What the alcohol doctor ordered from the neuroscientist: Theragnostic biomarkers for personalized treatments.

Major advances in the neuroscientific understanding of alcohol actions have so far not translated into measurably improved clinical outcomes in alcoholism. Future treatment development should be guided by accumulating insights into a diverse range of biological mechanisms that maintain the pathophysiology of alcoholism in different individuals, but also at different points in time within any given patient. This biological diversity calls for the development and use of biological markers predictive of treatment response in the individual case, at the specific stage of the disease, here called "theragnostics." As novel therapeutic mechanisms and molecules targeting these mechanisms are discovered, the use of theragnostics will be critical for their successful clinical development, as well as their optimal subsequent clinical use. During clinical development, lest theragnostics are utilized, efficacy signals will risk remaining undetected when diluted in study populations that are not appropriately selected. Similarly, for treatments that reach approval, clinical acceptance, and optimal use will require the proper identification of responsive patients. Here, we discuss desirable properties of theragnostic biomarkers in alcohol addiction using two examples: alcohol-induced activation of brain reward circuitry as assessed using positron emission tomography of functional magnetic resonance imaging; and central glutamate tone, as assessed using MR spectroscopy.