From research of mental disorders to clinical application - lessons from diabetes.

We are facing a crisis of translation of research into clinical application in psychiatry. Most diagnoses are thus still observer-based in clinical practice (rather than being based on objective neuronal and/or psychological markers). Moreover, therapy is often based on trial and error, hence the look toward research that may yield biomarkers for both objective diagnosis and therapeutic monitoring and guidance beyond trial and error. However, most research, including brain imaging and molecular, genetic and biochemical research, has not yet led to biomarkers for clinical diagnosis and therapy. We seem to miss some key ingredient that links basic pathophysiological mechanisms to the various symptoms in a symptomor disease-specific way. I here propose that the missing link is what the early psychiatrist Eugène Minkowski described as basic or generative disturbance1: rather than being the main cause, the basic or generative disturbance operates at an intermediate level, which is key in generating those pathophysiological mechanisms that drive and lead to the various psychopathological symptoms. Let me first draw an analogy and comparison of mental disorders with another disorder, diabetes mellitus (DM).