Table 2.
Summary of findings by diagnostic category.
| Study | Subjects | Gender (%F) | Markers | Stage | Phase | BMI | Smoking | Main findings |
|---|---|---|---|---|---|---|---|---|
| Schizophrenia | ||||||||
| Wong et al. [19] |
SCZ (Cohort 1) = 98 SCZ (Cohort 2) = 50 HC = 91 |
SCZ: 0% HC: 0% |
1. A-1-AT (blood) | Mixed | Mixed | Not reported | Not reported | 1. ↑ A-1-AT in SCZ vs. HC |
| Maes et al. [20] |
SCZ = 27 HC = 11 |
1. A-1-AT (blood) | Mixed/unclear | Mixed/unclear | Not reported | Not reported | 1. =levels of A-1-AT in SCZ vs. HC | |
| Yang et al. [21] |
SCZ = 22 HC = 20 |
SCZ: 0% HC: 0% |
1. A-1-AT (blood) | Mixed/unclear | Mixed/unclear | Not reported | Note reported | 1. ↑ A-1-AT in SCZ vs. HC |
| Severance et al. [47] |
SCZ = 363 HC = 207 |
SCZ: 32.7% HC: 72.9% |
1. ASCA (blood) | Mixed | Mixed | Not reported | Not reported | 1. ↑ ASCA in SCZ vs. HC |
| Severance et al. [22] |
SCZ = 141 HC = 39 |
SCZ: 39.7% HC: 71.8% |
1. sCD14 (blood) 2. LBP (blood) |
Unclear | Unclear | SCZ: 30.54 ± 0.61 |
SCZ: 58.9% HC: 17.9% |
1. ↑ sCD14 in SCZ vs. HC 2. =LBP between SCZ vs. HC |
| Dickerson et al. [23] |
SCZ = 249 rPsych = 79 HC = 260 |
SCZ: 31% rPsych: 34% HC: 61% |
1. ASCA (blood) |
Mixed Chronic (SCZ) and recent onset of psychosis (rPsych) |
Mixed |
SCZ: 30.8 ± 7.5 rPsych: 26.1 ± 7.5 HC: 27.5 ± 6.8 |
SCZ: 64% rPsych: 41% HC: 15% |
1. ↑ ASCA in SCZ vs. HC 2. ↓ ASCA in rPsych vs. HC |
| Dickerson et al. [24] |
Patients = 210 [SCZ = 90 BPD = 72 MDD = 48] Recent suicide attempt (rSA) HC = 72 |
Patients: 46.6% HC: 64% |
1. IgA-ASCA (blood) 2. IgA LPS (blood) |
Mixed/unclear | Mixed/unclear |
Patients: 31.19 ± 8.7 HC: 28.1 ± 7.3 |
Patients: 41.4% HC: 14% |
1. ↑ ASCA IgG in patients with rSA vs. HC 2. ↑ LPS-IgA in patients with rSA vs. HC |
| Weber et al. [25] |
SCZ = 80 HC = 80 |
SCZ: 15% HC: 15% |
1. sCD14 (blood) 2. LBP (blood) |
“Early stages” | Outpatient | N/A | N/A |
1. ↑ sCD14 in SCZ vs. HC 2. =LBP in SCZ vs. HC |
| Delaney et al. [26] |
Psychosis (Psych) = 42 Clinical high risk (CHR) = 17 HC = 33 |
Psych: 36% CHR: 35% HC: 57.5% |
1. IgA to LPS (blood) 2. IgG to LPS (blood) 3. IgM to LPS (blood) |
Mixed/unclear | Mixed/unclear |
Psych: 27.8 ± 7.88 CHR: 23.87 ± 4.02 HC: 24.84 ± 6.26 |
N/A |
1. =IgA, IgG, and IgM in Psych vs. HC 2. =IgA, IgG, and IgM in CHR vs. HC |
| Ciháková et al. [27] |
SCZ = 160 HC = 80 |
SCZ: 38% HC: 36% |
1. ASCA IgA (blood) 2. ASCA IgG (blood) |
Mixed/unclear | Mixed/unclear | N/A | N/A | 1. ↑ ASCA IgG in SCZ vs. HC |
