56 The above on and off cells, through data transmitted from the limbic forebrain and other structures transmitted through the RVM, may dampen or amplify pain impulses transmitted from the periphery56,59 Activation of the RVM off neurons or DLPT neurons via electrical stimulation dampens activity of nociceptive neurons in the dorsal horn.56,58 These bidirectional on/off systems determine vigilance to external threats as well as sensations coming from inside the

body56,59 Decrease of serotonin and/or norepinephrine neurotransmission as occurs in depression may lead this descending system to decrease its inhibitory Inhibitors,research,lifescience,medical effect so that nociceptive signals from the body are considered stronger and more salient.59 This may explain the clinical experience of patients with depression being quite focused on the Inhibitors,research,lifescience,medical bothersomeness of many physical symptoms. A recent systematic review of 31 studies found that comorbid depression in patients with chronic medical illnesses such as diabetes, congestive heart failure, CHD, osteoarthritis, rheumatoid arthritis, asthma, or COPD was associated with a significantly higher number of medical symptoms after controlling for severity of medical

illness.21 Across these Inhibitors,research,lifescience,medical medical conditions, depression was at least as strongly associated with the number of medical symptoms as were objective physiological measures.21 Figure 2 shows the relationship of both comorbid depression and number of diabetes complications with a 10item diabetes symptom scale.60 Inhibitors,research,lifescience,medical After controlling for socioeconomic factors and severity of medical illness, depression was more highly associated with each of these 10 symptoms than was the number of diabetes complications. Figure 2. Relationship of depression and diabetes complications to 10 diabetes symptoms. Reproduced from ref 60: Ludman EJ, Katon W, Russo J, et al. Depression and diabetes symptom burden. Gen Hosp Psychiatry. 2004;26:430-436. Copyright © Inhibitors,research,lifescience,medical Elsevier

2004 Three randomized controlled studies that tested depression interventions in patients with a specific chronic medical illness (COPD,61 osteoarthritis,62 or diabetes63) have also shown that, compared with controls, greater improvement in comorbid depressive symptoms in patients with chronic medical illness with the depression intervention was associated with improvement in medical why symptoms without improvement in physiologic measures. For instance, Ell and colleagues tested a PTC124 collaborative care intervention versus usual care in 387 patients with comorbid depression and diabetes. Compared with usual primary care, collaborative care was associated with improvements in quality of depression care, severity of depressive symptoms, and number of diabetes symptoms, but lack of change in HbA1c levels.