Skip to main content

Advertisement

SpringerLink
Log in

Immunoglobulin genotypes and cognitive functions in schizophrenia

  • Short Communication
  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

Exposure to neurotropic viruses, such as herpes simplex virus type 1 and human cytomegalovirus, has been reported to be associated with cognitive impairment in schizophrenia. These viruses have evolved highly sophisticated strategies for decreasing the efficacy of the host immune response and interfering with viral clearance. Particular immunoglobulin GM (γ marker) genotypes modulate these viral immunoevasion strategies, influence antibody responsiveness to viral proteins, and are also associated with susceptibility to schizophrenia, providing an excellent rationale for determining their possible involvement in the cognitive functions in this highly heritable neurodevelopmental disorder. In this investigation, we assessed the cognitive functions (verbal memory, working memory, motor speed, verbal fluency, attention and processing speed, and executive function) in 145 patients with schizophrenia and characterized their DNA for several GM and KM (κ marker) alleles. Particular KM and GM genotypes were significantly associated with verbal memory and attention and processing speed scores, respectively (P = 0.01 and 0.001). Epistatic effects of GM and KM genotypes on attention and processing speed, verbal fluency, and motor speed were also noted (P = 0.031, 0.047, 0.003). These results, for the first time, show that hitherto understudied immunoglobulin GM and KM genotypes—individually and epistatically—contribute to the magnitude of interindividual variability in the cognitive functions in patients with schizophrenia. Additional studies involving these highly polymorphic genes of the immune system are needed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  • Alaedini A, Okamoto H, Briani C, Wollenberg K, Shill HA et al (2007) Immune cross-reactivity in celiac disease: anti-gliadin antibodies bind to neuronal synapsin I. J Immunol 178:6590–6595

    Article  CAS  PubMed  Google Scholar 

  • Atherton A, Armour KL, Bell S, Minson AC, Clark MR (2000) The herpes simplex virus type 1 Fc receptor discriminates between IgG1 allotypes. Eur J Immunol 30:2540–2547

    Article  CAS  PubMed  Google Scholar 

  • Biggar RJ, Pandey JP, Henle W, Nkrumah FK, Levine PH (1984) Humoral immune response to Epstein-Barr virus antigens and immunoglobulin allotypes in African Burkitt lymphoma patients. Int J Cancer 33:577–580

    Article  CAS  PubMed  Google Scholar 

  • Brimberg L, Mader S, Fujieda Y, Arinuma Y, Kowal C et al (2015) Antibodies as mediators of brain pathology. Trends Immunol 36:709–724

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brüggemann M, Williams GT, Bindon CI, Clark MR, Walker MR et al (1987) Comparison of the effector functions of human immunoglobulins using a matched set of chimeric antibodies. J Exp Med 166:1351–1361

    Article  PubMed  Google Scholar 

  • Brusco A, de Lange GG, Boccazz C, Carbonara AO (1995) Molecular characterization of G2m(n+) and G2m(n-) allotypes. Immunogenetics 42:414–417

    Article  CAS  PubMed  Google Scholar 

  • Corrales-Aguilar E, Trilling M, Hunold K, Fiedler M, Le VT et al (2014) Human cytomegalovirus Fcγ binding proteins gp34 and gp68 antagonize Fcγ receptors I, II and III. PLoS Pathog 10:e1004131

    Article  PubMed  PubMed Central  Google Scholar 

  • Hilfiker S, Benfenati F, Doussau F, Nairn AC, Czernik et al (2005) Structural domains involved in the regulation of transmitter release by synapsins. J Neurosci 25:2658–2669

    Article  CAS  PubMed  Google Scholar 

  • Hori H, Yoshimura R, Katsuki A, Atake K, Igata R et al (2016) Relationships between serum brain-derived neurotrophic factor, plasma catecholamine metabolites, cytokines, cognitive function and clinical symptoms in Japanese patients with chronic schizophrenia treated with atypical antipsychotic monotherapy. World J Biol Psychiatry 15:1–8

    Article  Google Scholar 

  • Humeau Y, Doussau F, Vitiello F, Greengard P, Benfenati F et al (2001) Synapsin controls both reserve and releasable synaptic vesicle pools during neuronal activity and short-term plasticity in Aplysia. J Neurosci 21:4195–4206

    CAS  PubMed  Google Scholar 

  • Kaneda Y, Sumiyoshi T, Keefe R, Ishimoto Y, Numata S et al (2007) Brief assessment of cognition in schizophrenia: validation of the Japanese version. Psychiatry Clin Neurosci 61:602–609

    Article  PubMed  Google Scholar 

  • Li L, Chin LS, Shupliakov O, Brodin L, Sihra TS et al (1995) Impairment of synaptic vesicle clustering and of synaptic transmission, and increased seizure propensity, in synapsin I-deficient mice. Proc Natl Acad Sci U S A 92:9235–9239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moraru M, Black LE, Muntasell A, Portero F, López-Botet M et al (2015) NK cells and immunoglobulins interplay in defense against herpes simplex virus type 1: epistatic interaction of CD16A and IgG1 allotypes of variable affinity modulates antibody-dependent cellular cytotoxicity and susceptibility to clinical reactivation. J Immunol 195:1676–1684

