Demographic and clinical characteristics of the participants in the 18 studies (22 data sets) included in the meta-analysis
| Study | Participants, n (females) | Age, yr | Age at onset, yr | Illness duration, yr | Severity (scale type) | Diagnosis | Statistical threshold | Drug states | Mood states | Comorbidity* | Quality scores | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| BD | HC | BD | HC | ||||||||||
| Ambrosi et al., BD I19 | 25 (12) | 50 (24) | 48.6 | 48.3 | NA | 20.3 | 9.2 (HAMD) | BD I | p < 0.008 (multiple comparison) | 10 AD, 16 AP, 11 AE, 16 Li, 6 BDZ | NA | NA | 11.5 |
| Ambrosi et al., BD II19 | 25 (12) | 50 (24) | 48.3 | 48.3 | NA | 23.9 | 14.5 (HAMD) | BD II | p < 0.008 (multiple comparison) | 6 AD, 12 AP, 14 AE, 10 Li, 13 BDZ | NA | NA | 11.5 |
| Versace et al.17 | 31 (20) | 25 (14) | 35.9 | 29.5 | 25.4 | 12.3 | RBD 2.1, DBD 15.2 (HAMD) | BD I | p < 0.05 (multiple comparison) | 5 Li, 12 MS, 8 AP, 7 AD, 7 BDZ | 17 euthymic, 14 depressed | NA | 11.5 |
| Kumar et al.34 | 22 (7) | 41 (11) | 34.7 | 33.2 | NA | 10.7 | 8.57 (SSPI) | BD | pTFCE < 0.05 | 55 on medications, including AP and MS | NA | NA | 11 |
| Delaloye et al.35 | 15 (NA) | 15 (NA) | 67.9 | 68.3 | 34.1 | 33.8 | 1.00 (YMRS) | BD | pTFCE < 0.05 | 10 MS, 3 AD, 6 BDZ, 4 NL | Euthymic | NA | 10.5 |
| Haller et al.18 | 19 (14) | 47 (22) | 68.5 | 69.8 | 39.4 | 29.2 | 0.95 (YMRS) | BD I BD II | pTFCE < 0.05 | 15 MS, 5 AP, 7 BDZ, 5 NL, 3 UM | Euthymic | NA | 11.5 |
| Benedetti et al., FREE31† | 26 (17) | 21 (10) | 45.1 | 39.9 | 31.6 | 13.5 | 20.1 (HAMD) | BD I | pTFCE < 0.05 | 26 UM | Depressed | NA | 11 |
| Benedetti et al., TREAT31† | 14 (11) | 21 (10) | 47.8 | 39.9 | 31.1 | 17.6 | 19.1 (HAMD) | BD I | pTFCE < 0.05 | 14 Li | Depressed | NA | 11 |
| Chan et al.36 | 16 (4) | 16 (4) | 36.9 | 37.3 | NA | 0.2 | 3.8 (YMRS) | BD I | p < 0.001 (uncorrected) | 6 Li, 7 MS (sodium valproate), 12 AP | Euthymic | NA | 11 |
| Lagopoulos et al.37 | 58 (41) | 40 (24) | 23.0 | 24.1 | 15.4 | 7.5 | 13.4 (HAMD) | BD I, BD II, spectrum | pFWE < 0.05 | 25 AD, 23 MS, 37 AP, 8 UM | Depressed | NA | 11.5 |
| Mahon et al., SU32† | 14 (5) | 15 (7) | 33.3 | 33.7 | 20.8 | 12.5 | 6.8 (HAMD) | BD I | pFWE < 0.05 | 10 MS, 6 AP, 3 UM | NA | Yes | 10.5 |
| Mahon et al., NSU32† | 15 (6) | 15 (7) | 36.5 | 33.7 | 24.8 | 11.7 | 5.4 (HAMD) | BD I | pFWE < 0.05 | 14 AP, 14 MS | NA | Yes | 10.5 |
| Sprooten et al.38 | 64 (46) | 46 (31) | 31.7 | 30.1 | 18.0 | 10.0 | 2.0 (HAMD) | BD I | pFWE < 0.05 | 34 MS, 28 AD, 23 AP, 12 Li, 11 UM | Euthymic | Yes | 12 |
| Versace et al.39 | 15 (14) | 24 (15) | 36.3 | 27.7 | 21.6 | 14.7 | 14.9 (HAMD) | BD I | pTFCE < 0.05 | 10 MS, 10 AP, 8 AP, 6 BDZ | Depressed | NA | 11.5 |
| Wessa et al.40 | 22 (11) | 21 (9) | 45.4 | 43.0 | 23.0 | 22.0 | 0.1 (HAMD) | BD I, BD II | pFDR < 0.05 | 10 Li, 11 AC, 6 AD, 5 AP, 4 UM | Euthymic | Yes | 10.5 |
| Liu et al., BD I33 | 14 (7) | 21 (13) | 35.6 | 38.3 | NA | 7.3 | 6.7 (HAMD) | BD I | p < 0.001 (uncorrected) | 2 Li, 12 AC, 12 AD, 1 AP | 7 manic, 7 depressed | NA | 11 |
| Liu et al., BD II33 | 13 (11) | 21 (13) | 35.1 | 38.3 | NA | 9.4 | 9.5 (HAMD) | BD II | p < 0.001 (uncorrected) | 10 AC, 10 AD, 1 AP | 5 manic, 8 depressed | NA | 11 |
