Genetic overlap and causality between substance use disorder and attention‐deficit and hyperactivity disorder

Abstract

Substance use disorder (SUD) often co-occur at high prevalence with other psychiatric conditions. Among them, attention-deficit and hyperactivity disorder (ADHD) is present in almost one out of every four subjects with SUD and is associated with higher severity, more frequent polysubstance dependence and increased risk for other mental health problems in SUD patients. Despite studies suggesting a genetic basis in the co-occurrence of these two conditions, the genetic factors involved in the joint development of both disorders and the mechanisms mediating these causal relationships are still unknown. In this study, we tested whether the genetic liability to five SUD-related phenotypes share a common background in the general population and clinically diagnosed ADHD individuals from an in-house sample of 989 subjects and further explored the genetic overlap and the causal relationship between ADHD and SUD using pre-existing GWAS datasets. Our results confirm a common genetic background between ADHD and SUD and support the current literature on the causal effect of the liability to ADHD on the risk for SUD. We added novel findings on the effect of the liability of lifetime cannabis use on ADHD and found evidence of shared genetic background underlying SUD in general population and in ADHD, at least for lifetime cannabis use, alcohol dependence and smoking initiation. These findings are in agreement with the high comorbidity observed between ADHD and SUD and highlight the need to control for substance use in ADHD and to screen for ADHD comorbidity in all SUD patients to provide optimal clinical interventions.

The Burden of Undiagnosed Adults With Attention-Deficit/Hyperactivity Disorder Symptoms in Japan: A Cross-Sectional Study

“…In terms of health characteristics, previous studies have reported a higher risk of substance use and dependence, for example, consumption of alcohol and smoking, in patients with ADHD [32,33]. In addition, a possible genetic basis for the co-occurrence of substance use disorder and ADHD has been reported [34].…”

“…In terms of health characteristics, previous studies have reported a higher risk of substance use and dependence, for example, consumption of alcohol and smoking, in patients with ADHD [ 32 , 33 ]. In addition, a possible genetic basis for the co-occurrence of substance use disorder and ADHD has been reported [ 34 ]. Our study findings supported this, though fewer ASRS+ respondents reported currently drinking alcohol, alcoholism occurred at an approximately 4-36-fold greater rate among ASRS-positive respondents compared to ASRS-negative respondents.…”

Effects of family history of substance use disorder on reward processing in adolescents with and without attention‐deficit/hyperactivity disorder

“…Genome‐wide association studies (GWAS) have shown shared genetic liability between ADHD and substance use 6,7 . Recent Mendelian randomization studies have also revealed a causal pathway from liability for ADHD to tobacco and cannabis use, but evidence for causal effects on SUD is not conclusive 8–12 . ADHD and SUD patients also show many similarities at (endo)phenotypic level.…”

Genomics and epigenomics of substance use disorders: An introduction

“…This special issue includes a total of seven works (Cabrera-Mendoza et al, 2021;Gerring, Vargas, Gamazon, & Derks, 2020;Lai et al, 2020;Maldonado et al, 2021;Markunas et al, 2020;Soundararajan et al, 2021;Vilar-Rib o et al, 2020) that cover different topics on the genomics and epigenomics of SUD, one of them a review and the rest original research articles.…”

“…Vilar‐Ribó et al (2020) address the important topic of genetic overlap in psychiatric disorders. They use different tools to explore the shared genetics between SUD and attention‐deficit hyperactivity disorder (ADHD), two conditions that are frequently comorbid.…”