Abnormal brain connectivity during emotional processing is a key characteristic of major depressive disorder (MDD). Previous studies have lacked consistency in methodology, hindering the understanding of the functional implications of these alterations. However, the authors’ research has identified distinctive changes in emotion processing, differentiating between depressive pathology, at-risk/resilient individuals, and healthy subjects. Their findings reveal decreased effective connectivity in MDD patients, specifically from the left amygdala and left prefrontal cortex to the fusiform gyrus. Additionally, patients and relatives exhibit reduced connectivity from the right orbitofrontal cortex to the left insula and from the left orbitofrontal cortex to the right fusiform gyrus compared to controls. Notably, relatives show increased connectivity from the anterior cingulate cortex to the left dorsolateral prefrontal cortex.