| Mørch et al. [28] |
SCZ = 675 HC = 647 |
SCZ: 39.85% HC: 46.83% |
1. sCD14 (Blood) |
Mixed/unclear “The patients were recruited during early phase after an acute episode (post-acute episode)” |
Mixed “Mostly from outpatient clinics” |
SCZ: 26.4 ± 5.2 HC: 24.7 ± 3.5 |
SCZ: 46% HC: 9% |
1. ↓ sCD14 in SCZ vs. HC |
| Maes et al. [29] |
SCZ = 80 [n = 40 deficit schizophrenia] HC = 38 |
Not reported |
1. IgA gram-negative bacteria 2. (Blood) 3. IgM gram-negative bacteria 4. (Blood) |
Mixed/unclear | Outpatients | Not reported | Not reported |
1. ↑ IgA to four gram-negative bacteria in deficit SCZ vs. non-deficit SCZ and HC 2. ↑ IgM to five gram-negative bacteria in deficit SCZ vs. non-deficit SCZ and HC |
| Maes et al. [30] |
SCZ = 78 HC = 40 |
PT: 46.8% HC: 75% |
1. IgM zonulin 2. (Blood) 3. IgM occludin 4. (Blood) 5. IgM e-cadherin 6. (Blood) 7. IgA gram-negative bacteria 8. (Blood) |
Multi-episode | Mixed/unclear |
SCZ: 24.4 ± 5.14 HC: 24 ± 4.3 |
SCZ: 6.3% HC: 5% |
1. ↑ IgM to zonulin in SCZ vs. HC 2. ↑ IgM to occludin in deficit vs. non-deficit SCZ and HC |
| Maes et al. [31] |
SCZ = 79 HC = 40 |
PT: 46.8% HC: 75% |
1. IgA tight junctions + adherens junctions (blood) 2. e-Cadherin, occludin, claudin-5, beta-catenin 3. (Blood) 4. IgA gram-negative (blood) |
Mixed/unclear “stabilized phase of illness” | Mixed/unclear |
SCZ: 41.2 ± 11.1 HC: 24.0 ± 4.3 |
SCZ: 6.3% HC: 5% |
1. ↑ IgA to TJ/AJs in deficit SCZ vs. non-deficit SCZ and HC 2. ↑ IgA to gram-negative bacteria in deficit SCZ vs. non-deficit SCZ 3. ↑ IgA occludin associated with deficit SCZ vs. non-deficit SCZ |
| Bipolar disorder | ||||||||
| Maes et al. [20] |
BPD = 23 HC = 10 |
1. A-1-AT (blood) | Mixed/unclear | Mixed/unclear | Not reported | Not reported | 1. =levels of A-1-AT in BPD vs. HC | |
| Severance et al. [22] |
BPD = 75 HC = 39 |
BPD: 69.3% HC: 71.8% |
1. sCD14 (blood) 2. LBP (blood) |
Unclear | Unclear | BPD: 27.17 ± 0.77 |
BPD: 34.7% HC: 17.9% |
1. ↑ sCD14 in BPD vs. HC 2. =LBP in BPD vs. HC 3. ↑ LBP in BPD vs. SCZ |
| Severance et al. [32] |
BPD = 264 HC = 207 |
BPD: 69.7% HC: 72.9% |
1. IgG-ASCA (blood) | Mixed/unclear | Outpatients | Not reported | Not reported | 1. ASCA IgG in patients vs. controls |
| Jakobsson et al. [9] |
BPD = 221 HC = 112 |
BPD: 62% HC: 55% |
1. sCD14 (blood) | Mixed/unclear | Outpatients |
BPD: 24.86 HC: 23.46 |
BPD: 33% HC: 15.2% |
1. ↑ sCD14 in BD vs. HC |
| Tanaka et al. [13] |
BPD = 32 HC = 32 |
BPD: 56% HC: 56% |
