Table 1.
Study details on all prospective studies (N = 75), subdivided by the following biological sublevels: Neuroimaging, Gastrointestinal factors, Immunology, Neurotransmitters, Neurotrophic factors, Hormones: HPA axis, HPG axis, HPS axis, and HPT axis
| Neuroimaging | Baseline MDD excl. Y = yes, N = No | Baseline symptoms a = above cut-off, b = below cut-off, ? = unclear | Country and cohort information (nr indicates similar cohorts) | Total N | Onset (O) or relapse/ recurrence (R) of MDD N | Baseline age (mean or range) | % female | Follow-up time (years; mean or max) | MDD diagnostic interview; Diagnostic criteria | Biomarker of interest | Measure | Technical details | Direction result of biomarker predicting onset, relapse/ recurrence of MDD | Quality score |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Bress et al. [39]a | Y | b | USA | 68 | 16 O | [15–17] | 100 | 2 | DISC; ICD-10 | Frontal brain areas (ERP) | Activity: EEG | During reward task. comparing loss-gain | ↓ Frontal ERP | 7 |
| Davey et al. [49]a | Y | ? | Australia | 56 | 8 O | 17 | 45 | 2 | K-SADS-PL; DSM-IV (nm) | Amygdala-sgACC connectivity | RSFC fMRI | Resting state | ↑ Amygdala–sACC connectivity | 4 |
| Foland-Ross et al. [51]b | Y | b | USA | 33 | 18 O | 13 | 100 | 5 | K-SADS-PL and SCID; DSM-IV (nm) | 32 brain regions were used for support vector machine classification | Structure: MRI | Volumes | The most important classifiers for MDD were ↓ mOFC, PCG, ACC, and ↑ insula | 7 |
| Little et al. [73]c | Y | ? | Australia1 | 99 | 26 O | 13 | 29 | 6 | K-SADS-PL. MINI; DSM-IV (nm) | Hippocampus, amygdala, OFC and ACC | Structure: MRI | Volumes |
↓ Hippocampus NS amygdala, OFC and ACC |
6 |
| Little et al. [74] | ? | ? | Australia1 | 137 | 36 O | 13 | 52 | 6 | K-SADS-PL; DSM-IV (nm) | Hippocampus | Structure: MRI | Volumes | ↓ hippocampus | 5 |
| Nusslock et al. [83]a | ? | b | USA | 40 | 13 O | 20 | 43 | 3 | SADS-C; DSM-IV | Left frontal brain areas (Alpha power) | Activity: EEG | Rest. eyes-open and eyes-closed | ↓ Left frontal activity | 6 |
| Papmeyer et al. [85]a | Y | b | UK1 | 204 | 19 O | 21 | 56 | 2 | Clinical interview; DSM-IV (nm) | Frontal brain regions | Structure: MRI | Gray matter thickness | ↓ Right parahippocampal and fusiform gyrus | 9 |
| Papmeyer et al. [86]a | Y | b | UK1 | 204 | 19 O | 21 | 56 | 2 | Clinical interview; DSM-IV | Subcortical brain regions | Structure: MRI | Gray matter thickness | NS | 9 |
| Whalley et al. [99]a | Y | b | UK1 | 156 | 20 O | 21 | 52 | 2 | SCID ; DSM-IV | Brain regions activated by the task | Activity: fMRI | Cognitive sentence completion task: increase in difficulty | ↑ Insula activity | 7 |
| Whalley et al. [100]a | Y | b | UK1 | 50 | 11 O | 23 | Unclear | 2 | SCID; DSM-IV | Amygdala, insula, hippocampus, ACC, thalamus | Activity: fMRI | View emotional images vs neutral | ↑ Thalamus, insula, ACC activity | 7 |
| Nickson et al. [81]c | N | b | UK1 | 131 | 30 O | 21 | 69 | 4.9 | SCID; DSM-IV | VBM | Structure: MRI | Whole brain VBM | ↑Amygdala gray msatter volume | 7 |
