Curiosity and Crisis

tion. It has been suggested that utilizing evidence-based medicine is the best way to integrate clinical research within medical practice [4, 5] . Although evidence-based medicine is built upon the triad of the best research evidence available, clinical expertise and patient values, the role of the clinician’s experience is related to the lowest level of evidence [6] . It is here where the chasm between research data and the clinical encounter begins. The hierarchy of evidence clearly denigrates clinical observations which are considered ‘unsystematic’ [7] . At the top of the evidence ladder are studies comparing large groups of similar individuals over a long period of time who experience different treatments or behaviors with carefully crafted randomized controlled trials next in importance. A problem in such trials is that the clinical researcher enrolls patients that best fi ts the prototype of the disorder under study. Using operationalized DSM categorization is commonly a defi ning characteristic. While this reduces variability, it also makes generalization of fi ndings less useful in real world practice [8] . One reason for this is that DSM categories often rely more on symptoms than behaviors. In mood disorders, it is often the behavior of self-harm or excessive health seeking more than the cognitive or physical aspects of the affective disorder that are diffi cult to treat. Often, self-harm behaviors exclude subjects from the randomized drug trial. Dr. Fava correctly observes that subgroups who do not achieve the desired clinical response in randomized trials are often ignored since the larger group is the focus of measure. The importance of such subgroups of patients has been expanded by Akiskal and Benazzi [9, 10] who fi nd substantial numbers Dr. Fava’s call to arms alerts us to the limits of our current clinical paradigms but directs us to new approaches that can overcome the intellectual plateau found in contemporary clinical research [1] . It is a paradox that increasing information from psychiatric research has led to this intellectual crisis. The great strides in molecular biology utilizing genetic probes and proteonomic strategies may offer exciting diagnostic and therapeutic opportunities. Reports by Caspi et al. [2] and Kendler et al. [3] suggest that individuals with a specifi c genetic polymorphism may be more vulnerable to stressful life events and thereby foster depressive disorders. Such fi ndings begin to challenge the false dichotomy of nature vs. nurture that has led to so many debates about medication vs. therapy or biology versus psychodynamic theories. The data in these studies reify the clinical imperative that clinicians must focus upon both biologic factors and developmental vicissitudes. Nevertheless, it is my impression that there is a gap between published clinical research and the practicing clinician. The focus of the clinical investigation is to answer a clinical problem via a hypothesis and rational scientifi c methodology that is well described and replicable. Comparing cohorts of individuals with similar clinical and demographic characteristics via group means of psychological (rating scales) or physical measures (i.e. imaging) is common. The ultimate goal of clinical studies is to explain mechanisms of disorders or demonstrate successful treatment interventions. The clinician, on the other hand, is confronted by the individual patient whose multiple symptoms and behaviors often defy easy explana-