Are Epigenetic Biomarkers an Indicator of the Severity of Addiction in Active Opiate Abusers? A Pilot Study

Study rationale Opioid use disorder (OUD) is a chronic and severe condition, defined by problematic opioid use, which results from interactions among sociological factors, psychiatric symptoms and life experiences, altogether determining OUD severity.

Recently, behavioral epigenetics has emerged as a possible strategy to help identify molecular mechanisms that may explain how these various interactions result in dysregulations affecting gene expression, brain function, and, ultimately, emotional regulation.

Here the investigators propose a pilot study as a first step towards a larger multidisciplinary project whose goal will be to characterize simultaneously major psychiatric and social factors in individuals with OUD, across a wide range of disease severity. In the present pilot study, the investigators propose to first characterize technical feasibility of the molecular investigations proposed in these 2 projects.

OUD severity The severity of OUD is well defined in the DSM-5 (2013), with 3 categories, from mild to severe, on the basis of the number of dimensional criteria met by patients (among 11 criteria). These criteria relate to the following main aspects: tolerance, the need to increase the amount of drugs to avoid withdrawal; psychic and physic withdrawal in case of substance discontinuation; social and interpersonal consequences of drug use; biological and psychic consequences of use; and craving, the irrepressible need to consume1. Here, the investigators postulate that molecular adaptations detected in the blood of OUD patients may represent biomarkers of this severity.

Epigenetic blood biomarkers A main limitation for conducting peripheral blood biomarker investigations in active opioid abusers comes from the fact that phlebotomies are reputedly difficult & potentially iatrogenic in these subjects, as they associate with external cues and trigger internal states that are closely related to drug consumption. To overcome this difficulty, we propose to test the hypothesis that sufficient DNA amounts can be recovered from fingerstick blood drops (corresponding to capillary blood, similar to sugar testing) to generate robust and reliable DNA methylation measures in the full human epigenome. In other words, the investigators assume that DNA methylation can be measured using capillary blood.

Objectives The investigators will first investigate in healthy volunteers whether the method consisting in collecting and analyzing small DNA amounts from capillary blood (fingerstick blood drops) retrieves DNA methylation measures for a number of CG dinucleotide sites (where DNA methylation occurs in the mammalian genome) that is comparable to that classically observed using veinous blood (phlebotomy). Second, the investigators will test the feasibility of measuring DNA methylation using capillary blood samples collected from patients with OUD.

To this purpose, the investigators propose to collect veinous and capillary blood samples from healthy volunteers, and capillary blood from opioid users.