| Macoveanu et al. [77]b | Y | b | Denmark | 85 | 12 O | 39 | 65 | 7 | SCAN 2.1; (ICD-10) | VBM | Structure: MRI | Whole brain VBM | ↑ACC gray matter volume | 5 |
| Belden et al. [36]a | Y | ? | USA | 129 | 24 O + R | [6–12] | 48 | 10 | Clinician and TRD; DSM-5 | Anterior insula | Structure: MRI | Volumes | ↓ Insula volume | 6 |
| Rao et al. [91]a | Y | a | USA | 83 | 29 O + R | 15 | 58 | 5 | LIFE. PSR; DSM-IV (at baseline) | Hippocampus | Structure: MRI | Volumes | ↓ Hippocampus | 5 |
| Serra-Blasco et al. [95]a | N | a | Spain | 24 | 10 O + R | 48 | 75 | 5 | Life-Chart Manual for Recurrent Affective Illness; Unclear | Whole brain (Freesurfer) | Structure: MRI | Volumes | ↓rIFG, ACC, rMFG volumes predict recurrence | 8 |
| Allen et al. [31]a | Y | b | USA | 9 | 3 R | 49 | 61 | 0.5 | SCID; DSM-III-R | Frontal asymmetry | Activity: EEG | Rest. pre- post-tryptophan depletion | ↑ Right frontal activity after vs before TD predict lower change of recurrence at follow-up | 6 |
| Farb et al. [50]a | Y | b | Canada | 16 | 10 R | 39 | 69 | 1.5 | SCID; DSM-IV | ROI mPFC | Activity: fMRI | Viewing sad vs natural movie clips | ↑ mPFC activity | 7 |
| Frodl et al. [53]c | N | a | Germany1 | 30 | 12 R | 48 | 60 | 1.5 | Clinical interview, 2 psychiatrists; DSM-IV | Hippocampus and amygdala | Structure: MRI | Volumes |
↓ Hippocampus NS amygdala |
6 |
| Frodl et al. [54] | N | a | Germany1 | 30 | 13 R | 45 | 63 | 3 | SCID; DSM-IV | Hippocampus and amygdala | Structure: MRI | Volumes | NS | 6 |
| Kronmüller et al. [70]b | N | a | Germany | 57 | 21 R | 44 | 58 | 2 | SCID / LIFE; DSM-IV | Hippocampus | Structure: MRI | Volumes | ↓ Hippocampus | 5 |
| Lythe et al. [76]a | Y | b | UK | 95 | 25 R | 34 | 64 | 1.2 | LIFE; DSM-IV | ROI based on previous studies: ACC, temporal, striatal | Activity: fMRI | Activity during self-blame versus other-blame emotions | ↑ sgACC and temporal regions connectivity and putamen and claustrum connectivity in recurrent | 9 |
| Nixon et al. [117]a | Y | b | UK | 38 | 7 R | [24–63] | 33 | 1 | SCID; DSM-IV | ROI based on previous studies | Activity: fMRI | Go/Nogo task | ↓ Right dmPFC activity following errors and negative feedback compared to correct hits in recurrence vs other groups | 6 |
| Workman et al. [101]a | Y | ? | UK | 85 | 17 R | 37 | 64 | 1.2 | SCID; DSM-IV | sgACC | RSFC: fMRI | Rest. Left sgACC to right sgACC connectivity | Recurrent group was intermediate to resilient and control in sgACC connectivity | 9 |
| Langenecker et al. [71]a | Y | b | USA | 94 | 21 R | 21 | 63 | 4–6 | DIGS and longitudinal interval follow evaluation | fMRI | Activity: fMRI & RSFC fMRI | Go/No-Go task: successful vs unsuccessful inhibition | Successful regulation sgACC hyperactivation. Failed regulation; MFG hypoactivation. RSFC: altered MFG and sgACC connectivity. | 8 |
