The impact of creativity on functional outcome in schizophrenia: a mediational model

Functional impairment remains one of the most challenging issues for treatment in schizophrenia. However, previous studies have mainly focused on the negative impact of symptoms excluding variables that could positively impact functional outcome, such as creativity, which is considered an adaptive capacity for real-life problem-solving. This study analyzed the predictive role of creativity on functional outcome in 96 patients with schizophrenia through a mediational model, including sociodemographic, clinical, neurocognitive, and social cognitive variables. Path analysis revealed that creativity significantly mediated the relationship between neurocognition and functional outcome, and that creativity mediated between negative symptoms and functional outcome. Additionally, neurocognition was directly associated with functional outcome and social functioning was associated with creativity. The involvement of creativity in functional outcome could have relevant implications for the development of new interventions. These findings open up a new field of research on additional personal resources as possible factors of functional outcome in schizophrenia and other diseases

Neurocognitive, social cognitive, and clinical predictors of creativity in schizophrenia

Background: Creativity is considered an essential human accomplishment and a key component for daily life problem solving. It has been suggested that impairment in working memory, cognitive flexibility, and theory of mind could lead to lower creativity in schizophrenia. Additionally, other neurocognitive and social cognitive domains, as well as clinical symptoms could play a role in this relationship. However, the extent to which each of these domains influences creativity in schizophrenia remains unknown. Therefore, the aim of this study was to simultaneously investigate the specific contribution of neurocognitive, social cognitive, and clinical variables to creativity in schizophrenia. Methods: One hundred and one patients with schizophrenia were assessed in terms of sociodemographic, clinical, neurocognitive, social cognitive, and creativity variables. Results: After controlling for sociodemographic variables, regression analyses showed that higher social perception (beta = 0.286, p = .004) and processing speed (beta = 0.219, p = .023) predicted creativity total score. Higher social perception (beta = 0.298, p = .002) and processing speed (beta = 0.277, p = .004) explained figural creativity. Finally, lower negative symptoms (beta =-0.302, p = .002) and higher social perception (beta = 0.210, p = .029) predicted verbal creativity. Conclusions: Results suggest that neurocognitive, social cognitive, as well as clinical symptoms influence creativity of patients with schizophrenia. Moreover, these findings point out the prominent role of social cognition in creativity in schizophrenia.This study has been supported by the Spanish Ministry of Economy and Competitiveness (PI16/01022) and the Department of Education and Science of the Basque Government (Team A) (IT946-16). AS was supported by a Fellowship from the Fundacion Tatiana Perez de Guzman el Bueno. The funding agencies had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

Cognitive, creative, functional, and clinical symptom improvements in schizophrenia after an integrative cognitive remediation program: a randomized controlled trial

[EN] This study analyzed the effectiveness of an integrative cognitive remediation program (REHACOP) in improving neurocognition, social cognition, creativity, functional outcome, and clinical symptoms in patients with schizophrenia. In addition, possible mediators predicting improvement in functional outcomes were explored. The program combined cognitive remediation with social cognitive training and social and functional skill training over 20 weeks. The sample included 94 patients, 47 in the REHACOP group and 47 in the active control group (occupational activities). Significant differences were found between the two groups in change scores of processing speed, working memory, verbal memory (VM), inhibition, theory of mind, emotion processing (EP), figural creative strengths, functional competence, disorganization, excitement, and primary negative symptoms. A mediational analysis revealed that changes in VM, inhibition, and EP partially explained the effect of cognitive remediation on functional competence improvement. This study provides initial evidence of the effect of integrative cognitive remediation on primary negative symptoms and creativity.This work was supported by the Carlos III Health Institute of the Spanish Ministry of Economy and Competitiveness (PI16/01022); the Department of Education and Science of the Basque Government (Team A) (IT946-16); the Fundacion Tatiana Perez de Guzman el Bueno (to AS); and the University of the Basque Country (UPV/EHU) (PIF 19/40 to MTE). The funding agencies had no role in the design, data collection, and analysis, decision to publish, or preparation of the study. The authors thank all the participants and clinical teams who were involved in this study as well as the English language editing service. Our special thanks to Amaia Ortiz de Zarate, Edorta Elizagarate, and Isabel Hervella for all the support in the recruitment and management of patients

