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Table 2 Summary of neuroinflammatory and immunological abnormalities observed in pure psychiatric disorders

From: Neuroinflammation and psychiatric illness

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) [3541]; few exceptions [42, 43] Reduced or no change [37, 4446] Reduced or no change [3739, 4749][42, 50, 51] Insufficient data
  TDO, KYNA KYNA is increased [52, 53] Both are increased [21, 52]
Oligodendroglia
  Density Decreased [5458] Decreased [54, 5665] Decreased [5458, 66] Insufficient data
Microglial activation
  Trait and State markers Trait: no [53, 67, 68]; State (suicidal): yes [22, 68] Mixed data [53, 68, 69] Trait: no [70]; State (suicidal): yes [22, 68] Insufficient data; yet, Hoxb8 (-/-) mice exhibit OCD-like behavior [71, 72]
  IDO, KMO Both are increased [29] Both are decreased [21],[73]
  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] Both are increased in PFC [7981], and thalamus [82]
  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 [7981] and thalamus [82] EAAT3 is decreased in CSTC circuitry [77, 84]
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)    
  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]
  1. 5-HTTLPR, serotonin-transporter-linked polymorphic region; ANK3, ankyrin-3; ACC, anterior cingulate cortex; BDNF, brain-derived neurotrophic factor, BPD, bipolar disorder; COMT, catechol-O-methyl transferase; COX-2, cyclooxygenase 2; CSF, cerebrospinal fluid, CSTC, cortico-striatal-thalamic-cortico; DLPFC, dorsolateral prefrontal cortex; DMPFC, dorsomedial prefrontal cortex; EAAT, excitatory amino acid transporter: (EAATs 1 and 2 are expressed by astroglia, EAAT3 is expressed intracellularly in the post-synaptic neurons, and EAAT4 is expressed by Purkinje cells and frontal neurons); GABA, gamma aminobutyric acid; GLX 1H MRS: (detectable glutamate, glutamine, gamma aminobutyric acid composite); GWAS, genome-wide association study (single nucleotide polymorphisms identified across the entire genome of those with a given disorder (fourth row); includes immunologic genetic abnormalities (fifth row) whenever applicable); 1 H MRS, proton magnetic resonance spectroscopy; HLA, human leukocyte antigen; IDO, indoleamine-2,3-oxygenase; IFN-γ, interferon gamma; IL, interleukin, IL-1RA; interleukin 1 receptor antagonist; KMO, kynurenine monooxygenase; KYNA, kynurenic acid; MDD, major depressive disorder; OCC, occipital cortex; OCD, obsessive-compulsive disorder; OFC, orbitofrontal cortex; PBRM1, protein polybromo-1; PFC, prefrontal cortex; SRI, serotonin reuptake inhibitor; T regs, CD4+CD25+FOXP3+ T regulatory cells; TDO, tryptophan-2,3-dioxygenase, TGF-β, transforming growth factor beta; TNF-α, tumor necrosis factor alpha; VMPFC, ventromedial prefrontal cortex.