of treatment of depression in aging populations with chronic medical illness (Katon et al., 2004a).

Patients with chronic medical illness have been found to have two- to threefold higher rates of major depression compared with age- and gender-matched primary care controls (Katon, 2011). Rates of depression among primary care patients are between 5 and 10 percent (Katon and Schulberg, 1992), whereas prevalence rates of depression in patients with chronic medical illnesses, such as diabetes and coronary artery disease, have been estimated to be 12 to 18 percent (Ali et al., 2006) and 18 to 23 percent, respectively (Schleifer et al., 1989; Spijkerman et al., 2005). Rates of depression in complex multicondition aging populations may be as high as 25 percent (McCall et al., 2002).

Studies have suggested that there is a bidirectional relationship between depression and such chronic medical illnesses as diabetes, heart disease, and COPD (Figure A-1) (Katon, 2011). Depression often develops in the teenage years or early adulthood. Predisposing factors to depression include genetic factors as well as experiencing childhood adversities, such as the loss of one or both parents, neglect, and abuse (Kendler et al., 2002). Stressful life events in people with these vulnerabilities often precipitate depressive episodes (Caspi et al., 2003). Exposure to childhood adversity also often leads to problems with maladaptive attachment patterns in adult relationships, resulting in lack of social support and problems with interpersonal relationships (Bifulco et al., 2002). Lack of support and interpersonal problems may precipitate and prolong depressive episodes (Bifulco et al., 2002).

Depression in adolescence and early adulthood is associated with three health behaviors that have been estimated to cause 40 percent of premature mortality in the United States: obesity, smoking, and sedentary lifestyle (Katon et al., 2010c). Psychobiological changes that have been shown to be associated with depression, such as increased cortisol levels, sympathetic nervous system dysregulation, and increased proinflammatory factors, are likely to add to maladaptive health factors in increasing the risk of premature development of chronic illness (Katon, 2011).

Once chronic illness develops, comorbid depression is associated with poor self-care (DiMatteo et al., 2000; Lin et al., 2004) and increased risk of adverse outcomes (Lin et al., 2009; van Melle et al., 2004). As Figure A-1 shows, patients with comorbid depression and chronic medical illness often have problems collaborating with physicians and are less likely to adhere to self-care regimens (diet, cessation of smoking, exercise, and taking medications as prescribed) (Katon, 2011). These maladaptive patterns lead to a higher risk of medical complications, increased symptom burden, and worsening function, which can then in turn precipitate or worsen depressive episodes.

Extensive epidemiological data have shown that, after controlling for



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