Role of microglia disturbances and immune-related marker abnormalities in cortical circuitry dysfunction in schizophrenia

Neurobiology of Disease

Volumn 99, Issue , 2017, Pages 58-65

  Volk, David W ^a  

^a UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

Author keywords

Dendritic spine; GABA; Immune; Inflammation; Inhibitory; Microglia; Prefrontal cortex

Indexed keywords

BRAIN DYSFUNCTION; CEREBROSPINAL FLUID; CORTICAL CIRCUITRY DYSFUNCTION; DENDRITIC SPINE; GENETIC ASSOCIATION; GENETIC VARIATION; GENOME-WIDE ASSOCIATION STUDY; HUMAN; IMMUNE RESPONSE; IMMUNOCOMPETENT CELL; IMMUNOPATHOLOGY; MATERNAL EXPOSURE; MICROGLIA; NONHUMAN; PREFRONTAL CORTEX; PRIORITY JOURNAL; PYRAMIDAL NERVE CELL; REVIEW; SCHIZOPHRENIA; ANIMAL; METABOLISM; NERVE TRACT; PATHOLOGY;

ANIMALS; HUMANS; MICROGLIA; NEURAL PATHWAYS; PREFRONTAL CORTEX; SCHIZOPHRENIA;

EID: 85006862901     PISSN: 09699961     EISSN: 1095953X     Source Type: Journal    
DOI: 10.1016/j.nbd.2016.12.019     Document Type: Review

References (115)

