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No Effects of Cognitive Remediation on Cerebral White Matter in Individuals at Ultra-High Risk for Psychosis-A Randomized Clinical Trial.

ABSTRACT: Background:Individuals at ultra-high risk for psychosis (UHR) present with subtle alterations in cerebral white matter (WM), which appear to be associated with clinical and functional outcome. The effect of cognitive remediation on WM organization in UHR individuals has not been investigated previously. Methods:In a randomized, clinical trial, UHR individuals aged 18 to 40 years were assigned to treatment as usual (TAU) or TAU plus cognitive remediation for 20 weeks. Cognitive remediation comprised 20 x 2-h sessions of neurocognitive and social-cognitive training. Primary outcome was whole brain fractional anisotropy derived from diffusion weighted imaging, statistically tested as an interaction between timepoint and treatment group. Secondary outcomes were restricted to five predefined region of interest (ROI) analyses on fractional anisotropy, axial diffusivity, radial diffusivity and mean diffusivity. For significant timepoint and treatment group interactions within these five ROIs, we explored associations between longitudinal changes in WM and cognitive functions/clinical symptoms. Finally, we explored dose-response effects of cognitive remediation on WM. Results:A total of 111 UHR individuals were included. Attrition-rate was 26%. The cognitive remediation group completed on average 12 h of neurocognitive training, which was considerably lower than per protocol. We found no effect of cognitive remediation on whole-brain FA when compared to treatment as usual. Secondary ROI analyses revealed a nominal significant interaction between timepoint*treatment of AD in left medial lemniscus (P=0.016) which did not survive control for multiple comparisons. The exploratory test showed that this change in AD correlated to improvements of mental flexibility in the cognitive remediation group (p=0.001). We found no dose-response effect of neurocognitive training on WM. Conclusions:Cognitive remediation comprising 12 h of neurocognitive training on average did not improve global or regional WM organization in UHR individuals. Further investigations of duration and intensity of cognitive training as necessary prerequisites of neuroplasticity-based changes are warranted. Clinical Trial Registration:ClinicalTrials.gov, identifier NCT02098408.

SUBMITTER: Kristensen TD

PROVIDER: S-EPMC7485415 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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No Effects of Cognitive Remediation on Cerebral White Matter in Individuals at Ultra-High Risk for Psychosis-A Randomized Clinical Trial.

Kristensen Tina D TD Ebdrup Bjørn H BH Hjorthøj Carsten C Mandl René C W RCW Raghava Jayachandra M JM Jepsen Jens Richardt M JRM Fagerlund Birgitte B Glenthøj Louise B LB Wenneberg Christina C Krakauer Kristine K Pantelis Christos C Glenthøj Birte Y BY Nordentoft Merete M

Frontiers in psychiatry 20200828

<h4>Background</h4>Individuals at ultra-high risk for psychosis (UHR) present with subtle alterations in cerebral white matter (WM), which appear to be associated with clinical and functional outcome. The effect of cognitive remediation on WM organization in UHR individuals has not been investigated previously.<h4>Methods</h4>In a randomized, clinical trial, UHR individuals aged 18 to 40 years were assigned to treatment as usual (TAU) or TAU plus cognitive remediation for 20 weeks. Cognitive rem ...[more]

PMID: 33005161

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Project description:Cognitive dysfunction is a major feature of bipolar disorder with psychosis and is strongly associated with functional outcomes. Computer-based cognitive remediation has shown promise in improving cognition in patients with schizophrenia. However, despite similar neurocognitive deficits between patients with schizophrenia and bipolar disorder, few studies have extended neuroscience-based cognitive remediation programs to this population.The Treatment to Enhance Cognition in Bipolar Disorder study is an investigator-initiated, parallel group, randomized, blinded clinical trial of an Internet-based cognitive remediation protocol for patients with bipolar disorder I with psychosis (n = 100). We also describe the development of our dose-matched active control paradigm. Both conditions involve 70 sessions of computer-based activities over 24 weeks. The control intervention was developed to mirror the treatment condition in dose and format but without the neuroplasticity-based task design and structure. All participants undergo neuropsychological and clinical assessment at baseline, after approximately 25 hours of study activities, post treatment, and after 6 months of no study contact to assess durability. Neuroimaging at baseline and post treatment are offered in an "opt-in" format. The primary outcomes are scores on the MATRICS battery; secondary and exploratory outcomes include measures of clinical symptoms, community functioning, and neuroimaging changes. Associations between change in cognitive measures and change in community functioning will be assessed. Baseline predictors of treatment response will be examined.The present study is the first we are aware of to implement an Internet-based cognitive remediation program in patients with bipolar disorder with psychosis and to develop a comparable web-based control paradigm. The mixed online and study-site format allows accessible treatment while providing weekly staff contact and bridging. Based on user-provided feedback, participant blinding is feasible.ClinicalTrials.gov NCT01470781 ; 11 July 2011.

Dataset Information

No Effects of Cognitive Remediation on Cerebral White Matter in Individuals at Ultra-High Risk for Psychosis-A Randomized Clinical Trial.

Publications

No Effects of Cognitive Remediation on Cerebral White Matter in Individuals at Ultra-High Risk for Psychosis-A Randomized Clinical Trial.

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