A total of 13 patients (four men, nine women; mean (SD) age 62.8 (6.6) years) who met DSM‐IV criteria for unipolar major depression were enrolled in this study. We excluded patients with other axis I disorders including dementia, severe or acute medical illnesses (brain tumor, cardiac/hepatic/renal failure, and cardiac infarction within the last three months preceding the study), and neurological disorders (delirium, Parkinson's disease, and multiple sclerosis). We assessed cognitive function with the Mini‐Mental State Examination (MMSE), and patients with MMSE scores lower than 25 were excluded to ensure that people with dementia were not included in the study. T2‐weighted MRI of all patients did not show any white matter changes such as infarction or other vascular lesions. The patients had an average of one prior episode of depression with mean age of illness onset at 52.9 (7.3) years. The age of onset of nine subjects was 60 years or younger, and four patients developed depression after 60 years of age. The mean duration of illness was 4.0 (2.6) years. All patients were taking antidepressant medication: tricyclic antidepressants, or selective serotonin reuptake inhibitors, or serotonin noradrenaline reuptake inhibitors, or combination of these. We also recruited 13 age matched control subjects (four men, nine women; 61.5 (4.8) years). Depressive symptoms were assessed using the 17‐item Hamilton Depression Rating Scale (HDRS). The mean HDRS score was 33.4 (9.8) at the time of the study.
The protocol was approved by the Ethics Committee of Kansai Medical University Hospital, Osaka, Japan. All subjects gave informed consent before participating the study.
All subjects underwent DTI scanning, which can be implemented on conventional MR scanners. MR scans were taken with a 1.5 T General Electric Signa Horizon LX (GE Medical Systems, Milwaukee, WI). Head motion was minimised with restraining pads. Sagittal T1‐weighted images were acquired first, with a slice clearly displaying both the anterior commissure (AC) and the posterior commissure (PC). Then, a series of axial diffusion‐weighted images with a diffusion sensitising gradient (b value
) were obtained. Diffusion was measured along six non‐colinear directions. We used single shot spin‐echo echo‐planar sequences for our diffusion tensor analysis. All of the acquisitions paralleled the AC–PC line using the following parameters: TR
4000 msec, TE
103 msec, 128×128 matrix, FOV
24×24 cm, NEX
4, 6.0 mm slice thickness, 2.0 mm gap. The DTI acquisition time was less than five minutes.
The diffusion‐weighted images were transferred to a dedicated workstation (Advantage Workstation; GE Medical Systems, Milwaukee, WI) where the DTI data were post‐processed using Functool 2.2.49 (GE Medical Systems, Milwaukee, WI). Echo‐planar imaging (EPI) distortion was corrected automatically. The diffusion eigenvectors and eigenvalues (λ1
), which correspond to the main direction of diffusion and associated diffusivity, were calculated from the diffusion tensor. FA, which reveals information about the degree of diffusion anisotropy in white matter, was then calculated as follows8
Circular regions of interest (ROI) were positioned bilaterally at 8 mm above the AC–PC plane, at the AC–PC plane, and at 8 mm below the AC–PC plane in the frontal white matter (fig 1). In addition, elliptical ROI were placed in the genu and splenium of the corpus callosum, as well as bilaterally in temporal, parietal, and occipital white matter. The ROI, except for the genu and splenium, were standardised at 88 mm2 to minimise partial volume effects from grey matter. The ROI for the genu and splenium of the corpus callosum adjacent to the lateral ventricles were of a different shape and smaller in size (63 mm2) to avoid effects from the cerebrospinal fluid. The diffusion tensor was computed for each voxel, and the eigenvalues and eigenvectors were determined. The FA was computed from the diffusion tensor.
Figure 1Horizontal T2‐weighted images (top) and corresponding FA images (bottom) from a patient with late‐life depression. Regions of interest (ROI) were drawn in the frontal white matter (ROI 1 and 2) at 8 mm above the (more ...)
The unit of DTI analysis was regional white matter FA. Intraindividual hemispheric differences and intergroup (patients v control) differences in FA were examined with paired t tests and independent t tests, respectively. Spearman's rank correlation coefficient (rs) was used to test the correlation between the DTI regional measures and HDRS scores.