1. Akbarian, S., et al. Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics. Arch. Gen. Psychiatry 52 (1995), 258–266.
2. Anderson, S.A., et al. Synchronous development of pyramidal neuron dendritic spines and parvalbumin-immunoreactive chandelier neuron axon terminals in layer III of monkey prefrontal cortex. Neuroscience 67 (1995), 7–22.
3. Arion, D., et al. Molecular evidence for increased expression of genes related to immune and chaperone function in the prefrontal cortex in schizophrenia. Biol. Psychiatry 62 (2007), 711–721.
4. Arnold, S.E., et al. Absence of neurodegeneration and neural injury in the cerebral cortex in a sample of elderly patients with schizophrenia. Arch. Gen. Psychiatry 55 (1998), 225–232.
5. Bailey, C.C., et al. Ifitm3 limits the severity of acute influenza in mice. PLoS Pathog., 8, 2012, e1002909.
6. Bayer, T.A., et al. Evidence for activation of microglia in patients with psychiatric illnesses. Neurosci. Lett. 271 (1999), 126–128.
7. Benros, M.E., et al. The epidemiologic evidence linking autoimmune diseases and psychosis. Biol. Psychiatry 75 (2014), 300–306.
8. Benros, M.E., et al. A nationwide study on the risk of autoimmune diseases in individuals with a personal or a family history of schizophrenia and related psychosis. Am. J. Psychiatry 171 (2014), 218–226.
9. Bloomfield, P.S., et al. Microglial activity in people at ultra high risk of psychosis and in schizophrenia: an [(11)C]PBR28 PET brain imaging study. Am. J. Psychiatry 173 (2016), 44–52.
10. Brown, A.S., Derkits, E.J., Prenatal infection and schizophrenia: a review of epidemiologic and translational studies. Am. J. Psychiatry 167 (2010), 261–280.
11. Brown, A.S., et al. A.E. Bennett research award. Prenatal rubella, premorbid abnormalities, and adult schizophrenia. Biol. Psychiatry 49 (2001), 473–486.
12. Brown, A.S., et al. Serologic evidence of prenatal influenza in the etiology of schizophrenia. Arch. Gen. Psychiatry 61 (2004), 774–780.
13. Brown, A.S., et al. Elevated maternal interleukin-8 levels and risk of schizophrenia in adult offspring. Am. J. Psychiatry 161 (2004), 889–895.
14. Brown, A.S., et al. Maternal exposure to toxoplasmosis and risk of schizophrenia in adult offspring. Am. J. Psychiatry 162 (2005), 767–773.
15. Buka, S.L., et al. Maternal infections and subsequent psychosis among offspring. Arch. Gen. Psychiatry 58 (2001), 1032–1037.
16. Calabrese, L.H., Rose-John, S., IL-6 biology: implications for clinical targeting in rheumatic disease. Nat. Rev. Rheumatol. 10 (2014), 720–727.
17. Canetta, S., et al. Elevated maternal C-reactive protein and increased risk of schizophrenia in a national birth cohort. Am. J. Psychiatry 171 (2014), 960–968.
18. Canetta, S., et al. Maternal immune activation leads to selective functional deficits in offspring parvalbumin interneurons. Mol. Psychiatry 21 (2016), 956–968.
19. Chaudhry, I.B., et al. Minocycline benefits negative symptoms in early schizophrenia: a randomised double-blind placebo-controlled clinical trial in patients on standard treatment. J. Psychopharmacol. 26 (2012), 1185–1193.
20. Chen, Z., et al. Microglial displacement of inhibitory synapses provides neuroprotection in the adult brain. Nat. Commun., 5, 2014, 4486.
21. Chubb, J.E., et al. The DISC locus in psychiatric illness. Mol. Psychiatry 13 (2008), 36–64.
22. Clarke, M.C., et al. Increased risk of schizophrenia from additive interaction between infant motor developmental delay and obstetric complications: evidence from a population-based longitudinal study. Am. J. Psychiatry 168 (2011), 1295–1302.
23. Curley, A.A., et al. Cortical deficits of glutamic acid decarboxylase 67 expression in schizophrenia: clinical, protein, and cell type-specific features. Am. J. Psychiatry 168 (2011), 921–929.
24. Datta, D., et al. Altered expression of CDC42 signaling pathway components in cortical layer 3 pyramidal cells in schizophrenia. Biol. Psychiatry 78 (2015), 775–785.
25. Diamond, M.S., Farzan, M., The broad-spectrum antiviral functions of IFIT and IFITM proteins. Nat. Rev. Immunol. 13 (2013), 46–57.
26. Dickerson, F., et al. C-reactive protein is associated with the severity of cognitive impairment but not of psychiatric symptoms in individuals with schizophrenia. Schizophr. Res. 93 (2007), 261–265.
27. Doorduin, J., et al. Neuroinflammation in schizophrenia-related psychosis: a PET study. Eur. J. Nucl. Med. 50 (2009), 1801–1807.
28. Duncan, C.E., et al. Prefrontal GABA(A) receptor alpha-subunit expression in normal postnatal human development and schizophrenia. J. Psychiatr. Res. 44 (2010), 673–681.
29. Fernandes, B.S., et al. C-reactive protein is increased in schizophrenia but is not altered by antipsychotics: meta-analysis and implications. Mol. Psychiatry 21 (2016), 554–564.
