title: The Need for Treatment Responsive Translational Biomarkers in Alcoholism Research.
abstract: Over the past two decades, major advances have been made in the basic neuroscience of alcohol addiction. However, few of these have been translated into clinically useful treatments, which remain limited. In the past decade, psychiatric drug development in general has been stalled, with many preclinically validated mechanisms failing in clinical development. Despite the existence of appealing preclinical models in the area of addictive disorders, drug development for these conditions has been impacted by the exodus of major pharma from psychiatric neuroscience. Here, we discuss translational biomarker strategies that may help turn this tide. Following an approach patterned on an endophenotype approach to complex behavioral traits, we hypothesize that relatively simple biological measures should be sought that can be obtained both in experimental animals and in humans, and that may be responsive to alcoholism medications. These biomarkers have to be tailored to the specific mechanism targeted by candidate medications and may in fact also help identify biologically more homogeneous subpopulations of patients. We introduce as examples alcohol-induced dopamine (DA) release, measures of central glutamate levels, and network connectivity, and discuss our experience to date with these biomarker strategies.
authors.affiliation: Center for Social and Affective Neuroscience, Department of Clinical and Experimental Medicine, Linköping University, SE-58183, Linköping, Sweden. mheilig@mail.nih.gov.
authors.forename: Markus
authors.initials: M
authors.lastname: Heilig
authors.affiliation: Institute of Psychopharmacology, Central Institute of Mental Health, Faculty of Medicine Mannheim, University of Heidelberg, Heidelberg, Germany.
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Sommer
authors.affiliation: Institute of Psychopharmacology, Central Institute of Mental Health, Faculty of Medicine Mannheim, University of Heidelberg, Heidelberg, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Spanagel
mesh_terms: D000437:Alcoholism / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016739:Behavior, Addictive / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D058068:Endophenotypes; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D057170:Translational Research, Biomedical
chemical_list: D015415:Biomarkers; D018698:Glutamic Acid; D004298:Dopamine
keywords: Alcohol endophenotype; Biomarker genetics glutamate; CRF naltrexone dopamine; Research domain criteria