Table 1.
Characteristics of VBA studies included in meta-analysis.
| Paper | Patients male/female | HCs male/female | Contrast | Illness length (months) | Patient age mean (SD) | HC age mean (SD) | Meds | HRSD score mean (SD) # items | Dx tool | Excluded psychiatric comorbidities | B0 | Vox. size (mm) | Directions | Highest b (s/mm2) | p |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MDD | |||||||||||||||
| Arnold et al. (2012) | 4 M/13 F | 7 M/14 F | rMDD vs HC | N/A | 30.41 (11.35) | 26.90 (7.82) | No | 9.18 (6.82) 17 item | SCID-I mood sect. | Other psychiatric Dx as per the MINI, SUD | 1.5 | 2.5 × 2.5 × 2.5 | 30 | 900 | Cluster differences of p < 0.001, uncorrected |
| Blood et al. (2010) | 10 M/12 F | 10 M/12 F | MDD vs HC | N/A | 36.3 (12.1) | 35.3 (11.6) | Yes | NA, 31 items | SCID | Psychotic, BD, eating, OCD, SUD, GAD, PD, PTSD | 3 | 2 × 2 × 2 | 6 | 700 | p < 0.00005, whole-brain Bonferroni corrected |
| Choi et al. (2014) | 64 M/70 F | 28 M/26 F | MDD vs HC | 112.08 | 38.49 (11.09) | 34.42 (10.06) | Med. free | 19.28 (3.47) – 17 item | SCID | Psychotic, BD, OCD, SUD | 3 | 2 × 2 × 2 | 60 | 1000 | Permutation based TFCE, and FWE correction (p < 0.05, 10,000 permutations) used with estimation of cluster size |
| Jia et al. (2010) | Suicide attempt = 5 M/11 F; non-attempt = 20 M/16 F | 24 M/28 F | 1. suicide attempt vs HC; 2. non-attempt vs HC | attempt = 80.00; non-attempt = 21.00 | attempt = 34.2 (13.7); non-attempt = 34.7 (12.5) | 37.1 (16.0) | Med.- free for at least 2 weeks prior to study | attempt = 24.6 (3.8); non-attempt = 22.3 (4.3)- 17 item | SCID | Any DSM-IV axis I comorbidities, SUD | 3 | 1.9 × 1.9 × 3 | 15 | 1000 | Voxel-level p < 0.05 (FWE corrected), extent threshold p < 0.05 (uncorrected), k ≥ 50 |
| Ma et al. (2007) | 2 M/12 F | 2 M/12 F | 1st ep. MDD vs HC | 10.30 | 28.9 (8.0) | 27.1 (6.7) | Med. naïve | N/A (BDI = 37.5; 6.9) | SCID | “Any lifetime psychiatric disorder” | 1.5 | 1.9 × 1.9 × 4 | 13 | 1000 | Voxelwise p < 0.001 (uncorrected) & k ≥ 50 |
| Osoba et al. (2013) | 8 M/12 F | 8 M/12 F | MDD vs HC | N/A | 38.3 (11.6) | 33.8 (7.2) | All patient antidep | 15.1 (6.1) – 21 item | ICD-10 | Major medical Dx, seizures, ECT, psychiatric Dx, SUD | 3 | 2 × 2 × 2 | 12 | 1000 | Voxelwise p < 0.05 (corrected) & whole brain αSim correction height p < 0.001 (uncorrected) & k ≥ 256 |
| Ouyang et al. (2011) | 9 M/9 F | 9 M/9 F | 1st ep. MDD vs HC | 15.10 | 27.4 (6.4) | 27.0 (6.8) | Naïve | 24.2 (4.3) 17 item | SCID | Substance abuse Hx | 1.5 | 1.9 × 1.9 × 4 | 13 | 1000 | p < 0.001 (uncorrected), k ≥ 30 |
| Peng et al. (2013) | 19 M/11 F | 14 M/11 F | TRD vs HC | 56.16 | 26.77 (5.28) | 28.24 (4.98) | N/A, resistant to 2 + classes of antidep > 4 weeks at max. dose |
N/A BDI: 20.47 (4.45) | DSM-IV | DSM axis I or II Dx | 3 | 1.3 × 1.3 × 3 | 30 | 1000 | Voxelwise p < 0.05 (FDR corrected) & k ≥ 50, cluster level p < 0.05 (FDR corrected) |
| Tha et al. (2013) | 12 M/7 F | 13 M/6 F | MDD vs HC | 18.37 | 38.6 (13.5) | 36.5 (12.5) | Antidep free > 6 months | 19.0 (4.0) 17 item | DSM-IV-TR and MINI | DSM axis I or II Dx | 1.5 | 1.9 × 1.9 × 5 | 12 | 1000 | p < 0.001 (uncorrected), k ≥ 50 |