30. Fillman, S.G., et al. Increased inflammatory markers identified in the dorsolateral prefrontal cortex of individuals with schizophrenia. Mol. Psychiatry 18 (2013), 206–214.
31. Fillman, S.G., et al. Elevated peripheral cytokines characterize a subgroup of people with schizophrenia displaying poor verbal fluency and reduced Broca's area volume. Mol. Psychiatry 21 (2016), 1090–1098.
32. Frank, M.G., et al. Microglia serve as a neuroimmune substrate for stress-induced potentiation of CNS pro-inflammatory cytokine responses. Brain Behav. Immun. 21 (2007), 47–59.
33. Fromer, M., et al. De novo mutations in schizophrenia implicate synaptic networks. Nature 506 (2014), 179–184.
34. Fung, S.J., et al. Expression of interneuron markers in the dorsolateral prefrontal cortex of the developing human and in schizophrenia. Am. J. Psychiatry 167 (2010), 1479–1488.
35. Garver, D.L., et al. Elevated interleukin-6 in the cerebrospinal fluid of a previously delineated schizophrenia subtype. Neuropsychopharmacology 28 (2003), 1515–1520.
36. Giovanoli, S., et al. Stress in puberty unmasks latent neuropathological consequences of prenatal immune activation in mice. Science 339 (2013), 1095–1099.
37. Glantz, L.A., Lewis, D.A., Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Arch. Gen. Psychiatry 57 (2000), 65–73.
38. Glausier, J.R., Lewis, D.A., Dendritic spine pathology in schizophrenia. Neuroscience 251 (2013), 90–107.
39. Glausier, J.R., et al. Altered parvalbumin basket cell inputs in the dorsolateral prefrontal cortex of schizophrenia subjects. Mol. Psychiatry 19 (2014), 30–36.
40. Goldsmith, D.R., et al. A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression. Mol. Psychiatry 21 (2016), 1696–1709.
41. Gouin, J.P., et al. Chronic stress, daily stressors, and circulating inflammatory markers. Health Psychol. 31 (2012), 264–268.
42. Guidotti, A., et al. Decrease in reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder. Arch. Gen. Psychiatry 57 (2000), 1061–1069.
43. Hannestad, J., et al. The neuroinflammation marker translocator protein is not elevated in individuals with mild-to-moderate depression: a [(1)(1)C]PBR28 PET study. Brain Behav. Immun. 33 (2013), 131–138.
44. Hashimoto, T., et al. Gene expression deficits in a subclass of GABA neurons in the prefrontal cortex of subjects with schizophrenia. J. Neurosci. 23 (2003), 6315–6326.
45. Havik, B., et al. The complement control-related genes CSMD1 and CSMD2 associate to schizophrenia. Biol. Psychiatry 70 (2011), 35–42.
46. Hiles, S.A., et al. A meta-analysis of differences in IL-6 and IL-10 between people with and without depression: exploring the causes of heterogeneity. Brain Behav. Immun. 26 (2012), 1180–1188.
47. Hill, J.J., et al. Molecular mechanisms contributing to dendritic spine alterations in the prefrontal cortex of subjects with schizophrenia. Mol. Psychiatry 11 (2006), 557–566.
48. Hoftman, G.D., et al. Altered cortical expression of GABA-related genes in schizophrenia: illness progression vs developmental disturbance. Schizophr. Bull. 41 (2015), 180–191.
49. Horvath, S., Mirnics, K., Immune system disturbances in schizophrenia. Biol. Psychiatry 75 (2014), 316–323.
50. Huang, I.C., et al. Distinct patterns of IFITM-mediated restriction of filoviruses, SARS coronavirus, and influenza A virus. PLoS Pathog., 7, 2011, e1001258.
51. Huttenlocher, P.R., Synaptic density in human frontal cortex - developmental changes and effects of aging. Brain Res. 163 (1979), 195–205.
52. Ide, M., Lewis, D.A., Altered cortical CDC42 signaling pathways in schizophrenia: implications for dendritic spine deficits. Biol. Psychiatry 68 (2010), 25–32.
53. Imbesi, M., et al. Minocycline increases phosphorylation and membrane insertion of neuronal GluR1 receptors. Neurosci. Lett. 447 (2008), 134–137.
54. Ito, D., et al. Enhanced expression of Iba1, ionized calcium-binding adapter molecule 1, after transient focal cerebral ischemia in rat brain. Stroke 32 (2001), 1208–1215.
55. Jin, L.J., et al. The two different effects of the potential neuroprotective compound minocycline on AMPA-type glutamate receptors. Pharmacology 89 (2012), 156–162.
56. Johnsen, E., et al. The serum level of C-reactive protein (CRP) is associated with cognitive performance in acute phase psychosis. BMC Psychiatry, 16, 2016, 60.
57. Karlstetter, M., et al. Translocator protein (18 kDa) (TSPO) is expressed in reactive retinal microglia and modulates microglial inflammation and phagocytosis. J. Neuroinflammation, 11, 2014, 3.
58. Kelly, D.L., et al. Adjunctive minocycline in clozapine-treated schizophrenia patients with persistent symptoms. J. Clin. Psychopharmacol. 35 (2015), 374–381.
59. Kenk, M., et al. Imaging neuroinflammation in gray and white matter in schizophrenia: an in-vivo PET study with [18F]-FEPPA. Schizophr. Bull. 41 (2015), 85–93.
60. Khodaie-Ardakani, M.R., et al. Minocycline add-on to risperidone for treatment of negative symptoms in patients with stable schizophrenia: randomized double-blind placebo-controlled study. Psychiatry Res. 215 (2014), 540–546.
61. Kolluri, N., et al. Lamina-specific reductions in dendritic spine density in the prefrontal cortex of subjects with schizophrenia. Am. J. Psychiatry 162 (2005), 1200–1202.
62. Konopaske, G.T., et al. Prefrontal cortical dendritic spine pathology in schizophrenia and bipolar disorder. JAMA Psychiat. 71 (2014), 1323–1331.
63. Kuhlmann, A.C., Guilarte, T.R., Cellular and subcellular localization of peripheral benzodiazepine receptors after trimethyltin neurotoxicity. J. Neurochem. 74 (2000), 1694–1704.
64. Lee, Y.B., et al. Cytokines, chemokines, and cytokine receptors in human microglia. J. Neurosci. Res. 69 (2002), 94–103.
65. Levkovitz, Y., et al. A double-blind, randomized study of minocycline for the treatment of negative and cognitive symptoms in early-phase schizophrenia. J. Clin. Psychiatry 71 (2010), 138–149.
66. Lipina, T.V., et al. Maternal immune activation during gestation interacts with Disc1 point mutation to exacerbate schizophrenia-related behaviors in mice. J. Neurosci. 33 (2013), 7654–7666.
67. Liu, F., et al. Minocycline supplementation for treatment of negative symptoms in early-phase schizophrenia: a double blind, randomized, controlled trial. Schizophr. Res. 153 (2014), 169–176.
68. Maeda, J., et al. Phase-dependent roles of reactive microglia and astrocytes in nervous system injury as delineated by imaging of peripheral benzodiazepine receptor. Brain Res. 1157 (2007), 100–111.
69. Maes, M., et al. The effects of psychological stress on humans: increased production of pro-inflammatory cytokines and a Th1-like response in stress-induced anxiety. Cytokine 10 (1998), 313–318.
70. Mellios, N., et al. Molecular determinants of dysregulated GABAergic gene expression in the prefrontal cortex of subjects with schizophrenia. Biol. Psychiatry 65 (2009), 1006–1014.
71. Miller, B.J., et al. Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol. Psychiatry 70 (2011), 663–671.
72. Modabbernia, A., et al. Cytokine alterations in bipolar disorder: a meta-analysis of 30 studies. Biol. Psychiatry 74 (2013), 15–25.
73. Oya, K., et al. Efficacy and tolerability of minocycline augmentation therapy in schizophrenia: a systematic review and meta-analysis of randomized controlled trials. Humanist. Psychol. 29 (2014), 483–491.
74. Paolicelli, R.C., et al. Synaptic pruning by microglia is necessary for normal brain development. Science 333 (2011), 1456–1458.
75. Perkins, D.O., et al. Towards a psychosis risk blood diagnostic for persons experiencing high-risk symptoms: preliminary results from the NAPLS project. Schizophr. Bull. 41 (2015), 419–428.
76. Petanjek, Z., et al. Extraordinary neoteny of synaptic spines in the human prefrontal cortex. Proc. Natl. Acad. Sci. U. S. A. 108 (2011), 13281–13286.
77. Potvin, S., et al. Inflammatory cytokine alterations in schizophrenia: a systematic quantitative review. Biol. Psychiatry 63 (2008), 801–808.
78. Purcell, S.M., et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460 (2009), 748–752.
79. Radewicz, K., et al. Increase in HLA-DR immunoreactive microglia in frontal and temporal cortex of chronic schizophrenics. J. Neuropathol. Exp. Neurol. 59 (2000), 137–150.
80. Rao, J.S., et al. Increased excitotoxicity and neuroinflammatory markers in postmortem frontal cortex from bipolar disorder patients. Mol. Psychiatry 15 (2010), 384–392.
81. Richetto, J., et al. Prenatal immune activation induces maturation-dependent alterations in the prefrontal GABAergic transcriptome. Schizophr. Bull. 40 (2014), 351–361.
82. Ridler, K., et al. Fronto-cerebellar systems are associated with infant motor and adult executive functions in healthy adults but not in schizophrenia. Proc. Natl. Acad. Sci. U. S. A. 103 (2006), 15651–15656.
83. Ripke, S., et al. Genome-wide association study identifies five new schizophrenia loci. Nat. Genet. 43 (2011), 969–976.
84. Roge, R., et al. Immunomodulatory effects of clozapine and their clinical implications: what have we learned so far?. Schizophr. Res. 140 (2012), 204–213.
85. Saetre, P., et al. Inflammation-related genes up-regulated in schizophrenia brains. BMC Psychiatry, 7, 2007, 46.
