Characteristics of studies included in the systematic review (part 1 of 3)
| Author (year) | Participants, n (% female, mean age) | MRI scanner | Segmentation method | Study design | Main findings |
|---|---|---|---|---|---|
| Alnæs et al.42 (2019)*† | Schizophrenia, 1151 (31%, 34 y) Healthy controls, 2010 (44%, 33 y) | 1.5 T and 3.0 T | Automatic (FreeSurfer 6.0¶) | Cross-sectional design, case–control, cohort, multisite; genes | Smaller volume in all subfields; larger left and right hippocampal fissure |
| Brown et al.43 (2019) | MDD, 24 (38%, 40 y) Healthy controls, 20 (25%, 40 y) | 7.0 T | Automatic (FreeSurfer 6.0¶) | Cross-sectional design, case–control, cohort | No significant difference |
| Cao et al.44 (2018) | MDD, 24 (58%, 31 y) Healthy controls, 15 (66%, 33 y) | 3.0 T | Automatic (FreeSurfer 5.3¶) | Longitudinal design, case–control; ECT | Baseline: no significant difference Longitudinal changes: increased left CA2/3, left and right CA4, left and right granule cell layer of the dentate gyrus, left subiculum |
| Cao et al.31 (2017) | MDD, 86 (70%, 41 y) Healthy controls, 152 (63%, 35 y) | 1.5 T | Automatic (FreeSurfer 5.3¶) | Cross-sectional design, case–control | No significant difference |
| Doolin et al.32 (2018) | MDD, 74 (64%, 33 y) Healthy controls, 37 (51%, 31 y) | 3.0 T | Automatic (FreeSurfer 6.0¶) | Cross-sectional design, case–control, cohort | Smaller left CA1, left and right CA2/3, right CA4 |
| du Plessis et al.33 (2020) | First-episode schizophrenia, 79 (27%, 23 y) Healthy controls, 82 (43 %, 23) | 3.0 T | Automatic (FreeSurfer 6.0¶) | Cross-sectional design, case–control, cohort | Statistical analysis between 2 groups was not available |
| Frodl et al.45 (2014) | MDD, 43 (60%, 41 y) Healthy controls, 43 (60%, 37 y) | 3.0 T | Automatic (FreeSurfer**) | Cross-sectional design, case–control; genes | Smaller CA1, CA2/3, CA4/dentate gyrus, subiculum |
| Frodl et al.46 (2014) | MDD, 38 (66%, 41 y) Healthy controls, 44 (61%, 36 y) | 3.0 T | Automatic (FreeSurfer**) | Cross-sectional design, case–control; genes | Smaller left CA2/3, left CA4/dentate gyrus |
| Han et al.21 (2019)‡ | MDD, 102 (59%, 36 y) Healthy controls, 135 (58%, 36 y) | 3.0 T | Automatic (FreeSurfer 6.0¶) | Cross-sectional design, case–control | Smaller left and right whole hippocampus, left and right CA1, left CA2/3, left and right CA4, left and right granule cell layer of the dentate gyrus, right subiculum, right presubiculum, left and right molecular layer |
| Han et al.47 (2017)‡ | MDD, 105 (82%, 43 y) Healthy controls, 85 (71%, 40 y) | 3.0 T | Automatic (FreeSurfer 5.3¶) | Cross-sectional design, case–control; genes | No significant difference |
| Han et al.48 (2016) | MDD, 20 (100%, 42 y) Healthy controls, 21 (100%, 42 y) | 1.5 T | Automatic (FreeSurfer 5.3**) | Cross-sectional design, case–control | Smaller left whole hippocampus, left CA2/3, left CA4/dentate gyrus, left and right subiculum |
| Harel et al.49 (2016) | MDD, 15 (53%, 36 y) Healthy controls, 15 (47%, 37 y) | 3.0 T | Automatic (FreeSurfer 5.3**) | Cross-sectional design, case–control | Smaller right whole hippocampus, right CA1, right CA2/3, right CA4/dentate gyrus |
| Ho et al.16 (2017) | Schizophrenia, 155 (32%, 32 y) Healthy controls, 79 (35%, 31 y) | 3.0 T | Automatic (FreeSurfer 5.3¶) | Cross-sectional design, case–control; longitudinal design in a subcohort; multisite | Schizophrenia: smaller left and right whole hippocampus, left CA1 Early-course schizophrenia: smaller left and right whole hippocampus, left and right CA1, right granule cell layer of the dentate gyrus Longitudinal changes: decreased left and right CA1, right CA2/3, left and right granule cell layer of the dentate gyrus, right molecular layer |
