3.1. Overview of Cluster Analysis Results
As shown in , cluster analysis yielded a 6-cluster solution, with the following distribution of individuals (% of the total) across the 6 clusters: Cluster 1 [“Heavy, Cocaine Use Predominant,” N = 336 (24.1%)], Cluster 2 [“Heavy, Mixed Drug Injector,” N = 303 (21.8%)], Cluster 3 [“Heavy Cocaine Use, Later Onset,” N = 350 (25.1%)], Cluster 4 [“Moderate Cocaine and Opioid Use,” N = 258 (18.5%)], Cluster 5 [“Low Cocaine and Opioid Abuse,” N = 104 (7.5%)], and Cluster 6 [“Opioid Abuse,” N = 42 (3%)]. Comparison of the clusters on demographic features showed significant differences among clusters on age, sex, race, and marital status. Clusters 1 and 3 contain predominantly AA women who were never married. Cluster 2 has the oldest subjects, contains the fewest women, and, together with Clusters 5 and 6, the fewest AAs. Clusters 2 and 6 also contain the largest percentage of individuals who were divorced, separated, or widowed. Although Clusters 4, 5, and 6 are all roughly evenly divided by sex, with the majority of individuals in each having never married, these clusters differ substantially from one another on race, with Cluster 5 containing the largest proportion of Hispanics.
3.2. Features of Cocaine Use Behavior by Cluster
The clusters were clearly differentiated on cocaine use characteristics, cocaine-related effects, and on cocaine treatment history ().
Cocaine Use Characteristics, Cocaine-Related Effects, and Cocaine Treatment History by Cluster
3.2.1. Heavy Cocaine Use Clusters
Consistent with the prevalence of CD in the clusters, Clusters 1, 2, and 3 each included a high percentage of individuals who reported having used cocaine daily or almost daily (96.2%, 96.4% and 92.0%, respectively). However, members of Clusters 1 and 2 reported earlier ages of initial cocaine use and of heaviest use than members of Cluster 3. Members of Cluster 1 were more likely than those of Clusters 2 or 3 to endorse having gotten higher and stayed higher longer than others when they first started to use cocaine. With respect to other measures of cocaine-related effects, including adverse ones, Clusters 1 and 2 were comparable to one another and generally higher than all other clusters, including Cluster 3. Subjects in Clusters 1 and 2 were more likely than those in Cluster 3 to have received formal treatment for cocaine abuse, but comparable proportions of the three clusters reported ever having attended a self-help group meeting due to cocaine abuse.
Cluster 2 members were predominantly intravenous cocaine users who progressed to their periods of heaviest cocaine use sooner after initiating cocaine use than did the members of Clusters 1 or 3 (6.8 vs. 8.3 years for both Clusters 1 and 3). The high rate of intravenous drug use is consistent with the high rate of opioid dependence in this cluster.
As shown in , members of Cluster 3 were more likely than those in Clusters 4, 5, or 6 to endorse a variety of cocaine use characteristics and cocaine-related effects. However, Cluster 3 individuals reported a later age of initial cocaine use than did Cluster 4 members, and their heaviest use occurred later than it did for members of Clusters 4, 5, or 6.
3.2.2. Low-to-Moderate Cocaine Use Clusters
Although more than 90% of Cluster 4 members endorsed having used cocaine daily or almost daily, the prevalence of cocaine dependence was lower in this cluster than for the heavy cocaine use clusters. However, Cluster 4 had a higher prevalence of opioid dependence and a higher rate of intravenous cocaine use than did Clusters 1 or 3. More than one-third of Cluster 5 members met criteria for CD, though fewer than 3% endorsed daily or almost daily use of cocaine. However, more than 40% of this cluster met criteria for opioid dependence and nearly 20% endorsed intravenous cocaine use. Both Clusters 4 and 5 contained substantial proportions of individuals who endorsed cocaine-related effects and cocaine treatment histories.