Amyloid-driven tau accumulation on mitochondria potentially leads to cognitive deterioration in alzheimer’s disease

Despite the well-accepted role of the two main neuropathological markers (β-amyloid and tau) in the progression of Alzheimer’s disease, the interaction and specific contribution of each of them is not fully elucidated. To address this question, in the present study, an adeno-associated virus (AAV9) carrying the mutant P301L form of human tau, was injected into the dorsal hippocampi of APP/PS1 transgenic mice or wild type mice (WT). Three months after injections, memory tasks, biochemical and immunohistochemical analysis were performed. We found that the overexpression of hTauP301L accelerates memory deficits in APP/PS1 mice, but it did not affect memory function of WT mice. Likewise, biochemical assays showed that only in the case of APP/PS1-hTauP301L injected mice, an important accumulation of tau was observed in the insoluble urea fraction. Similarly, electron microscopy images revealed that numerous clusters of tau immunoparticles appear at the dendrites of APP/PS1 injected mice and not in WT animals, suggesting that the presence of amyloid is necessary to induce tau aggregation. Interestingly, these tau immunoparticles accumulate in dendritic mitochondria in the APP/PS1 mice, whereas most of mitochondria in WT injected mice remain free of tau immunoparticles. Taken together, it seems that amyloid induces tau aggregation and accumulation in the dendritic mitochondria and subsequently may alter synapse function, thus, contributing to accelerate cognitive decline in APP/PS1 mice.We gratefully acknowledge grant funding support from Ministry of Science and Innovation (MINECO) with exp. PID2019-104921RB-I00/MCI/AEI/10.13039/501100011033 as well as to the Foundation for Applied Medical Research, the University of Navarra (Pamplona, Spain) for financial support and the Asociación de Amigos of the University of Navarra for the grant to M.P.-G. and S.B. We also gratefully acknowledge grant funding support from Spanish Ministerio de Economía y Competitividad (RTI2018-095812-B-I00 MCIN/ AEI/10.13039/501100011033) y por FEDER una manera de hacer Europa and Junta de Comunidades de Castilla-La Mancha (SBPLY/17/180501/000229) to RL, from the Spanish Ministry of Science Innovation and Universities (Ref. PID2019-110356RB-I00/AEI/10.13039/501100011033) to J.F.-I. and E.S and from the Department of Economic and Business Development from Government of Navarra (INNOLFACT project; Ref. 0011-1411-2020-000028)

Analyzing structural and functional brain changes related to an integrative cognitive remediation program for schizophrenia: A randomized controlled trial

Cognitive remediation has been shown to improve cognition in schizophrenia, but little is known about the specific functional and structural brain changes related to the implementation of an integrative cognitive remediation program. This study analyzed the functional and structural brain changes identified after implementing an integrative cognitive remediation program, REHACOP, in schizophrenia. The program combined cognitive remediation, social cognitive training, and functional and social skills training. The sample included 59 patients that were assigned to either the REHACOP group or an active control group for 20 weeks. In addition to a clinical and neuropsychological assessment, T1-weighted, diffusion-weighted and functional magnetic resonance images were acquired during a resting-state and during a memory paradigm, both at baseline and follow-up. Voxel-based morphometry, tract-based spatial statistics, resting-state functional connectivity, and brain activation analyses during the memory paradigm were performed. Brain changes were assessed with a 2 × 2 repeated-measure analysis of covariance for group x time interaction. Intragroup paired t-tests were also carried out. Repeated-measure analyses revealed improvements in cognition and functional outcome, but no significant brain changes associated with the integrative cognitive remediation program. Intragroup analyses showed greater gray matter volume and cortical thickness in right temporal regions at post-treatment in the REHACOP group. The absence of significant brain-level results associated with cognitive remediation may be partly due to the small sample size, which limited the statistical power of the study. Therefore, further research is needed to clarify whether the temporal lobe may be a key area involved in cognitive improvements following cognitive remediation.This study has been supported by the Carlos III Health Institute of the Spanish Ministry of Economy and Competitiveness (PI16/01022) and the Department of Education and Science of the Basque Government (Team A; IT946-16). AS was supported by a Fellowship from the Fundación Tatiana Pérez de Guzmán el Bueno. MTE was supported by a Fellowship from University of the Basque Country (UPV/EHU; PIF 19/40). The funding agencies had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

