The International Journal of Neuropsychopharmacology

Decreased frontal white-matter volume in chronic substance abuse

Thomas E. Schlaepfer a1a2a3c1, Eric Lancaster a2, Rebecca Heidbreder a3, Eric C. Strain a2, Markus Kosel a1a3, Hans-Ulrich Fisch a3 and Godfrey D. Pearlson a2
a1 Brain Stimulation Group, Department of Psychiatry, University Hospital, Bonn, Germany
a2 Division of Psychiatric Neuroimaging, Department of Psychiatry, The Johns Hopkins Medical Institution, Baltimore, MD, USA
a3 Psychiatric Neuroimaging Group, Department of Psychiatry, University Hospital, Bern, Switzerland

Article author query
schlaepfer te   [PubMed][Google Scholar] 
lancaster e   [PubMed][Google Scholar] 
heidbreder r   [PubMed][Google Scholar] 
strain ec   [PubMed][Google Scholar] 
kosel m   [PubMed][Google Scholar] 
fisch hu   [PubMed][Google Scholar] 
pearlson gd   [PubMed][Google Scholar] 


There is quite a body of work assessing functional brain changes in chronic substance abuse, much less is known about structural brain abnormalities in this patient population. In this study we used magnetic resonance imaging (MRI) to determine if structural brain differences exist in patients abusing illicit drugs compared to healthy controls. Sixteen substance abusers who abused heroin, cocaine and cannabis but not alcohol and 16 age-, sex- and race-matched controls were imaged on a MRI scanner. Contiguous, 5-mm-thick axial slices were acquired with simultaneous T2 and proton density sequences. Volumes were estimated for total grey and white matter, frontal grey and white matter, ventricles, and CSF using two different methods: a conventional segmentation and a stereological method based on the Cavalieri principle. Overall brain volume differences were corrected for by expressing the volumes of interest as a percentage of total brain volume. Volume measures obtained with the two methods were highly correlated (r=0.65, p<0.001). Substance abusers had significantly less frontal white-matter volume percentage than controls. There were no significant differences in any of the other brain volumes measured. This difference in frontal lobe white matter might be explained by a direct neurotoxic effect of drug use on white matter, a pre-existing abnormality in the development of the frontal lobe or a combination of both effects. This last explanation might be compelling based on the fact that newer concepts on shared aspects of some neuropsychiatric disorders focus on the promotion and inhibition of the process of myelination throughout brain development and subsequent degeneration.

(Published Online July 8 2005)
(Received January 25 2005)
(Reviewed March 1 2005)
(Revised April 15 2005)
(Accepted April 27 2005)

Key Words: Brain development; magnetic resonance imaging (MRI); neuroplasticity; structural neuroimaging; substance abuse.

c1 Brain Stimulation Group, Department of Psychiatry, University Hospital, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany. Tel.: +49 228 287 5715 Fax: +49 228 287 5025 E-mail: