Translating from neuroscience to psychiatry (and back translating from psychiatry to neuroscience)

In this issue of Acta Psychiatrica Scandinavica, several articles appear (1–5) that signal a new era in publishing in this distinguished journal. Known for decades as a journal with a solid clinical orientation, in recent years, Acta Psychiatrica Scandinavica added a very popular feature, ‘clinical overviews’ that summarize important clinical topics for the clinical reader. Acta Psychiatrica Scandinavica is now embarking on publishing another new feature for the clinical reader, namely ‘translational articles’. What are translational articles? Literally, their purpose is to ‘translate’ preclinical neuroscience findings for the clinician, showing how they are clinically relevant. Sometimes, the ideas and jargon of science are literally expressed in a different language from clinical vocabulary, and this can amount to a barrier that delays the permeation of new concepts from the laboratory to the bedside. Translational articles seek to breakdown these barriers by showing how neuroscience concepts can inform and neurobiologically empower the practicing clinician. Translational articles also generate ideas for new proof of preclinical concept studies in man by clinical investigators. Translation is actually a two-way street: Successful clinical articles also elucidate clinical problems and unmet needs that neurobiologists can take from the bedside back to the laboratory to explore and ultimately attempt to clarify and explain. Thus, preclinical neurobiologists can benefit from explanations of clinical vocabulary and jargon in a way that stimulates new preclinical models and tests of disease concepts and treatments. In this issue of Acta Psychiatrica Scandinavica, a preclinical article and several clinical articles aim at elucidating the role of serotonin in numerous cognitive and behavioral aspects of attention deficit hyperactivity disorder (ADHD) by utilizing a translational tool, namely acute tryptophan depletion (6–8). The preclinical article (1) introduces a new idea about this test, which is known to reduce brain serotonin synthesis and deplete brain serotonin transiently (6–8). These investigators propose that perhaps the effects of acute tryptophan depletion might be mediated by reductions in cerebral blood flow (1). This has implications for explaining the effects of acute tryptophan depletion in patients with ADHD (2–5). That is, serotonin has wellestablished links to aggression (9), and thus, the changes in aggressive behavior of ADHD patients after acute tryptophan depletion (2) might be explained not only by reductions in serotonin levels (6–8) but also by changes in cerebral blood flow (1). Acute tryptophan depletion alters some measures of attention in ADHD (6) but not of verbal declarative memory (7) nor perception of affective prosody (8) in the articles reported in this issue. Does this mean that aggression and attention but not memory or perception are mediated by serotonin? This depends upon whether acute tryptophan depletion is essentially a technique that only reduces serotonin levels, or has other effects such as changes in cerebral blood flow. Such a question requires more analysis of what acute tryptophan depletion is doing in the brain (back translation to animal models). These results overall stimulate not only attempts to replicate them in ADHD but also to see whether aggression and attention are regulated by serotonin in conditions other than ADHD (forward translation). The point here is not really the specifics of these studies nor even whether their results are right or wrong. Remembering the teachings of Karl Popper, the same can be said of the value of translational articles: Their value is not really whether their hypotheses are right or wrong; their value is in their ability to generate attempts to prove or refute the ideas proposed. This is what gets us rapidly to the truth and is really what science is all about.