The research program is dedicated to delineating genetic influences on behavior, including behavioral disorders. The program includes both human studies and genetic investigations of animal models for behavioral disorders. One investigation has been a genetic association study of bipolar (manic-depressive) disorder. A bipolar susceptibility gene has been localized to the peri-centromeric region of chromosome 18, and efforts are devoted to examining regional candidate genes for mutations which explain the linkage statistics.
Genetic dissection of a murine model for opioid addiction has revealed that most of the genetic variance in voluntary morphine intake is attributable to a locus on proximal chromosome 10, where the mu opioid receptor gene maps. This suggests that naturally-occurring variation in the mu opioid receptor gene influences voluntary morphine intake. Currently, we are examining two inbred strains of mice for genetic differences in the regulation of the mu opioid receptor gene. In a human extension of this research, the mu opioid receptor gene sequence is being examined among individuals on methadone maintenance for variations which may convey risk for opioid dependence. In an extension of the study of the mu opioid receptor gene in addictions, we are investigating mu opioid receptor interacting proteins for the roles they may play in human opioid dependence and in murine models of this addiction. We are examining the pharmacogenetics of naltrexone response among alcoholics, determining whether a functional mis-sense SNP (A118G, N40D) in the mu opioid receptor gene predicts therapeutic response among alcoholics.
We have also studied genetics of nicotine dependence, establishing a role for the alpha 3 and alpha 5 nicotinic receptor subunit genes in risk for nicotine addiction. The biological significance of the associated SNPs is being investigated.
We are studying genetics of anorexia nervosa, using a whole genome association approach.
Dr. Berrettini is an expert in using medications to help individuals suffering from unipolar and bipolar disorders.
Lohoff FW., Dahl JP., Ferraro TN., Arnold SE., Gallinat J., Sander T., Berrettini WH.: Variations in the vesicular monoamine transporter 1 gene (VMAT1/SLC18A1) are associated with bipolar i disorder. Neuropsychopharmacology 31(12): 2739-47, Dec 2006.
Crowley JJ., Brodkin ES., Blendy JA., Berrettini WH., Lucki I.: Pharmacogenomic evaluation of the antidepressant citalopram in the mouse tail suspension test. Neuropsychopharmacology 31(11): 2433-42, Nov 2006.
Corradi JP, Ravyn V, Robbins AK, Hagan KW, Bostwick R, Buono RJ, Berrettini
WH, Furlong ST: Alternative transcripts and evidence of imprinting of GNAL on
18p11.2, a region linked to schizophrenia and bipolar disorder displaying
parent-of-origin effects. Mol Psychiatry 10: 1017-25, November 2005.
Ferraro TN, Golden GT, Smith GG, Martin JF, Schwebel CL, Doyle GA, Buono RJ,
Berrettini WH: Confirmation of a major QTL influencing oral morphine intake in
C57 and DBA mice using reciprocal congenic strains. Neuropsychopharmacology
30: 742-6, 2005.
Berrettini W, Bierut L, Crowley TJ, Cybells JF, Frascella J, Gelernter J,
Hewitt JK, Kreek MH, Lachman H, Leppert M, Li MD, Lachman H, Leppert M, Li MD,
Madden P, Miner C, Pollock JD, Pomerleau O, Rice JP, Rutter JL, Shurtleff D,
Swan GE, Tischfield JA, Tsuang M, Uhl GR, Vanyukov M, Volkow N, Wanke K: Setting priorities for genomic research. Science 304: 1445-7, November 2004.
Oslin D, Berrettini WH, Kranzler HR, Pettinati H, Gelernter J, Volpicelli JR, O’Brien CP: A functional polymorphism in the mu opioid receptor gene is associated with therapeutic response in alcohol-dependent patients treated with naltrexone. Neuropsychopharmacol 28: 1546-52, 2003.
Berrettini WH: Are schizophrenic and bipolar disorders related: Review of family and molecular studies. Biological Psychiatry 48: 531-538, 2000.
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Last updated: 08/23/2012
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