Table 2 Summary of neuroinflammatory and immunological abnormalities observed in pure psychiatric disorders
Abnormalities | Major depression | Bipolar disorder | Schizophrenia | OCD |
|---|---|---|---|---|
Genetics | ||||
  Concordance | 37% to 38% [24] | 40% to 70% [25] | 40% to 50% [26] | 80% to 87% [27] |
  GWAS genes | Tryptophan hydroxylase-1, BDNF, 5-HTTLPR, PBRM1 [24] | Tryptophan hydroxylase-2, Voltage-gated Ca2+ channel α1C, PBRM1, D22S278, ANK3 [25] | GABAAR B2 subunit, COMT, Neuregulin-1, DISC1 [26] HLA (B, C, DRA1, and DRB1; antigen presentation, autoimmunity) [28] | EAAT3 (SLC1A1) [27] |
  Immunologic genes | Proteasome β4 subunit (antigen processing) [21], T-box 21 (T cell differentiation) [21], IL-1 [29], TNF-α [29], G-765C (COX-2) [30], BDNF [24] | BDNF gene [31]; consistent with decreased serum BDNF levels | S100B [32, 33]; consistent with increased brain and CSF S100B levels | TNF-α [34] |
Astroglia | ||||
  Density | Decreased (highly reproducible) [35–41]; few exceptions [42, 43] | Insufficient data | ||
  TDO, KYNA | … | … | ||
Oligodendroglia | ||||
  Density | Insufficient data | |||
Microglial activation | ||||
  Trait and State markers | Trait: no [70]; | Insufficient data; yet, Hoxb8 (-/-) mice exhibit OCD-like behavior [71, 72] | ||
  IDO, KMO | Both are increased [29] | … | … | |
  Quinolinic acid | Increased [53] | … | … | … |
Lymphocytes | ||||
  T cells, T regs, B cells | T cells are decreased [15, 74]; T regs are decreased [15, 74] | T regs are increased [75] | T cells are decreased [76]; ‘CD4+ : CD8+ ratio’ is decreased [76]; B cells are increased [21, 76] | ‘CD4+ : CD8+ ratio’ is decreased [77] (normalized after SRI treatment) |
EAAT | ||||
  EAATs 1,2 (astroglial) | Both are decreased in the DLPFC and ACC [78] | EAAT1 is increased, EAAT2 is decreased in PFC [79] | … | |
  EAATs 3,4 (neuronal) | EAAT4 is decreased in striatum [83] | Both are decreased in striatum [79] | EAAT3 is decreased in striatum [83]; Both are increased in PFC [79–81] and thalamus [82] | |
Glutamate, GABA | ||||
  Post-mortem brain tissue | Glutamate and D-serine are increased in the frontal cortex [85, 86] | Glutamate and D-serine are increased in DLPFC and hippocampus [86]. Increased glutamine in ACC/Parietal-OCC [78] | Glutamine synthetase is increased [87] | … |
  CSF, serum | Glutamate is increased in both; serum levels normalized after 5-week antidepressant course [85, 86]; GABA is decreased in both [85, 86] | … | … | CSF glutamate is increased [88]; normalized after one dose of ketamine (NMDAR antagonist) |
   1H MRS | Glutamate is increased [85, 89] Decreased glutamine synthetase, glutamine, and GABA (ACC, PFC, DMPFC, VMPFC, amygdala, hippocampi; normalized with ECT and disease remission) [78] | GLX is increased in medial PFC (ACC, DLPFC, parietal-OCC, OCC, insula, hippocampus) [78, 79]; independent of disease state. | Glutamate is decreased in medial PFC (including ACC); Increased glutamine synthetase, glutamine, and ‘glutamine:glutamate ratio’ in PFC [90] | GLX is increased in left caudate and OFC (normalized after successful SRI treatment); GLX is decreased in ACC [84] |
Cytokines (serum) | Â | Â | Â | |
  Phenotype | Proinflammatory are increased [91] | Proinflammatory are increased [92]; IL-1β, IL-1R, and IL-6 correlate with post-mortem brain mRNA expression [69] | Mixed data: antiinflammatory and/or proinflammatory, are increased [52, 94, 93] | Mixed data: TNF-α is increased or decreased; IL-6 is increased or no change; IL-1β is decreased [95] |
  Trait and State markers | Trait markers: TNF-α, IL-6, and sIL-2R are increased [91] State markers (suicidal): TNF-α and IL-6 are increased, and IL-2 is decreased [96]. | Depressive state: IL-6 Euthymic state: IL-4 Manic state: IL-2, IL-4, IL-6 [92] | Trait makers: IFN-γ, TNF-α, IL-12, sIL-2R, IL-1RA, sIL-2R [93] State markers: IL-1β, IL-6, TGF-β [93] | Trait markers: mixed data LPS-induced: TNF-α and IL-6 are decreased [95] |