| Schizophrenia, 46 (22%, 43 y) Healthy controls, 46 (22%, 42 y) | Smaller left and right whole hippocampus, left and right CA1, left and right CA2/3, left and right CA4, left and right granule cell layer of the dentate gyrus, left and right subiculum, left and right molecular layer, left and right hippocampal tail | ||||
| Hu et al.66 (2020) | Never-treated long-term schizophrenia, 29 (55%, 46 y) Treated long-term schizophrenia, 40 (55%, 48 y) Healthy controls, 40 (55%, 48 y) | 3.0 T | Automatic (FreeSurfer 6.0¶) | Cross-sectional design, case–control | Never-treated long-term schizophrenia: smaller left and right whole hippocampus, right CA1 (body), left and right CA2/3 (head), right CA2/3 (body), left and right CA4 (head), left and right CA4 (body), left and right granule cell layer of the dentate gyrus (head), left and right granule cell layer of the dentate gyrus (body), left and right subiculum (body), left and right molecular layer (body), left and right hippocampal tail Treated long-term schizophrenia: smaller left and right whole hippocampus, left CA4 (body), left granule cell layer of the dentate gyrus (body), left and right subiculum (body), left and right molecular layer (body), left and right hippocampal tail |
| Hu et al.50 (2019) | Nonresponding MDD, 13 (38%, 36 y) Early responding MDD, 25 (44%, 36 y) Healthy controls, 55 (62%, 36 y) | 3.0 T | Automatic (FreeSurfer 5.3**) | Cross-sectional design, case–control, cohort | MDD: no significant difference Nonresponding MDD: larger left and right CA1, left CA2/3, left CA4/dentate gyrus, left and right subiculum |
| Huang et al.67 (2013)§ | Unmedicated MDD, 9 (44%, 33 y) Medicated MDD, 11 (55%, 37 y) Healthy controls, 27 (70%, 33 y) | 4.7 T | Manual | Cross-sectional design, case–control | Unmedicated MDD: smaller CA1–3 (body), dentate gyrus |
| Hýža et al.51 (2016) | First-episode schizophrenia, 58 (0%, 23 y) Healthy controls, 58 (0%, 24 y) | 1.5 T | Automatic (FreeSurfer 5.2**) | Cross-sectional design, case–control | Larger left CA1 |
| Jiang et al.52 (2019) | Schizophrenia with symptom remission after ECT, 10 (50%, 30 y) Schizophrenia without symptom remission after ECT, 11 (55%, 28 y) Schizophrenia treated by ECT (with and without symptom remission), 21 (52%, 29 y) Schizophrenia with symptom remission after antipsychotic medication, 12 (75%, 31 y) Schizophrenia without symptom remission after antipsychotic medication, 9 (33%, 30 y) Schizophrenia treated by antipsychotic medication (with and without symptom remission), 21 (57%, 31 y) Healthy controls, 23 (52%, 31 y) | 3.0 T | Automatic (FreeSurfer 6.0¶) | Longitudinal design, cohort; ECT | Longitudinal changes: schizophrenia treated by ECT (with and without symptom remission), increased left and right whole hippocampus |
| Kakeda et al.53 (2018) | First-episode MDD, 40 (50%, 47 y) Healthy controls, 47 (28%, 41 y) | 3.0 T | Automatic (FreeSurfer 6.0¶) | Cross-sectional design, case–control | No significant difference |
| Kawano et al.68 (2015) | First-episode schizophrenia, 19 (53%, 25 y) Subchronic schizophrenia, 6 (50%, 22 y) Chronic schizophrenia, 9 (33%, 37 y) Healthy controls, 15 (33%, 25 y) | 1.5 T | Automatic (FreeSurfer 5.1**) | Cross-sectional design, case–control; longitudinal design in a subcohort | Baseline: first-episode schizophrenia, smaller left CA2/3, left CA4/ dentate gyrus Subchronic schizophrenia: smaller left whole hippocampus, left CA2/3, left CA4/ dentate gyrus Chronic schizophrenia: smaller left whole hippocampus, left CA2/3, left CA4/ dentate gyrus |
