Open Collections

Gregory, Elizabeth Charlotte

University of British Columbia

Introduction: Cognitive dysfunction (CD) is a commonly reported symptom of Major Depressive Disorder (MDD) and recognized as a distinct symptom domain. Patients with treatment-resistant depression (TRD) tend to experience greater rates of CD, however cognition is not well-characterized in this population and treatment options remain scarce. Repetitive Transcranial Magnetic Stimulation (rTMS) is effective in treating affective symptoms in TRD, but its effect on CD in TRD has not been established. Objectives: (1) To characterize CD in TRD; (2) to assess whether rTMS is associated with cognitive improvement. Methods: This study used data from a non-inferiority clinical trial investigating two excitatory rTMS protocols to the left dorsolateral prefrontal cortex in unipolar outpatients with TRD. Cognitive testing was performed at baseline and 3 months post-treatment in patients and a demographically matched cohort of healthy volunteers (HV). A MANOVA was performed on baseline data to assess the effects of TRD on cognition using both normative and individualized adjustments. K-means clustering was performed on the patient sample to elucidate cognitive subgroups, and binomial logistic regression was subsequently performed to determine significant clinical and demographic predictors of cluster belonging. Changes in cognitive performance from baseline to post-treatment were assessed using repeated-measures ANOVA. Results: At baseline, TRD showed selective impairment compared to HV in domains of verbal memory, speeded attention, set shifting, and inhibitory control. Relative cognitive scoring revealed greater differences in scores between TRD and HV across all cognitive domains. Clustering revealed two cognitive subgroups in TRD, namely a global impairment (GI, 57%) and a selective executive dysfunction (SE, 43%) subgroup. Belonging to the GI subgroup was predicted by benzodiazepine use and older age. Only the GI subgroup showed meaningful changes in cognitive performance at 3 months post-treatment, with significant improvements in verbal memory. Further, improvement in verbal memory was associated with improvements in affective symptoms. Conclusions: This research provides new insights into the cognitive heterogeneity of TRD by identifying cognitive subgroups and predictors of cognitive functioning. Furthermore, the findings suggest that rTMS to the left DLPFC may improve verbal memory in a subgroup of TRD patients.

Text

2021-05-04

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/78084

Experimental Medicine

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/