Negative memory bias is thought to be one of the main cognitive risk and maintenance factors for depression, but its neural substrates are largely unknown. Here, we studied whether memory bias is related to amygdala and hippocampal volume, two structures that are critical for emotional memory processes and that show consistent volume alterations in depression.

Structural magnetic resonance imaging (MRI) was carried out in 272 healthy participants (62% female, 18–50 years old). All images were acquired on 1.5 T Siemens MRI scanners. Automatic segmentation of amygdala and hippocampus was performed using the FIRST module of FSL. Negative memory bias was assessed by the self-referent encoding/evaluation test.

Negative memory bias was associated with larger amygdala (p=0.042) and smaller hippocampal (p=0.029) volumes. In additional analyses, we found that, compared with the associations found with hippocampus and amygdala volume separately, a stronger association was found between negative memory bias and the ratio of amygdala:hippocampus volume (p=0.021).

In non-depressed subjects we found that larger amygdala and smaller hippocampal volumes are associated with negative memory bias. This suggests that an increased amygdala:hippocampus volume ratio plays a role in cognitive vulnerability often seen in individuals with high risk for depression and that these structural brain differences may pre-date the onset of depression.