Amygdala responsivity related to memory of emotionally neutral stimuli constitutes a trait factor for depression

Episodic memory impairment is considered to be a core cognitive deficit of Major Depressive Disorder (MDD) and has motivated a line of research investigating the role of the amygdala and the hippocampus in depression. While functional neuroimaging studies have focused on memory for emotional but not for neutral stimuli, in order to probe amygdala function, structural imaging studies have tied episodic memory to hippocampal function. We therefore investigated the neural correlates of episodic memory formation for neutral stimuli in 20 patients with a first depressive episode, 20 patients recovered from a first episode and 20 healthy controls. Because there is evidence that the amygdala exhibits hyperactive responses even to neutral stimuli in depressed subjects, we specifically explored the potential role of the amygdala in forming episodic memories with neutral content. Both patient groups showed stronger subsequent memory effects in the amygdala when compared to controls, in the absence of any differences in hippocampal activity between groups. Patients with a first episode of MDD showed increased activity related to episodic memory formation in a fronto-limbic network. These state-related activations may be related to a compensatory mechanism, which is supported by the absence of any differences in memory performance between groups. These findings represent initial evidence for a neurocognitive trait or vulnerability marker of depression-amygdala involvement in episodic memory formation of neutral stimuli.