Lost in translation: toward clinically effective translational research

Despite the increased access to and variety of psychotropic drugs available for treatment of mood and anxiety disorders, the prevalence of these disorders is still rising, indicating that current treatment approaches are broadly ineffective. We suggest that this inefficacy is due in large part to the current approach to translational research between neuroscience and psychiatry. Animal models aim to replicate, as closely as possible, the symptoms of disorders observed in people. These models are then used to assess genetic susceptibilities and neurophysiological and cellular underpinnings of functional impairments and to search for observable biomarkers and druggable targets. At the same time, clinical work is focused on symptom diagnosis and management, often relying on the same druggable targets that have been fed up the translational chain. This approach has in large part resulted from psychiatry's historical medicalization of mental illness that encourages both basic and clinical researchers to limit the search to treatable biological causes for mood disorders, often based on a single chemical or neurotransmitter explanation. By reviewing results from both animal and patient studies, we show that the methods and diagnostic frameworks employed do not adequately capture either the symptoms of disorders of interest or the effects of drugs measured in animal models, or the development, life course, and trajectory of mood disorders in people. This failure results in a bidirectional self-reinforcing cycle of inefficacy of translational research. We suggest that a focus on the environmental, social and psychological context in which mood disorders arise and are treated is crucial to developing truly translational models and research strategies.