2001). Broader models linking stress, HPA axis, and neurocognitive as well as cognitive and interpersonal factors, for example, are urgently needed. Limited integrative empirical approaches that include biological factors are emerging, including complex quantitative genetic, environmental, and personal factors (e.g., Kendler, Gardner, and Prescott, 2002, 2006) and gene-environment analyses (e.g., Caspi et al., 2003). Studies that link neuroendocrine, stress, and social-cognitive factors are particularly needed.

CO-OCCURRING DISORDERS

As this chapter has indicated, depression co-occurs with a host of stressful life events, early adversities, and ongoing strains, and it is also commonly associated with a variety of interpersonal difficulties and problematic traits and behavioral tendencies. A further complexity is introduced by the reality that depression typically does not occur in a “pure” form, independent of the effects of additional psychological disorders. In both the original U.S. National Comorbidity Study and the recent replication, of all the community residents who met the criteria for lifetime or 12-month major depression or both, approximately 75 percent had at least one other diagnosis, with only a minority having pure cases of depression (Kessler et al., 2003). For patients with a diagnosis of current major depression, only 40–45 percent had depression in isolation, and 60–65 percent had at least one comorbid diagnosis; similar rates have been reported in different countries (e.g., Blazer et al., 1994; De Graaf et al., 2002; Rush et al., 2005; Zimmerman, Chelminski, and McDermut, 2002).

Approximately 60 percent of comorbid disorders are anxiety disorders, particularly generalized anxiety disorder, panic disorder, social phobia, and posttraumatic stress disorders (Mineka, Watson, and Clark, 1998). Among patients with anxiety disorders, approximately 30 percent have a comorbid mood disorder (Brown et al., 2001). The onset of anxiety disorders typically precedes the onset of depression, with earlier-onset anxiety disorders (panic, social anxiety, generalized anxiety disorder) predicting the subsequent first onset of depression (Andrade et al., 2003; Kessler et al., 1996; Stein et al., 2001; but see Moffitt et al., 2007). So common is the overlap between depressive and anxiety disorders that some have argued that major depression and generalized anxiety disorder may virtually be the same disorder or closely associated, genetically mediated distress disorders (e.g., Kendler et al., 2007; Moffitt et al., 2007).

Besides anxiety disorders, substance abuse and alcoholism and eating disorders are frequently accompanied by depressive disorders, in both clinical and community samples (Rohde, Lewinsohn, and Seeley, 1991; Sanderson, Beck, and Beck, 1990; Swendsen and Merikangas, 2000). Several recent large epidemiological studies found rates of 25–30 percent for



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