    Article  CAS  PubMed  Google Scholar 

  • Moxley GM, Gibbs RS (1992) Polymerase chain reaction-based genotyping for allotypic markers of immunoglobulin kappa shows allelic association of Km with kappa variable segment. Genomics 13:104–108

    Article  CAS  PubMed  Google Scholar 

  • Namboodiri AM, Pandey JP (2011) The human cytomegalovirus TRL11/IRL11-encoded FcγR binds differentially to allelic variants of immunoglobulin G1. Arch Virol 156:907–910

    Article  CAS  PubMed  Google Scholar 

  • Okun E, Mattson MP, Arumugam TV (2010) Involvement of Fc receptors in disorders of the central nervous system. NeuroMolecular Med 12:164–178

    Article  CAS  PubMed  Google Scholar 

  • Oxelius VA, Pandey JP (2013) Human immunoglobulin constant heavy G chain (IGHG) (Fcγ) (GM) genes, defining innate variants of IgG molecules and B cells, have impact on disease and therapy. Clin Immunol 149:475–486

    Article  CAS  PubMed  Google Scholar 

  • Pandey JP, Kistner-Griffin E, Radwan FF, Kaur N, Namboodiri AM et al (2014) Immunoglobulin genes influence the magnitude of humoral immunity to cytomegalovirus glycoprotein B. J Infect Dis 210:1823–1826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pandey JP, Namboodiri AM, Radwan FF, Nietert PJ (2015) The decoy Fcγ receptor encoded by the cytomegalovirus UL119-UL118 gene has differential affinity to IgG proteins expressing different GM allotypes. Hum Immunol 76:591–594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pandey JP, Namboodiri AM, Elston RC (2016) Immunoglobulin G genotypes and the risk of schizophrenia. Hum Genet 135:1175–1179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pandey JP, Namboodiri AM, Mohan S, Nietert PJ, Peterson L (2017) Genetic markers of immunoglobulin G and immunity to cytomegalovirus in patients with breast cancer. Cell Immunol 312:67–70

    Article  CAS  PubMed  Google Scholar 

  • Perneger TV (1998) What’s wrong with Bonferroni adjustments. BMJ 316:1236–1238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Presumey J, Bialas AR, Carroll MC (2017) Complement system in neural synapse elimination in development and disease. Adv Immunol 135:53–79

    Article  PubMed  Google Scholar 

  • Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014) Biological insights from 108 schizophrenia-associated genetic loci. Nature 511:421–427

    Article  PubMed Central  Google Scholar 

  • Sekar A, Bialas AR, de Rivera H, Davis A, Hammond TR et al (2016) Schizophrenia risk from complex variation of complement component 4. Nature 530:177–183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shim SM, Cheon HS, Jo C, Koh YH, Song J, Jeon JP (2017) Elevated Epstein-Barr virus antibody level is associated with cognitive decline in the Korean elderly. J Alzheimers Dis 55:293–301

    Article  CAS  PubMed  Google Scholar 

  • Shirts BH, Prasad KM, Pogue-Geile MF, Dickerson F, Yolken RH et al (2008) Antibodies to cytomegalovirus and herpes simplex virus 1 associated with cognitive function in schizophrenia. Schizophr Res 106:268–274

    Article  PubMed  PubMed Central  Google Scholar 

  • Trampush JW, Yang ML, Yu J, Knowles E, Davies G, Liewald DC et al (2017) GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium. Mol Psychiatry 22:336–345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weiss JB, Austin RK, Schanfield MS, Kagnoff MF (1983) Gluten-sensitive enteropathy. Immunoglobulin G heavy-chain (Gm) allotypes and the immune response to wheat gliadin. J Clin Invest 72:96–101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We are grateful to the patients who participated in this study.

Funding

This work was supported in part by the NIH grant MH104613.

Author information

Authors and Affiliations

  1. Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, 29425, USA

    Janardan P. Pandey & Aryan M. Namboodiri

  2. Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, 29425, USA

    Paul J. Nietert

  3. Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan

    Reiji Yoshimura & Hikaru Hori

Authors
  1. Janardan P. Pandey
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aryan M. Namboodiri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul J. Nietert
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Reiji Yoshimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hikaru Hori
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Janardan P. Pandey.

Ethics declarations

The study was approved by the University Ethics Committee, using the ethical standards of the Declaration of Helsinki.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pandey, J.P., Namboodiri, A.M., Nietert, P.J. et al. Immunoglobulin genotypes and cognitive functions in schizophrenia. Immunogenetics 70, 67–72 (2018). https://doi.org/10.1007/s00251-017-1030-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00251-017-1030-6

Keywords

Search

Navigation