Discrete Global but No Focal Gray Matter Volume Reductions in Unmedicated Adult Patients With Attention-Deficit/Hyperactivity Disorder

Simon Maier; Evgeniy Perlov; Erika Graf; Elena Dieter; Esther Sobanski; Marthe Rump; Andreas Warnke; Dieter Ebert; Mathias Berger; Swantje Matthies; Alexandra Philipsen; Ludger Tebartz van Elst

doi:10.1016/j.biopsych.2015.05.012

Discrete Global but No Focal Gray Matter Volume Reductions in Unmedicated Adult Patients With Attention-Deficit/Hyperactivity Disorder

Biol Psychiatry. 2016 Dec 15;80(12):905-915. doi: 10.1016/j.biopsych.2015.05.012. Epub 2015 May 27.

Authors

Affiliations

¹ Section for Experimental Neuropsychiatry, Clinic for Psychiatry and Psychotherapy, Freiburg, Germany.; Freiburg Brain Imaging, Freiburg, Germany.
² Section for Experimental Neuropsychiatry, Clinic for Psychiatry and Psychotherapy, Freiburg, Germany.
³ Clinical Trials Unit, Medical Center-University of Freiburg, Freiburg, Germany.
⁴ Central Institute for Mental Health, Mannheim, Germany.
⁵ Department for Child and Adolescent Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany.
⁶ Clinic of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Freiburg, Germany.
⁷ Section for Experimental Neuropsychiatry, Clinic for Psychiatry and Psychotherapy, Freiburg, Germany.; Freiburg Brain Imaging, Freiburg, Germany.. Electronic address: tebartzvanelst@uniklinik-freiburg.de.

PMID: 26115789
DOI: 10.1016/j.biopsych.2015.05.012

Abstract

Background: Gray matter reduction mainly in the anterior cingulate cortex, the basal ganglia, and the cerebellum has been reported in attention-deficit/hyperactivity disorder (ADHD). Yet, respective data remain contradictory and inconclusive. To clarify if structural alteration in these brain areas can be verified in a large cohort of adult patients and if a history of stimulant medication has an effect on brain structure, magnetic resonance imaging was performed in the context of a clinical trial on the efficacy of group psychotherapy, clinical management, methylphenidate, and placebo (Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study Trial).

Methods: Between January 2007 and August 2010, 1480 patients from seven study centers across Germany, aged 18 to 58, were prescreened; 518 were assessed for eligibility; 433 were randomized; and 187 were eligible for neuroimaging. The control group included 121 healthy volunteers. Structural magnetic resonance imaging data sets were acquired. Following strict quality control, 131 patient and 95 control data sets could be analyzed. All patients were unmedicated for at least 6 months. The established method of voxel-based morphometry (VBM8 segmentation and diffeomorphic anatomical registration through exponentiated lie normalization) was used to assess global and regional brain volumes.

Results: Patients displayed subtle global cerebral volume reductions. There was no evidence of regional gray matter volume abnormalities. The inattentive ADHD subtype was linked to smaller volumes in the left dorsolateral prefrontal cortex. A history of previous medication did not modulate brain volumes.

Conclusions: ADHD in adulthood is associated with global rather than regional volumetric abnormalities. Previous use of stimulant medication does not seem to modify subsequent brain volumes in a significant way.

Keywords: Adults; Attention-deficit/hyperactivity disorder; Brain imaging; Combined subtype; Inattentive subtype; Voxel-based morphometry.

Publication types

Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Attention Deficit Disorder with Hyperactivity / diagnostic imaging*
Attention Deficit Disorder with Hyperactivity / physiopathology
Female
Gray Matter / diagnostic imaging*
Humans
Magnetic Resonance Imaging / methods*
Male
Middle Aged

Associated data

ISRCTN/ISRCTN54096201