The Dark and Gloomy Brain: Grey Matter Volume Alterations in Major Depressive Disorder–Fine-Grained Meta-Analyses

Table 1

Studies included in the meta-analysis.

Study	Sample size (MDD vs. HC)	Age (MDD vs. HC)	Sex (MDD vs. HC)	Drug status	Diagnosis	Depression severity mean (scale type)	Anxiety symptom severity mean (scale type)	Anxiety comorbidity	Atrophy	Hypertrophy	Coordinate system
Wagner et al., [45]	15 vs. 16	41.4 vs. 38.8	15f vs. 16f	Drug-free	DSM-IV	23.5 (HAMD), 28.1 (BDI)	NA	No	Yes	No	Talairach
Leung et al., [46]	17 vs. 17	45.5 vs. 45.8	17f vs. 17f	Medicated	ICD-10	29.7 (BDI)	NA	No	Yes	Yes	Talairach
Mak et al., [47]	17 vs. 17	45.5 vs. 45.8	17f vs. 17f	Medicated	ICD-10	29.7 (BDI)	NA	No	Yes	No	MNI
Zou et al., [48]	23 vs. 23	31.1 vs. 36.6	13f/10m vs. 13f/10m	Drug-naïve	DSM-IV	24.4 (HAMD)	NA	No	Yes	No	Talairach
Cheng et al., [49]	68 vs. 68	29.91 vs. 29.91	47f/21m vs. 47f/21m	Drug-naïve	DSM-IV	22.32 (HAMD)	16.65 (HAMA)	No	Yes	No	MNI
Hwang et al., [50]	70 vs. 26	79.4 vs. 79.5	70m vs. 26m	NA	DSM-IV	29.1 (HAMD)	NA	No	Yes	Yes	Talairach
Scheuerecker et al., [51]	13 vs. 15	37.9 vs. 35.5	3f/10m vs. 5f/10m	Drug-free	DSM-IV	20.5 (HAMD)	NA	No	Yes	Yes	MNI
Amico et al., [52]	33 vs. 30	32 vs. 30.7	14f/19m vs. 13f/17m	Medicated	NA	23 (HAMD)	NA	No	No	Yes	MNI
Salvadore et al., [53]	58 vs. 107	38.8 vs. 36.2	37f/21m vs. 60f/47m	Drug-free	DSM-IV	26 (MADRS)	NA	No	Yes	No	Talairach
Ma et al., [54]	17 vs. 17	26.71 vs. 24.24	7f/10m vs. 7f/10m	Drug-naïve	DSM-IV	25.58 (HAMD)	NA	No	Yes	No	MNI
Wang et al., [55]	18 vs. 18	34 vs. 35	9f/9m vs. 9f/9m	Drug-naïve	DSM-IV	25 (HAMD)	17 (HAMA)	No	Yes	No	MNI
Grieve et al., [56]	102 vs. 34	31.5 vs. 33.8	54f/48m vs. 16f/18m	Drug-free	DSM-IV	21 (HAMD)	NA	No	Yes	No	MNI
Chaney et al., [57]	37 vs. 46	39.75 vs. 40.25	21f/16m vs. 28f/18m	Medicated	DSM-IV	28.6 (HAMD), 34.1 (BDI)	NA	No	Yes	Yes	MNI
Guo et al., [58]	44 vs. 44	27.52 vs. 29.39	22f/22m vs. 24f/20m	Drug-naïve	DSM-IV	25.18 (HAMD)	NA	No	Yes	No	MNI
Jung et al., [59]	24 vs. 29	43 vs. 43.6	17f/7m vs. 21f/8m	Medicated	DSM-IV	20.9 (HAMD)	NA	No	Yes	No	MNI
Kong et al., [60]	28 vs. 28	34.42 vs. 32.07	17f/11m vs. 14f/14m	Drug-naïve	DSM-IV	21.65 (HAMD)	NA	No	Yes	Yes	MNI
Lai et al., [61]	38 vs. 27	36.57 vs. 38.29	20f/18m vs. 15f/12m	Drug-naïve	DSM-IV	22.26 (HAMD)	2.36 (HAMA)	No	Yes	No	MNI
