Table 2a Differential biological mechanisms in subtypes of depression—melancholic vs atypical vs non-melancholic/atypical
Authors | Objective | Design/sample | Subjects | Procedure | Depressive subtypes | Results |
|---|---|---|---|---|---|---|
Maes et al.21 | Examine if severe depression characterized by IL-6 production, if IL-6 activity in depression is related to alterations in APPs and HPA axis activity | Cross-sectional/clinical | 24 unipolar depressed inpatients and 8 control subjects | SCID, HSRD assessed depression | md, MMD, NMMD | PBMC IL-6 production: MMD >NMMD/md/controls (P<0.02) Haptoglobin: MDD/NMMD >controls/md (P<0.014) Transferrin: MDD/NMMD/md >controls (P<0.007) All other subgroup comparisons non-significant. DST non-significant. |
Maes et al.79 | Determine if platelet aggregation, APTT or PT are disordered in subtypes of depression | Cross-sectional/clinical | 40 NMMD, 23 MMD, 16 MD and 16 controls | SCID assessed depression | NMMD, MMD, md | No significant difference between any subtypes and controls in PT, APTT or platelet aggregation to collagen or ADP. |
Nelson and Davis78 | To perform a meta-analysis of DST studies published before 1997 | Meta-analysis of cross-sectional studies | 708 non-psychotic, 276 psychotic, 662 MMD and 617 NMMD | Meta-analysis | MMD, NMMD, psychotic/non-psychotic | Psychotic: OR of DST non-suppression in psychotic patients: 3.0 (95% CI, 2.2–4.1) Effect size did not differ significantly between studies (P=0.58) Melancholic: OR of DST non-suppression in MMD patients: 2.0 (95% CI, 1.5–2.6) Effect size varied significantly between studies (P<0.001) No effect for MMD when controlled for inpatient/outpatient status. |
Ravindran et al.83 | Examine the levels of circulating lymphocyte subsets in depressive subtypes | Cross-sectional/clinical | 153 outpatients and 44 controls | MINI, HAM-D, BDI assessed depression | Depression, atypical depression, Dt, atypical Dt | NK cell counts: Typical MDD >atypical MDD/typical dysthymia >controls (P<0.01) No significant difference for atypical dysthymia No significant differences between T-cell populations in typical/atypical depression/dysthymia and controls. |
Anisman et al.81 | Determine if cytokine alterations associated with depression related to neurovegative Sx or illness chronicity | Prospective/clinical | 74 depressed outpatients and 27 controls | HAM-D, MADRS and BDI measured depressive symptoms | Depression, atypical depression, Dt, atypical Dt | Relative to controls, ACTH levels elevated in atypical MD. Modest ACTH elevation in typical MD, but not in Dt. ↓ cortisol levels in atypical groups compared with typical groups. IL-1β levels elevated in Dt, irrespective of typical or atypical features. IL-1β correlated with illness duration. IL-2 production ↓ among each group. |
Zaharia et al.84 | Examine mitogen-stimulated lymphocyte proliferation in subtypes of depression before and after treatment | Prospective/clinical | 88 depressed outpatients and 17 controls | SCID, CGI, MADRS, HAM-D, Atypical Depression Diagnostic Scale assessed depression | Depression, atypical depression, Dt, atypical Dt | Lymphocyte proliferative response to mitogen is reduced in both atypical and typical dysthymia relative to controls. Atypical dysthymia vs typical dysthymia=no significant difference. Typical MDD: attenuated proliferative response to Con A and low-dose PHA Atypical MDD: no difference in Con A response. Attenuated response to low-dose PHA. |
Rothermundt et al.75 | Examine lymphocyte patterns in MMD and NMMD including whole blood mitogen-stimulated cytokine production | Prospective/clinical | 43 patients with depression and 43 controls | CIDI and HAM-D assessed depression. Immune functioning assessed at T1 (admission), T2 (after 2 weeks treatment), T3 (after 4 weeks treatment) | MMD, NMMD | IL-2: MMD < NMMD and controls at baseline (P<0.01) IFN-γ: MMD <NMMD and controls at baseline (P<0.05) Absolute lymphocyte count: NMMD >MMD and controls at all time points (P<0.05) No significant difference in serum cortisol, IL-10. |
