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Opioid use disorder (OUD) is a heterogeneous disorder. However, there is a lack of deep phenotyping investigations focusing on important psychological constructs such as resilience that may impact OUD. The present study aimed to investigate the relationship between trait resilience and the five-factor model of personality (FFM) among individuals with opioid use disorder (OUD). We also explored whether the FFM and trait resilience form specific phenotypes associated with psychological functioning. This secondary analysis of an epigenetic study included participants of African ancestry ( n  = 72), an understudied population, who met DSM-5 criteria for OUD. Participants completed measures to assess personality traits, trait resilience, current and previous drug use, and psychological functioning (depression, anxiety, and stress). Linear regression revealed a significant relationship between resilience (CD-RISC-25 score) and the FFM,  R2  = 0.56,  F (5,62) = 15.7,  p &lt;.001. Further, a two-cluster classification emerged as the optimal solution from the cluster analysis. Cluster 1 ( n  = 33, 45.8% of the sample) showed lower resilience (CD-RISC-25 score:  M  = 58.6, SD = 11.2) compared to Cluster 2 ( n  = 35, 48.6%; CD-RISC-25 score:  M  = 76.1, SD = 11.9). The “High-Resilience Cluster” (Cluster 2) was characterized by higher FFM traits of: Extraversion, Openness, Agreeableness, and Conscientiousness, and lower Neuroticism versus Cluster 1. Multivariate analysis of variance revealed statistically significant differences between the two resilience clusters concerning other psychological symptoms,  Λ  = 0.732,  F (4, 50) = 7.05,  p  &lt; 0.003. These findings suggest associations between the FFM and trait resilience among individuals with OUD. Two distinct “resilience phenotypes” emerged, with high-resilience individuals displaying less stress, anxiety, and depressive symptoms. Results highlight the clinical importance of resilience as a potential target for intervention in people with OUD.

Resilience Phenotypes and Psychological Functioning among Individuals with Opioid Use Disorder