Is chronic pain an affective disorder? Moderation of resting-state functional connectivity within the emotional brain by depressive symptoms

Background. Depressive symptoms are often comorbid to chronic pain. These conditions share aberrant emotion processing and regulation, as well as common brain networks. However, the relationship between depressive symptoms and chronic pain on emotional brain function is unclear. Methods. Participants were 26 individuals with chronic pain (referred to as the Pain group) and 32 healthy controls (HC), who underwent resting-state functional magnetic resonance imaging and completed the Beck Depressive Inventory. Main effects of group, depressive symptom severity (total score), and their interaction were evaluated on functional connectivity from three seed regions (separately, the left and right amygdalae, the medial prefrontal cortex, mPFC) and the rest of the brain. In case of significant interaction, moderation analyses were conducted. Results. The group-by-depressive symptoms interaction was significantly associated with changes in connectivity between the right amygdala and the mPFC (pFWEc<0.001). Moderation analysis indicated that, compared to the HC group, the Pain group showed weaker connectivity between these regions at lower levels of depressive symptoms (p=0.018), and stronger connectivity at higher levels of depressive symptoms (p=0.001). In addition, the strength of connectivity decreased in the HC (p=0.004) and increased in the Pain group (p=0.011) as the severity of depressive symptoms increased. Finally, the Pain group showed significant weaker connectivity between the mPFC seed and the left parahippocampal gyrus compared to the HC group (pFWEc=0.015). Conclusions. These results indicate that depressive symptoms moderate the impact of chronic pain on the emotional brain function and highlight potential implications for the choice of treatment for chronic pain.