| Gastrointestinal factors | Baseline MDD excl. Y = yes, N = No | Baseline symptoms a = above cut-off, b = below cut-off, ? = unclear | Country and cohort information (nr indicates similar cohorts) | Total N | Onset (O) or relapse/ recurrence (R) of MDD (N) | Baseline age (mean or range) | % female | Follow-up time (years; mean or max) | MDD diagnostic interview; Diagnostic criteria | Biomarker of interest | Measure | Technical details | Direction result of biomarker predicting onset, relapse/recurrence of MDD | QA score |
| Campo et al. [40] ° | Y | ? | USA | 119 | 14 O | [6–12] | ? | 7.5 | K-SADS-E; DSM-IV (nm) | L-5-hydroxytryptophan injection at baseline | Abdominal discomfort, nausea, or vomiting in response to the L-5HTP infusion; GI distress | L-5HTP infusion; Survival curve (groups high vs. low sensitive) | ↑GI distress after serotonin challenge | 6 |
| Immunology | Baseline MDD excl. Y = yes, N = No | Baseline symptoms a = above cut-off, b = below cut-off, ? = unclear | Country and cohort information (nr indicates similar cohorts) | Total N | Onset (O) or relapse/ recurrence (R) of MDD (N) | Baseline age (mean or range) | % female | Follow-up time (years; mean or max) | MDD diagnostic interview; Diagnostic criteria | Biomarker of interest | Measure | Technical details | Direction result of biomarker predicting onset, relapse/ recurrence of MDD | QA score |
| Chocano-Bedoya et al. [43]c | N | ? | USA | 4403 | 81 O | 56 | 100 | 12 | Self-report of diagnosis; Unclear | CRP, IL-6, TNFα-R2 | Blood, 1 time point | hs-CRP IA. EIA | NS | 4 |
| Haastrup et al. [61]a | N | ? | Denmark | 9275 | 22 O | [18–47] | 48 | 5 | prescriptions for antidepressant medication or had a hospital discharge diagnose with the codes F.32 or F.33; ICD-10 | suPAR | Blood plasma, 1 time point | ELISA | ↑Increased risk (shorter time) to onset of depression with higher SuPAR | 6 |
| Rudaz et al. [94] | Y | ? | Switzerland1 | 1524 | 192 O | 51 | 43 | 5.5 | Diagnostic Interview for Genetic Studies (DIGS); DSM-IV | CRP, IL-1ß, IL-6, TNFα | Blood serum, 1 time point | hs-CRP IA. multiplexed particle-based flow cytometric cytokine assay | ↓TNFα, NS for CRP, IL-1ß, IL-6 | 8 |
| Copeland et al. [46]c | Y | b | USA | 5810 | 169 O + R | 14 | 49 | 12 | CAPA, YAPA; DSM-IV | CRP | Blood spot, 1 time point | hs-CRP IA | NS | 9 |
| Glaus et al. [55]c | Y/N | ? | Switzerland1 | 2580 | 608 O + R | [35–66] | 54 | 5.5 | DIGS | CRP, IL-6, TNFα | Serum, 1 time pont | IA and latex HS | O + R: ↓TNFα | 7 |
| Khandaker et al. [69]c | N | ? | UK | 2447 | 422 O + R | 9 | 51 | 9 | CIS-R; ICD-10 | CRP, IL-6 | Blood serum, 1 time point | hs-CRP essay. ELISA | NS | 5 |
| Pasco et al. [87]a | Y | ? | Australia | 822 | 151 O + R | 49 | 100 | 10 | SCID; DSM-IV-TR | CRP | Blood serum, 1 time point | hs-CRP IA | ↑ CRP reduced time till depression (HR) | 7 |
| Neurotransmitters | Baseline MDD excl. Y = yes, N = No | Baseline symptoms a = above cut-off, b = below cut-off, ? = unclear | Country and cohort information (nr indicates similar cohorts) | Total N | Onset (O) or relapse/ recurrence (R) of MDD (N) | Baseline age (mean or range) | % female | Follow-up time (years; mean or max) | MDD diagnostic interview; Diagnostic criteria | Biomarker of interest | Measure | Technical details | Direction result of biomarker predicting onset, relapse/ recurrence of MDD | QA score |