Rothermundt et al.75 | Examine innate immune patterns MMD and NMMD via whole blood LPS-stimulated cytokine production | Prospective/clinical | 43 patients with depression and 43 controls | CIDI and HAM-D assessed depression. Immune functioning assessed at T1 (admission), T2 (after 2 weeks treatment), T3 (after 4 weeks treatment) | MMD, NMMD | MMD had ↑ monocyte count and α-2-macroglobulin relative to NMMD and controls NMMD had ↑ CRP at T2 relative to MMD and controls. No significant differences for haptoglobins and ex-vivo whole blood-mitogen stimulated IL-1β production. |
Schlatter et al.77 | Examine differences in lymphocyte and lymphocyte produced cytokines in MMD and NMMD | Prospective/clinical | 42 inpatients with depression and 20 controls | SCID, HAM-D, Newcastle Endogenicity Scale, assessed depression | MMD, NMMD | MMD had ↑CD4 and CD4:CD8 ratio >NMMD and controls (P=0.038). Difference remains in remission. No significant differences for CD8 or memory cells. MMD had ex-vivo PBMC mitogen-stimulated production ↑IL-2 >NMMD and controls (P=0.008). Normalized in remission. No significant differences for IL-4. ↓NK cell activity in NMMD patients in remission. Negative correlation between HAM-D and NK cell activity in NMMD patients at baseline. |
Gecici et al.82 | Determine if serum leptin levels differ between depressive disorders with/without atypical features | Cross-sectional/clinical | 57 drug-free patients with depression and 26 controls | HDRS+unspecified assessment of atypical features | Depressive symptoms +/− atypical features | ↑Serum leptin in patients with atypical features relative to controls and those without atypical features. No significant difference between patients without atypical features and controls. |
Kaestner et al.72 | Determine if HPA axis hyperactivity ↓ pro-inflammatory response in acute MD and if HPA axis hyperactivity and cytokine production normalizes during remission | Prospective/clinical | 37 acute MD inpatients and 37 controls | SCID and Newcastle Endogenicity Scale assessed depression | Acute and remitted MMD and NMMD | ACTH and serum cortisol concentrations ↑ MMD but not NMMD. NMMD >baseline IL-1β and IL-1RA than MMD and controls. Compared with MMD, NMMD had ↓ IL-1 RA/IL-1β ratio and ↑ upon remission. |
Huang and Lee71 | Determine if there are differential serum cytokine expression profiles in patients with/without melancholic features and with/without suicide attempts | Cross-sectional/clinical | 42 inpatients with depression and 40 controls | SCID, HDRS assessed depression | MMD, NMMD | IL-1β: MMD >NMMD (P=0.023) IL-1β/IL-10 ratio: MMD >NMMD (P=0.015) No significant difference for TNF-α or IL-10 (P=0.22 and 0.17, respectively) |
Marques-Deak et al.74 | Examine the levels of circulating cortisol and cytokines in patients with subtypes of MDD | Prospective/clinical | 46 female inpatients with depression and 41 controls | SCID, HDRS, CGI assessed depression | MMD, NMMD | No significant differences in serum IL-1β, IL-6, IFN-γ, cortisol between depressed patients and controls or MMD and NMMD. |
Erdem et al.76 | Examine whether serum haptoglobin concentrations vary between patients with MMD, NMMD and controls | Cross-sectional/clinical | 37 MMD, 45 NMMD and 40 controls | SCID, HDRS assessed depression | MMD, NMMD | Serum haptoglobin was significantly higher in patients with MMD than NMMD (P<0.001). |
Yoon et al.80 | Examine the profile of whole blood LPS stimulated cytokine expression in patients with major depression +/− atypical features | Cross-sectional/clinical | 70 patients with MDD and 35 patients with Atypical MDD | SCID, HDRS, BPRS assessed depression | MDD, Atypical MDD | TNF-α: no significant difference (P=0.64) IL-6: no significant difference (P=0.32) IL-2: atypical >non-atypical (P=0.002) IL-4: non-atypical >atypical (P=0.035) IL-2/IL-4: atypical >non-atypical (P=0.011) |
Maes et al.73 | Examine indices of cell mediated immunity according to various symptom subgroups within depressive disorders | Cross-sectional/clinical | 83 patients with MDD and 26 controls | SCID, HDRS assessed depression | MMD, NMMD | Serum neopterin: MMD >NMMD (P=<10−6), depressed >controls. (P=4 × 10−5) Serum TNF-α: MMD >NMMD (P=6 × 10−6), depressed >controls. (P=5 × 10−5) Serum IL-1β: MMD=NMMD (P=0.08), depressed >controls (P=0.008). |