| Wang et al. (2013) | 5 M/16 F | 8 M/14 F | MDD pre-treatment vs HC | 14.20 | 29.6 (12.6) | 30.2 (10.2) | Yes | 20.4 (6.3) -17 item | DSM-IV | Other psychiatric Dx or Hx of symptoms | 3 | 1 × 1 × 5 | 14 | 1000 | p < 0.001, k ≥ 50, & αSim correction at p < 0.05 (height threshold p < 0.001, k ≥ 23) |
| Wu et al. (2011) | 10 M/13 F | 9 M/12 F | 1st ep., treatment-naïve MDD vs HC | 2.17 | 31.4 (8.8) | 30.4 (8.2) | Naïve | 21.8 (3.8) 17 item | SCID | DSM axis I or II Dx | 1.5 | 1 × 1 × 4 | 13 | 1000 | p < 0.001 (uncorrected), k ≥ 30 |
| Zou et al. (2008) | 15 M/30 F | 15 M/30 F | MDD vs HC | 20.00 | 33.2 (8.9) | 31.0 (10.3) | Yes | 23.8 (3.3) 17 item | DSM-IV | Major psychiatric Dx including schizophrenia, BD, affective disorder, personality disorder, substance abuse, SUD | 3 | 1.9 × 1.9 × 3 | 15 | 1000 | Cluster threshold p < 0.001 (uncorrected), p < 0.05 at voxel-level after FDR correction |
| BD | |||||||||||||||
| Bruno et al. (2008) | 13 M/23 F | Total N = 28, # M/F not reported | BD (I&II) vs HC | 165.60 | 39 (no SD) | N/A other than matchBD group (range 21–63) | Yes | N/A | SCID | “Comorbid psychiatric conditions” | 1.5 | 2.5 × 2.5 × 5 | 7 | 4 values between 0 and 700 | p < 0.05 at cluster level after FWE correction for multiple comparisons |
| Chaddock et al. (2009) | 9 M/10 F | 10 M/8 F | Psychotic BD I in remission vs HC | N/A | 43.3 (10.2) | 41.7 (12.2) | Yes | N/A but BDI mean = 7.9 (7.0) | SADS-LV | SUD | 1.5 | 2.5 × 2.5 × 2.5 | 64 | 1300 | Voxelwise p < 0.05, the permutation tested with expected number of false positives < 1 per analysis |
| Chen et al. (2012) | 18 M/0 F | 27 M/0 F | BD (I & II 1st ep. Mania) vs HC | Median 50.40 | 32.0 (7.6) | 31.3 (6.8) | Yes but not > 5 days prior | 3.2 (1.1) – 17 item | SCID | Axis I Dx, Hx of drug or alcohol abuse | 3 | 1.9 × 1.9 × 3 | 15 | 1000 | p < 0.05 (FDR corrected) and k ≥ 50 |
| Cui et al. (2011) | 10 M/8 F | 18 M/12 F | BD I (current manic ep.) vs HC | 57.60 | 27.9 (5.7) | 23.9 (10.2) | Yes | 3.1 (2.2) | SCID | Hx substance abuse | 3 | 1.9 × 1.9 × 3 | 15 | 1000 | Voxelwise p < 0.001 (uncorrected) and k ≥ 50 |
| Ha et al. (2011) | BD I = 3 M/9 F; BD II = 2 M/10 F | 5 M/17 F | 1. BD I vs HC; 2. BD II vs HC | BD I = 159.60; BD II = 159.60 | BD I = 37.3 (10.59); BD II = 35.6 (7.56) | 34.7 (7.12) | Yes | BP I = 5.5 (6.9); BP II = 4.2 (4.43) - 17 item | SCID | Hx substance abuse, current “severe mood episode” | 1.5 | 2 × 2 × 3 | 15 | 600 | p < 0.001 (uncorrected), k ≥ 40 |
| Liu et al. (2010) | BD I = 7 M/7 F; BD II = 2 M/11 F | 8 M/13 F | 1. BD I vs HC; 2. BD II vs HC |
BD I = 87.60; BD II = 112.8 | BD I = 35.6 (10.9); BD II = 35.1 (9.8) | 38.3 (11.9) | Yes | BP I = 6.7 (5.8); BP II = 9.5 (6.6) 17 item | SCID | N/A | 1.5 | 2 × 2 × 2.2 | 13 | 900 | p < 0.001 (uncorrected, k ≥ 50), then applied SVC to significant clusters using 8 mm radius at peak with FDR p < 0.001 |
| Mahon et al. (2009) | 15 M/15 F | 22 M/16 F | BD (I, II & NOS) vs HC | N/A | 33.4 (8.7) | 31.9 (8.6) | Yes | N/A | SCID | N/A | 1.5 | 1.7 × 1.7 × 5 | 25 | 1000 | Voxelwise p < 0.001, k ≥ 50 & FDR corrected p < 0.015 |
