Effects of substance misuse on reward-processing in patients with attention-deficit/hyperactivity disorder


Attention-Deficit/Hyperactivity Disorder (ADHD) and Substance Use Disorder (SUD) often co-occur and are associated with treatment resistance. Both disorders are characterized by similar reward-processing deficits with decreased striatal responses to reward anticipation, though literature is inconsistent. It is unclear whether substance misuse exaggerates reward-processing deficits observed in ADHD. The aim of this study was to examine substance misuse effects on reward-processing in ADHD. Functional MRI data in a Monetary Incentive Delay (MID) task from a multi-site study were compared across ADHD groups with and without substance misuse (ADHD + SM and ADHD-only, respectively) and healthy controls (n = 40/group, 74 males and 46 females, aged 13.7–25.9 years). Substance misuse was defined as misuse of alcohol, nicotine, or drugs. Groups were matched with presence/absence of parental SUD to avoid interference with SUD trait effects. Compared to ADHD-only and controls, ADHD + SM showed hyperactivation in putamen during reward anticipation. Compared to controls, the ADHD groups showed hypoactivation in motor/sensory cortices and hyperactivation in frontal pole and OFC during reward outcome. ADHD + SM also showed hyperactivation in frontal pole during neutral outcome. Moreover, ADHD + SM patients showed higher callous-unemotional (CU) traits that were positively correlated with putamen responses to reward anticipation. Our results show distinct condition-independent neural activation profile for ADHD + SM compared to ADHD-only and controls. Effects of comorbid substance misuse and variability of its prevalence across ADHD studies might have contributed to inconsistencies in ADHD literature. Contrasted with findings for reward-processing in SUD literature, results potentially suggest distinct underlying mechanisms for SUD subgroups with different characteristics, like antisocial/psychopathic traits.

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Fig. 1: Whole-brain group differences during reward anticipation.
Fig. 2: Whole-brain group differences during reward outcome.
Fig. 3: Whole-brain group differences during neutral outcome.


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MP has contributed to the design of project, the data analysis and interpretation of the results and the writing of the manuscript. She has also agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. DVR has contributed to the design of the work, the data acquisition and analysis, the interpretation of the results, the writing and revision of the manuscript. AB has contributed to the design of the project, the interpretation of the results and the revision of the manuscript for important intellectual content. RC has contributed to the data analysis and the revision of the manuscript for important intellectual content. ML has contributed to the revision of the manuscript for important intellectual content. AHS has contributed to the design of the work, the interpretation of the results and the revision of the manuscript for important intellectual content. JKB has contributed to the design of the project, the interpretation of the results and the revision of the manuscript for important intellectual content. AFAS has contributed to the conception and design of the project, the data analysis, the interpretation of the results, the writing and revision of the manuscript for important intellectual content. All authors have approved the publication of the manuscript.

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Paraskevopoulou, M., van Rooij, D., Batalla, A. et al. Effects of substance misuse on reward-processing in patients with attention-deficit/hyperactivity disorder. Neuropsychopharmacol. (2020). https://doi.org/10.1038/s41386-020-00896-1

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