focused empirical research.
The model of mediation that was tested in this study would benefit from further examination because it would, if validated through longitudinal observational and experimental designs, have implications for intervention. Considering the central role that neurocognitive deficits play in relationship to daily functioning in schizophrenia, it is not surprising that cognitive deficits have emerged as important targets for new treatments (Green and Nuechterlein, 1999
; Carpenter and Gold, 2002
; Carpenter, 2004
; Gold, 2004
). If the relationship between neurocognition and functional outcome is partially mediated by negative symptoms, then perhaps negative symptoms should be an additional treatment target as a means to improve functional outcome.