| Magioncalda et al.41 | 61 (43) | 42 (27) | 44.6 | 44.3 | 25.1 | 19.6 | 6.9 manic, 21.5 depressed, 3.6 euthymic (HAMD) | BD I | pTFCE < 0.01 | 52 MS, 22 AD, 35 AP, 21 BDZ, 2 UM | 21 manic, 20 depressed, 20 euthymic | NA | 11.6 |
| Oertel-Knochel et al.42 | 30 (14) | 32 (16) | 39.2 | 39.2 | NA | 10.2 | NA | BD I | pTFCE < 0.01 | 24 MS, 12 AD, 13 NL, 5 AL | Euthymic | NA | 10.5 |
| Gao et al.43 | 18 (12) | 18 (12) | 15.1 | 14.1 | 13.8 | 1.3 | 33.4 (YMRS) | BD I, BD II | pTFCE < 0.05 | 2 UM, 8 VP, 7 Li, 13 AP, 3 AD | Manic | Yes | 11 |
| Teixeira et al.44 | 18 (6) | 20 (6) | 12.3 | 12.7 | 9.5 | 2.8 | 8.7 (YMRS) | BD I, BD II, BD NOS‡ | pTFCE < 0.05 | All UM | 6 manic, 8 euthymic, 4 mixed | Yes | 11 |
| Haarman et al.45 | 21 (12) | 22 (11) | 44.7 | 38.2 | 19.5 | 25.2 | 0.2 (YMRS) | BD I | pTFCE < 0.05 | Medicated | Euthymic | No | 11.5 |
AC = anticonvulsant; AD = antidepressant medication; AE = antiepileptic medication; AL = anxiolytics; AP = antipsychotic medication; BD = bipolar disorder; BDZ = benzodiazepine; DBP = depressed with bipolar disorder; FDR = false discovery rate; FWE = family-wise error corrected; HAMD = Hamilton Depression Rating Scale; HC = healthy controls; Li = lithium; MS = mood-stabilizing medication; NA = not available; NL = neuroleptics; NOS = not otherwise specified; RBD = remitted with bipolar disorder; SSPI = Signs and Symptoms in Psychotic Illness scale; TFCE = threshold-free cluster enhancement; UM = unmedicated; VP = valproate; YMRS = Young Mania Rating Scale.
↵* Comorbidity:
• Mahon et al., SU: substance abuse or dependence (n = 3), anorexia nervosa (n = 1), panic disorder with (n = 1) and without (n = 1) a history of agoraphobia, anxiety disorder NOS (n = 2), posttraumatic stress disorder (n = 2), generalized anxiety disorder (n = 1), specific phobia (n = 1) and bulimia nervosa (n = 1).
• Mahon et al., NSU: substance abuse or dependence (n = 5), obsessive–compulsive disorder (n = 1) and agoraphobia without a history of panic disorder (n = 1).
• Sprooten et al.: anxiety disorder (n = 30), alcohol use disorder (n = 33), substance use disorder (n = 29), nicotine dependence, current (n = 21).
• Gao et al.: anxiety (n = 1), attention-deficit hyperactivity disorder (n = 1), obsessive–compulsive disorder (n = 2).
• Teixeira et al.: attention-deficit/hyperactivity disorder (n = 9), oppositional defiant disorder (n = 5), generalized anxiety disorder (n = 3), conduct disorder (n = 2), simple phobia (n = 2), posttraumatic stress disorder (n = 2), panic disorder (n = 1), separation anxiety disorder (n = 1), obsessive–compulsive disorder (n = 1) and Tourette syndrome (n = 1).
• Wessa et al.: panic disorder (n = 1).
↵† FREE indicates that the study includes a subgroup of drug-free patients with BD. TREAT indicates that the study includes a subgroup of lithium-treated patients with BD. SU indicates that the study includes subgroup of patients with a previous suicide attempt. NSU indicates that the study includes subgroup of patients without a previous suicide attempt.
↵‡ Children and adolescents were diagnosed as BD NOS if they presented with clear manic or hypomanic episodes with elation and/or grandiosity but lacked the duration needed to be classified as BD I or BD II.