| Johnston et al. [68]a | N | a | UK | 31 | 20 R | 47 | 71 | 8 | SCID I/P; DSM-III-R | Plasma Norepinephrine, cortisol | Blood plasma, 1 time point | Chromatography, RIA | ↓ Norepinephrine, shorter time to first recurrence. | 6 |
| Neurotrophic factors and oxidative stress | Baseline MDD excl. Y = yes, N = No | Baseline symptoms a = above cut-off, b = below cut-off, ? = unclear | Country and cohort information (nr indicates similar cohorts) | Total N | Onset (O) or relapse/ recurrence (R) of MDD (N) | Baseline age (mean or range) | % female | Follow-up time (years; mean or max) | MDD diagnostic interview; Diagnostic criteria | Biomarker of interest | Measure | Technical details | Direction result of biomarker predicting onset, relapse/recurrence of MDD | QA score |
| Pasquali et al. [88]a | N | b | USA | 148 | 37 O | 40 | 100 | 3 | SCID; DSM-IV | Neurotrophic: BDNF Immunology: HSP70, 3-Nitrotyrosine,, Oxidative stress: Protein carbonyl, Lipid peroxidation, Thiol content | Blood serum, 1 time point | ELISA, quantitative sandwich enzyme immunoassay, colorimetric assay (thiol) | ↑ heat-shock protein 70, 3-nitrotyrosine, protein carbonyl, and lipid peroxidation ↓BDNF | 6 |
| Vinberg et al. [97]a | Y | ? | Denmark | 234 | 24 O | 44 | 65 | 7.5 | SCAN; ICD 8/ICD-10 | BDNF | Blood, 1 time point | Two-site sandwich ELISA | NS | 5 |
| Hormones: HPA | Baseline MDD excl. Y = yes, N = No | Baseline symptoms a = above cut-off, b = below cut-off, ? = unclear | Country and cohort information (nr indicates similar cohorts) | Total N | Onset (O) or relapse/ recurrence (R) of MDD (N) | Baseline age (mean or range) | % female | Follow-up time (years; mean or max) | MDD diagnostic interview; Diagnostic criteria | Biomarker of interest | Measure | Technical details | Direction result of biomarker predicting onset, relapse/ recurrence of MDD | QA score |
| Adam et al. [30]c | N | ? | USA | 230 | 18 O | 17 | 75 | 1 | SCID; DSM-IV | AUC, CAR, diurnal, slope | Saliva, 3 days, 6 times a day | DELFIA | NS | 7 |
| Colich et al. [45]c | Y | b | USA1 | 89 | 31 O | 12 | 100 | 6 | K-SADS. SCID; DSM-IV | Cortisol pre- post- trier social stress test | Saliva, 4 time points | LIA | ↓ cortisol reactivity in early puberty ↑cortisol reactivity in late puberty | 9 |
| Goodyer et al. [56] | ? | ? | UK2 | 171 | 30 O | 14 | 59 | 1 | K-SADS; DSM-IV | Peaks 8:00, cortisol and DHEA | Saliva 4 days, 2 time points | ELISA | ↑ cortisol & DHEA | 6 |
| Goodyer et al. [57] | ? | ? | UK2 | 234 | 31 O | 14 | 53 | 1 | K-SADS; DSM-IV | Morning and evening cortisol, DHEA | Saliva 4 days, 2 time points | ELISA | ↑ DHEA, NS cortisol | 7 |
| Goodyer et al. [58]c | ? | b | UK2 | 367 | 32 O | 14 | 46 | 1 | K-SADS; DSM-IV | Morning cortisol | Saliva 4 days, 1 time point | ELISA | ↑ cortisol | 6 |
