White matter hyperintensities and gray matter lesions in physically healthy depressed subjects

Objective: Previous studies reported that depressed subjects had more white matter hyperintensities on magnetic resonance imaging scans than control s ubjects, but the subjects had cerebrovascular disease risk factors. This st udy used subjects with a history of recurrent major depression and matched comparison subjects, screened to exclude cerebrovascular disease risk facto rs, to determine whether depressed subjects had more white matter hyperinte nsities and other lesions. Method: A semiautomated volumetric computer prog ram was used to compare numbers and volumes of white matter hyperintensitie s, basal ganglia lesions, and total lesions in 24 women with a history of r ecurrent major depression and 24 comparison subjects case-matched on age an d education and group-matched on height. In addition, images were measured with the use of a validated categorical scale. All subjects were screened t o exclude cerebrovascular disease risk factors. Results: There were no sign ificant differences in the total volumes or total numbers of lesions; Howev er, multiple linear regression showed a significant correlation of age and depression with number of lesions; this was accounted for by a greater numb er of small lesions (diameter less than or equal to 0.4 cm). Conclusions: T hese findings suggest that cerebrovascular disease risk factors most likely mediated the relationship between depression and white matter hyperintensi ties seen in previous studies. However, the independent effect of depressio n, as well as an age-by-depression interaction, for small lesions suggests a causal role of depression in certain types of white matter pathology irre spective of other cerebrovascular disease risk factors. The volumetric meth od used in this study may be more sensitive than other methods in determini ng lesion characteristics and correlations with clinical variables.