No Evidence of Structural Abnormality of the Substantia Nigra in Adult Attention-Deficit/Hyperactivity Disorder: A Cross-Sectional Cohort Study

Background: Attention-deficit/hyperactivity disorder (ADHD) is a common neuropsychiatric disorder that has recently been associated with an increased risk of developing movement disorders such as Parkinson's disease (PD), particularly in individuals treated with psychostimulants. Abnormal expansion of the echogenic area of the substantia nigra (SN), a trait marker for PD, is also commonly found in children with ADHD, in whom this feature was attributed to maturational delay of the dopaminergic system. Here, we investigated the structural integrity of the SN in adults with ADHD and its relationship to symptomatic treatment with psychostimulants. Methods: In this cross-sectional cohort study, we performed transcranial sonography of the SN in 30 adults (mean age 33.3 ± 7.6 years, 11 females) diagnosed with ADHD according to DSM-V criteria. The cumulative dose of methylphenidate was extrapolated based on the treating physicians’ documentation and patient’s reports. Results: The mean echogenic SN area in our cohort amounted to 0.17 ± 0.04 cm² (mean ± standard deviation), which is well within the normal range of echogenic SN area according to consensus criteria and did not significantly differ from the mean echogenic SN area observed in two independent control groups previously collected at our site (all p ≥ 0.297). Importantly, we observed no significant treatment-associated changes of SN echogenicity with respect to the extrapolated cumulative dose of methylphenidate derivates (r=-0.261, p = 0.163). Conclusions: Our results indicate that expansion of the echogenic SN area is, unlike evidence in children with ADHD, not useful as an ADHD biomarker in adults. The current results, furthermore, challenge the view that abnormal expansion of the echogenic SN in ADHD may reflect maturational delay of the dopaminergic system, at least it does not persist into adulthood. Therefore, if there is an intrinsic link between ADHD and PD, it is not reflected by structural alterations of SN echogenicity. Importantly, we found no evidence of treatment-associated changes in structural SN integrity mitigating concerns about a possible causal relationship between therapeutic psychostimulant use in ADHD and an increased risk of PD.