| Kraus et al.54 (2019) | Acute MDD, 20 (70%, 31 y) Remitted MDD, 28 (57%, 27 y) Healthy controls, 22 (55%, 26 y) | 7 T | Automatic (FreeSurfer 6.0¶) | Longitudinal design, open-label trial | Time 1: remitted MDD, larger right hippocampal fissure Longitudinal changes: no significant difference Time 2: remitted MDD, larger right HATA |
| Li et al.55 (2018) | First-episode schizophrenia, 41 (59%, 24 y) Healthy controls, 39 (51%, 24 y) | 3.0 T | Automatic (FreeSurfer 6.0¶) | Cross-sectional design, case–control; longitudinal design; antipsychotics | Baseline: larger left and right CA4, left and right granule cell layer of the dentate gyrus, left and right molecular layer Longitudinal changes: decreased left and right whole hippocampus, left CA1, left CA2/3, left and right CA4, left and right granule cell layer of the dentate gyrus, left and right molecular layer, left and right hippocampal tail, left fimbria After treatment: larger left and right CA4 |
| Maller et al.20 (2018) | MDD, 182 (52%, 33 y) Healthy controls, 68 (50%, 30 y) | 3.0 T | Automatic (FreeSurfer 6.0¶) | Open-label trial | Baseline: larger hippocampal tail |
| Mathew et al.69 (2014) | Schizophrenia, 219 (34%, 35 y) Healthy controls, 337 (55%, 37 y) | Unknown | Automatic (FreeSurfer 5.1**) | Cross-sectional design, case–control, multisite | Smaller left and right whole hippocampus, left and right CA1, left and right CA2/3, left and right CA4/dentate gyrus, left and right subiculum, left and right presubiculum |
| Mikolas et al.56 (2019) | MDD, 85 (67%, 39 y) Healthy controls, 67 (67%, 36 y) | 3.0 T | Automatic (FreeSurfer 5.3¶) | Cross-sectional design, case–control; genes | Smaller whole hippocampus, CA1, CA2/3, CA4, granule cell layer of the dentate gyrus, molecular layer |
| Na et al.57 (2014) | MDD, 45 (76%, 42 y) Healthy controls, 72 (71%, 41 y) | 3.0 T | Automatic (FreeSurfer 5.0**) | Cross-sectional design, case–control; genes | No significant difference |
| Na et al.34 (2018) | MDD, 47 (100%, 45 y) Healthy controls, 30 (100%, 43 y) | 3.0 T | Automatic (FreeSurfer 6.0¶) | Cross-sectional design, case–control; genes | No significant difference |
| Nakahara et al.35 (2020) | Schizophrenia, 176 (25%, 39 y) Healthy controls, 173 (29%, 38 y) | 3.0 T | Automatic (FreeSurfer 6.0¶) | Cross-sectional design, case–control, multisite | Smaller CA1, CA4, granule cell layer of the dentate gyrus, molecular layer, hippocampal tail; larger hippocampal fissure |
| Nguyen et al.58 (2019) | First-episode MDD, 38 (47%, 47 y) Healthy controls, 39 (28%, 41 y) | 3.0 T | Automatic (FreeSurfer 6.0¶) | Cross-sectional design, case–control; genes | No significant difference |
| Ohi et al.36 (2021) | Schizophrenia, 138 (60%, 42 y) Healthy controls, 162 (33%, 37 y) | 3.0 T | Automatic (FreeSurfer 6.0¶) | Cross-sectional design, case–control | Smaller right HATA; larger right hippocampal fissure |
| Orfei et al.59 (2017) | Schizophrenia, 45 (33%, 40 y) Healthy controls, 45 (33%, 40 y) | 3.0 T | Automatic (FreeSurfer**) | Cross-sectional design, case–control | Smaller left and right whole hippocampus, left and right CA1, left and right CA2/3, left and right CA4/dentate gyrus, left subiculum, left and right presubiculum, left and right hippocampal fissure |
| Ota et al.23 (2017) | Schizophrenia, 20 (25%, 37 y) MDD, 36 (47%, 38 y) Healthy controls, 35 (46%, 39 y) | 3.0 T | Automatic (ASHS) | Cross-sectional design, case–control | Schizophrenia: smaller whole hippocampus, CA1, dentate gyrus than healthy controls, smaller whole hippocampus, dentate gyrus than MDD without medication MDD: no significant difference |
| Otsuka et al.60 (2019) | First-episode MDD, 27 (41%, 46 y); Healthy controls, 42 (26%, 41 y) | 3.0 T | Automatic (FreeSurfer 6.0¶) | Cross-sectional design, case–control; genes | No significant difference |
