Reward processing in Attention-Deficit/Hyperactivity Disorder and healthy controls at high risk for Substance Use Disorders

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) and Substance Use Disorder (SUD) often co-occur and are both associated with alterations in reward sensitivity. This might suggest that shared preexisting alterations of reward processing might play a key role in SUD development [1,2]. However, findings in ADHD individuals regarding the nature of these alterations are rather inconsistent. Both state and trait effects of SUD might contribute to these inconsistencies. Here we focus on the trait effects of familial loading for SUD on reward processing in individuals with ADHD and healthy controls at high risk for SUD. Objective: To investigate (1) the effect of familial loading for SUD on reward sensitivity and (2) the interaction effect of familial loading for SUD and ADHD diagnosis on reward sensitivity. Methods: Our sample consisted of four groups without SUD: ADHD with negative family history of SUD (FH-; n = 30), ADHD with positive family history of SUD (FH+; n = 37), control FH- (n = 33) and control FH+ (n = 33). Functional MRI (fMRI) data during a Monetary Incentive Delay (MID) task were collected. Neural activation during anticipation and outcome of reward and neutral trials was examined. Pre-processing of the fMRI data was performed with ICAAROMA and first-level analysis with a fixed-effects model (FSL). Group-level analysis included a mixed-effects model with 5000 random permutations and 3 f-tests: (a) ADHD effect, (b) FH effect, (c) ADHD∗FH effect. For significant clusters (t>2.3 & p<0.05), beta-values were extracted and used in post-hoc comparisons. Results: Regarding familial SUD effects (1), we found hypoactivation of bilateral parahippocampal gyri for FH+ groups during reward (p = .0002, p = .003) and neutral anticipation (p = .0008, p = .008) and hyperactivation of the hippocampus for FH+ groups during reward outcome (p<.001). With respect to familial SUD and ADHD interaction (2), we found hypoactivation of dorsal striatum during neutral anticipation (p = .0002) and hyperactivation of several frontal areas (i.e. frontal pole, MFG, SFG) during reward (p≤.001) and neutral outcome (p≤.0002) for the ADHD groups regardless of family history for SUD. We also found a significant ADHD∗FH effect on ventral striatum during reward (p = .0009) and neutral outcome (p = .002). In both conditions, ADHD FH- (p = .03, p = .001) and control FH+ (p = .006, p = .02) activated striatum more than control FH-. Conclusion: SUD trait effects, as indexed by a positive family history for SUD, affect reward processing in both ADHD patients and healthy controls without SUD. Results indicate that (1) familial trait effects of SUD are possibly associated with altered hippocampal activation during both anticipation and outcome. Although hippocampus was linked to a disrupted dopaminergic system in other psychiatric disorders [3], its role in SUD is not clear yet. On the other hand (2), altered activation of frontal areas during outcome seems to be related to ADHD regardless of family history for SUD. Results also show differential familial SUD effects on striatal activation for ADHD and controls. Finally, hyperactivation for ADHD FH-, but not for ADHD FH+, could potentially reflect different underlying neurobiological mechanisms for ADHD patients with and without parental SUD.