The simplistic monoamine depletion hypothesis as an explanation for major depression or any psychiatric disorder is rapidly undergoing critical re-evaluation and restructuring. Of course, it is illogical to think that one neurotransmitter is responsible for one diagnostic category. In addition, our categorical style of making diagnoses is imperfect. Perhaps major depressive disorder is the end-stage syndrome with a multitude of originating etiologies, both psychological and physiological. In addition, there is overlap, not only in illness comorbidity, but also overlap with one individual illness symptomatology and another based on DSM-IV criteria. A good example is major depressive disorder and post-traumatic stress disorder (PTSD). Both illnesses indeed frequently occur together in the same patient. Even though the criteria may seem to separate these diagnoses, in real clinical practice, it is unusual to make the diagnosis of PTSD in a treatment-seeking patient without also diagnosing major depression, given the extreme overlap in DSM-IV criteria. What do anxiety disorders and mood disorders have in common? Can it be that they are more similar than different and the specific symptom profile reflects different stages in the course or evolution of illness?
Indeed, a common clinical phenomenon is that what begins as an anxiety disorder typically evolves into a depressive disorder. In fact, patients with obsessive-compulsive disorder develop major depression in 95% of cases, with post-traumatic stress disorder in about 85% of cases, and with panic disorder in over 50% of cases.13 The converse is not generally true. In other words, patients who begin their psychiatric morbidity with a diagnosis of major depressive disorder do not tend to proceed to develop panic disorder or obsessive-compulsive disorder in any great proportion. Thus, in many patients, depression and anxiety represent different phases of the same disease process. This may help to explain the similarities in clinical findings of serotonergic abnormalities in patients' anxiety and mood disorders prior to treatment, and the therapeutic response of patients with anxiety and mood disorders to serotonergic agents.
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