| Goodyer et al. [59] | ? | b | UK2 | 357 | 40 O | 14 | 47 | 1 | K-SADS; DSM-IV | Morning cortisol | Saliva 4 days, 1 time point | ELISA | ↑ cortisol | 6 |
| Grynderup et al. [60]c | Y | ? | Denmark | 2920 | 62 O | 56 | 78 | 2 | SCAN; ICD-10-DSR | Morning, diurnal, evening, morning to evening slope in cortisol | Saliva, 2 hours after awakening, and between 5PM and 4AM | RIA | ↓ difference in morning to evening cortisol | 9 |
| Harris et al. [63]c | ? | ? | UK | 116 | 28 O | 39 | 100 | 1 | SCAN; DSM-IV | DHEA and cortisol | Saliva, 4 days, 2 time points | ELISA | NS | 6 |
| Herbert et al. [65]c | Y | ? | UK | 279 | 53 O | 37 | 100 | 1 | SCAN; DSM-IV | Morning cortisol | Saliva 4 days, 1 time point | ELISA | ↑ cortisol predicts MDD | 8 |
| LeMoult et al. [72] | Y | b | USA1 | 62 | 26 O | 12 | 100 | 6.5 | K-SADS. SCID; DSM-IV | Morning cortisol | Saliva, 2 days, 4 time points | ELISA | ↑ cortisol predicts MDD | 9 |
| Rao et al. [93]c | Y | b | USA2 | 89 | 14 O | 15 | 58 | 5 | K-SADS; DSM-IV | Saliva, NUFC | Saliva, 3 time points before sleep and Urine 1 time point before sleep | RIA | ↑ cortisol predicts MDD | 6 |
| Carnegie et al. [41]c | N | ? | UK | 841 | 46 O + R | 15 | 49 | 3 | CIS-R; ICD-10 | AUC, CAR, DD, bedtime (m), waking (m), TEC | Urine, over 24 h | EIA | NS | 5 |
| Vrshek-Schallhorn et al. [98]c | Y | ? | USA | 270 | 42 O + R | 17 | 72 | 4 | SCID; DSM-IV | AUC, CAR, diurnal slope | Saliva, 3 days, multiple time points | Time-resolved fluorescent-detection IA | ↑ cortisol recurrence | 9 |
| Appelhof et al. [32]c | N | a | Spain | 45 | 22 R | 50 | 44 | 22 | At baseline: SCID. Relapse: HRSD. MADRS. and BD; DSM-IV | Post dex cortisol, Max ACTH, Delta ACTH, Max cortisol, delta cortisol, discharge, difference cortisol | Blood, 2 days, multiple time points before and after DEX/CRH combined with TRH | luminescen-ce enzyme IA | ↑ maximal cortisol after DEX/CRH predicts relapse | 6 |
| Aubry et al. [34]b | Y | a | Switzerland | 34 | 12 R | 44 | 56 | 1 | MINI; DSM-III-R/IV. ICD-10 | Cortisol after DEX/CRH test | Blood, 2 days, multiple time points before and after DEX/CRH | Immulite 2000 analyser | ↑ AUC and delta in relapse | 8 |
| Banki et al. [35]b | N | a | Hungary | 24 | 9 R | 51 | 100 | 0.5 | Hospital diagnosis; DSM-III-R | CRH, SRIF | CSF, 1 time point | Sensitive and specific IA | ↑ CRF in relapse | 3 |
| Bockting et al. [37]c | Y | b | Netherlands1 | 55 | 43 R | 44 | 73 | 5.5 | SCID; DSM-IV | Morning and evening cortisol | Saliva, 2 days, 1–2 time points a day | RIA | ↓ cortisol related to relapse | 7 |
| Bouhuys et al. [38]c | N | b | Netherlands | 77 | 21 R | 44 | 66 | 2 | CIDI; DSM-IV | 24 h urine | RIA | NS | 6 | |
| Charles et al. [42]c | N | ? | Belgium | 13 | 7 R | [33–67] | 77 | 1.5 | SADS-L; DSM-III and RDC | Morning after DST | Blood plasma, 2 time points after taking DEX | RIA | ↑ cortisol (non suppression at recovery) higher rates of MDD readmission | 4 |
| Chopra et al. [44]b | Y | b | Canada | 55 | 28 R | 39 | 64 | 1.5 | SCID; DSM-IV | Morning/evening (before mood induction) | Saliva, 4 time points | EIA | ↑ cortisol | 4 |