Improvement of cognitive function in wild-type and Alzheimer´s disease mouse models by the immunomodulatory properties of menthol inhalation or by depletion of T regulatory cells

A complex network of interactions exists between the olfactory, immune and central nervous systems. In this work we intend to investigate this connection through the use of an immunostimulatory odorant like menthol, analyzing its impact on the immune system and the cognitive capacity in healthy and Alzheimer’s Disease Mouse Models. We first found that repeated short exposures to menthol odor enhanced the immune response against ovalbumin immunization. Menthol inhalation also improved the cognitive capacity of immunocompetent mice but not in immunodeficient NSG mice, which exhibited very poor fear-conditioning. This improvement was associated with a downregulation of IL-1β and IL-6 mRNA in the brain´s prefrontal cortex, and it was impaired by anosmia induction with methimazole. Exposure to menthol for 6 months (1 week per month) prevented the cognitive impairment observed in the APP/PS1 mouse model of Alzheimer. Besides, this improvement was also observed by the depletion or inhibition of T regulatory cells. Treg depletion also improved the cognitive capacity of the APPNL-G-F/NL-G-F Alzheimer´s mouse model. In all cases, the improvement in learning capacity was associated with a downregulation of IL-1β mRNA. Blockade of the IL-1 receptor with anakinra resulted in a significant increase in cognitive capacity in healthy mice as well as in the APP/PS1 model of Alzheimer´s disease. These data suggest an association between the immunomodulatory capacity of smells and their impact on the cognitive functions of the animals, highlighting the potential of odors and immune modulators as therapeutic agents for CNS-related diseases

Mediating role of cognition and social cognition on creativity among patients with schizophrenia and healthy controls: Revisiting the Shared Vulnerability Model

Aim As suggested by the Shared Vulnerability Model, impairment in executive functions could lead to worse creative performance among individuals with schizophrenia. Another impaired function in schizophrenia, previously related to creativity in healthy people, is theory of mind. However, little is known about the effect of theory of mind in creativity in schizophrenia. Therefore, the aim of this study was to analyze differences in creativity among patients with schizophrenia compared to healthy controls (HC) and to explore the potential role of executive functions and theory of mind as mediators of this relation. Methods Forty-five patients with schizophrenia and 45 HC underwent a neuropsychological assessment, including executive functions (cognitive flexibility and working memory), theory of mind, and verbal and figural creativity. Results As expected, patients with schizophrenia obtained lower scores in creativity, cognitive flexibility, working memory, and theory of mind compared to HC. Path analysis showed that theory of mind mediated the relation between group (schizophrenia or HC) and both figural (Z = 2.075, P = 0.037) and verbal creativity (Z = 2.570, P = 0.010). Working memory mediated the relation between group and figural creativity (Z = 2.034, P = 0.041) and was marginally significant for verbal creativity (Z = 1.930, P = 0.053). Finally, cognitive flexibility mediated between group and figural creativity (Z = 2.454, P = 0.014). Conclusion Results suggest that the lower performance in creativity among patients with schizophrenia was partly due to an impairment in executive functions and theory of mind. The involvement of theory of mind opens up a new field of research as a possible risk factor in the Shared Vulnerability Model.This study has been supported by the Ministry of Economy and Competitiveness (PI16/01022) from Spain. A.S. was supported by a Fellowship from the Fundacion Tatiana Perez de Guzman el Bueno. The funding agencies had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors thank all the participants and clinical clusters who were involved in the study