title: Family history of alcoholism is related to increased D2/D3receptor binding potential: a marker of resilience or risk?
abstract: The aim of this study was to examine the relationship between family history of alcohol use disorder and striatal dopamine using positron emission tomography imaging. Participants were 84 healthy, 18- to 30-year-old, social drinkers recruited via fliers and newspaper advertisements. At assessment, participants completed measures of lifetime personal and family substance use and psychiatric symptoms. Participants underwent two consecutive positron emission tomography scans using the D2/D3dopamine receptor radioligand [11C]raclopride. Scans were preceded by intravenous saline and amphetamine 0.3 mg/kg, providing measures of baseline [11C]raclopride binding potential (BPND) and change in [11C]raclopride (ΔBPND). Subjective ratings of stimulant drug effects were collected during scans. Subjects were classified as family history positive (FHP) if they reported any first-degree relative with alcohol use disorder (AUD) and family history negative (FHN) if no first-degree relatives had history of AUD. Participants were predominantly White (69.0 percent) and male (62.1 percent). Baseline [11C]raclopride BPNDwas generally higher in FHP compared with FHN subjects across striatal subdivisions. There were no differences in ΔBPNDacross regions. Negative subjective drug effects were more pronounced in FHP than in FHN subjects. While FHN subjects evidenced the expected positive relationship between ΔBPNDand positive subjective drug effects, this relationship was disrupted in FHP subjects. There are key differences in dopamine status and subjective stimulant drug experiences as a function of family AUD history. These findings have important implications for understanding risk for AUD development in FHP offspring.
authors.affiliation: Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Anika A H
authors.initials: AA
authors.lastname: Alvanzo
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Gary S
authors.initials: GS
authors.lastname: Wand
authors.affiliation: Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kuwabara
authors.affiliation: Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.|Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Dean F
authors.initials: DF
authors.lastname: Wong
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: McCaul
mesh_terms: D000293:Adolescent; D000328:Adult; D000437:Alcoholism / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D005192:Family Health / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D055500:Resilience, Psychological; D012306:Risk; D055815:Young Adult
chemical_list: D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3
keywords: Alcohol use disorder; amphetamine; dopamine release; family history; mesolimbic dopamine; positron emission tomography (PET)