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Aims: We performed a latent class analysis (LCA) in a sample ascertained for addiction phenotypes to investigate cocaine use disorder (CoUD) subgroups related to polysubstance addiction (PSA) patterns and characterized their differences with respect to psychiatric and somatic comorbidities. Design: Cross-sectional study Setting: United States Participants: Adult participants aged 18-76, 39% female, 47% African American, 36% European American with a lifetime DSM-5 diagnosis of CoUD (N=7,989) enrolled in the Yale-Penn cohort. The control group included 2,952 Yale-Penn participants who did not meet for alcohol, cannabis, cocaine, opioid, or tobacco use disorders. Measurements: Psychiatric disorders and related traits were assessed via the Semi-structured Assessment for Drug Dependence and Alcoholism. These features included substance use disorders (SUD), family history of substance use, sociodemographic information, traumatic events, suicidal behaviors, psychopathology, and medical history. LCA was conducted using diagnoses and diagnostic criteria of alcohol, cannabis, opioid, and tobacco use disorders. Findings: Our LCA identified three subgroups of PSA (i.e., low, 17%; intermediate, 38%; high, 45%) among 7,989 CoUD participants. While these subgroups varied by age, sex, and racial-ethnic distribution (p<0.001), there was no difference in education or income (p>0.05). After accounting for sex, age, and race-ethnicity, the CoUD subgroup with high PSA had higher odds of antisocial personality disorder (OR=21.96 vs. 6.39, difference-p=8.08e-6), agoraphobia (OR=4.58 vs. 2.05, difference-p=7.04e-4), mixed bipolar episode (OR=10.36 vs. 2.61, difference-p=7.04e-4), posttraumatic stress disorder (OR=11.54 vs. 5.86, difference-p=2.67e-4), antidepressant medication use (OR=13.49 vs. 8.02, difference-p=1.42e-4), and sexually transmitted diseases (OR=5.92 vs. 3.38, difference-p=1.81e-5) than the low-PSA CoUD subgroup. Conclusions: We found different patterns of PSA in association with psychiatric and somatic comorbidities among CoUD cases within the Yale-Penn cohort. These findings underscore the importance of modeling PSA severity and comorbidities when examining the clinical, molecular, and neuroimaging correlates of CoUD.

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Background: Accumulating data suggest that the symptom structure of posttraumatic stress disorder (PTSD) may be more nuanced than proposed by prevailing nosological models. Emerging theory further suggests that an 8-factor model with separate internally- (e.g., flashbacks) and externally- (e.g., trauma cue-related emotional reactivity) generated intrusive symptoms may best represent PTSD symptoms. To date, however, scarce research has evaluated the fit of this model and whether index traumas are differentially associated with it in populations at high risk for trauma exposure, such as military veterans. Methods: Data were analyzed from a nationally representative sample of 3,847 trauma-exposed U.S. military veterans who participated in the National Health and Resilience in Veterans Study. Confirmatory factor analyses were conducted to evaluate PTSD symptom structure.Results: The 8-factor model fit the data significantly better than the 7-factor hybrid and 4-factor DSM-5 models. Combat exposure and harming others were more strongly associated with internally-generated intrusions, while interpersonal violence and disaster/accident showed stronger significant associations with externally-generated intrusions.Limitations: The 8-factor model requires validation in non-veteran and more diverse populations, as well as with clinician-administered interviews. Conclusions: Findings support an 8-factor model of PTSD symptoms that separates out internally- and externally-generated intrusions. They also provide preliminary evidence that certain index traumas may lead to differential expression of these intrusive symptoms. Results support that PTSD symptoms may be better characterized by a more nuanced phenotypic structure, which is differentially linked to index traumas.