| Cosgriff et al. [48]c | N | b | New Zealand | 13 | 4 R | 51 | 54 | 0.25 | Clinical readmission; Unclear | Mean cortisol, Delta TSH | Blood, 10–12 time points | EIA/RIA | ↑ cortisol | 5 |
| Hardeveld et al. [62]c | Y | a | Netherlands | 549 | 193 R | 45 | 71 | 4 | CIDI; DSM-IV | Salivary CAR, evening, DST | Saliva, 2 days, 6 times day 1, 1 time day 2 after DEX | EIA | AUC increase differed, and related to time to recurrence. Other measures, mean evening, DST and AUC were not predictive | 7 |
| Hatzinger et al. [64]b | N | a | Switzerland | 20 | 12 R | 52 | 70 | 1 | SCID; ICD-10 | Cortisol after DEX/CRH | Blood plasma, 1 time point after DEX/CRH | RIA | DEX/CRH test | 7 |
| Lok et al. [75] | Y | b | Netherlands1 | 187 | 102 R | 44 | 68 | 2 | SCID; DSM-IV | Morning and evening cortisol | Saliva, 2 days, 3 time points | RIA | NS | 8 |
| Mander et al. [78]c | N | ? | UK | 70 | 32 R | Unclear | Unclear | 3 | SCID; DSM-III | DEX suppression | Saliva, 1 day, 3 time points day after DEX | RIA | NS | 5 |
| Mocking et al. [118]c | Y | b | Netherlands1 | 187 | 154 R | 44 | 68 | 10 | SCID; DSM-IV | Cortisol/ DHEAS ratio | Saliva, 2 days, 2 time points a day. | RIA | ↓DHEAS diurnal course, ↑ cortisol/DHEAS ratio diurnal course | 6 |
| Morris et al. [80]c | Y | a/b | USA | 32 | 9 R | 23 | 63 | 0.75 | SCID; DSM-IV | Cortisol pre- post- TSST | Saliva, 6 time points | ELISA | NS | 8 |
| Pintor et al. [89] | N | a | Spain1 | 43 | 18 R | 51 | 53 | 2 | SCID; DSM-IV | Cortisol and ACTH after CRF injection | Blood plasma, 6 time points around CRF injection | EIA/RIA | NS Cortisol and ACTH AUC, ACTH after CRF | 6 |
| Pintor et al. [90]c | N | a | Spain1 | 43 | 18 R | 51 | 46 | 2 | SCID; DSM-IV | Cortisol and ACTH after CRF injection | Blood plasma, 6 time points around CRF injection | EIA/RIA | ↑ cortisol (NAUCC) after CRF, ↓ACTH after CRF | 5 |
| Rao et al. [92] | N | b | USA2 | 47 | 20 R | 15 | 64 | 3.5 | K-SADS-PL; DSM-IV | NUFC | Urine before and after sleep | RIA | ↑ cortisol | 5 |
| Tsuru et al. [96]c | N | a | Japan | 25 | 9 R | 41 | 64 | 10 | SCID; DSM-IV | ACTH and cortisol, TSH | Blood, 2 days, day 1 TRH test 5 time points, day 2 DEX /CRH-test, 10 time points | IRMA | NS cortisol and ACTH,↑TSH after TRH test in recurrence | 5 |
| Zimmerman et al. [102]c | N | ? | USA | 165 | 47 R | 40 | 73 | 0.5 | Unclear; DSM-III | DEX suppression | Blood, 2 time points after DEX | RIA | NS | 6 |
| Zobel et al. [103] | N | a | Germany2 | 40 | 10 R | 50 | 65 | 0.5 | Unclear; DSM-IV | DEX/CRH test | Blood, 9 time points DEX/CRH-test | Unclear | ↑ cortisol after DEX/CRH at discharge predicts MDD relapse | 3 |
| Zobel et al. [104]c | N | a | Germany2 | 74 | 13 R | 50 | 59 | 0.5 | Unclear; DSM-IV | DEX/CRH test, cortisol and ACTH | Blood, 5 time points DEX/CRH-test | RIA | ↑ cortisol predicts MDD, ACTH NS | 5 |
