Environmentally derived subgroups of preadolescents with family history of substance use exhibit distinct patterns of psychopathology and reward-related behaviors: insights from the ABCD study

Srinivasan Anantha Ramakrishnan¹Riaz Shaik²Siddhartha Peri²Faith Adams²Shalaila Siobhán Haas²Sophia Frangou^2,3Shankar Srinivasan¹Omar El-Shahawy⁴Christopher Joseph Hammond⁵Iliyan Ivanov²Muhammad A Parvaz^2*

• ¹Department of Health Informatics, Rutgers - School of Health Professions, Piscataway, New Jersey, United States
• ²Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, United States
• ³University of British Columbia, Vancouver, British Columbia, Canada
• ⁴Langone Medical Center, New York University, New York City, New York, United States
• ⁵Johns Hopkins Medicine, Johns Hopkins University, Baltimore, Maryland, United States

Background: Family history of substance use (FHSU), along with sociodemographic and psychosocial factors, has been identified as a key risk factor for adolescent substance use and progression to substance use disorders (SUD). However, the interaction between distinct sociodemographic and psychosocial profiles in adolescents with FHSU and constitutional factors, such as psychopathological symptom severity, impulsivity, and reward processing, remains unclear. Given the complexity of these factors, it is crucial to explore how these elements contribute to the differential vulnerability to SUD among youth with family history of substance use. Particularly as, the identification of clinically relevant subgroups of at-risk youth may inform precision prevention and treatment approaches to reduce adverse outcomes related to SUDs. Methods: Here, we used data from the Adolescent Brain Cognitive Development (ABCD) study and grouped the participants (age: 9 – 10 years) into positive and negative FHSU [i.e., FHSU-P (n=1955; female 49.7%, White 57.95%), and FHSU-N (n=4369; female 48.33%, White 61.16%), respectively]. We used K-means clustering to identify latent subgroups in the FHSU-P population based on psychosocial variables and then compared the resulting subgroups on internalizing, externalizing, and total psychopathology, impulsivity, and reward prediction errors. Results: K-means clustering revealed five subgroups within FHSU-P: Subgroups 1 (n=744) and 2 (n=300) exhibited favorable psychosocial profiles, marked by higher school involvement, social engagement, and parental acceptance. Subgroups 3 (n=267), 4 (n=201), and 5 (n=443) were characterized by lower engagement across peer, school, and parental domains. Group comparisons showed that Subgroups 1 and 2 had comparable levels of psychopathology and impulsivity, while Subgroups 3, 4, and 5 displayed higher psychopathology and impulsivity. Reward prediction errors were similar across all subgroups. Other group differences are also presented and discussed in the main text. Conclusion: These findings highlight significant heterogeneity within the FHSU-P group and emphasize the importance of stratifying adolescents based on sociodemographic and psychosocial factors. Such stratification can help identify adolescents at higher risk for psychopathologies, including SUDs, offering insights for targeted prevention and intervention strategies.