A functional magnetic resonance imaging investigation of emotion processing in remitted major depressive disorder: towards the identification of neurobiological trait markers and clinical implications for treatment

Abstract

Emotional dysregulation is a core feature of Major Depressive Disorder (MDD), manifested by perceptual biases in processing positive and negative emotional stimuli. In support, a constellation of neuroimaging studies have consistently reported abnormalities in brain areas during the processing of negative and positive emotional stimuli in acutely depressed patients during a major depressive episode. These areas, which are pivotal for bottom-up emotion generation processes and top-down cognitive control of emotion through reciprocal connections, include lateral prefrontal cortical (PFC) regions (dorsolateral PFC, ventrolateral PFC), medial PFC regions (orbitofrontal cortex) and subcortical regions (amygdala, ventral striatum). However despite considerable progress into identifying the neural circuitry involved in MDD, a neural circuitry marker for the MDD trait has not yet been defined. Studying individuals in remission from MDD who are euthymic and medication-free, allows for the examination of enduring abnormalities in the neural circuitry supporting emotion processing and its regulation that may represent trait markers of the illness. Therefore the aims of this thesis were to examine, by means of two functional magnetic resonance imaging (fMRI) studies, neural activation in key areas subserving emotion processing and higher-order cognitive control processes, to determine whether abnormalities in the circuit persist into remission and thus represent trait-like markers of MDD. Using blood oxygen level dependent (BOLD) fMRI, 19 remitted medication-free individuals with recurrent MDD (rMDD) (mean age 33.6 ± 13.64) and 20 healthy controls (HC) (mean age 35.8 ± 12.10) completed an implicit gender-labelling emotion processing task (study 1), and a working memory task with emotional distracter stimuli (study 2). In each study faces depicting negative (fearful), positive (happy) and neutral emotions were used. Brain imaging data were analyzed in SPM2 using a whole-brain and region-of-interest approach corrected for multiple comparisons using AlphaSim (PFWE