| Hormones: HPG | Baseline MDD excl. Y = yes, N = No | Baseline symptoms a = above cut-off, b = below cut-off, ? = unclear | Country and cohort information (nr indicates similar cohorts) | Total N | Onset (O) or relapse/ recurrence (R) of MDD (N) | Baseline age (mean or range) | % female | Follow-up time (years; mean or max) | MDD diagnostic interview; Diagnostic criteria | Biomarker of interest | Measure | Technical details | Direction result of biomarker predicting onset, relapse/ recurrence of MDD | QA score |
| Asselmann et al. [33]a | Germany | 1760 | 165 O | 45 | 50 | 9 | DIA-X/M-CIDI | Testosterone, Androstenedione, sex hormone-binding globuline | Blood serum 8AM-7PM | Liquid-chromatography-tandem mass spectrometry and RIA | NS | 6 | ||
| Hormones: HPS axis | Baseline MDD excl. Y = yes, N = No | Baseline symptoms a = above cut-off, b = below cut-off, ? = unclear | Country and cohort information (nr indicates similar cohorts) | Total N | Onset (O) or relapse/ recurrence (R) of MDD (N) | Baseline age (mean or range) | % female | Follow-up time (years; mean or max) | MDD diagnostic interview; Diagnostic criteria | Biomarker of interest | Measurement | Technical details | Direction result of biomarker predicting onset, relapse/ recurrence of MDD | QA score |
| Coplan et al. [47]c | Y | ? | USA | 34 | 13 O | 15 | 52 | 9.6 | K-SADS & K-SADS-E & SADS-LA; RDC | Growth hormone (sleep) | Blood over 2 nights, 72 time points | RIA | ↑GH secretion | 8 |
| Franz et al. [52]c | N | a | USA3 | 29 | 22 R | 40 | 100 | 3 | SADS; RDC | Growth hormone (sleep) | Blood before onset of and during sleep, every 20 min | RIA | ↑GH secretion | 5 |
| Jarrett et al. [66]b | N | a | USA3 | 29 | 22 R | 40 | 100 | 3 | SADS; RDC | Growth hormone (sleep) | Blood before onset of and during sleep, every 20 min | RIA | NS | 6 |
| Owashi et al. [84]c | N | b | Japan | 26 | 6 R | 57 | 76 | 0.5 | Unclear; DSM-IV | Growth hormone, ACTH, cortisol | Blood after DEX/CRH and GHRH test, 5 time points | RIA | ↓GH after GHRH at time of discharge. Cortisol and ACTH around DEX/CRH: NS | 4 |
| Hormones: HPT axis | Baseline MDD excl. Y = yes, N = No | Baseline symptoms a = above cut-off, b = below cut-off, ? = unclear | Country and cohort information (nr indicates similar cohorts) | Total N | Onset (O) or relapse/ recurrence (R) of MDD (N) | Baseline age (mean or range) | % female | Follow-up time (years; mean or max) | MDD diagnostic interview; Diagnostic criteria | Biomarker of interest | Measurement | Technical details | Direction result of biomarker predicting onset, relapse/ recurrence of MDD | QA score |
| Joffe et al. [67]a | N | a | Canada | 75 | 71 R | 38 | 66 | 10 | SADS-L; RDC | T4, T3, TSH | Unclear | Unclear |
↓T3 was significantly related to time to recurrence. T4, TSH NS |
4 |