Modinos et al., [62]	23 vs. 46	44.6 vs. 25.3	20f/3m vs. 14f/32m	NA	DSM-IV	NA	NA	No	Yes	No	MNI
Nakano et al., [63]	36 vs. 54	49 vs. 45.4	22f/14m vs. 27f/27m	Medicated	DSM-IV-TR	15.4 (HAMD)	NA	No	Yes	No	MNI
Peng et al., [44]	20 vs. 28	27.75 vs. 28.61	13f/7m vs. 13f/15m	Medicated	DSM-IV	25.95 (HAMD), 55.05 (SDS)	NA	No	Yes	Yes	MNI
	18 vs. 28	31.06 vs. 28.61	12f/6m vs. 13f/15m	Medicated	DSM-IV	24.06 (HAMD), 56.94 (SDS)	NA	No	Yes	No	MNI
Qi et al., [64]	18 vs. 28	31.06 vs. 28.61	11f/7m vs. 13f/15m	Drug-free	DSM-IV	22.28 (HAMD), 51.67 (SDS)	8.11 (HAMA), 27.67 (SAS)	No	Yes	No	MNI
Qiu et al., [65]	46 vs. 46	34.9 vs. 35.4	33f/13m vs. 33f/13m	Drug-naïve	DSM-IV	23.3 (HAMD)	NA	No	No	Yes	MNI
Cai et al., [66]	23 vs. 23	30 vs. 28.2	10f/13m vs. 10f/13m	Medicated	DSM-IV	29.7 (HAMD)	9.22 (HAMA)	No	Yes	No	MNI
Dannlowski et al., [67]	171 vs. 512	38.65 vs. 33.5	105f/66m vs. 289f/223m	Medicated	DSM-IV	23.6 (BDI)	59.35 (STAI-trait)	No	Yes	No	MNI
Fang et al., [68]	20 vs. 18	59.2 vs. 59.1	8f/12m vs. 8f/10m	Medicated	DSM-IV	26.6 (HAMD)	NA	No	Yes	No	MNI
Lai et al., [69]	53 vs. 54	40.07 vs. 40.38	28f/25m vs. 29f/25m	Drug-naïve	DSM-IV	22.43 (HAMD)	2.20 (HAMA)	No	Yes	No	Talairach
Vasic et al., [70]	43 vs. 29	37.1 vs. 34.5	26f/17m vs. 18f/11m	Medicated	DSM-IV	20.09 (HAMD), 29 (BDI)	NA	No	Yes	No	MNI
Watanabe et al., [71]	29 vs. 45	41.05 vs. 41.4	13f/16m vs. 12f/33m	Drug-free	DSM-IV-TR	21.05 (HAMD)	NA	No	Yes	No	Talairach
Yang et al., (a) [72]	50 vs. 50	31.12 vs. 31.30	31f/19m vs. 31f/19m	Drug-free	DSM-IV	23.10 (HAMD)	16.12 (HAMA)	No	Yes	Yes	MNI
Yang et al., (b) [73]	51 vs. 51	30.98 vs. 31.14	31f/20m vs. 31f/20m	Drug-free	DSM-IV	22.90 (HAMD)	16.18 (HAMA)	No	Yes	Yes	MNI
Chen et al., [74]	27 vs. 28	33 vs. 33	14f/13m vs. 14f/14m	Drug-naïve	DSM-IV	22 (HAMD)	NA	No	No	Yes	MNI
Opel et al., [75]	20 vs. 20	37.9 vs. 36.3	10f/10m vs. 10f/10m	Medicated	DSM-IV	22.2 (HAMD), 45.3 (BDI)	NA	No	Yes	No	MNI
Qiu et al., [76]	12 vs. 15	34.4 vs. 33.7	8f/4m vs. 10f/5m	Drug-free	DSM-IV	35.9 (HAMD)	NA	No	Yes	No	MNI
Shen et al., [77]	147 vs. 130	30.58 vs. 30.09	97f/50m vs. 81f/49m	Drug-naïve	DSM-IV	23.83 (HAMD)	NA	No	Yes	Yes	MNI
Wang et al., [78]	25 vs. 35	32.11 vs. 33.28	11f/14m vs. 16f/19m	Medicated	DSM-IV	29.32 (HAMD)	5.32 (HAMA)	No	Yes	No	MNI
