Adverse childhood experiences (ACEs) have been demonstrated to be a risk factor for substance use disorder (SUD). We hypothesized that distrustfulness due to the accumulation of ACEs is the key psychological factor that drives those at risk to rely on substances of abuse, instead of healthy interpersonal relationships, to cope with negative emotions. To examine this hypothesis that addiction develops from distrustfulness created by ACEs, we carried out covariance structure analysis to clarify the mediating factors that link ACEs with the severity of SUD.
 Subjects: SUD patients who first visited the Kanagawa Psychiatric Center Addiction Clinic (Japan) between May 2015 and November 2016 were asked to complete a series of self-administered questionnaires, including 17 items concerning ACEs, the sense of trust scale, sense of rejection scale, sense of coherence (SOC) scale, Alcohol Use Disorders Identification Test (AUDIT), and Drug Abuse Screening Test (DAST-20). In total, 437 SUD patients were subject to our analysis, among whom 217 had alcohol use disorder (AUD) and 220 had drug use disorder (DUD); the mean age on admission was 48.2±10.5 years and 37.3±10.1 years, respectively.
 Method: Covariance structure analysis was performed to investigate the hypothetical model that the accumulation of ACEs increases distrustfulness and the sense of rejection in SUD patients, which in turn reduces the SOC.
 Results: In AUD patients, the sense of rejection was directly associated with the AUDIT score, whereas in DUD patients, the SOC scale was directly associated with the DAST score.
 The mediation analysis confirmed that in AUD patients, the positive association between ACEs and AUDIT score, and negative association between ACEs and SOC scale was partly mediated by distrustfulness and sense of rejection. In DUD patients, the positive association between ACEs and DAST score was partly mediated by distrustfulness, sense of rejection, and SOC.
 A high goodness of fit was obtained for each path model (AUD: goodness of fit index［GFI］=0.993, adjusted GFI［AGFI］=0.967, comparative fit index［CFI］=0.998, root mean square error of approximation［RMSEA］=0.029, DUD: GFI=0.993, AGFI=0.966, CFI=0.998, RMSEA=0.033).
 Conclusion: The present path model revealed that, in both AUD and DUD patients, the total number of ACEs was directly and positively associated with the degree of distrustfulness, sense of rejection, and AUDIT and DAST scores, whereas the SOC scale was not. The association between ACEs and the SOC scale was mediated by distrustfulness and the sense of rejection. The resulting psychological isolation may cause SUD patients to rely more on substances of abuse to cope with negative emotions, as reflected by the increased AUDIT and DAST scores. For AUD patients, the sense of rejection is a significant trigger for drinking behavior, whereas for DUD patients, the subjective feeling of incompetence in dealing with stresses may be a stronger trigger for drug use. The present analysis underscores the significance of childhood adverse experiences in the severity of SUD, and highlights the importance of supporting children and adolescents at risk as a substance abuse prevention strategy.
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