Functional connectivity of the nucleus accumbens predicts clinical course in medication adherent and non-adherent adult ADHD

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that persists into adulthood, contributing to a negative trajectory characterized by worsening symptoms, impaired daily functioning, and reduced quality of life over time. We studied seed-based functional connectivity (FC) as a predictive tool for ADHD’s clinical course. We conducted a longitudinal follow-up of 54 adult ADHD patients who underwent functionale magnetic resonance imaging (fMRI). All patients received stimulant treatment during an initial run-in period. After an average of three years, only subjective responders adhered to treatment (n = 34), whereas non-adherent discontinued (n = 20). We reassessed patients to (1) evaluate the prediction of individual outcome by baseline fMRI and (2) to investigate differences in prediction by baseline fMRI according to long-term treatment vs. discontinuation. We investigated the relationship between nucleus accumbens’ (NAc) FC and symptom development. Reduced FC of the NAc to the default mode network (DMN) associated with higher initial symptom burden, whereas improvement correlated with reduced FC between the NAc and the salience network (SN). In contrast, higher NAc FC to the SN associated with better outcomes in patients receiving long-term treatment, while lower NAc FC to SN was associated with a positive prognosis in non-adherent patients. This work highlights the potential of dopaminergic FC as a prognostic factor in ADHD and the role of the NAc in its prognosis.