title: Reduced cortical gray matter density in human MDMA (Ecstasy) users: a voxel-based morphometry study.
abstract: The popular recreational drug, 3,4-methylenedioxymethamphetamine (MDMA) exerts its actions in part via blockade of serotonin and dopamine reuptake. Many animal and human studies have demonstrated long-lasting reductions in measures of central nervous system (CNS) serotonin function following MDMA administration. One emerging role of serotonin function in the CNS is a positive trophic effect via stimulation of intracellular signaling pathways and trophic factors. We hypothesized that human MDMA users might display neocortical gray matter reductions due to loss of serotonergically mediated trophic effects on cortical cells. However, unlike animal models, most human MDMA users worldwide are polydrug users, thereby complicating the assessment of MDMA toxicity in this group. Structural magnetic resonance imaging (MRI) scans of 31 MDMA polydrug users versus 29 non-MDMA users were compared using voxel-based morphometry (VBM) to assess regional brain gray and white matter concentration. VBM employs gray/white matter segmentation and statistical parametric mapping (SPM) analysis to calculate a voxel-wise comparison of regional gray or white matter concentration. Using this method, we consistently found several brain regions having decreased gray matter concentration in MDMA polydrug users. These regions were localized to neocortex in bilateral Brodmann area (BA) 18, left BA 21, and left BA 45, as well as bilateral cerebellum, and midline brainstem. Overall, these preliminary findings suggest that MDMA polydrug users have multiple regions of gray matter reduction, potentially accounting for previously reported neuropsychiatric impairments in MDMA users. Additional animal model and human studies of the CNS effects of MDMA and combined MDMA-polydrug toxicity are needed to further explain these findings. Potential explanations for our results including pre-existing brain differences predisposing to MDMA polydrug use, direct MDMA and polydrug toxicity, indirect changes due to MDMA and polydrug toxicity, or combinations of all these factors.
authors.affiliation: Brain Imaging Center, Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA. ronald.l.cowan@vanderbilt.edu
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Cowan
authors.forename: In Kyoon
authors.initials: IK
authors.lastname: Lyoo
authors.forename: Seung Mo
authors.initials: SM
authors.lastname: Sung
authors.forename: Kyung Heup
authors.initials: KH
authors.lastname: Ahn
authors.forename: Minue J
authors.initials: MJ
authors.lastname: Kim
authors.forename: Jaeuk
authors.initials: J
authors.lastname: Hwang
authors.forename: Erika
authors.initials: E
authors.lastname: Haga
authors.forename: Ram Lakhan Panday
authors.initials: RL
authors.lastname: Vimal
authors.forename: Scott E
authors.initials: SE
authors.lastname: Lukas
authors.forename: Perry F
authors.initials: PF
authors.lastname: Renshaw
mesh_terms: D000293:Adolescent; D000328:Adult; D001931:Brain Mapping / Q000295:instrumentation; D002540:Cerebral Cortex / Q000473:pathology*; D005260:Female; D006801:Humans; D013287:Illicit Drugs / Q000009:adverse effects; D007091:Image Processing, Computer-Assisted / Q000295:instrumentation; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000009:adverse effects*; D012701:Serotonin / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000473:pathology
chemical_list: D013287:Illicit Drugs; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine