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

From: Neuroinflammation and psychiatric illness


Major depression

Bipolar disorder





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]



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


KYNA is increased [52, 53]

Both are increased [21, 52]



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]


Both are increased [29]

Both are decreased [21],[73]

  Quinolinic acid

Increased [53]


  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)


  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)



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.