Alcoholism is a complex, multidimensional disorder. A variety of typologic approaches have been used to categorize its diverse manifestations (Babor & Lauerman 1986
, Hesselbrock & Hesselbrock 2006
, Leggio et al. 2009
). Although more complex typologies have been proposed, the dichotomous typologies of Cloninger (1987)
and Babor et al. (1992)
have received considerable research attention, perhaps in part because they can readily be considered as moderators of treatment response. Cloninger (1987)
differentiated Type 1 and Type 2 alcoholics using family data from a Swedish adoption study in which the prevalence and characteristics of alcoholism were compared in offspring of biological and adoptive parents with alcoholism. Babor and colleagues (1992)
applied an empirical clustering technique to data obtained from alcoholics in treatment to differentiate two homogeneous subtypes: Type A and Type B. Cloninger’s Type 1 alcoholic shares with Babor’s Type A alcoholic a later onset of alcohol-related problems and the absence of antisocial characteristics. Cloninger’s Type 2 alcoholic shares with Babor’s Type B alcoholic an early onset of alcohol-related problems and the presence of antisocial characteristics, particularly when the individual is intoxicated.
Biological features have also been used to differentiate alcoholic subtypes. Buydens-Branchey et al. (1989a)
distinguished early-onset alcoholics (EOAs) from late-onset alcoholics (LOAs) admitted to a rehabilitation program. Among EOAs (who reported more frequent incarceration for violent crimes, more suicide attempts, and more frequent depression than LOAs), central serotonergic activity (i.e., measured as the ratio of plasma tryptophan to other amino acids competing for brain entry) was inversely related to depression and aggression. Swann et al. (1999)
found that individuals with low activity on this measure of serotonergic function were more anxious and had antisocial personality characteristics and an early age of onset of alcoholism. In another sample of recently abstinent alcoholics, EOAs also had a more severe course of alcoholism and a lower mean cerebrospinal fluid concentration of 5-hydroxyindoleacetic acid, the major serotonin metabolite, than LOAs (Fils-Aime et al. 1996
Considered together, these studies provide substantial empirical evidence for a dichotomous typology of alcoholism, a key dimension of which is age of alcoholism onset. Further, the pathologic mood and behavioral dimensions that distinguish EOAs from LOAs may reflect abnormalities in serotonergic neurotransmission. These differences may help explain why later-onset/lower vulnerability alcoholics show different responses than earlier-onset/higher vulnerability alcoholics to treatment with serotonergic medications (see Kenna 2010
for a comprehensive review), including selective serotonin reuptake inhibitors (Kranzler et al. 1996
, Pettinati et al. 2000
, Chick et al. 2004
) and the serotonin-3 receptor antagonist ondansetron (Johnson et al. 2000a
, Kranzler et al. 2003
Although both the subtyping approaches of Babor et al. (1992)
and Cloninger (1987)
are of theoretical interest, neither can be applied easily to patient care, as the cluster analytic approach demands a moderately large sample and is applied post hoc
and Cloninger’s approach does not categorize all patients (Lamparski et al. 1991
). However, age of onset alone may be a clinically meaningful approach to categorizing alcoholic subtypes (Irwin et al. 1990
; Johnson et al. 2000b
). Roache et al. (2008)
used a similar approach in a sample of patients participating in a placebo-controlled trial of ondansetron (Johnson et al. 2000a
) and obtained a 2-cluster solution similar to that obtained by Babor et al. (2002). The same patients were grouped into EOAs (onset at ≤ 25 years of age) or LOAs (onset at > 25 years of age) using a single question about the age at which drinking problems began. Seventy-two percent of high-risk/vulnerability (Type B) patients were EOAs and 67% of low-risk/vulnerability (Type A) patients were LOAs. Although Type B alcoholics had a better response to treatment with ondansetron than placebo, age of onset was a substantially better moderator of this response than the cluster-derived subtypes.
In a clinical trial of sertraline for alcohol dependence, Kranzler et al. (2011)
used the Structured Clinical Interview for DSM-IV (SCID, First et al. 2001
) to ascertain age of onset (early ≤ 25 years vs. late > 25 years) of alcohol dependence. This study showed differential effects of sertraline that were dependent upon the combination of age of onset and genotype (5-HTTLPR, S′ carriers vs. L′ homozygotes). They found that age of onset of alcohol dependence moderated the response to sertraline in L′ homozygotes, but not in S′ allele carriers. Among L′ homozygotes LOAs reported fewer drinking and heavy drinking days when treated with sertraline than placebo and EOAs showed the opposite effect.
In this study, we compared two additional alcoholic subtype categorization methods to the method employed by Kranzler et al. (2011)
. Specifically, we examined a cluster analytic classification (Babor et al. 2002) with one based on the age of onset of alcohol problems, which was determined using a single item. Based on the findings that the interaction of subtype by medication was significant only when conditioned on variation in the serotonin-transporter-linked promoter region (5-HTTLPR) (Kranzler et al. 2011
), we included genotype as a variable in the comparisons involving treatment outcome. Because in that prior study, the effect was limited to individuals with the L′L′ genotype, we anticipated that any differences would be limited to that genotype group.