This study aimed to further shed light on the complex mechanisms through which neurocognition influences functional outcome in schizophrenia. We systematically reviewed studies investigating the mediating role of social cognition and conducted a mediation analysis by the means of SEM. Despite wide variations in the selection of cognitive and outcome domains and measures, the most consistent finding was that at least part of this relationship is mediated by a pathway through social cognitive domains (ES = .20 for the mean standardized indirect effect). This implies that neurocognitive impairments may have an adverse effect on social cognition and thereby exert a negative influence on functional status. The results of our own statistical analysis are in line with these conclusions: Social cognition comprising emotion perception and social knowledge completely mediated a significant indirect relationship between neurocognition and functional outcome.
Some issues warrant caution when interpreting these findings. One38
of 15 studies found only support for a moderation but not for a mediation effect between early visual processing and social problem solving skills through emotion perception. Another research group48
used the same neurocognitive measure but revealed evidence for mediation. However, they differed in that they focused on other levels of functioning and on other social cognitive aspects. At a conceptual level, these different results could be attributable to the existence of differential mediation patterns: Each neuro- and social cognitive domain may provide a separate mediating pathway and may be differentially predictive of functional status at different points of time (eg, early visual processing-social perception and community functioning). Therefore, a critical question is which social cognitive domains are effective mediators and with regard to which time period. In our review, most studies that reported mediation effects investigated emotion perception and to a lesser degree social perception. This corresponds well with a recent research finding suggesting that the social cognitive factor comprising emotion and social perception showed the highest correlation with neurocognition and functional outcome compared with both other dimensions named “attributional style” and “higher level inferential and regulatory processes”.31
In contrast, other studies identified ToM to have the highest correlations with functional outcome17
and to be the most potent mediator.39
Calculating the standardized indirect effects in our review revealed the largest effect sizes for social knowledge (ES = .28) and social perception (ES = .21). However, these results are only preliminary as they are based on few studies differing in the number and type of employed measures. Clearly, more research is needed to assess a wide range of social cognitive domains to unravel their differential relationships with neurocognition and functional outcome. Yet, most studies used neurocognitive composites scores in order to reduce model complexity. This may mask specific predictor-mediator-outcome links. Another reason for the varying patterns of relationships may be the differential validity of the postulated mediation model. Therefore, it may be crucial to determine whether or not the mediation effect remains constant across various contexts or subgroups of schizophrenia patients. This effect is called moderated mediation.76
Additionally, recent innovations in SEM technique allow evaluating how well models fit at the level of the individual participant.77
These analyses could sharpen current mediation models by identifying clinical and demographic characteristics of subgroups that do fit the model to a high degree or that do not fit the model (yet) (eg, education, duration of illness, premorbid social functioning). These results may be important with regard to a differential indication of integrated cognitive remediation therapy approaches.
In the current review, a moderate amount of variance (25%) in functional outcome was accounted for by neuro- and social cognition. In accordance with a recent meta-analysis17
and our own study (21%), a large proportion of variance in functional outcome is therefore left unexplained by neuro- and social cognitive performance. These results and the small effect size of the indirect effect indicate that functional disability is multiply determined by a host of other factors. Accordingly, models including additional mediators had a better fit to the observed data43
and could explain more variability in functional outcome.43,44
Recent studies found, for example, support for a mediating effect of motivation,77
and negative symptoms.46,50,81,82
Moreover, most of the reviewed studies assessed global levels of community functioning as outcome variable (eg, social and work functioning). In contrast, performance-based measures of functional outcome seem to be less influenced by environmental factors as they evaluate what an individual is capable of doing in specific situations and not what it actually performs in real world. Therefore, they are theoretically and empirically more closely related to cognitive measures. Recent studies found evidence that such functional capacity measures mediate the relationship between cognitive variables and global functional outcome.81,82
This may lead to higher amounts of explained variance in functional outcome.
Investigating mediator variables allows directing and refining the development of Cognitive Remediation Therapy (CRT) approaches by identifying elements crucial for enhancing generalization of therapy effects on functional outcome. Therefore, these study findings have important clinical implications. They suggest that a combined treatment of neuro- and social cognition may reveal synergistic effects and be integral to creating and maintaining change in functional outcome domains.83,84
An adequate level of functional outcome may first require rehabilitation of rudimentary neuro- and social cognitive functions.42
Such multimodal CRT approaches like the Integrated Psychological Therapy15
(IPT), the Cognitive Enhancement Therapy85,86
(CET), and the Neurocognitive Enhancement Therapy87,88
(NET) found improvements both in the proximal outcome of neuro- and social cognitive performance and in the more distal areas of psychopathology and functional outcome.15,89
The underlying therapy rationale was also supported by an analysis of IPT interventions indicating that the combined treatment of neuro- and social cognitive subprograms had superior effects in proximal and distal outcomes than neurocognitive intervention alone.90
Eack et al91
investigated the mechanism of change during integrated cognitive remediation therapy more directly. They found that changes in neurocognition and social cognition separately mediated functional improvements in schizophrenia patients. The authors came to the same conclusion that CRT may need to target neuro- and social cognition to achieve an optimal functional response.
There are several limitations to our study. First, we used only a cross-sectional design, which does not allow firm conclusions about the causality between the investigated variables. It seems possible that functional deficits may have an adverse effect on cognitive domains as well. For example, negative social interactions at work may drive the development of biases in perceiving and evaluating other persons. Although we used a theory-driven approach, clearly more long-term studies are needed. Second, global measures like the GAF may not be precise enough to detect individual differences in functional status. This could lead to a restriction in the range of functional deficits. This seems to be one explanation why we found no significant associations between vocational functioning and cognitive variables in our study and why we had to exclude vocational functioning from all further analysis. Due to this post hoc model modification, the final model should be cross-validated using other samples. Third, our study participants were willing to engage in a 12-month long intervention. Moreover, according to our inclusion criteria, they had an IQ of at least 80 and no comorbid diagnosis of substance dependence. Therefore, our sample may not be representative of all individuals with schizophrenia. Fourth, it would have been very interesting to explore differential pathways between neuro-, social cognitive, and functional domains. However, our sample comprised 148 schizophrenia patients and it was necessary to reduce the number of parameter estimated in the model by forming latent variables.
The current review raises a number of issues that need to be considered in future research. All but 2 studies42,43
used a cross-sectional design. Therefore, future studies should employ a longitudinal design in order to investigate the temporal order of causation suggested by the mediator model. This could clarify if the mediation model is also valid in predicting long-term functional outcome or if other factors become more influential. Furthermore, there was an extensive range of cognitive tests and functional outcome measures administered across the studies. Due to the heterogeneous assessment, we were unable to draw any firm conclusions about which tests are the most powerful predictors and mediators. Therefore, future studies should use multiple assessments of functional status that range from functional capacity to more distal real-world performance measures.92
Additionally, it seems an important next step to develop or select a social cognitive test-battery with adequate psychometric properties, which can be applied to schizophrenia patients and which measures a broad range of social cognitive domains. Clearly, more guidelines with regard to the statistical procedure to assess mediation effects are needed. This could increase the comparability of study results. Providing information about the correlations among study measures, the regression coefficients, indirect effects as well as the amount of explained variance in each dependent variable would allow calculating more reliable effect sizes based on a larger number of studies.52
Despite these limitations, it seems clear that certain social cognitive domains are one of the key mediators of the cognition-outcome relationship. Research should focus on differential mediation pathways between neurocognition and functional outcome. Future studies should also consider the interaction with other prognostic factors, additional mediators, and moderators in order to increase the predictive power and to target those factors relevant for optimizing therapy effects.