The amygdala in adolescents with attention-deficit/hyperactivity disorder: Structural and functional correlates of delay aversion

Abstract

Objectives

Recent magnetic resonance imaging (MRI) studies implicate structural alterations of amygdala, a brain region responsible for processing and experiencing negative emotions, in adolescents with attention-deficit/hyperactivity disorder (ADHD). Here we examined ADHD-related structural correlates of amygdala functional activity elicited during a functional MRI task designed to test behavioural and brain responses to the imposition of delay – an event known to both elicit amygdala hyperactivation and aversity in ADHD.

Methods

Structural MRI scans from 28 right-handed male adolescents with combined type ADHD and 32 age-matched controls were analysed. Regional grey matter volumes of ADHD and control participants (P[FWE] < 0.05) were correlated with delay aversion self-ratings and neural activity in response to delay-related cues on the Escape Delay Incentive fMRI task.

Results

ADHD was associated with significantly reduced volumes in bilateral amygdala, parahippocampal and temporal gyrus (P[FWE] < 0.05), greater basolateral amygdala activation to delay-related cues (P[FWE] < 0.05) and higher delay aversion self-ratings. Amygdala volume reductions were significantly correlated with, and statistically mediated the pathway from ADHD to, delay-cue-related amygdala hyperactivity (P < 0.01) and self-reported delay aversion (P < 0.01).

Conclusions

We provide the first evidence of the functional significance of reduced amygdala volumes in adolescents with ADHD by highlighting its relation to delay-induced brain activity that is linked to delay aversion.

Keywords:

• ADHD
• amygdala
• delay aversion
• functional magnetic resonance imaging
• voxel-based morphometry

Acknowledgments

The authors are thankful to Dr. Ron Peeters (KU Leuven, Belgium) for his help with the MRI scan protocol, and to Dr. Ahmed Radwan and Dr. Charlotte Sleurs (KU Leuven, Belgium) for their help with the amygdala subfields analysis.

Statement of interest

JVD, MM, SVdO, JL and SM have no disclosures. ES-B received speaker fees, research funding and conference support from and has served as consultant to Shire Pharma and received speaker fees from Janssen-Cilag; he served as consultant to Neurotech Solutions, Aarhus University, Copenhagen University and Berhanderling, Skolerne, Copenhagen and KU Leuven. He has received royalties from Oxford University Press and Jessica Kingsley. MD was a paid member of advisory boards for Shire, a paid speaker at conferences supported by Shire, Novartis and Medice.

Additional information

Funding

This work was supported by Research Foundation - Flanders (FWO) under Grant G.0821.11N and a KU Leuven Research Fund Grant OT/12/096. JVD is a FWO research fellow under Grant 11.ZU.117N.