Caroline Vintergaard Ott defends her PhD thesis
Title
‘Cognitive impairment in bipolar disorder: Effects of Action-Based Cognitive Remediation, its neuronal mechanisms and methodological recommendations’
Time and place
Thursday, 17 December 2020 at 13:00.
The defence will take place online on Zoom.
Click here to attend the defence on Zoom.
Passcode: 803440.
Assessment committee
- Professor Thomas Habekost, Department of Psychology, University of Copenhagen, Denmark (chair)
- Professor Åsa Hammar, University of Bergen, Norway
- Associate professor Torill Ueland, University of Oslo, Norway
Supervisors
- Professor MSO Kamilla Woznica Miskowiak, University of Copenhagen, Denmark (principal supervisor)
- Professor Lars Vedel Kessing, University of Copenhagen, Denmark (co-supervisor)
Abstract
Cognitive impairments are prevalent in patients with bipolar disorder (mania and depression) even when patients have minimal mood symptoms. The cognitive impairments are associated with reduced functioning and quality of life. However, no treatment targeting cognition has shown robust and enduring effects in bipolar disorder. This is partly thought to be due to methodological challenges within the field, including lack of consensus on whether and how to screen for cognitive impairments in cognition trials and limited insight into the neuronal underpinnings of these impairments and cognitive improvements.
The thesis provides (I) development of demographically adjusted norms and change norms for the cognition screening instrument, SCIP (Screen for Cognitive Impairment in Psychiatry), (II) assessment of the associations between measures of cognition and functioning in patients with bipolar disorder and (III) a randomized controlled trial assessing the effects of Action-Based Cognitive Remediation on neurocognitive and functional outcomes as well as treatment-related neuronal changes in patients with bipolar disorder.
The key findings are norms on the SCIP adjusted for sex, age and years of education and cognitive change norms adjusted for baseline cognition and age, which can be used clinically and in cognition trials for precise estimation of whether patients are cognitively impaired. Further, the findings indicate that a performance-based (but not self-report) measure of functioning shows the strongest association with objective cognition, making this measure relevant to include in future cognition trials. The randomised controlled trial revealed no significant effect of Action-Based Cognitive Remediation on the primary outcome, a cognitive composite score. However, there was a significant and large effect on the secondary cognitive outcome, a measure of executive function, and some tertiary outcomes including verbal memory. The improvement in executive function was accompanied by an early increase in the dorsal prefrontal cortex response during working memory after only two weeks of treatment, an effect that predicted subsequent improvement of executive function.
The implications of the findings of the thesis are a more precise screening for cognitive impairments in bipolar disorder in the clinic and in cognition trials. In research trials, this can aid enrichment of populations for cognitive impairments that can increase the chances of detecting efficacy on cognition. Finally, Action-Based Cognitive Remediation seems to be particularly relevant for improvement of executive function and is accompanied by early increase in the dorsal prefrontal cortex response. Implementation of fMRI to investigate neurocircuitry target engagement is a promising approach to screen for pro-cognitive efficacy in treatment development strategies targeting cognitive impairments.
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