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Meeting ID: 813 3381 1866
Disturbed cognition is a common but often overlooked symptom in Major Depressive Disorder (MDD). The disturbances are typically expressed across a wide spectrum of cognitive functions and may critically impair the patient’s ability to function in everyday life. Recently, researchers have begun to explore the potential of cognitive markers to inform clinical decision-making in the treatment of depression. However, there are still many unanswered questions about the patterns and severity of different types of cognitive deficits during a depressive episode and how they relate to underlying depressive pathology and clinical outcomes. In particular, little is known about the differences and co-occurrence of hot (emotion-dependent) and cold (emotion-independent) cognitive disturbances in depression. The purpose of this PhD was therefore to improve the current knowledge about cognitive disturbances in depression in the hope that this would not only aid our understanding of the disease mechanisms in MDD but also offer clinical insight to help improve patient care.
In Study I, we tested 100 healthy Danish participants with the hot cognitive EMOTICOM test battery to establish the psychometric properties of the battery and create a Danish reference sample. Although select EMOTICOM tasks exhibited problematic test-retest reliability and/or floor and ceiling effects, we found that the test battery as a whole offers a useful set of cognitive tools for measuring hot cognition.
In Study II, we investigated cognitive disturbances in 92 antidepressant-free patients with a moderate to severe depressive episode. We found that performance of the MDD patients was disturbed across both hot and cold cognitive domains relative to healthy controls. However, the severity of cognitive disturbances was not related to the severity of depressive symptoms. We also identified three distinct clusters of cognitive profiles within the MDD cohort: One cluster was characterized by pronounced negative affective biases in emotion processing with minimal disturbances across other cognitive domains; the second cluster was characterized by positive affective biases in emotion processing and moderate deficits in cold cognitive domains; the last cluster was characterized by large global deficits across all domains. The globally impaired cluster had slightly more severe depressive symptoms compared with the other two clusters.
In Study III, we investigated the association between pre-treatment cognitive performance and antidepressant response as well as the effect of 12 weeks of standard treatment with Selective Serotonin Reuptake Inhibitors on cognition in MDD patients. Although we found no association between performance on any single cognitive outcome at baseline and later clinical treatment response, patients from the globally impaired cluster had worse clinical response after 8 but not 12 weeks of treatment compared with the other two clusters. This suggests that severe cognitive disturbances may delay antidepressant treatment effects. Overall cognitive performance improved during the course of treatment, although these improvements were not related to improvement in clinical symptoms indicating a dissociation between cognitive and depressive symptoms in MDD.
In conclusion, we translated and validated the EMOTICOM test battery in Danish, providing new set of hot cognitive tools for future clinical and research use. In addition, the results from this thesis provide new insights into the role of hot and cold cognitive disturbances in depression and emphasize that cognition should be viewed as a distinct symptom and treatment target in MDD. Importantly, we also showed that cognitive profiles may be useful tools for stratifying patients in a precision medicine approach.
Professor Lars Vedel Kessing, Department of Psychiatry RH & Department of Clinical Medicine UCPH (chair)
Professor Catherine Harmer, Department of Psychiatry, Oxford University, UK
Associate professor Vibeke Fuglsang Bliksted, Department of Clinical Medicine, Aarhus University
Principal supervisor: Professor Gitte Moos Knudsen, Neurobiology Research Unit & UCPH
Primary co-supervisor: Associate professor Vibe Gedsø Frøkjær, Neurobiology Research Unit & UCPH
Co-supervisor: Associate professor Dea Siggaard Stenbæk, Neurobiology Research Unit & UCPH