Familial association of abstinent remission from alcohol use disorder in first‐degree relatives of alcohol‐dependent treatment‐seeking probands

Abstract

BACKGROUND AND AIMS Studies that have included family history of alcohol use disorder (AUD) as a predictor of remission from AUD have yielded few significant results. The goals of this study were to estimate the association of persistent AUD, non-abstinent remission and abstinent remission (“AUD/remission status”) in a proband with AUD/remission status in a relative and to test whether this association differed in related and unrelated proband-relative pairs. DESIGN High-risk family study of alcohol dependence. Probands were recruited from treatment settings and relatives were invited to participate. Baseline assessments occurred between 1991–1998 with follow-up between 1996–2005. Half of probands were matched with a biological 1st-degree relative with lifetime AUD (related group) and half of probands were paired with an unrelated individual with lifetime AUD (unrelated group). SETTING Brooklyn, New York; Indianapolis, Indiana; Iowa City, Iowa; San Diego, California; Farmington, Connecticut; and St. Louis, Missouri, USA. PARTICIPANTS 606 probands (25.7% female, mean age 37.7) with baseline and follow-up data and 606 of their 1st degree relatives who had lifetime AUDs (45.8% female, mean age 36.2). MEASUREMENTS Persistent AUD, non-abstinent remission, and abstinent remission were based on self-report interview data on most recent AUD symptoms and alcohol consumption. Dependent variable was relatives’ AUD/remission status. Independent variable was probands’ AUD/remission status. FINDINGS 34.6% of probands and 20.6% of relatives were abstinent and 11.1% of probands and 22.8% of relatives were in non-abstinent remission. AUD/remission status was significantly correlated in related (r=.23, p=.0037) but not in unrelated pairs. A significant interaction of probands’ abstinent remission with a variable representing related (versus unrelated, p=.003) pairs suggested a familial association for abstinent remission. In related pairs, individuals with an abstinent proband were more likely to be abstinent themselves than were individuals whose proband had persistent AUD (relative risk ratio=3.27, 95% CI=1.56–6.85, p=.002); this association was not significant in unrelated pairs. CONCLUSIONS The likelihood of abstinent remission among people with alcohol use disorder (AUD) appears to be more than 3 times greater for individuals who are related to an abstinent proband versus those related to a proband with persistent AUD.

A 22‐Year Follow‐Up (Range 16 to 23) of Original Subjects with Baseline Alcohol Use Disorders from the Collaborative Study on Genetics of Alcoholism

“…One potential desirable outcome for any age‐group is Abstinence, which is a goal for most AUD treatment programs, especially for people with alcohol dependence (Center for Behavioral Health Statistics and Quality, ; Probst et al., ), although this is a relatively narrow perspective on recovery. Another positive outcome involves extended periods of nonproblem drinking with quantities consumed that conform to National Institute on Alcohol Abuse and Alcoholism (NIAAA) guidelines for Low‐Risk Drinking (McCutcheon et al., ; Witkiewitz et al., ,b). On the other hand, adverse outcomes include exceeding Low‐Risk Drinking limits in the absence of multiple alcohol problems (High‐Risk Drinking), and drinking associated with multiple problems (Problem Drinking).…”

The Genetic Relationship Between Alcohol Consumption and Aspects of Problem Drinking in an Ascertained Sample

“…Fourth, we found little evidence for shared genetic overlap between weekly alcohol consumption and reduction/cessation of problematic drinking. Prior studies have identified candidate variants related to treatment‐dependent remission (e.g., Karpyak et al., ), and emerging evidence suggests high sibling concordance for abstinent remission (McCutcheon et al., ), suggesting heritable influences on the transition from active AUD to low‐risk drinking and abstinence. However, while PRS distinguished those without a lifetime history of DSM‐5 AUD from those with an active diagnosis or high‐risk drinking, they were unrelated to low‐risk drinking or abstinence in those with a lifetime history of DSM‐5 AUD.…”

“…An unordered categorical measure was created to represent 3 groups: (i) those who did not meet criteria for DSM‐5 AUD during their lifetime; (ii) individuals who had a lifetime history of DSM‐5 AUD and were current problematic drinkers due to an active AUD diagnosis in the past 12 months or were high‐risk drinkers (defined as men: ≥5 drinks/d or ≥15 drinks in 1 week; women: ≥4 drinks/d or ≥8 in 1 week; National Institute on Alcohol Abuse and Alcoholism, ); and (iii) those who had a lifetime history of AUD but had reduced/ceased their drinking and either did not report any AUD criteria (except craving), or were not high‐risk drinkers, or were abstinent from alcohol, all in the past 12 months (McCutcheon et al., ; Schuckit et al., ). A comparison of Group A against either Group B or Group C contrasts presence or absence of a lifetime diagnosis of DSM‐5 AUD, while the comparison of Group B and Group C stratifies those with a lifetime diagnosis into high‐risk drinkers, including those with active AUD, and low‐risk drinkers who may also be in abstinent remission.…”

“…A binary measure representing whether at least one of the biological parents of the respondent had a history of DSM‐5 AUD was used. Various sources of information were used to derive family history (e.g., parental interview, respondent report; see Bucholz et al., ; McCutcheon et al., , for details). Of the analytic sample, 1,656 individuals did not have a report on family history, and 485 individuals had a missing report on 1 parent while the other parent was confirmed to be family history negative.…”

Commentary on McCutcheon et al. (2017): Familial transmission of abstinent remission and social cognition

“…The paper by McCutcheon et al . is based on analyses of data from the COGA sample designed to answer an important question; namely, do heritable traits run in families that predict remission from alcohol use disorder (AUD)? Noting the lack of evidence that family history of AUD is useful in predicting outcome, the authors speculated that a separate set of traits related to remission in probands would be seen in relatives.…”