title: Effects of depressive symptoms and peripheral DAT methylation on neural reactivity to alcohol cues in alcoholism.
abstract: In alcohol-dependent (AD) patients, alcohol cues induce strong activations in brain areas associated with alcohol craving and relapse, such as the nucleus accumbens (NAc) and amygdala. However, little is known about the influence of depressive symptoms, which are common in AD patients, on the brain's reactivity to alcohol cues. The methylation state of the dopamine transporter gene (DAT) has been associated with alcohol dependence, craving and depression, but its influence on neural alcohol cue reactivity has not been tested. Here, we compared brain reactivity to alcohol cues in 38 AD patients and 17 healthy controls (HCs) using functional magnetic resonance imaging and assessed the influence of depressive symptoms and peripheral DAT methylation in these responses. We show that alcoholics with low Beck's Depression Inventory scores (n=29) had higher cue-induced reactivity in NAc and amygdala than those with mild/moderate depression scores (n=9), though subjective perception of craving was higher in those with mild/moderate depression scores. We corroborated a higher DAT methylation in AD patients than HCs, and showed higher DAT methylation in AD patients with mild/moderate than low depression scores. Within the AD cohort, higher methylation predicted craving and, at trend level (P=0.095), relapse 1 year after abstinence. Finally, we show that amygdala cue reactivity correlated with craving and DAT methylation only in AD patients with low depression scores. These findings suggest that depressive symptoms and DAT methylation are associated with alcohol craving and associated brain processes in alcohol dependence, which may have important consequences for treatment. Moreover, peripheral DAT methylation may be a clinically relevant biomarker in AD patients.
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Laboratory of Neuroimaging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Wiers
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Laboratory of Neuroimaging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: E
authors.initials: E
authors.lastname: Shumay
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Laboratory of Neuroimaging, National Institutes of Health, Bethesda, MD, USA.|National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA.
authors.forename: N D
authors.initials: ND
authors.lastname: Volkow
authors.affiliation: Department of Psychiatry, Socialpsychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Frieling
authors.affiliation: Department of Psychiatry, Socialpsychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Kotsiari
authors.affiliation: Salus Clinic, Lindow, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Lindenmeyer
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.|Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Walter
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.|Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Bermpohl
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000150:complications / Q000378:metabolism; D000679:Amygdala / Q000503:physiopathology*; D066249:Craving / Q000502:physiology; D003463:Cues; D003863:Depression / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008745:Methylation; D008875:Middle Aged; D009714:Nucleus Accumbens / Q000503:physiopathology*; D065840:Protective Factors; D011569:Psychiatric Status Rating Scales; D055502:Secondary Prevention; D013223:Statistics as Topic
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D000431:Ethanol