Opposing and emotion-specific associations between frontal activation with depression and anxiety symptoms during facial emotion processing in generalized anxiety and depression

Major depression (MDD) and generalized anxiety disorder (GAD) have become one of the leading global causes of disability and both are characterized by marked interpersonal and social impairments. However, despite high comorbidity and overlapping social-emotional deficits, it remains unclear whether MDD and GAD share a common neural basis during interpersonal processing. In the present study, we combined an emotional face processing paradigm with fMRI and dimensional and categorical analyses in a sample of unmedicated MDD and GAD patients (N = 72) as well as healthy controls (N = 35). No group differences were found in categorical analyses. However, the dimensional analyses revealed that dorsolateral prefrontal cortex (dlPFC) reactivity to sad facial expressions was positively associated with depression symptom load, yet negatively associated with anxiety symptom load in the entire sample. On the network level depression symptom load was positively associated with functional connectivity between the bilateral amygdala and a widespread network including the anterior cingulate and insular cortex. Together, these findings suggest that the dlPFC - engaged in cognitive and emotional processing - exhibits symptom- and emotion-specific alteration during interpersonal processing. Dysregulated communication between the amygdala and core regions of the salience network may represent depression-specific neural dysregulations.