Increased mesolimbic cue-reactivity in carriers of the mu-opioid-receptor gene OPRM1 A118G polymorphism predicts drinking outcome: a functional imaging study in alcohol dependent subjects.
The endogenous opioid system is involved in the pathophysiology of alcohol-use disorders. Genetic variants of the opioid system alter neural and behavioral responses to alcohol. In particular, a single nucleotide polymorphism rs1799971 (A118G) in the mu-opioid receptor gene (OPRM1) is suggested to modulate alcohol-related phenotypes and neural response in the mesocorticolimbic dopaminergic system. Little is known about the clinical implications of these changes. The current study investigated the relationship of genotype effects on subjective and neural responses to alcohol cues and relapse in a sample of abstinent alcohol-dependent patients. Functional magnetic resonance imaging (fMRI) was used to investigate alcohol cue-reactivity and drinking outcome of 81 abstinent alcohol-dependent patients. G-allele carriers displayed increased fMRI cue-reactivity in the left dorsal striatum and bilateral insulae. Neural responses to alcohol cues in these brain regions correlated positively with subjective craving for alcohol and positive expectations of alcohol׳s effects. Moreover, alcohol cue-reactivity in the left dorsal striatum predicted time to first severe relapse. Current results show that alcohol-dependent G-allele carriers׳ increased cue-reactivity is associated with an increased relapse risk. This suggests that genotype effects on cue-reactivity might link the OPRM1 A118G risk allele with an increased relapse risk that was reported in earlier studies. From a clinical perspective, risk-allele carriers might benefit from treatments, such as neuro-feedback or extinction-based therapy that are suggested to reduce mesolimbic reactivity.
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Square J5, D-68159 Mannheim, Germany. Electronic address: patrick.bach@zi-mannheim.de.
Patrick
P
Bach
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Square J5, D-68159 Mannheim, Germany.
Sabine
S
Vollsta Dt-Klein
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Square J5, D-68159 Mannheim, Germany.
Martina
M
Kirsch
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Square J5, D-68159 Mannheim, Germany.
Sabine
S
Hoffmann
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Square J5, D-68159 Mannheim, Germany.
Anne
A
Jorde
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Germany.
Josef
J
Frank
Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin, Germany.
Katrin
K
Charlet
Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin, Germany.
Anne
A
Beck
Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin, Germany.
Andreas
A
Heinz
Division of Mind and Brain Research, Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin, Germany.
Henrik
H
Walter
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Square J5, D-68159 Mannheim, Germany; Institute of Psychopharmacology, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Germany.
Wolfgang H
WH
Sommer
Institute of Psychopharmacology, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Germany.
Rainer
R
Spanagel
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Germany.
Marcella
M
Rietschel
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Square J5, D-68159 Mannheim, Germany.
Falk
F
Kiefer
D000293:Adolescent; D000328:Adult; D000368:Aged; D064829:Alcohol Abstinence; D019973:Alcohol-Related Disorders / Q000235:genetics* / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D003463:Cues; D005260:Female; D005500:Follow-Up Studies; D060005:Genotyping Techniques; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D017450:Receptors, Opioid, mu / Q000235:genetics*; D016019:Survival Analysis; D055815:Young Adult
C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu
Alcoholism; Endogenous opioids; OPRM1; Relapse; Single nucleotide polymorphism; fMRI