Antidepressant short-term and long-term brain effects during self-referential processing in major depression.

Acute depression is associated with impaired self-referential processing. Antidepressant effects on the neural bases of self-referential processing in depression are unknown. This study aimed to assess short- and long-term effects of agomelatine on these neural bases in depressed patients and the association between pre-treatment brain activation and remission of depression 6 months later. We conducted a randomized double-blind, placebo-controlled, functional magnetic resonance imaging (fMRI) study during an emotional self-referential task, including three scanning sessions (baseline, after 1 week, and after 7 weeks). Twenty-five depressed outpatients were included, all treated with agomelatine or placebo for 1 week. Then, all patients received agomelatine for 24 weeks. Fourteen matched healthy volunteers (HV) who received placebo for 1 week were also included. After 7 days, only depressed patients receiving agomelatine significantly deactivated the ventrolateral prefrontal cortex during self-referential processing, as observed in HV at baseline. After 7 weeks, depressed patients significantly increased the activation of the ventral anterior cingulate cortex. Finally dorsomedial prefrontal cortex and precuneus activations at baseline significantly separated remitters from non-remitters at 24 weeks. In depressed patients, agomelatine had short- and long-term effects on brain structures involved in anhedonia and emotional regulation during self-referential processing. Activation of the dorsomedial prefrontal cortex and precuneus could be informative in the development of biomarker-based treatment of major depression.

Episodic autobiographical memory in depression: Specificity, autonoetic consciousness, and self-perspective.

Autobiographical memory (AM) and the self are closely linked. AM retrieval in depression is characterized by a lack of specificity, suggesting an impairment of episodic AM. Autonoetic consciousness and self-perspective, which are critical to episodic AM, have never been addressed in depression. Twenty-one depressed inpatients and 21 matched controls were given an episodic AM task designed to assess positive and negative memories regarding specificity, autonoetic consciousness (remember/know procedure), and self-perspective (field/observer procedure). For specificity, "remember", and "field" responses, ANOVAs revealed a main group effect and a group x valence interaction. Between groups, patients showed lower scores than controls for positive memories. Within groups, patients showed greater scores for negative memories, and controls showed greater scores for positive memories. There is a global episodic AM impairment of positive memories in depression regarding specificity, autonoetic consciousness, and self-perspective. Our results suggest new cognitive interventions to improve the self-relevance of positive memories in depression.