3.2.3. Occasional or No Cocaine Use Cluster
Members of Cluster 6 reported the latest onset of both cocaine use and heavy cocaine use among the clusters. Cluster 6 also consistently had the lowest proportion of members who endorsed cocaine-related effects and cocaine treatment. However, this cluster had the second-highest prevalence of opioid dependence.
3.3. Substance Dependence and Psychiatric Disorders by Cluster
As can be seen in , more than 99% of individuals in Clusters 1-3 met lifetime DSM-IV diagnostic criteria for CD, a significantly higher percentage than that in Clusters 4, 5, or 6 (78%, 38%, and 7%, respectively, all significantly different from one another). Based on these findings and other characteristics described below, we identified these groups as Heavy Cocaine Use (Clusters 1-3), Low-to-Moderate Cocaine Use (Clusters 4 and 5), and Occasional or No Cocaine Use (Cluster 6) clusters.
Lifetime Prevalence of Substance Use and Psychiatric Disorders by Cluster [N (%)1]
Significant differences exist among the clusters on the lifetime prevalence of all other substance dependence diagnoses (). The Heavy Cocaine Use clusters showed a higher prevalence of nearly all substance dependence diagnoses than the other three clusters (which did not differ consistently from one another). Of the Heavy Cocaine Use clusters, Cluster 2 showed the highest prevalence of all categories of substance dependence, particularly opioid dependence; Clusters 4, 5, and 6 also showed a high prevalence of opioid dependence, despite having a lower prevalence of the other substance dependence diagnoses. The prevalence of cannabis dependence was highest in Clusters 1 and 2, with Clusters 3 and 4 being intermediate, and Clusters 5 and 6 having the lowest prevalence of this disorder.
Subjects in Clusters 1 and 2 also had the highest prevalence of major depressive episode (MDE), antisocial personality disorder (ASPD), and posttraumatic stress disorder (PTSD), with no consistent pattern of differences among the other clusters on these disorders. Differences in the prevalence of compulsive gambling, panic disorder, and agoraphobia showed a similar pattern, but were less pronounced, possibly due to the lower overall prevalence of these disorders.
Although not a co-morbid disorder, cocaine-induced paranoia (CIP) is a psychopathologic feature that occurs commonly among individuals with CD (Satel et al., 1991a
; Brady et al., 1991
; Rosse et al., 1995
; Bartlett et al., 1997
; Cubells et al., 2005
). There is evidence that CIP is genetically influenced (Gelernter et al., 1994
; Cubells et al., 2000
). The prevalence of CIP varied significantly across clusters in a pattern similar to the co-morbid substance use and psychiatric disorders (Cluster 1: 87.5%, Cluster 2: 78.2%, Cluster 3: 52.9%, Cluster 4: 38.4%, Cluster 5: 35.6%, Cluster 6: 4.8%) [□2(5)
= 295.8, p < 0.001].
3.4. Heritability of the Clusters
All of the clusters showed significant heritability, with the estimate for each of the first four clusters exceeding 30% (). Although the size of the clusters was not fully explained by their size, the two smallest clusters (Clusters 5 and 6) showed the lowest heritability estimates.
Heritability Estimates for the Clusters
3.5. Linkage Analysis of the Clusters
As reported previously, we (Gelernter et al., 2005
) conducted linkage analysis on a sub-sample of 986 individuals from the present study sample using CD diagnosis, CIP, and cluster membership as phenotypes. Interestingly, of the phenotypes examined (which included DSM-IV CD, CIP, and cluster membership), the strongest linkage results were observed for cluster membership. These findings included a lod score of 4.66 for membership in Cluster 1 on chromosome 12 (in EAs only) and a lod score of 3.35 for membership in Cluster 4 on chromosome 18 (in AAs only). In addition, there was suggestive evidence of linkage for Cluster 1 on chromosome 3 (in EAs only), for Clusters 1 or 3 on chromosome 6 (in the total sample), and for Cluster 3 on chromosome 2 (in AAs only).