Igata et al., [79]	27 vs. 44	45.8 vs. 41.2	12f/15m vs. 12f/32m	Drug-naïve	DSM-IV-TR	21.8 (HAMD)	NA	No	Yes	No	MNI
Yang et al., [80]	82 vs. 82	28.85 vs. 27.72	53f/29m vs. 53f/29m	Drug-free	DSM-IV-TR	23.1 (HAMD)	NA	No	Yes	No	MNI
Zhao et al., [81]	37 vs. 41	26.7 vs. 27.1	12f/25m vs. 15f/26m	Drug-naïve	DSM-IV	25 (HAMD)	28.1 (HAMA)	No	Yes	Yes	MNI
Zhuo et al., [82]	45 vs. 48	38.8 vs. 38.6	26f/19m vs. 27f/21m	Medicated	DSM-IV	27.8 (HAMD)	NA	No	Yes	No	MNI
Chang et al., [83]	108 vs. 156	20.61 vs. 22.25	70f/38m vs. 93f/63m	Medicated	DSM-IV	20.15 (HAMD)	14.94 (HAMA)	No	Yes	No	MNI
Chen et al., [84]	36 vs. 47	30.7 vs. 29.7	16f/20m vs. 25f/22m	Drug-free	DSM-IV	28 (HAMD)	NA	No	Yes	Yes	MNI
Lu et al., [85]	76 vs. 86	33.4 vs. 34.65	44f/32m vs. 43f/43m	Drug-free	DSM-IV	33.3 (HAMD)	NA	No	Yes	Yes	MNI
Zaremba et al., [86]	37 vs. 54	37 vs. 37.5	19f/18m vs. 24f/30m	Medicated	DSM-IV	22.9 (HAMD)	NA	No	Yes	No	MNI
Zhou et al., [87]	114 vs. 111	28.17 vs. 27.63	54f/60m vs. 58f/53m	Drug-free	DSM-IV-TR	No less than 17 (HAMD)	NA	No	Yes	No	MNI
Gong et al., [88]	92 vs. 201	34.96 vs. 29.61	49f/43m vs. 123f/78m	Drug-naïve	DSM-IV	23.06 (HAMD)	NA	No	No	Yes	MNI
Hellewell et al., [89]	98 vs. 66	33.3 vs. 30.09	45f/53m vs. 33f/33m	Drug-free	DSM-IV	21.1 (HAMD)	NA	No	Yes	No	MNI
	131 vs. 66	33.2 vs. 30.09	77f/54m vs. 33f/33m	Drug-free	DSM-IV	21.9 (HAMD)	NA	No	Yes	No	MNI
Kandilarova et al., [90]	39 vs. 42	47.7 vs. 42.6	29f/10m vs. 29f/13m	Medicated	DSM-IV-TR	29.1 (MADRS)	NA	No	Yes	No	MNI
Li et al., [91]	56 vs. 56	35.1 vs. 30.7	36f/20m vs. 23f/33m	Drug-naïve	DSM-IV-TR	25.1 (HAMD)	NA	No	Yes	Yes	MNI
Liu et al., [92]	24 vs. 30	34.79 vs. 33.43	15f/9m vs. 14f/16m	Drug-naïve	DSM-5	25.5 (HAMD)	NA	No	Yes	No	MNI
	21 vs. 30	34.14 vs. 33.43	11f/10m vs. 14f/16m	Drug-naïve	DSM-5	24.48 (HAMD)	NA	No	Yes	Yes	MNI
Peng et al., [93]	104 vs. 160	33 vs. 32	62f/42m vs. 93f/67m	NA	DSM-IV	28 (HAMD)	28 (HAMA)	No	Yes	Yes	MNI
	57 vs. 160	31 vs. 32	36f/21m vs. 93f/67m	NA	DSM-IV	24 (HAMD)	17 (HAMA)	No	No	Yes	MNI
Straub et al., [94]	42 vs. 43	NA vs. 17.62	NA vs. 38f/5m	Medicated	DSM-IV	NA	NA	No	No	Yes	MNI
Chen et al., [95]	22 vs. 22	28.7 vs. 27.4	18f/4m vs. 18f/4m	Medicated	DSM-5	24.5 (MADRS)	NA	No	Yes	No	MNI
Liu et al., [96]	22 vs. 27	32.09 vs. 32.44	12f/10m vs. 14f/13m	Drug-naïve	DSM-5	27.03 (HAMD)	NA	No	Yes	Yes	MNI
