“…Lastly, Nicassio et al [45] reported that depressive symptoms mediated 38% of the total effect of pain on sleep. While not directly related to our results, the mediators identified in these studies (e.g., depression and/or anxiety, attention to pain, pain helplessness, activation of the stress system, fatigue, and physical activity) have all been related to structural changes in the brain [31] , with sleep problems [14] , [26] , [32] , [39] , [40] , [64] , and chronic pain [2] , [12] , [34] , [42] , [56] , [61] , [63] , [71] . For example, patients with major depressive disorder have a reduction in gray matter in the left anterior cingulate cortex, as well as in the orbital, ventrolateral prefrontal and hippocampal cortices.…”