WHEN ADHD AND SUBSTANCE USE DISORDERS COEXIST Etiology and Pharmacological Treatment

Individuals with attention-deficit hyperactivity disorder (ADHD) and comorbid substance use disorder (SUD) comprise a significant group of patients displaying various degrees of personal suffering, entailing a substantial economical burden on society and presenting with challenges in treatment. The overlap between the two disorders is well established, but the underlying genetic and environmental mechanisms of their coexistence, are poorly understood. Furthermore, little is known about the effectiveness and safety of stimulant medication when ADHD and SUD coexist. This thesis aimed to investigate the etiological relationship between ADHD and substance use problems (Studies I and II) and to explore doses of, and adherence to, pharmacological treatment for ADHD in the presence of SUD (Studies III and IV). Quasi-experimental methods (Study I) were used to investigate whether smoking during pregnancy (SDP) is causally associated with ADHD in offspring. A family design (Study II) was applied to explore whether the overlap between ADHD and SUD arises from shared familial factors or is better explained by harmful effects of ADHD medication. Nationwide population-based cohort designs (Study III) were used to explore differences in and development of methylphenidate (MPH) doses in ADHD patients with and without SUD, and the impact of MPH doses on adherence to treatment in individuals with SUD (Study IV). The results show that the increased risk for ADHD in individuals exposed to SDP was attenuated when familial factors were accounted for, suggesting that genetically transmitted factors explain the association. Furthermore, genetic relatedness to an ADHD proband predicts SUD in ADHD-free relatives suggesting that the co-occurrence of ADHD and SUD may be due to common genetic factors shared between the two disorders. The studies focusing on stimulant treatment show that patients with comorbid SUD are prescribed higher MPH doses and have higher adherence to MPH treatment compared to patients with ADHD only. In both groups MPH doses stabilized within two years of treatment. Higher doses of MPH were associated with increased adherence to treatment. In conclusion, the collective findings from this thesis suggest that ADHD and SUD share common genetic underpinnings, that individuals with comorbid SUD receive higher stimulant doses than individuals with ADHD only, without signs of tolerance, and that stimulant doses predict adherence to pharmacological treatment in individuals with comorbid SUD. LIST OF SCIENTIFIC PAPERS I. Familial Confounding of the Association Between Maternal Smoking During Pregnancy and ADHD in Offspring Charlotte Skoglund, Qi Chen, Brian M D′Onofrio, Paul Lichtenstein, Henrik Larsson Journal of Child Psychology and Psychiatry, Volume 55, Issue 1, pages 61–68, January 2014 II. Attention-Deficit/Hyperactivity Disorder and Risk for Substance Use Disorders in Relatives Charlotte Skoglund, Qi Chen, Johan Franck, Paul Lichtenstein, Henrik Larsson Biological Psychiatry, Volume 77, Issue 10, pages 880–6, May 2015 III. Methylphenidate Doses in Attention-Deficit/Hyperactivity Disorder and Comorbid Substance Use Disorders Charlotte Skoglund, Lena Brandt, Brian D’Onofrio, Catarina Almqvist, Henrik Larsson, Johan Franck (Manuscript) IV. Predictors of Adherence to Methylphenidate Treatment in Patients with Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder Charlotte Skoglund, Lena Brandt, Brian D’Onofrio, Catarina Almqvist, Maija Konstenius, Johan Franck, Henrik Larsson (Manuscript) Reprints were made with permission from the respective publishers