	36 vs. 27	35.75 vs. 32.44	21f/15m vs. 14f/13m	Drug-naïve	DSM-5	24.45 (HAMD)	NA	No	Yes	No	MNI
Meng et al., [97]	159 vs. 53	33.71 vs. 35.64	83f/76m vs. 25f/28m	Drug-naïve	DSM-5	23.6 (HAMD)	NA	No	Yes	No	MNI
Nan et al., [98]	166 vs. 166	33.69 vs. 34.64	115f/51m vs. 115f/51m	Drug-naïve	DSM-IV	23.75 (HAMD)	NA	No	Yes	Yes	MNI
Yang et al., [99]	68 vs. 103	32.8 vs. 32.1	54f/14m vs. 67f/36m	Drug-free	DSM-IV	24 (HAMD)	NA	No	Yes	Yes	MNI
	119 vs. 103	34.6 vs. 32.1	65f/54m vs. 67f/36m	Drug-free	DSM-IV	21.9 (HAMD)	NA	No	Yes	No	MNI
Zhang et al., [100]	53 vs. 50	38.1 vs. 34.2	34f/19m vs. 34f/16m	Drug-naïve	ICD-10	19.83 (HAMD)	NA	No	Yes	No	MNI
Jiang et al., [101]	20 vs. 30	27.4 vs. 26.47	12f/8m vs. 15f/15m	Drug-naïve	DSM-IV	21.25 (HAMD)	18.81 (HAMA)	No	Yes	No	MNI
Liu et al., [102]	149 vs. 446	30.76 vs. 33.15	93f/56m vs. 252f/194m	NA	DSM-IV	19.28 (HAMD)	NA	No	Yes	Yes	MNI
	335 vs. 446	34.35 vs. 33.15	219f/116m vs. 252f/194m	NA	DSM-IV	23.68 (HAMD)	NA	No	No	Yes	MNI
Ma et al., [103]	52 vs. 65	24.98 vs. 25.25	34f/18m vs. 32f/33m	Medicated	DSM-IV-TR	NA	NA	No	Yes	No	MNI
Takamiya et al., [104]	48 vs. 52	74.1 vs. 72.4	33f/15m vs. 37f/15m	Medicated	DSM-IV-TR	23.1 (Geriatric Depression Scale)	NA	No	Yes	No	MNI
Zhang et al., [105]	20 vs. 20	28 vs. 31.7	13f/7m vs. 10f/10m	Drug-free	DSM-IV	26.5 (HAMD)	NA	No	Yes	Yes	MNI
Zhou et al., [106]	109 vs. 163	27.43 vs. 28.1	72f/37m vs. 96f/67m	Drug-free	DSM-IV-TR	20.4 (HAMD)	16.22 (HAMA)	No	Yes	No	MNI
Kang et al., [107]	77 vs. 111	22.09 vs. 26.01	62f/15m vs. 87f/24m	Medicated	DSM-5	NA	NA	No	Yes	No	MNI
Li et al., [108]	30 vs. 25	14.6 vs. 15.48	22f/8m vs. 19f/6m	Drug-free	DSM-IV	29.03 (HAMD)	NA	No	Yes	No	MNI
Liu et al., [109]	64 vs. 61	28.47 vs. 30.49	37f/27m vs. 25f/36m	Drug-free	DSM-IV	27.78 (HAMD)	NA	No	Yes	No	MNI
Lu et al.,[110]	108 vs. 99	33.56 vs. 35.93	63f/45m vs. 50f/49m	Medicated	DSM-IV-TR	27.07 (HAMD)	NA	No	Yes	No	MNI
Lu et al., [111]	22 vs. 20	28.6 vs. 27.7	17f/5m vs. 10f/10m	Drug-free	DSM-IV-TR	25.2 (HAMD)	NA	No	Yes	No	MNI
Sun et al., [112]	342 vs. 510	35.98 vs. 33.24	221f/121m vs. 291f/219m	NA	DSM-IV or ICD-10	24.36 (HAMD)	NA	No	Yes	Yes	MNI
	208 vs. 510	31.24 vs. 33.24	131f/77m vs. 291f/219m	NA	DSM-IV or ICD-10	16.83 (HAMD)	NA	No	Yes	No	MNI
Wang et al., [113]	1082 vs. 990	37.23 vs. 37.45	678f/404m vs. 580f/410m	Medicated	DSM-5 or ICD-10	20.75 (HAMD)	19.09 (HAMA)	No	Yes	No	MNI