| Roddy et al.70 (2019) | MDD, 80 (71%, 35 y) Healthy controls, 83 (59%, 32 y) | 3.0 T | Automatic (FreeSurfer 6.0¶) | Cross-sectional design, case–control | Smaller left CA1, left and right CA2/3, left and right CA4, left and right granule cell layer of the dentate gyrus, left and right subiculum, left hippocampal tail; larger right molecular layer |
| Sasabayashi et al.37 (2021) | Schizophrenia, 77 (49%, 29 y) Healthy controls, 87 (47%, 26 y) | 3.0 T | Automatic (FreeSurfer 6.0¶) | Cross-sectional design, case–control, cohort | Smaller left and right CA1, left and right molecular layer, left hippocampal tail |
| Tannous et al.71 (2020) | MDD, 71 (55%, 32 y) Healthy controls, 46 (54%, 32 y) | 7.0 T | Automatic (FreeSurfer 6.0¶) | Cross-sectional design, case–control, cohort | No significant difference |
| Tesli et al.61 (2020)† | Schizophrenia with a history of violence, 24 (4%, 34 y) Schizophrenia with no history of violence, 51 (2%, 29 y) Healthy controls, 90 (3%, 33 y) | 3.0 T | Automatic (FreeSurfer 6.0¶) | Cross-sectional design, case–control, cohort, multisite | Schizophrenia with a history of violence: smaller whole hippocampus, CA1, molecular layer, fimbria, HATA; larger hippocampal fissure Schizophrenia with no history of violence: no significant difference |
| Travis et al.62 (2015)§ | MDD, 15 (80%, 38 y) Healthy controls, 15 (67%, 35 y) | 4.7 T | Manual | Cross-sectional design, case–control, cohort | Smaller dentate gyrus (body) |
| Travis et al.63 (2016)§ | MDD, 14 (64%, 36 y) Healthy controls, 14 (71%, 33 y) | 4.7 T | Manual | Cross-sectional design, case–control, cohort | No significant difference |
| Vargas et al.64 (2018) | Schizophrenia, 91 (26%, 38 y) Healthy controls, 70 (56%, 18 y) | 3.0 T | Automatic (FreeSurfer 5.3**) | Cross-sectional design, case–control | Smaller left and right whole hippocampus, right CA1, left and right CA2/3, left and right CA4/dentate gyrus, left and right subiculum, left and right presubiculum |
| Xiu et al.38 (2021) | First-episode schizophrenia, 39 (59%, 29 y) Healthy controls, 30 (57%, 28 y) | 3.0 T | Automatic (FreeSurfer 5.3¶) | Cross-sectional design, case–control | No significant difference |
| Xu et al.39 (2018) | MDD, 15 (100%, 35 y) Healthy controls, 12 (100%, 34 y) | 3.0 T | Automatic (FreeSurfer 6.0¶) | Cross-sectional design, case–control | Smaller left fimbria |
| Yuan et al.40 (2020) | MDD, 41 (59%, 35 y) Healthy controls, 44 (59%, 33 y) | 3.0 T | Automatic (FreeSurfer 6.0¶) | Cross-sectional design, case–control | No significant difference |
| Zheng et al.41 (2019)* | Schizophrenia, 69 (16%, 38 y) Healthy controls, 72 (29%, 36 y) | 3.0 T | Automatic (FreeSurfer 6.0¶) | Cross-sectional design, case–control | Smaller left and right whole hippocampus, left CA1, left subiculum, left and right presubiculum, right parasubiculum, left and right molecular layer, left hippocampal tail |
| Zhou et al.65 (2020) | MDD, 44 (64%, 35 y) Healthy controls, 45 (53%, 33 y) | 3.0 T | Automatic (FreeSurfer 6.0¶) | Longitudinal design; ketamine treatment | Baseline: smaller left and right whole hippocampus Longitudinal changes: increased right whole hippocampus, right CA4 (head), left CA4 (body), left granule cell layer of the dentate gyrus (body), right molecular layer (head) |
ASHS = Automatic Segmentation of Hippocampal Subfields; CA = cornu ammonis; ECT = electroconvulsive therapy; HATA = hippocampus–amygdala transition area; MDD = major depressive disorder.
↵* Overlapped data.
↵† Overlapped data.
↵‡ Overlapped data.
↵§ Overlapped data.
↵** Atlas by van Leemput and colleagues.72
↵¶ Atlas by Iglesias and colleagues.15