Forty patients were included in this prospective study between November 2016 and October 2017. Patients’ ages ranged between 21 and 36 years with a mean age of 27. Thirty patients with MS (24 females and 6 males) were divided into two groups. Group 1 included 20 patients with relapsing-remitting MS (RRMS) with depressive symptoms diagnosed according to McDonald’s criteria 2010 and diagnosed with depression according to DSM-V (Diagnostic and Statistical Manual of Mental Disorders). Group 2 consisted of 10 patients with MS without symptoms of depression. Both depressed and non-depressed groups were similar with regard to several variables, including demographics, cognitive performance, disease duration and lesion load. The control group consisted of 10 age-matched healthy individuals. Written informed consent was signed by all patients before the examination. The study was conducted with the approval of our institutional review board.
Inclusion criteria
Exclusion criteria
All patients were subjected to the following:
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Full neurological and clinical examination by an experienced neurologist
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Beck Depression Inventory (BDI): The BDI was developed in 1961, adapted in 1969, and copyrighted in 1979. It becomes one of the most widely used measures to assess the severity of depression whether in adolescents or adults. The BDI is composed of 21 questions or items with four possible responses. Each response is assigned to a score from zero to three, with the sum of the scores indicating the severity of the symptom with higher scores indicating a more severe depression [18]. For people who have been clinically diagnosed, scores from 0 to 9 represent minimal depressive symptoms, scores from 10 to 16 indicate mild depression, scores from 17 to 29 indicate moderate depression and scores from 30 to 63 indicate severe depression
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Tests for cognitive skills (PASAT): Paced Auditory Serial Addition Test (PASAT) (B). The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability [19]. This assessment was initially developed by Gronwall in 1977. Stimulus presentation rates were adapted for use with patients with MS by Rao and colleagues in 1989
MRI examination
MRI was performed without prior preparation or anaesthesia. Imaging was performed using a standard 1.5 Tesla unit (Achieva, Philips). A standard head coil was used. The sequences obtained were axial T1 (TR 450 ms, TE 15 ms, flip angle 69°, matrix 180 × 169, FOV 210 × 236, number of excitation: 2, slice thickness: 6.0/1.5), axial T2 (TR 3619 ms, TE 100 ms, flip angle 90°, matrix 192 × 165, FOV 210 × 236, number of excitation: 2, slice thickness: 6.0/1.5), axial and sagittal FLAIR (TR 2000 ms, TE 120 ms, flip angle 90°, matrix 208 × 192, FOV 210 × 236, number of excitation: 2, slice thickness: 6.0/1.5) and diffusion WIs (diffusion weighting factor of zero, 500 and 1000 s/ mm2, TR 4100 ms, TE 115 ms, flip angle 90°, matrix 132 × 105, FOV 210 × 236, number of excitation: 2, slice thickness: 6.0/1.5).
DTI obtained for all patients consisted of a single-shot, spin-echo echoplanar sequence in 12 encoding directions. A diffusion weighting factor of 800 s/mm2 was used. The imaging parameters were as follows: TR 8000 ms, TE 67 ms, flip angle 90°, matrix 112 × 110, FOV 210 mm, number of excitations 2, and slice thickness 2 mm.
All images were transferred to a workstation (Philips Extended MR Workspace, 2.6.3.5) for post-processing. FA maps, directionally encoded colour FA maps and 3D fibre tractography, were obtained.
FA values were measured in the main white matter connections of the limbic system, including the cingulum cingulate part (Fig. 1), UF (Fig. 2), fornix (Fig. 3) and anterior thalamic radiations (Fig. 4). Freehand drawings of the regions of interest (ROIs) were made at the FA colour map overlaid on T2 or FLAIR images. Measurements were performed at the normal-appearing white matter without demyelinating plaques. The number of voxels for each ROI ranged between 2 and 6. The multi-ROI technique was used, and a software algorithm tracked the white matter tracts that passed through these ROIs. Four pathways were identified bilaterally using a prior anatomical knowledge and established tractography protocols [20, 21].
Correlations were performed between the mean FA values of the white matter tracts in the depressed and non-depressed MS groups, between the depressed group and the normal healthy individuals and between the non-depressed group and normal healthy group.
Statistical analysis
The results are expressed as the mean ± standard deviation or number (percentage). Correlations between the FA of the different groups were performed using the paired Student’s t test. P values below 0.05 were considered statistically significant. SPSS software (version 16 windows) was used for data analysis.