Transdiagnostic neural correlates of affective face processing in anxiety and depression

Background: It is unknown whether there are neurobiologic differences between various anxiety and depressive disorders, or whether they are characterized by shared neurobiologic variation that cuts across diagnostic boundaries. For instance, multiple anxiety disorders and depression may be characterized by abnormalities in blood oxygen-level dependent (BOLD) response during the processing of affective scenes and faces. To interrogate the shared or unique nature of these aberrations, research that examines the influence of transdiagnostic, dimensional predictors across multiple diagnoses is needed. Methods: One hundred ninety-nine individuals, 142 with primary diagnoses of social anxiety disorder (SAD), generalized anxiety disorder (GAD), or major depressive disorder (MDD) and 57 free from psychiatric diagnoses (healthy controls, HCs), performed a face-matching task involving fearful, angry, and happy faces (and geometric shapes) while undergoing functional magnetic resonance imaging. Results: Across the three primary diagnoses, anxiety symptom scores were associated with increased Angry > Shapes activation in the bilateral insula, anterior/midcingulate, and dorsolateral prefrontal cortex (dlPFC), while depressive symptoms were associated with reduced dlPFC activation for Angry > Shapes. Patient > HC differences were limited to non a priori regions, and no differences in BOLD activation were observed between diagnostic groups. Conclusions: (1) Activation in paralimbic, cingulate, and lateral prefrontal regions in response to angry faces is associated with transdiagnostic anxiety and depressive symptomatology. (2) Anxiety and depressive symptoms may exert opposing influences on lateral prefrontal activation. (3) Abnormal threat processing in GAD, SAD, and MDD may reflect shared neural dysfunction that varies with symptom load.