fMRI investigation of the neural mechanisms of Emotional Cognitive Bias Modification as an adjunct therapy to SSRIs in depression.

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Processing of emotional information is critical to social functioning but is disrupted in many psychiatric disorders, including Major Depressive Disorder (MDD). Negative processing biases are present in depression and predict relapse in remitted patients, suggesting that biases play a causal role in the onset and maintenance of depression. A recent large trial (STAR*D) indicates that pharmacotherapy is ineffective in one-third to a half of patients. Furthermore, mounting evidence suggests that antidepressant drugs (e.g., selective serotonin reuptake inhibitors, SSRIs) do not sufficiently improve the absence of positive affect in patients alone, and that they work best in combination with psychological therapies. While recent advances in psychological therapy for depression focus on promoting positive biases, there are still difficulties in treating anhedonia, which is associated with poorer outcomes. There is little work to determine what the minimum effective psychological intervention may be in addition to drug treatment, and a similar lack of studies examining mechanisms of action of such adjunct therapies. We will investigate whether a remotely delivered psychological intervention can provide sufficient opportunity for relearning about emotion to improve the therapeutic effectiveness of SSRI, as indexed by neural responses to emotional faces.fMRI studies have provided good evidence that SSRIs reduce neural responses, particularly in the amygdala, to negative emotional faces. Both behavioural and neural changes in response to emotional stimuli are associated with later improvement in mood. Our brief, automated, Emotional Cognitive Bias Modification (CBM) technique leads to robust and generalizable changes in emotional expression perception, with fMRI results in adults with low mood demonstrating it also increases amygdala activity in response to expressions of happiness. Notably, it has less effect on responses to negative emotions, in contrast to SSRI-induced effects which primarily impact the processing of negative emotions. This suggests that the combination of CBM and SSRI treatment might be particularly effective. We aim to investigate whether a psychological therapy that improves the way we see emotion in others could improve antidepressant drug efficacy. Specifically, we will deliver both CBM training and SSRI pharmacotherapy in patients with a new episode of depression, to investigate whether this enhances the reduced amygdala activity in response to negatively valenced emotions (that typically results from SSRI therapy) and increases amygdala activity in response to positive expressions (a key result from our earlier work that is rarely seen in SSRI studies). Mechanistically, we have clear predictions about how such effects will be instantiated in neural responses to emotional stimuli. Therapeutically, this combination of inetreventions has the potential to address depressive symptoms that are currently difficult to treat.