PMID- 25680673 OWN - NLM STAT- MEDLINE DCOM- 20160901 LR - 20220317 IS - 1873-2402 (Electronic) IS - 0006-3223 (Print) IS - 0006-3223 (Linking) VI - 79 IP - 1 DP - 2016 Jan 1 TI - Common Polymorphisms in the Age of Research Domain Criteria (RDoC): Integration and Translation. PG - 25-31 LID - S0006-3223(15)00004-9 [pii] LID - 10.1016/j.biopsych.2014.12.020 [doi] AB - The value of common polymorphisms in guiding clinical psychiatry is limited by the complex polygenic architecture of psychiatric disorders. Common polymorphisms have too small an effect on risk for psychiatric disorders as defined by clinical phenomenology to guide clinical practice. To identify polymorphic effects that are large and reliable enough to serve as biomarkers requires detailed analysis of a polymorphism's biology across levels of complexity from molecule to cell to circuit and behavior. Emphasis on behavioral domains rather than clinical diagnosis, as proposed in the Research Domain Criteria framework, facilitates the use of mouse models that recapitulate human polymorphisms because effects on equivalent phenotypes can be translated across species and integrated across levels of analysis. A knockin mouse model of a common polymorphism in the brain-derived neurotrophic factor gene (BDNF) provides examples of how such a vertically integrated translational approach can identify robust genotype-phenotype relationships that have relevance to psychiatric practice. CI - Copyright (c) 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved. FAU - Glatt, Charles E AU - Glatt CE AD - Department of Psychiatry, Weill Cornell Medical College of Cornell University, New York, New York.. Electronic address: ceg2004@med.cornell.edu. FAU - Lee, Francis S AU - Lee FS AD - Department of Psychiatry, Weill Cornell Medical College of Cornell University, New York, New York.; Department of Pharmacology, Weill Cornell Medical College of Cornell University, New York, New York.; Sackler Institute for Developmental Psychobiology, Weill Cornell Medical College of Cornell University, New York, New York. LA - eng GR - P50 MH079513/MH/NIMH NIH HHS/United States GR - R01 NS052819/NS/NINDS NIH HHS/United States GR - MH079513/MH/NIMH NIH HHS/United States GR - NS052819/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20150108 PL - United States TA - Biol Psychiatry JT - Biological psychiatry JID - 0213264 RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM MH - Animals MH - *Behavior MH - Brain-Derived Neurotrophic Factor/genetics MH - Disease Models, Animal MH - Gene Knock-In Techniques MH - Humans MH - Mental Disorders/*diagnosis/*genetics MH - Mice MH - *Phenotype MH - *Polymorphism, Genetic PMC - PMC4496317 MID - NIHMS654279 OTO - NOTNLM OT - Anxiety OT - BDNF Val66Met OT - Behavioral dimension OT - Common polymorphism OT - Fear learning OT - Genetic biomarker COIS- The authors report no biomedical financial interests or potential conflicts of interest. EDAT- 2015/02/15 06:00 MHDA- 2016/09/02 06:00 PMCR- 2017/01/01 CRDT- 2015/02/15 06:00 PHST- 2014/10/28 00:00 [received] PHST- 2014/11/25 00:00 [revised] PHST- 2014/12/27 00:00 [accepted] PHST- 2015/02/15 06:00 [entrez] PHST- 2015/02/15 06:00 [pubmed] PHST- 2016/09/02 06:00 [medline] PHST- 2017/01/01 00:00 [pmc-release] AID - S0006-3223(15)00004-9 [pii] AID - 10.1016/j.biopsych.2014.12.020 [doi] PST - ppublish SO - Biol Psychiatry. 2016 Jan 1;79(1):25-31. doi: 10.1016/j.biopsych.2014.12.020. Epub 2015 Jan 8.