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

  • Author Footnotes
    1 Authors SM and EP contributed equally to this work.
    Simon Maier
    Footnotes
    1 Authors SM and EP contributed equally to this work.
    Affiliations
    Section for Experimental Neuropsychiatry, Clinic for Psychiatry and Psychotherapy, Freiburg, Germany.

    Freiburg Brain Imaging, Freiburg, Germany.
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  • Author Footnotes
    1 Authors SM and EP contributed equally to this work.
    Evgeniy Perlov
    Footnotes
    1 Authors SM and EP contributed equally to this work.
    Affiliations
    Section for Experimental Neuropsychiatry, Clinic for Psychiatry and Psychotherapy, Freiburg, Germany.
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  • Erika Graf
    Affiliations
    Clinical Trials Unit, Medical Center-University of Freiburg, Freiburg, Germany.
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  • Elena Dieter
    Affiliations
    Section for Experimental Neuropsychiatry, Clinic for Psychiatry and Psychotherapy, Freiburg, Germany.

    Freiburg Brain Imaging, Freiburg, Germany.
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  • Esther Sobanski
    Affiliations
    Central Institute for Mental Health, Mannheim, Germany.
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  • Marthe Rump
    Affiliations
    Section for Experimental Neuropsychiatry, Clinic for Psychiatry and Psychotherapy, Freiburg, Germany.

    Freiburg Brain Imaging, Freiburg, Germany.
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  • Andreas Warnke
    Affiliations
    Department for Child and Adolescent Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany.
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  • Dieter Ebert
    Affiliations
    Clinic of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Freiburg, Germany.
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  • Mathias Berger
    Affiliations
    Clinic of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Freiburg, Germany.
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  • Swantje Matthies
    Affiliations
    Clinic of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Freiburg, Germany.
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  • Author Footnotes
    2 AP is currently affiliated with the Department of Psychiatry and Psychotherapy (Karl Jaspers Clinic), Faculty of Medicine and Health Sciences, European Medical School, Carl von Ossietzky University of Oldenburg, Oldenburg, Germany.
    Alexandra Philipsen
    Footnotes
    2 AP is currently affiliated with the Department of Psychiatry and Psychotherapy (Karl Jaspers Clinic), Faculty of Medicine and Health Sciences, European Medical School, Carl von Ossietzky University of Oldenburg, Oldenburg, Germany.
    Affiliations
    Clinic of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Freiburg, Germany.
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  • Ludger Tebartz van Elst
    Correspondence
    Address correspondence to Ludger Tebartz van Elst, M.D., South German Brain Imaging Center, Section for Experimental Neuropsychiatry, Hauptstr. 5, Freiburg 79104, Germany.
    Affiliations
    Section for Experimental Neuropsychiatry, Clinic for Psychiatry and Psychotherapy, Freiburg, Germany.

    Freiburg Brain Imaging, Freiburg, Germany.
    Search for articles by this author
  • Author Footnotes
    1 Authors SM and EP contributed equally to this work.
    2 AP is currently affiliated with the Department of Psychiatry and Psychotherapy (Karl Jaspers Clinic), Faculty of Medicine and Health Sciences, European Medical School, Carl von Ossietzky University of Oldenburg, Oldenburg, Germany.

      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

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      Linked Article

      • The Architecture of Cortex—in Illness and in Health
        Biological PsychiatryVol. 80Issue 12
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          In the same way that much can be gleaned by simply listening to a patient, much can be gleaned by simply looking at the brain. The most striking feature of the human brain is the cerebral cortex. The cortex is a 1- to 4.5-mm-thick sheet of cells (totaling 19–22 billion neurons) that delicately wraps the two hemispheres of the brain. Much like foil covering a piece of candy, the cortex drapes and folds over the subcortical structures and coalescing white matter (myelinated axons traversing between brain structures).
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