Studies are sorted by the inclusion of participants with onset (O), relapse and recurrence (R) of MDD or both (O + R). The second and third columns represent information on the certainty of including healthy individuals at baseline, where the second column shows if baseline MDD diagnosis was excluded with a clinical interview at baseline, and the third column represents whether symptoms were measured with questionnaires (e.g. Hamilton depression scale, beck depression inventory) and whether participants scored above or below the questionnaires cut-off for clinical symptoms at baseline. Basic information on the demographics of participants and study measures, technical details and outcome are also given. The quality score (range 0–9) represents the overall quality of the studies, where a score > 6 represents good quality, indicative of a low risk of bias and < 4 represents poor quality, a high risk of bias.
Specific abbreviations will be mentioned per subsection
General abbreviations: DIGS Diagnostic Interview for Genetic Studies, DSM diagnostic statistical manual of mental disorders, ICD International Statistical Classification of Diseases and Related Health Problems, MINI mini-international neuropsychiatric interview, nm not mentioned, NS nonsignificant, RDC research diagnostic criteria, SCAN schedules for clinical assessment in neuropsychiatry, SCID Structured Clinical Interview for DSM, K-SADS Kiddie Schedule for Affective Disorders and Schizophrenia.
Neuroimaging abbreviations: ACC anterior cingulate cortex, dmPFC dorsal medial prefrontal cortex, EEG electroencephalography, f functional, IFG inferior frontal gyrus, MFG middle frontal gyrus, mOFC medial orbitofrontal cortex, MRI magnetic resonance imaging, orbitofrontal cortex (OFC), PCG precentral gyrus, ROI region of interest, RSFC resting state functional connectivity, sg subgenual
Gastrointestinal abbreviations: GI gastrointestinal, L-5HTP L-5-Hydroxytryptophan
Immunology abbreviations: CAPA Child and Adolescent Psychiatric Assessment, CRP c-reactive protein, ELISA enzyme-linked immunosorbent assay, HR hazard ratio, IL interleukin, SRIF somatostatin, TNF tumor necrosis factor, YAPA Young Adult Psychiatric Assessment, IA immunoassay
Neurotransmitters abbrevations: RIA radioimmunoassay
Neurotrophic and oxidative stress abbreviations: ELISA enzyme-linked immunosorbent assay, BDNF brain-derived neurotrophic factor
HPA abbreviations: ACTH adrenocorticotropic hormone, AUC area under the curve, CAR Cortisol awakening response, CRH Corticotropin-releasing hormone, DEX/CRH combined dexamethason-cortisol releasing hormone test, DST dexamethasone suppression test, DHE adehydroepiandosterone, ELISA enzyme-linked immunosorbent assay, HRSD Hamilton Rating Scale for Depression, IA immunoassay, LIA line immunoassay, MADRS montgomery-Asberg Depression Rating Scale, NUFC nocturnal urinary free cortisol, RIA radioimmunoassay, TSST trier social stress test.
HPG abbreviations: DIA-X/M-CIDI Munich-Composite International Diagnostic Interview, RIA radioimmunoassay
HPS: GH growth hormone, GHRH growth hormone resleasing hormone, RIA radioimmunoassay
HPT abbreviations: T3 triiodothyronine, T4 thyroxine, TSH thyroid stimulating hormone
aNot enough studies to meta-analyze
bNot enough data reported in this study to include in meta-analysis
cIncluded in meta-analysis