Effects of prolonged methylphenidate treatment on amygdala reactivity and connectivity: a randomized controlled trial in stimulant treatment-naive, male participants with ADHD

Antonia Kaiser, Marco A Bottelier, Michiel B de~Ruiter, Michelle M Solleveld, Hyke G H Tamminga, Cheima Bouziane, Hilde M Geurts, Ramon J L Lindauer, J J Sandra Kooij, Paul J Lucassen, Anouk Schrantee, Liesbeth Reneman, M.B. de Ruiter

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background
Problems with emotional processing are widely reported in individuals with attention-deficit/hyperactivity disorder (ADHD). Although methylphenidate (MPH) effectively alleviates inattention and hyperactivity symptoms in ADHD, its effects on emotional processing and internalizing symptoms have remained elusive. While we previously found that acute MPH administration modulated neural mechanisms underlying emotional processing in an age-dependent manner, the effects of prolonged administration remained unknown.

Objectives
Therefore, we investigated: (i) whether prolonged MPH treatment influences neural substrates (amygdala reactivity and connectivity) of emotional processing, and (ii) whether these effects are modulated by age.

Methods
The “effects of Psychotropic drugs On Developing brain-MPH” (“ePOD-MPH”) randomized controlled trial was a 16-week double-blind, placebo-controlled, multi-center trial with MPH in 50 boys (10–12 years of age) and 49 men (23–40 years of age), all stimulant treatment-naive and diagnosed with ADHD. Participants performed an emotional face-matching task during functional magnetic resonance imaging. We assessed their symptoms of ADHD and internalizing symptoms at baseline, during the trial (8 weeks), and 1 week after the trial end (17 weeks).

Results and Conclusions
We did not find effects of prolonged MPH treatment on emotional processing, as measured by amygdala reactivity and connectivity and internalizing symptoms in this trial with stimulant treatment-naive participants. This differs from our findings on emotional processing following acute MPH administration and the effects of prolonged MPH treatment on the dopamine system, which were both modulated by age. Interestingly, prolonged MPH treatment did improve ADHD symptoms, although depressive and anxiety symptoms showed a medication-independent decrease. Furthermore, our data indicate that baseline internalizing symptoms may be used to predict MPH treatment effects on ADHD symptoms, particularly in (male) adults with ADHD.
Original languageEnglish
Pages (from-to)152-163
Number of pages12
JournalPsychoradiology
Volume1
Issue number3
DOIs
Publication statusPublished - 1 Sept 2021

Cite this