Psychological Medicine

Original Articles

Localization of white-matter lesions and effect of vascular risk factors in late-onset major depression

R. B. Dalbya1 c1, M. M. Chakravartya2a3a4, J. Ahdidana1, L. Sørensena5, J. Frandsena4, K. Y. Jonsdottira4, E. Tehrania1, R. Rosenberga1, L. Østergaarda4 and P. Videbecha1

a1 Center for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark

a2 Allen Institute for Brain Science, Seattle, WA, USA

a3 PET Center, Aarhus University Hospital, Aarhus Sygehus, Aarhus, Denmark

a4 Center of Functionally Integrative Neuroscience (CFIN), Aarhus University, Aarhus, Denmark

a5 Department of Neuroradiology, Aarhus University Hospital, Aarhus Sygehus, Aarhus, Denmark


Background Several studies suggest that patients with late-onset major depression (MD) have an increased load of cerebral white-matter lesions (WMLs) compared with age-matched controls. Vascular risk factors such as hypertension and smoking may confound such findings. Our aim was to investigate the association between the localization and load of WMLs in late-onset MD with respect to vascular risk factors.

Method We examined 22 consecutive patients with late-onset first-episode MD and 22 age- and gender-matched controls using whole-brain magnetic resonance imaging (MRI). The localization, number and volume of WMLs were compared between patients and controls, while testing the effect of vascular risk factors.

Results Among subjects with one or more WMLs, patients displayed a significantly higher WML density in two white-matter tracts: the left superior longitudinal fasciculus and the right frontal projections of the corpus callosum. These tracts are part of circuitries essential for cognitive and emotional functions. Analyses revealed no significant difference in the total number and volume of WMLs between groups. Patients and controls showed no difference in vascular risk factors, except for smoking. Lesion load was highly correlated with smoking.

Conclusions Our results indicate that lesion localization rather than lesion load differs between patients with late-onset MD and controls. Increased lesion density in regions associated with cognitive and emotional functions may be crucial in late-onset MD, and vascular risk factors such as smoking may play an important role in the pathophysiology of late-onset MD, consistent with the vascular depression hypothesis.

(Received March 16 2009)

(Revised August 10 2009)

(Accepted September 28 2009)

(Online publication November 09 2009)


c1 Address for correspondence: Dr R. B. Dalby, Center for Psychiatric Research, Aarhus University Hospital, Skovagervej 2, DK-8240 Risskov, Denmark. (Email: