title: Discrete Global but No Focal Gray Matter Volume Reductions in Unmedicated Adult Patients With Attention-Deficit/Hyperactivity Disorder.
abstract: 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Section for Experimental Neuropsychiatry, Clinic for Psychiatry and Psychotherapy, Freiburg, Germany.; Freiburg Brain Imaging, Freiburg, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Maier
authors.affiliation: Section for Experimental Neuropsychiatry, Clinic for Psychiatry and Psychotherapy, Freiburg, Germany.
authors.forename: Evgeniy
authors.initials: E
authors.lastname: Perlov
authors.affiliation: Clinical Trials Unit, Medical Center-University of Freiburg, Freiburg, Germany.
authors.forename: Erika
authors.initials: E
authors.lastname: Graf
authors.affiliation: Section for Experimental Neuropsychiatry, Clinic for Psychiatry and Psychotherapy, Freiburg, Germany.; Freiburg Brain Imaging, Freiburg, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Dieter
authors.affiliation: Central Institute for Mental Health, Mannheim, Germany.
authors.forename: Esther
authors.initials: E
authors.lastname: Sobanski
authors.affiliation: Section for Experimental Neuropsychiatry, Clinic for Psychiatry and Psychotherapy, Freiburg, Germany.; Freiburg Brain Imaging, Freiburg, Germany.
authors.forename: Marthe
authors.initials: M
authors.lastname: Rump
authors.affiliation: Department for Child and Adolescent Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Warnke
authors.affiliation: Clinic of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Freiburg, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Ebert
authors.affiliation: Clinic of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Freiburg, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Berger
authors.affiliation: Clinic of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Freiburg, Germany.
authors.forename: Swantje
authors.initials: S
authors.lastname: Matthies
authors.affiliation: Clinic of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Freiburg, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Philipsen
authors.affiliation: Section for Experimental Neuropsychiatry, Clinic for Psychiatry and Psychotherapy, Freiburg, Germany.; Freiburg Brain Imaging, Freiburg, Germany.. Electronic address: tebartzvanelst@uniklinik-freiburg.de.
authors.forename: Ludger
authors.initials: L
authors.lastname: Tebartz van Elst
mesh_terms: D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000000981:diagnostic imaging* / Q000503:physiopathology; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged
keywords: Adults; Attention-deficit/hyperactivity disorder; Brain imaging; Combined subtype; Inattentive subtype; Voxel-based morphometry