nisms by which environmental factors (including behavioral therapy) might affect drug abuse, or the mechanisms by which genetic factors predispose to drug abuse.
Ultimately, brain imaging and neurobiological studies have a singular purpose—to better understand drug dependence and other neuropsychiatric disorders so that more effective treatments can be developed. In this scheme, studies in molecular and cellular neurobiology identify candidate neuropathic processes relevant to neuropsychiatric disorders. Such information is validated by the tools of behavioral neuroscience in animal models of the disorders. These studies in animals then direct human genetic studies aimed at identifying specific genes that contribute to the disorders in people. Identification of proteins relevant to the disorders directs brain imaging studies to examine the status of the proteins and related systems in patients' brains. Such knowledge then defines further clinical studies of the course and treatment of specific illnesses. Of course, insight evolving from the clinical work, including brain imaging, feeds back and informs ongoing preclinical studies of the underlying mechanisms involved.
The major psychiatric disorders associated with drug dependence are depression and personality disorders (see Chapter 5). Epidemiological data indicate that the rates of affective disorders among drug abusers are substantially higher than the expected rates of co-occurring disorders based in the general population (see Chapters 4 and 5). For example, lifetime rates of major depressive disorders range up to 50 percent in drug dependent patients compared with only 7 percent in a community sample (Rounsaville et al., 1982, 1987, 1991), and some form of drug abuse has been identified in more than 83 percent of individuals with personality disorders (Regier et al., 1990). Psychotic disorders, such as schizophrenia, represent only about 3 percent of drug abusers, but up to 50 percent of psychotic patients have addictive disorders.
The underlying neurobiology may differ for each of those disorders and for each drug of abuse. A number of neurochemical hypotheses are based largely on pharmacological interactions with these disorders or the symptoms of these disorders. For example, people with schizophrenia taking dopamine antagonists may use cocaine to relieve the antagonistinduced dysphoria, presumably because cocaine makes dopamine available to stimulate other dopamine receptors (e.g., D-1) that can also lead to euphoria. Another speculation about schizophrenia involves excitatory amino acids and PCP (phencyclidine) leading to psychotic illnesses (Javitt and Zukin, 1991). For depression, the underlying neurobiology is less