Yang et al., [114]	85 vs. 95	32.44 vs. 30.21	51f/34m vs. 48f/47m	Medicated	DSM-IV	18.6 (BDI)	42.83 (BAI)	No	Yes	No	MNI
Yu et al., [115]	35 vs. 53	30.26 vs. 27.47	20f/15m vs. 31f/22m	Medicated	DSM-IV	21.83 (HAMD)	NA	No	Yes	No	MNI
Zhang et al., [116]	26 vs. 35	26.42 vs. 25.45	13f/13m vs. 18f/17m	Drug-free	DSM-IV	21.12 (HAMD)	NA	No	No	Yes	MNI
Lai et al., [117]	16 vs. 15	37.91 vs. 34.3	11f/5m vs. 11f/4m	Drug-naïve	DSM-IV	35.91 (HAMD), 26.09 (QIDS-SR16)	33 (HAMA), 18.55 (PDSS)	Yes (16 patients with comorbid panic disorder)	Yes	No	MNI
Qi et al., [64]	20 vs. 28	28.65 vs. 28.61	9f/11m vs. 13f/15m	Drug-free	DSM-IV	20.25 (HAMD), 51.67 (SDS)	16.80 (HAMA), 47.10 (SAS)	Yes (patients with comorbid anxiety disorders)	No	Yes	MNI
Stratmann et al., [118]	132 vs. 132	37.86 vs. 37.82	76f/56m vs. 74f/58m	Medicated	DSM-IV	20.15 (HAMD), 21.95 (BDI)	NA	Yes (41 patients with comorbid anxiety disorders)	Yes	No	MNI
Harada et al., [119]	45 vs. 61	60.2 vs. 62.9	26f/19m vs. 44f/17m	Medicated	DSM-IV-TR	24.8 (BDI), 17.3 (SIGH-D)	NA	Yes (1 patient with comorbid panic disorder; 1 patient with comorbid social anxiety disorder)	Yes	No	MNI
Yang et al., [120]	35 vs. 23	44.54 vs. 39.09	35f vs. 23f	Drug-free	DSM-IV	28.29 (HAMD)	20.17 (HAMA)	Yes (patients with high rates of comorbid anxiety disorders)	Yes	No	MNI
Lu et al., [121]	30 vs. 48	23.95 vs. 21.5	13f/17m vs. 30f/18m	Drug-free	DSM-IV	30.1 (HAMD), 71.5 (SDS)	NA	Yes (patients with comorbid anxiety disorders)	Yes	Yes	MNI
Zhang et al., [122]	30 vs. 63	25 vs. 23	21f/9m vs. 39f/24m	Drug-naïve	DSM-5	26.5 (HAMD)	28 (HAMA)	Yes (patients with comorbid anxiety disorders)	Yes	No	MNI

Abbreviations: BAI = Beck Anxiety Inventory; BDI = Beck Depression Inventory; DSM = Diagnostic and Statistical Manual of Mental Disorders; HAMA = Hamilton Anxiety Rating Scale; HAMD = Hamilton Rating Scale for Depression; ICD = International Classification of Diseases; MADRS = Montgomery-Asberg Depression Rating Scale; QIDS-SR16 = Quick Inventory of Depressive Symptomatology; PDSS = Panic Disorder Severity Scale; SAS = Zung’s Self-Rating Anxiety Scale; SDS = Zung’s Self-Rating Depression Scale; SIGH-D = Structured Interview Guide for the Hamilton Depression Rating Scale; STAI = State-Trait Anxiety Inventory.