Demographic and clinical characteristics
Our results showed no significant differences in age, gender, education, BMI, ICV, and duration of illness among the NMD, MD, and HCs groups (all P > 0.05). However, there were significant differences between the NMD and MD groups in MADRS score, HDRS score, and HDRS factor scores, with NMD having significantly lower scores than MD (all P < 0.01) (Table 1).
Table 1 Demographic and clinical characteristics of MD, NMD, and HCs
Variable
|
MD (n=72)
|
NMD (n=74)
|
HCs (n=81)
|
F/t/χ2
|
P
|
Sex (M/F)
|
16/56
|
26/48
|
25/56
|
3.035
|
0.219
|
Age (years)
|
35.49 ± 11.12
|
33.99 ± 9.75
|
35.25 ± 11.56
|
0.408
|
0.665
|
Education (years)
|
11.82 ± 3.81
|
11.20 ± 4.67
|
12.43 ± 4.39
|
1.571
|
0.210
|
BMI (kg/m2)
|
21.13 ± 2.76
|
20.94 ± 2.85
|
21.71 ± 2.97
|
1.537
|
0.217
|
ICV (mm3)
|
1290856.17 ± 180328.07
|
1344408.00 ± 173137.61
|
1325802.47 ± 165573.73
|
1.805
|
0.167
|
EHI-SF
|
98.44 ± 7.55
|
97.97 ± 8.54
|
98.61 ± 9.27
|
0.114
|
0.892
|
HDRS
|
26.10 ± 4.83
|
21.31 ± 3.28
|
|
6.986
|
<0.001
|
MADRS
|
33.76 ± 6.65
|
25.85 ± 5.21
|
|
7.991
|
<0.001
|
Anxiety/somatization factor
|
8.82 ± 2.16
|
7.88 ± 1.74
|
|
2.907
|
0.004
|
Weight factor
|
1.11 ± 0.88
|
0.35 ± 0.67
|
|
5.850
|
<0.001
|
Cognitive dysfunction factor
|
4.42 ± 1.85
|
3.12 ± 1.46
|
|
4.682
|
<0.001
|
Retardation factor
|
7.81 ± 1.90
|
6.74 ± 2.14
|
|
3.167
|
0.002
|
Sleep disorder factor
|
4.76 ± 1.50
|
3.70 ± 1.86
|
|
3.799
|
<0.001
|
Abbreviations: MD, Melancholic depression; NMD, Non-melancholic depression; HCs, healthy controls; HDRS, Hamilton Depression Rating Scale; MADRS, Montgomery-Asberg Depression Rating Scale; ICV, Intracranial volume; EHI-SF , Edinburgh Handedness Inventory-short form; BMI, Body Mass Index
Hippocampal volume differences among MD, NMD and HCs
After adjusting for age, gender, education and ICV, the MANCOVA analysis revealed a significant difference in the GMV of right hippocampal tail across three groups (P < 0.001, Bonferroni corrected). Post-hoc analysis indicated that the GMV of right hippocampal tail was significantly smaller in the MD group compared to HCs group (P < 0.001, Bonferroni corrected). However, after applying the Bonferroni-adjusted threshold, there were no statistically significant differences in the GMV of the right hippocampal tail between the NMD group and either the MD or HCs groups (Table 2, Fig. 1).
Table 2 Differences in GMV of the hippocampal subregions between MD, NMD, and HCs
Subregions
|
MD (n=72)
|
NMD (n=74)
|
HCs (n=81)
|
F
|
P
|
Post-hoc
|
MD vs. NMD
|
MD vs. HCs
|
NMD vs. HCs
|
Left hemisphere
|
|
|
|
|
|
|
|
|
Parasubiculum
|
62.52 ± 11.31
|
63.79 ± 11.53
|
64.50 ± 11.89
|
0.371
|
0.691
|
0.907
|
0.502
|
0.430
|
Presubiculum
|
310.00 ± 34.09
|
315.39 ± 39.58
|
317.5 ± 46.66
|
0.254
|
0.776
|
0.905
|
0.589
|
0.508
|
Subiculum
|
425.94 ± 40.93
|
437.71 ± 49.07
|
444.61 ± 55.61
|
1.993
|
0.139
|
0.603
|
0.056
|
0.169
|
CA1
|
610.84 ± 61.98
|
619.01 ± 64.43
|
624.93 ± 68.58
|
0.574
|
0.564
|
0.784
|
0.456
|
0.305
|
CA3
|
198.30 ± 23.52
|
200.08 ± 25.70
|
201.56 ± 25.29
|
0.153
|
0.858
|
0.873
|
0.709
|
0.592
|
CA4
|
242.47 ± 21.64
|
242.48 ± 24.67
|
245.91 ± 24.87
|
0.551
|
0.577
|
0.482
|
0.760
|
0.304
|
GC-ML-DG
|
282.80 ± 24.70
|
284.23 ± 28.83
|
287.35 ± 28.70
|
0.428
|
0.652
|
0.606
|
0.695
|
0.356
|
ML
|
544.84 ± 45.16
|
551.51 ± 49.86
|
560.57 ± 54.31
