ABSTRACT
BACKGROUND: Based on animal research several authors have warned that the application of methylphenidate, the first-line drug for the treatment of attention-deficit/hyperactivity disorder (ADHD), might have neurotoxic effects potentially harming the brain. We investigated whether methylphenidate application, over a 1-year period, results in cerebral volume decrease. METHODS: We acquired structural MRIs in a double-blind study comparing methylphenidate to placebo. Global and regional brain volumes were analyzed at baseline, after 3 months and after 12 months using diffeomorphic anatomic registration through exponentiated lie algebra. RESULTS: We included 131 adult patients with ADHD into the baseline sample, 98 into the 3-month sample (54 in the methylphenidate cohort and 44 in the placebo cohort) and 76 into the 1-year sample (37 in the methylphenidate cohort and 29 in the placebo cohort). Methylphenidate intake compared with placebo did not lead to any detectable cerebral volume loss; there was a trend toward bilateral cerebellar grey matter increase. LIMITATIONS: Detecting possible neurotoxic effects of methylphenidate might require a longer observation period. CONCLUSION: There is no evidence of grey matter volume loss after 1 year of methylphenidate treatment in adult patients with ADHD.
Subject(s)
Attention Deficit Disorder with Hyperactivity/diagnostic imaging , Attention Deficit Disorder with Hyperactivity/therapy , Brain/drug effects , Brain/diagnostic imaging , Central Nervous System Stimulants/therapeutic use , Methylphenidate/therapeutic use , Adult , Central Nervous System Stimulants/adverse effects , Double-Blind Method , Female , Follow-Up Studies , Gray Matter/diagnostic imaging , Gray Matter/drug effects , Humans , Magnetic Resonance Imaging , Male , Methylphenidate/adverse effects , Organ Size , Psychotherapy , Time Factors , Treatment OutcomeABSTRACT
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.
