Previous structural brain-imaging studies in first-degree relatives of depressed patients showed alterations that are generally accepted as vulnerability markers for depression. However, only half of the relatives had depression at follow-up, while the other half did not. The aim of this study was to identify the brain areas associated with resilience to depression in high-risk subjects with familial depression. We recruited 59 young women with a history of depressed mothers. Twenty-nine of them (high-risk group [HRG]) had no depression history, while 30 (depressive group) had at least 1 depressive episode in adolescence. The brain structures of the groups were compared through voxel-based morphometry and analysis of cortical thickness. Individual amygdala nuclei and hippocampal subfield volumes were measured. The analysis showed larger amygdala volume, thicker subcallosal cortex and bilateral insula in the women in the HRG compared with those in the depressive group. In addition, we detected more gray matter in the left temporal pole in the HRG. The larger gray matter volume and increased cortical thickness in the key hub regions of the salience network (amygdala and insula) and structurally connected regions in the limbic network (subcallosal area and temporal pole) might prevent women in the HRG from converting to depression.