|
1.534
|
0.218
|
0.851
|
0.164
|
0.114
|
HATA
|
54.33 ± 9.57
|
54.98 ± 8.50
|
53.52 ± 8.40
|
0.500
|
0.607
|
0.711
|
0.325
|
0.548
|
Fimbria
|
80.28 ± 16.80
|
82.33 ± 16.16
|
81.56 ± 14.72
|
0.088
|
0.916
|
0.679
|
0.876
|
0.787
|
Tail
|
599.10 ± 62.59
|
607.27 ± 77.67
|
626.71 ± 77.95
|
2.347
|
0.098
|
0.931
|
0.058
|
0.072
|
Fissure
|
146.32 ± 25.96
|
147.05 ± 29.82
|
150.08 ± 25.94
|
0.361
|
0.697
|
0.732
|
0.624
|
0.400
|
Whole hippocampus
|
3411.43 ± 260.91
|
3458.79 ± 306.12
|
3508.71 ± 331.67
|
1.608
|
0.203
|
0.863
|
0.150
|
0.107
|
Right hemisphere
|
|
|
|
|
|
|
|
|
Parasubiculum
|
60.95 ± 8.75
|
62.29 ± 11.08
|
60.91 ± 10.17
|
0.301
|
0.741
|
0.837
|
0.593
|
0.456
|
Presubiculum
|
292.00 ± 34.62
|
301.05 ± 40.60
|
297.60 ± 38.52
|
0.211
|
0.810
|
0.519
|
0.785
|
0.694
|
Subiculum
|
425.60 ± 45.65
|
440.44 ± 49.66
|
443.57 ± 48.45
|
1.730
|
0.180
|
0.294
|
0.065
|
0.443
|
CA1
|
660.47 ± 68.13
|
673.85 ± 75.85
|
682.20 ± 82.83
|
1.015
|
0.364
|
0.935
|
0.208
|
0.241
|
CA3
|
219.55 ± 26.08
|
225.79 ± 28.24
|
222.04 ± 28.21
|
0.241
|
0.786
|
0.535
|
0.955
|
0.559
|
CA4
|
253.08 ± 24.09
|
258.08 ± 25.97
|
256.38 ± 26.80
|
0.080
|
0.923
|
0.691
|
0.818
|
0.857
|
GC-ML-DG
|
294.87 ± 27.90
|
302.27 ± 30.30
|
300.27 ± 31.78
|
0.250
|
0.779
|
0.503
|
0.593
|
0.875
|
ML
|
571.30 ± 51.31
|
584.29 ± 54.84
|
588.70 ± 61.05
|
1.014
|
0.364
|
0.633
|
0.164
|
0.369
|
HATA
|
58.27 ± 9.50
|
58.27 ± 9.58
|
57.30 ± 9.38
|
0.463
|
0.630
|
0.627
|
0.337
|
0.647
|
Fimbria
|
75.95 ± 14.74
|
80.37 ± 13.89
|
78.78 ± 15.74
|
0.466
|
0.628
|
0.340
|
0.545
|
0.704
|
Tail
|
600.55 ± 59.79
|
625.55 ± 67.67
|
648.47 ± 84.88
|
7.659
|
<0.001*
|
0.175
|
<0.001*
|
0.016
|
Fissure
|
151.92 ± 24.46
|
162.03 ± 34.13
|
159.49 ± 29.66
|
1.643
|
0.196
|
0.085
|
0.177
|
0.668
|
Whole hippocampus
|
3512.59 ± 294.61
|
3612.26 ± 322.89
|
3636.24 ± 368.49
|
1.712
|
0.183
|
0.386
|
0.066
|
0.344
|
Notes: The data in the second, third and fourth columns of the table represent the mean volume ± standard deviation, Unit: mm3. *P-value: Bonferroni corrected. Abbreviations: MD, Melancholic depression; NMD, Non-melancholic depression; HCs, Healthy controls; CA, cornu ammonis; GC-ML-DG, granule cell and molecular layer of the dentate gyrus; ML, molecular layer; HATA, hippocampus-amygdala transition area
Amygdala volume differences among MD, NMD and HCs
After adjusting for age, gender, education, and ICV, the MANCOVA analysis did not reveal any significant differences in the total or subregional gray matter volume (GMV) of the amygdala among the three groups, based on the Bonferroni-adjusted threshold (Table S1).
Correlation analysis of altered subregion of hippocampus and clinical characteristics
In the MD group, Pearson partial correlation analysis did not reveal any significant correlations between the GMV of the right hippocampal tail and illness duration (r = 0.121, P = 0.325), HDRS score (r = 0.121, P = 0.325), or MADRS score (r = 0.043, P = 0.727). Furthermore, there were no significant correlations between the GMV of the right hippocampus tail and the five factor scores of HDRS, including anxiety/somatization (r = 0.048, P = 0.700), and weight (r = 0.067, P = 0.586), cognitive dysfunction (r = 0.137, P = 0.266), retardation (r = 0.221, P = 0.070), and sleep disorder (r = -0.097, P = 0.433), after controlling for gender, age, education, and ICV.