1. sCD14 (blood) | Mixed/unclear | Outpatients | N/A |
BPD: 52.5% HC: 40.6% |
1. ↑ sCD14 in BPD vs. HC |
| Kılıç et al. [33] |
BPD = 41 HC = 41 |
BPD: 56.1% HC: 48.7% |
1. Zonulin (blood) 2. Claudin-5 (blood) |
Mixed/unclear | Mixed/unclear |
BPD: 26.4 ± 2.9 HC: 25.3 ± 3.3 |
BPD: 43.9% HC: 36.5% |
1. ↑ Zonulin in BPD vs. HC 2. ↑ Claudin-5 in BPD vs. HC |
| Depression | ||||||||
| Maes et al. [34] |
MDD with melancholy (M) = 22 MDD without M = 20 HC = 26 |
N/A but controlled for sex | 1. A-1-AT (blood) | Multi-episode | Mixed/unclear | N/A | N/A | 1. ↑ A-1-AT in MDD with and without M vs. HC |
| Maes et al. [20] |
MDD = 29 HC = 21 |
Not reported | 1. A-1-AT (blood) | Mixed/unclear | Mixed/unclear | Not reported | Not reported | 1. =levels of A-1-AT in MDD vs. HC |
| Papakostas et al. [35] |
Pilot study: MDD = 36 HC = 43 Replication study: MDD = 34 |
Pilot study: MDD = 36.1% HC = 67.4% Replication study: MDD = 55.8% |
1. A-1-AT (blood) | Multi-episode | Mixed/unclear |
Pilot: MDD = 27.7 ± 5.8 HC = 24.4 ± 3.5 Replication: MDD = 30.6 ± 9.7 |
N/A | 1. ↑ A-1-AT in MDD patients vs. HC (both pilot and replication study) |
| Maes et al. [48] |
MDD = 113 HC = 28 |
MDD: 52.2% HC: 67.9% |
1. IgM to LPS (blood) 2. IgA to LPS (blood) |
Mixed/unclear | Outpatients | N/A, but BMI > 30 excluded | Smokers excluded from study | 1. ↑ IgM and IgA to LPS in MDD vs. HC |
| Stevens et al. [36] |
MDD or ANX = 22 HC = 27 |
N/A |
1. LPS (blood) 2. Zonulin (blood) 3. I-FABP (blood) |
Mixed/unclear | Mixed/unclear | N/A | N/A |
1. ↑ LPS in MDD/ANX vs. HC 2. ↑ Zonulin in MDD/ ANX vs. HC 3. ↑ I-FABP in MDD/ ANX vs. HC |
| Gomes et al. [37] |
MDD = 24 HC = 23 |
N/A | 1. LPS (root canal) | Mixed/unclear | Outpatients | N/A | N/A |
1. ↑ LPS in MDD vs. HC 2. ↑ LPS associated with severity of depression |
| Ohlsson et al. [38] |
MDD = 13 Recent suicide attempt (rSA) = 54 HC = 17 |
MDD: 53.8% rSA: 55.5% HC: 47.1% |
1. Zonulin (blood) 2. I-FABP (blood) 3. sCD14 (blood) |
Mixed/unclear | Mixed/unclear |
MDD: 25.9 ± 8.7 rSA: 25.7 ± 4.4 HC: 23.1 ± 3.1 |
N/A |
1. ↓ Zonulin in rSA vs. HC 2. ↑ I-FABP in rSA vs. HC 3. =Zonulin, I-FABP, and sCD14 in MDD vs. HC |
| Alvarez-Mon et al. [39] |
MDD = 22 HC = 14 |
MDD: 59.1% HC: 57.1% |
1. LBP (blood) 2. Zonulin (blood) 3. I-FABP (blood) |
Mixed/unclear | 1. Outpatient |
MDD: 26.45 ± 4.04 HC: 25.26 ± 3.87 |
MDD: 22.7% HC: 21.4% |
1. ↑ LBP in MDD vs. HC 2. ↑ I-FABP in MDD vs. HC 3. =Zonulin in MDD vs. HC |
| Maes et al. [40] |
MOOD = 96 [27 BPD1, 25 BPD2, 44 MDD] HC = 22 |