| Sussmann et al. (2009) | 22 M/20 F | 19 M/19 F | BD I vs HC | 219.60 | 39.6 (10.1) | 37.2 (11.9) | Yes | 2.3 (5.8) | SCID | N/A | 1.5 | 1.7 × 1.7 × 2.8 | 51 | 1000 | p < 0.001 (uncorrected) |
| Wessa et al. (2009) | 11 M/11 F | 12 M/9 F | BD I & BD II (remitted) vs HC | 264 | 45.41 (12.60) | 42.95 (13.17) | Yes | 1.55 (1.53) | DIGS | N/A | 1.5 | 1.9 × 1.9 × 2 | 41 | 700 | For VBA: p < 0.05 (FDR corrected), k ≥ 70 |
| Zanetti et al. (2009) | 13 M/24 F | 12 M/14 F | BD I (active & remitted) vs HC | 139.20 | 34.1 (9.0) | 28.8 (9.5) | Yes | 9.4 (9.4) 25 item | SCID | Borderline personality disorder, current alcohol or substance abuse or dependence | 3 | 1.6 × 1.6 × 3 | 6 | 850 | Voxelwise p < 0.001 (uncorrected), k ≥ 50 |
| SAD | |||||||||||||||
| Baur et al. (2011) | 18 M/7 F | 18 M/7 F | SAD vs HC | 192 | 32 (10.4) | 32 (10.1) | Yes | N/A BDI = 15 (10.8) | MINI | N/A | 3 | 0.9 × 0.9 × 3.2 | 21 | 1000 | Voxelwise p < 0.00001 (uncorrected), cluster-extent FWE correction p < 0.05, k ≥ 48 |
| Phan et al. (2009) | 15 M/15 F | 10 M/20 F | SAD vs HC | N/A | 27.20 (7.80) | 29.90 (8.13) | Free for < 8 weeks (except n = 1) | N/A BDI = 10.7 (6.51) | SCID | OCD, PTSD, BD, psychotic disorder | 3 | 0.9 × 0.9 × 3 | 12 | 900 | p < 0.01 (uncorrected) volume ≥ 100 mm3 |
| Qiu et al. (2014) | 12 M/6 F | 12 M/6 F | SAD vs HC | 49.22 | 22.72 (3.85) | 21.78 (3.90) | Naïve | N/A | SCID | DSM axis I or II disorders, drug abuse or dependence | 3 | 1.9 × 1.9 × 3 | 15 | 1000 | p < 0.01, uncorrected |
| OCD | |||||||||||||||
| Admon et al. (2012) | 10 M/3 F | 10 M/3 F | OCD vs HC | 96 | 25.5 (1.0) | 27.0 (0.5) | All taking | N/A | SCID | Substance abuse | 1.5 | 1.6 × 1.6 × 3 | 6 | 1000 | Cluster p < 0.005, k ≥ 10, uncorrected |
| Cannistraro et al. (2007) | 3 M/5 F | 4 M/6 F | OCD vs HC | N/A | 26.4 (5.9) | 23.3 (1.5) | Med-free 4 + weeks | N/A | SCID | Current or past axis I Dx | 1.5 | 2 × 2 × 2 | 6 | 600 | Voxelwise p < 0.05, k ≥ 20, uncorrected, then cluster p < 0.005, uncorrected |
| Garibotto et al. (2010) | 15 M/0 F | 16 M/0 F | OCD vs HC | 121.56 | 31.87 (7.92) | 29.67 (6.3) | Yes | N/A | DSM-IV | Hoarding behavior, motor tics, Tourette's, axis I or II Dx | 1.5 | 1.9 × 1.9 × 2.3 | 35 | 1000 | p < 0.005, uncorrected, k ≥ 20 |
| Li et al. (2014) | Both OCD N = 11 (M/F N/A) | N = 11 (M/F N/A) | 1. TROCD vs HC; 2. OCD vs HC | TROCD = 23.4; OCD = 18.6 | N/A | N/A | All | TROCD = 15.36 (4.30); OCD = 13.55 (2.94) | SCID | Current axis I Dx or psychiatric Dx in past year | 3 | 2 × 2 × 2 | 30 | 1000 | p < 0.05 FDR corrected, k ≥ 50 |
| Menzies et al. (2008) | 9 M/21 F | 10 M/20 F | OCD vs HC | N/A | 32.2 (11.1) | 33.7 (11.2) | Yes | N/A | DSM-IV, MINI | Hoarding or motor tics, Hx of substance abuse, DSM-IV axis I Dx (except PD) | 1.5 | 2.3 × 1.9 × 4 | 25 | 1000 | Cluster p < 0.017, uncorrected |
| Nakamae et al. (2008) | 9 M/6 F | 9 M/6 F | OCD vs HC | 121.2 | 29.7 (6.9) | 29.1 (6.0) | All currently taking | N/A | SCID | SUD, schizophrenia, schizoaffective disorder, delusional disorder, brief reactive psychosis, psychotic disorder NOS | 1.5 | 1.8 × 2.2 × 3 | 15 | 1000 | p < 0.001 (uncorrected), k ≥ 100 |
