Genetic overlap and causality between substance use disorder and attention-deficit and hyperactivity disorder.

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.

Epigenome-wide association study of attention-deficit/hyperactivity disorder in adults.

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder that often persists into adulthood. There is growing evidence that epigenetic dysregulation participates in ADHD. Given that only a limited number of epigenome-wide association studies (EWASs) of ADHD have been conducted so far and they have mainly focused on pediatric and population-based samples, we performed an EWAS in a clinical sample of adults with ADHD. We report one CpG site and four regions differentially methylated between patients and controls, which are located in or near genes previously involved in autoimmune diseases, cancer or neuroticism. Our sensitivity analyses indicate that smoking status is not responsible for these results and that polygenic risk burden for ADHD does not greatly impact the signatures identified. Additionally, we show an overlap of our EWAS findings with genetic signatures previously described for ADHD and with epigenetic signatures for smoking behavior and maternal smoking. These findings support a role of DNA methylation in ADHD and emphasize the need for additional efforts in larger samples to clarify the role of epigenetic mechanisms on ADHD across the lifespan.

The Impact of Emotional Lability Symptoms During Childhood in Adults With ADHD.

OBJECTIVE: To determine whether emotional lability (EL) in adult ADHD patients can already be identified during their childhood and the extent to which this childhood symptomatology can predict EL in adulthood. METHOD: Seven hundred eighteen adults with ADHD were examined. EL in adulthood was assessed using the Conners' Adult ADHD Rating Scales (CAARS). According to Conners' definition of EL, seven items from the Wender Utah Rating Scale (WURS) were used to determine this symptomatology in childhood. RESULTS: EL was identified in 31.1% of the participants, and 29.6% of this subgroup reported EL symptoms in childhood. Childhood EL was the strongest predictor of these symptoms in adulthood (odds ratio [OR] = 6.18). ADHD subtype, female sex, family history of ADHD, psychiatric comorbidities, and physical abuse were also related to EL development/persistence. CONCLUSION: Screening for EL symptoms in children with ADHD is important, as they are the strongest predictor of this symptomatology in adulthood.