Mood and anxiety disorders are prevalent in all countries and cultures, which becomes obvious when standardized diagnostic and evaluation techniques are utilized. It is estimated that ~450 million people worldwide suffer from psychiatric illness. In the United States alone, epidemiologic research has identified that tens of millions of Americans suffer from major depressive disorder (MDD) annually, with many of them being in the prime of their adult lives. In addition to medical, personal, and social costs, depression is also believed to have a significant impact on work productivity. Further epidemiologic research indicates that nearly half of all individuals meeting lifetime criteria for MDD also have met criteria for a comorbid anxiety disorder. With an average age of 16 years for the onset of any lifetime anxiety disorder, anxiety disorders appear to predispose affected individuals to a substantial lifetime risk for MDD. In order to improve outcomes in depression and anxiety disorders, clinicians must enhance the entire process of recognition, diagnosis, and treatment.

The behavioral syndrome of trichotillomania (TTM) is well characterized, but challenges pertaining to TTM remain in several areas, including diagnostic classification, assessment of severity, and determination of relevance of comorbid psychiatric disorders. Acute pharmacological studies have focused on serotonin transport inhibitors, and preliminary evidence suggests that inhibition of both serotonin and norepinephrine transporters (ie, by clomipramine and venlafaxine) provides a clinical improvement. Dopamine antagonists are promising agents in need of systematic evaluation in TTM. Cognitive-behavioral therapy appears to achieve a decrease in acute symptoms in many patients. However, longitudinal maintenance of benefits has not been rigorously tested with either pharmacological or behavioral therapy. Clinical impressions and treatment data indicate that achieving durability of treatment benefits remains a major challenge in many patients with TTM, although there is evidence of improved outcome with comprehensive multimodal treatment.

The number of graduating psychiatry residents who choose a career in academic medicine is remarkably small, and the percentage who become National Institutes of Health (NIH)-funded investigators is even smaller. Although this trend for a reduced number of physician-scientists is true in all branches of medicine and has reached criticialproportions, the perception is that this shortage is even more severe in psychiatry. The purpose of this essay is to increase awareness of the problem and begin a discussion of the reasons why the field finds itself in this problematic situation.

First, however, it is important to more clearly define the nature of the problem. At the current time, NIH funding for research and training grants (Research Career Development Awards) has attained unprecedentedly high levels, with the percent of submitted applications that are funded higher than ever thought possible. Physicians who submit NIH grant applications are as successful as their PhD colleagues, dispelling the myth that physicians cannot compete with PhDs for such funding. Others have raised the question as to whether physicians are necessary or even desirable as investigators. In other words, the entire concept of a clinician-scientist is considered by some to be simply passé.

The concatenation of convergent lines of evidence from basic to clinical research continues to reveal that norepinephrine (NE) is a crucial regulator of a myriad of behaviors ranging from stress response to memory formation. Furthermore, many neuropsychiatric disorders involve neurocircuitry that is directly modulated by NE. This report summarizes the physiological roles of NE, as well as the main findings implicating a role for NE system dysfunction in mood and anxiety disorders, posttraumatic stress disorder, attention-deficit/hyperactivity disorder, and Alzheimer's disease. In each of these disorders, there appears to be a complex dysregulation of NE function, with changes in locus ceruleus firing, NE availability, and both pre- and postsynaptic receptor regulation. Many symptoms of these disorders are attributable to abnormalities within distributed neural circuits regulated by NE. Appreciation of NE's role in modulating the neural circuitry mediating cognition and affect should help elucidate the pathophysiology of a variety of neuropsychiatric disorders and the development of novel treatments.