Influence of Atomoxetine on Relationship Between ADHD Symptoms and Prefrontal Cortex Activity During Task Execution in Adult Patients.

Atsunori Sugimoto,Toshiyuki Someya,Naoki Orime,Jun Egawa,Taketsugu Hayashi,Kiyohiro Yoshinaga,Takuro Sugai,Yutaro Suzuki,Shin Ono

doi:10.3389/fnhum.2021.755025

Abstract

Objective: We conducted this non-randomized prospective interventional study to clarify the relationship between improved attention-deficit hyperactivity disorder (ADHD) symptoms and regional brain activity.Methods: Thirty-one adult patients underwent near-infrared spectroscopy examinations during a go/no-go task, both before and 8 weeks after atomoxetine administration.Results: Clinical symptoms, neuropsychological results of the go/no-go task, and bilateral lateral prefrontal activity significantly changed. A positive correlation was observed between right dorsolateral prefrontal cortex activity and Conners’ Adult ADHD Rating Scales scores. Before atomoxetine administration, no correlations between prefrontal cortex activity and clinical symptoms were observed in all cases. When participants were divided into atomoxetine-responder and non-responder groups, a positive correlation was observed between prefrontal cortex activity and clinical symptoms in the non-responder group before treatment but not in the responder group, suggesting that non-responders can activate the prefrontal cortex without atomoxetine.Conclusions: Individuals with increased ADHD symptoms appear to recruit the right dorsolateral prefrontal cortex more strongly to perform the same task than those with fewer symptoms. In clinical settings, individuals with severe symptoms are often observed to perform more difficultly when performing the tasks which individuals with mild symptoms can perform easily. The atomoxetine-responder group was unable to properly activate the right dorsolateral prefrontal cortex when necessary, and the oral administration of atomoxetine enabled these patients to activate this region. In brain imaging studies of heterogeneous syndromes such as ADHD, the analytical strategy used in this study, involving drug-responsivity grouping, may effectively increase the signal-to-noise ratio.

Highlights

Atomoxetine (ATX) is a representative drug used to treat attention-deficit hyperactivity disorder (ADHD) and is ranked as a first-line, non-stimulant treatment in national guidelines [Saito et al, 2016; Attention deficit hyperactivity disorder guideline committee of National Institute for Health and Care Excellence (NICE), 2018; Wolraich et al, 2019; Canadian ADHD Resource Alliance (CADDRA), 2020]
The ∆[Oxy-Hb] values before and after ATX administration are shown in Table 2, and activity changed in bilateral lateral prefrontal cortex (PFC) (Ch 5, 6, 17, 18)
The results of this study suggested that ATX administration increased lateral PFC activity, indicating that right dorsolateral PFC (DLPFC) activity may be related to clinical ADHD symptoms

Summary

Introduction

If stimulants cause serious cardiovascular problems or growth retardation, they must be discontinued. In such cases, atomoxetine is an important option. Animal studies have revealed that ATX increases dopamine (DA) levels in the synaptic cleft by inhibiting NET activity in PFC (Bymaster et al, 2002; Ding et al, 2014), which is considered to be the primary mechanism through which ATX improves ADHD symptoms. We conducted a non-randomized prospective interventional study using near-infrared spectroscopy (NIRS) measurement in ADHD patients before and after ATX administration to clarify the relationship between improved symptoms and lateral PFC activity

Methods

Results

Discussion

Conclusion