| Szeszko et al. (2005) | 10 M/5 F | 10 M/5 F | OCD vs HC | 259.2 | 38.5 (10.9) | 38.5 (11.8) | Yes | 13.9 (4.9) | SCID | SUD, schizophrenia, schizoaffective disorder, delusional disorder, brief reactive psychosis, psychotic disorder NOS | 1.5 | 1.7 × 1.7 × 5 | 25 | 1000 | p < 0.005, k ≥ 20 (uncorrected) |
| Yoo et al. (2007) | 8 M/5 F | 8 M/5 F | OCD pre-treatment vs HC | 86.4 | 27.8 (7.3) | 26.9 (7.0) | Naïve | 12.5 (7.6) | SCID | Psychosis, BD, SUD, Tourette's or other tic-related conditions | 1.5 | 1.7 × 1.7 × 4 | 6 | 600 | p > 0.001 (uncorrected), k ≥ 20 |
| PTSD | |||||||||||||||
| Kennis et al. (2015) | rPTSD = 15 M/0 F; PTSD = 18 M/0 F | 24 M/0 F | Non-blast PTSD vs combat controls prior to PTSD treatment | N/A | rPTSD = 34.38 (9.58); PTSD = 36.61 (8.74) | 37.64 (10.97) | Yes | N/A | DSM-IV | Alcohol or substance dependence | 3 | 1.9 × 1.9 × 2 | 30 | 1000 | TFCE p < 0.05, corrected |
| Kim et al. (2005) | 8 M/12 F | 9 M/11 F | PTSD vs HC | N/A | 28.4 (8.9) | 30.6 (8.9) | N/A | N/A | SCID and CAPS | Premorbid axis I Dx, antisocial or borderline personality disorder, ADHD or lifetime exposure to illicit substances | 3 | 0.9 × 0.9 × 3.5 | 25 | 1000 | p < 0.05, corrected |
| Sun et al. (2013) | 8 M/13 F | 9 M/13 F | Trauma exposed with PTSD vs trauma exposed without PTSD | All scans within 2 days of trauma, Dx made at 1 or 6 months | 40.86 (12.26) | 40.23 (12.54) | Med-free for 4 weeks prior to MRI | N/A | MINI and CAPS | Axis I Dx, drug or alcohol abuse or dependence within 6 months | 3 | 2 × 2 × 2 | 20 | 1000 | αSim p < 0.05 corrected, with voxel p < 0.001, cluster k ≥ 76 |
| Zhang et al. (2011) | 17 M/0 F | 14 M/14 F | First episode PTSD vs HC | N/A | 34.06 (4.97) | 28.96 (6.22) | Naive | N/A | SCID | Any current or past comorbid psychiatric Dx | 1.5 | 1.9 × 1.9 × 4 | 13 | 1000 | p < 0.001, uncorrected, k ≥ 100 |
Note. Abbreviations: αSim = AlphaSim, antidep = antidepressant = BD = bipolar, CAPS = Structured Clinician-Administered PTSD Scale for DSM-IV, DIGS = Diagnostic Interview for Genetic Studies, DSM = Diagnostic and Statistical Manual, Dx = diagnosis, eating = eating disorder, ECT = electroconvulsive therapy, ep. = episode, FDR = False Discovery Rate, FWE = family-wise error, GAD = generalized anxiety disorder, HC = healthy control, HRSD = Hamilton Rating Scale for Depression, Hx = history, k = cluster size threshold, max = maximum, MDD = major depressive disorder, med = medication, MINI = Mini-International Neuropsychiatric Interview, NOS = not otherwise specified, OCD = obsessive compulsive disorder, PD = panic disorder, psychotic = psychotic disorder, PTSD = post-traumatic stress disorder, rMDD = remitted major depressive disorder, rPTSD = remitted post-traumatic stress disorder, SAD = Social Anxiety Disorder, SADS-LV = Schedule for Affective Disorders – Lifetime Version, SCID = Structured clinical interview for DSM disorders, SD = standard deviation, sect. = section, SVC = small volume correction, SUD = substance use disorder, TCFE = threshold-free cluster enhancement, TRD = treatment resistant depression, TROCD = treatment resistant obsessive compulsive disorder, VBA = voxel based analysis, vox size (mm) = voxel size in millimeters.