MOOD: 46.8% HC: 36.3% |
1. IgM/IgA gram-negative bacteria (blood) | Multi-episode | Outpatient |
MOOD: 25.4 ± 2.8 HC: 25.3 ± 3.8 |
MOOD: 79.1% HC: 95.4% |
1. ↑ IgM/IgA to gram-negative bacteria in MOOD patients vs. HC |
| Simeonova et al. [41] |
MDD = 44 HC = 30 |
MDD: 47.7% HC: 66.6% |
1. IgM/IgA to gram-negative bacteria (blood) | Multi-episode | Mixed/unclear |
MDD: 24.83 ± 3.01 HC: 24.74 ± 2.72 |
MDD: 93% HC: 96.5% |
1. ↑ IgM/IgA in MDD vs. HC |
| Song et al. [49] |
Depressed = 10 HC = 8 |
Depressed: N/A HC: 50% |
1. A-1-AT (blood) | Unclear | Unclear | N/A | N/A | 1. ↑ A-1-AT in depressed patients vs. HC |
| Chronic fatigue | ||||||||
| Maes et al. [42] |
CFS = 15 HC = 11 |
CFS: 66.7% HC: 72.7% |
1. IgM to LPS* (blood) 2. IgA to LPS* (blood) *LPS from seven different bacterial strains |
N/A | Outpatient | N/A | N/A |
1. ↑ IgA LPS in all 7 bacteria in CFS vs. HC 2. ↑ IgM LPS in 3/7 bacteria in CFS vs. HC |
| Maes et al. [43] | CFS = 41 | CFS: 82.9% |
1. IgM LPS (blood) 2. IgA LPS (blood) |
N/A | Outpatient | N/A | N/A |
1. ↓ in IgM and IgA to LPS post-NAIOS treatment 2. ↓ in FFS symptoms post- NAIOS treatment, especially in younger patients with shorter DOI |
| Maes et al. [44] |
CFS = 90 CF, undiagnosed = 31 |
CFS = 83.3% CF = 71% |
1. IgA LPS (blood) 2. IgM LPS (blood) |
N/A | Mixed/unclear | N/A | N/A | 1. ↑ IgM and IgA LPS in CFS vs. CF |
| Maes et al. [45] |
CFS = 90 CF, undiagnosed = 31 |
CFS: 80.9% CF: 73.5% |
1. IgM LPS (blood) 2. IgA LPS (blood) |
N/A | Mixed/unclear | N/A | N/A |
1. ↑ levels of IgM for LPS in CFS patients vs. CF patients 2. ↑ levels of IgA for LPS in patients vs. CF patients |
| Giloteaux et al. [46] |
CFS = 49 HC = 39 |
CFS: 77.6% HC: 76.9% |
1. LPS (blood) 2. I-FABP (blood) 3. sCD14 (blood) 4. LBP (blood) |
N/A | Mixed/unclear |
CFS: 25.5 ± 4.9 HC: 27.1 ± 6.1 |
N/A |
1. ↑ LPS in CFS vs. HC 2. = I-FABP in CFS v. HC 3. ↑ levels of sCD14 in CFS vs. HC 4. ↑ levels of LBP in CFS vs. HC |
↑ = significantly higher, ↓ = significantly lower, = means no significant difference.
A-1-AT alpha-1-antitrypsin, ANX anxiety disorder, BPD bipolar disorder, CF formally undiagnosed chronic fatigue, CFS chronic fatigue syndrome, HC healthy controls, I-FABP intestinal fatty-acid binding protein, LBP lipopolysaccharide binding protein, LPS lipopolysaccharide, MDD major depressive disorder, MOOD mood disorders, noSA no suicide attempt, PT patients, rPsych recent onset of psychosis, rSA recent suicide attempt, SCZ schizophrenia.