Correlates of creativity and effects of integrative cognitive remediation in schizophreniaa multimodal neuroimaging study

Resumen

The idea that there is a relationship between creativity and schizophrenia has been a research topic of great interest for centuries. It is now suggested that people with schizophrenia show an impaired creative capacity. Nevertheless, the cognitive, clinical and brain underpinnings of the relationship between creativity and schizophrenia, and the possible role of creativity in functional outcome remain almost unknown. Being one of the most disabling disorders in the world, the improvement of functional outcome is considered the main treatment target in this disease. Cognitive remediation has shown to be an effective intervention in improving functional outcome as well as cognition and clinical symptoms in schizophrenia. However, results among studies are still heterogeneous and little is known about the effectiveness of the combination of cognitive remediation with other trainings in improving creativity, primary negative symptoms, and brain structure and function in schizophrenia. Moreover, it is unclear which domains predict the improvement in functional outcome. The present thesis is composed by six scientific contributions. The first study (Psychiatry and Clinical Neurosciences) aimed to analyze differences in creativity between patients with schizophrenia and healthy controls as well as the mediating role of cognitive flexibility, working memory, and theory of mind in the relationship between schizophrenia and creativity. The second study (Journal of Psychiatric Research) investigated simultaneously the specific contribution of multiple neurocognitive, social cognitive and clinical variables to creativity in schizophrenia. The third study (npj Schizophrenia) assessed the predictive role of creativity on functional outcome through a mediational model including sociodemographic, clinical, neurocognitive, and social cognitive variables among patients with schizophrenia. The fourth study (Frontiers in Neuroscience) analyzed whole brain white matter correlates of different creativity dimensions in schizophrenia. The fifth study (npj Schizophrenia) evaluated the effectiveness of an integrative cognitive remediation program (REHACOP) that combined training in neurocognition, social cognition, as well as social and functional skills among patients with schizophrenia in multiple domains: creativity, neurocognition, social cognition, functional outcome, and clinical symptoms. An additional aim of the fifth study was to explore the mediators predicting improvement in functional outcome after the integrative cognitive remediation. Finally, the sixth study (under review) explored the structural and functional brain changes induced by the REHACOP program in patients with schizophrenia. Results showed that patients with schizophrenia obtained lower scores in creativity compared to healthy controls and that this lower performance was partly due to an impairment in cognitive flexibility, working memory, and theory of mind. Moreover, creative performance of patients with schizophrenia was explained by multiple neurocognitive, social cognitive and clinical variables. In addition, creativity mediated the relationship between neurocognition and functional outcome as well as the relationship between negative symptoms and functional outcome in patients with schizophrenia. White matter mean fractional anisotropy adjacent to multiple brain regions, including frontal, temporal, subcortical, brain stem, and interhemispheric regions, correlated positively with creativity and specifically, with figural originality, among patients with schizophrenia. Furthermore, the integrative cognitive remediation was effective in producing significant changes in neurocognition, social cognition, creativity, functional outcome, and clinical symptoms. Besides, changes in verbal memory, inhibition, and emotion processing partially explained the effect of cognitive remediation on functional competence. Finally, the integrative cognitive remediation failed to produce structural and functional brain changes in patients with schizophrenia. However, the REHACOP group showed greater grey matter volume and cortical thickness in right temporal regions at post-treatment. In conclusion, the present thesis provides on the one hand, a better understanding of the role of creativity on schizophrenia, through the interaction of multiple neurocognitive, social cognitive, clinical, functional outcome, and brain characteristics. On the other hand, this thesis reinforces the effectiveness of integrative cognitive remediation in multiple cognitive and functional outcome domains, and provides initial evidence of the effect of cognitive remediation in creativity and primary negative symptoms among patients with schizophrenia. Moreover, this thesis attempts to better understand the effects of integrative cognitive remediation in brain structure and function, suggesting that further research should clarify whether the temporal lobe may be a key area involved in neuroprotective processes of cognitive remediation.