Do DSM-5 substance use disorder criteria differ by user care settings? An item response theory analysis approach.

AIM: To examine differences in the psychometric characteristics of diagnostic criteria for Substance Use Disorders (SUD) between substance users in harm reduction settings (HR) and substance users seeking treatment (Tx). METHODS: Differential Item and Test Functioning (DIF & DTF) analysis were performed to examine differences in the difficulty of endorsement and in discrimination of the 11 diagnostic criteria and to test if the criteria set as a whole (the "test") functioned differently by care settings (Tx vs. HR) for alcohol, cocaine, cannabis, opiates and tobacco. To test uniform and nonuniform DIF, multiple indicator multiple cause (MIMIC) structural equation models were used. RESULTS: Regardless of the substance, the DSM-5 criteria "craving", "large amount", "time spent", "tolerance" and "activities given up" had similar functioning by care settings. Little evidence for DIF was found for other criteria. The criteria set as a whole did not function differently by care settings for alcohol, cocaine and tobacco. At the same trait severity, compared to HR, the Tx subgroup had a greater number of endorsed criteria for cannabis and a smaller number of endorsed criteria for opioids. CONCLUSION: The unidimensionality of the 11 DSM-5 criteria and applicability of all criteria and diagnosis was confirmed in this large sample of problematic substance users. While the majority of the criteria related to loss of control of substance use, functioned well in both care settings, the criteria related to consequences of substance use had several differential functioning.

Kappa opioid receptor antagonism and chronic antidepressant treatment have beneficial activities on social interactions and grooming deficits during heroin abstinence.

Addiction is a chronic brain disorder that progressively invades all aspects of personal life. Accordingly, addiction to opiates severely impairs interpersonal relationships, and the resulting social isolation strongly contributes to the severity and chronicity of the disease. Uncovering new therapeutic strategies that address this aspect of addiction is therefore of great clinical relevance. We recently established a mouse model of heroin addiction in which, following chronic heroin exposure, 'abstinent' mice progressively develop a strong and long-lasting social avoidance phenotype. Here, we explored and compared the efficacy of two pharmacological interventions in this mouse model. Because clinical studies indicate some efficacy of antidepressants on emotional dysfunction associated with addiction, we first used a chronic 4-week treatment with the serotonergic antidepressant fluoxetine, as a reference. In addition, considering prodepressant effects recently associated with kappa opioid receptor signaling, we also investigated the kappa opioid receptor antagonist norbinaltorphimine (norBNI). Finally, we assessed whether fluoxetine and norBNI could reverse abstinence-induced social avoidance after it has established. Altogether, our results show that two interspaced norBNI administrations are sufficient both to prevent and to reverse social impairment in heroin abstinent animals. Therefore, kappa opioid receptor antagonism may represent a useful approach to alleviate social dysfunction in addicted individuals.

Dissociation of heroin-induced emotional dysfunction from psychomotor activation and physical dependence among inbred mouse strains.

RATIONALE: Opiate addiction is a brain disorder emerging through repeated intoxication and withdrawal episodes. Epidemiological studies also indicate that chronic exposure to opiates may lead in susceptible individuals to the emergence of depressive symptoms, strongly contributing to the severity and chronicity of addiction. We recently established a mouse model of heroin abstinence, characterized by the development of depressive-like behaviors following chronic heroin exposure. OBJECTIVES: While genetic factors regulating immediate behavioral responses to opiates have been largely investigated, little is known about their contribution to long-term emotional regulation during abstinence. Here, we compared locomotor stimulation and physical dependence induced by heroin exposure, as well as emotional dysfunction following abstinence, across mice strains with distinct genetic backgrounds. METHODS: Mice from three inbred strains (C57BL/6J, Balb/cByJ, and 129S2/SvPas) were exposed to an escalating chronic heroin regimen (10-50 mg/kg). Independent cohorts were used to assess drug-induced locomotor activity during chronic treatment, naloxone-precipitated withdrawal at the end of chronic treatment, and emotional-like responses after a 4-week abstinence period. RESULTS: Distinct behavioral profiles were observed across strains during heroin treatment, with no physical dependence and low locomotor stimulation in 129S2/SvPas. In addition, different behavioral impairments developed during abstinence across the three strains, with increased despair-like behavior in 129S2/SvPas and Balb/cByJ, and low sociability in 129S2/SvPas and C57BL/6J. CONCLUSIONS: Our results indicate that depressive-like behaviors emerge during heroin abstinence, whatever the severity of immediate behavioral responses to the drug. In addition, inbred mouse strains will allow studying several aspects of mood-related deficits associated with addiction.