86. Sasayama, D., et al. Increased cerebrospinal fluid interleukin-6 levels in patients with schizophrenia and those with major depressive disorder. J. Psychiatr. Res. 47 (2013), 401–406.
87. Schafer, D.P., et al. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74 (2012), 691–705.
88. Schizophrenia Working Group of the Psychiatric Genomics Consortium, Biological insights from 108 schizophrenia-associated genetic loci. Nature 511 (2014), 421–427.
89. Schwieler, L., et al. Increased levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia—significance for activation of the kynurenine pathway. J. Psychiatry Neurosci. 40 (2015), 126–133.
90. Sekar, A., et al. Schizophrenia risk from complex variation of complement component 4. Nature 530 (2016), 177–183.
91. Setiawan, E., et al. Role of translocator protein density, a marker of neuroinflammation, in the brain during major depressive episodes. JAMA Psychiatry 72 (2015), 268–275.
92. Shi, J., et al. Common variants on chromosome 6p22.1 are associated with schizophrenia. Nature 460 (2009), 753–757.
93. Siegel, B.I., et al. Elevated viral restriction factor levels in cortical blood vessels in schizophrenia. Biol. Psychiatry 76 (2014), 160–167.
94. Soderlund, J., et al. Activation of brain interleukin-1beta in schizophrenia. Mol. Psychiatry 14 (2009), 1069–1071.
95. Sorensen, H.J., et al. Early developmental milestones and risk of schizophrenia: a 45-year follow-up of the Copenhagen Perinatal Cohort. Schizophr. Res. 118 (2010), 41–47.
96. Stefansson, H., et al. Common variants conferring risk of schizophrenia. Nature 460 (2009), 744–747.
97. Steiner, J., et al. Distribution of HLA-DR-positive microglia in schizophrenia reflects impaired cerebral lateralization. Acta Neuropathol. 112 (2006), 305–316.
98. Steptoe, A., et al. The effects of acute psychological stress on circulating inflammatory factors in humans: a review and meta-analysis. Brain Behav. Immun. 21 (2007), 901–912.
99. Stevens, B., et al. The classical complement cascade mediates CNS synapse elimination. Cell 131 (2007), 1164–1178.
100. Straub, R.E., et al. Allelic variation in GAD1 (GAD67) is associated with schizophrenia and influences cortical function and gene expression. Mol. Psychiatry 12 (2007), 854–869.
101. Takano, A., et al. Peripheral benzodiazepine receptors in patients with chronic schizophrenia: a PET study with [11C]DAA1106. Int. J. Neuropsychopharmacol. 13 (2010), 943–950.
102. Takao, K., et al. Deficiency of schnurri-2, an MHC enhancer binding protein, induces mild chronic inflammation in the brain and confers molecular, neuronal, and behavioral phenotypes related to schizophrenia. Neuropsychopharmacology 38 (2013), 1409–1425.
103. Tang, B., et al. Epigenetic changes at gene promoters in response to immune activation in utero. Brain Behav. Immun. 30 (2013), 168–175.
104. Trapp, B.D., et al. Evidence for synaptic stripping by cortical microglia. Glia 55 (2007), 360–368.
105. Tremblay, M.E., et al. Microglial interactions with synapses are modulated by visual experience. PLoS Biol., 8, 2010, e1000527.
106. van Berckel, B.N., et al. Microglia activation in recent-onset schizophrenia: a quantitative (R)-[11C]PK11195 positron emission tomography study. Biol. Psychiatry 64 (2008), 820–822.
107. Volk, D.W., et al. Decreased glutamic acid decarboxylase67 messenger RNA expression in a subset of prefrontal cortical gamma-aminobutyric acid neurons in subjects with schizophrenia. Arch. Gen. Psychiatry 57 (2000), 237–245.
108. Volk, D.W., et al. Deficits in transcriptional regulators of cortical parvalbumin neurons in schizophrenia. Am. J. Psychiatry 169 (2012), 1082–1091.
109. Volk, D.W., et al. Cortical inhibitory neuron disturbances in schizophrenia: role of the ontogenetic transcription factor Lhx6. Schizophr. Bull. 40 (2014), 1053–1061.
110. Volk, D.W., et al. Molecular mechanisms and timing of cortical immune activation in schizophrenia. Am. J. Psychiatry 172 (2015), 1112–1121.
111. Wake, H., et al. Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. J. Neurosci. 29 (2009), 3974–3980.
112. Wierzba-Bobrowicz, T., et al. Quantitative analysis of activated microglia, ramified and damage of processes in the frontal and temporal lobes of chronic schizophrenics. Folia Neuropathol. 43 (2005), 81–89.
113. Wolf, J., et al. Interleukin-6 and its receptors: a highly regulated and dynamic system. Cytokine 70 (2014), 11–20.
114. Wong, A.M., et al. Macrosialin increases during normal brain aging are attenuated by caloric restriction. Neurosci. Lett. 390 (2005), 76–80.
115. Zhang, L., et al. Minocycline attenuates hyperlocomotion and prepulse inhibition deficits in mice after administration of the NMDA receptor antagonist dizocilpine. Neuropsychopharmacology 32 (2007), 2004–2010.