Autoantibodies to the NMDA Receptor in Schizophrenia: A Literature Review

Authors

  • Liam Kennedy School of Medicine, Trinity College, University of Dublin, Ireland

Keywords:

Medicine

Abstract

Schizophrenia is a chronic mental illness characterised by positive and negative symptoms, and cognitive dysfunction. The aetiology of the condition is poorly understood; among the various proposed hypotheses are theories involving glutamate transmission and autoimmunity. The N-methyl-D-aspartate receptor (NMDAR) is an ionotropic glutamate receptor expressed widely in the CNS, it is involved in long-term potentiation, memory and learning, and regulation of glutamatergic transmission via GABA-ergic interneurons. Pharmacological blockade of NMDARs induces positive and negative symptoms of schizophrenia in healthy subjects, and exacerbates symptoms in patients. NMDA hypo-function has been demonstrated to cause localised glutamate excito-toxicity in schizophrenia. Anti-NMDAR auto-encephalitis is a recently described neuro-immune condition, which often presents with acute psychosis. Due to the behavioural symptoms caused by the condition, 65% of those who develop anti-NMDAR auto-encephalitis are initially seen by psychiatric services. Studies of anti-NMDAR antibody prevalence in schizophrenic patients and the general population have found conflicting results. Analysis is complicated by variance between studies in terms of antibody specificity and assays used. Further work in this expanding field will help delineate the exact relevance of antibody seropositivity to the development of schizophrenia or psychosis. Anti-NMDAR auto-encephalitis represents an important aetiological factor of psychosis to be considered in the clinical assessment of acute psychosis.

Author Biography

Liam Kennedy, School of Medicine, Trinity College, University of Dublin, Ireland

M.Sc. Neuroscience

References

1 Wright, P., Stern, J. & Phelan, M. Core Psychiatry. (Else- vier Health Sciences UK, 2012).
2 Davison, K. Autoimmunity in psychiatry. The British journal of psychiatry : the journal of mental science 200, 353-355, doi:10.1192/bjp.bp.111.104471 (2012).
3 Chen, S.-J. et al. Prevalence of autoimmune diseases in in-patients with schizophrenia: nationwide population-based study. The British journal of psychiatry : the journal of mental science 200, 374-380, doi:10.1192/bjp.bp.111.092098 (2012).
4 Vitaliani, R. et al. Paraneoplastic encephalitis, psychiat- ric symptoms, and hypoventilation in ovarian teratoma. Annals of neurology 58, 594-604, doi:10.1002/ana.20614 (2005).
5 Dalmau, J. et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet neurology 7, 1091-1098, doi:10.1016/S1474-4422(08)70224-2 (2008).
6 Dalmau, J., Lancaster, E., Martinez-Hernandez, E., Ros- enfeld, M. R. & Balice-Gordon, R. Clinical experience and laborato- ry investigations in patients with anti-NMDAR encephalitis. The Lancet Neurology 10, 63-74, doi:10.1016/s1474-4422(10)70253-2 (2011).
7 Lennox, B., Coles, A. & Vincent, A. Antibody-mediat- ed encephalitis: a treatable cause of schizophrenia. The British journal of psychiatry : the journal of mental science 200, 92-94, doi:10.1192/bjp.bp.111.095042 (2012).
8 Moghaddam, B. & Javitt, D. From revolution to evolution: the glutamate hypothesis of schizophrenia and its implication for treatment. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 37, 4-15, doi:10.1038/npp.2011.181 (2012).
9 Lin, C. H., Lane, H. Y. & Tsai, G. E. Glutamate signaling in the pathophysiology and therapy of schizophrenia. Pharma- cology, biochemistry, and behavior 100, 665-677, doi:10.1016/j. pbb.2011.03.023 (2012).
10 Gilmour, G. et al. NMDA receptors, cognition and schizo- phrenia--testing the validity of the NMDA receptor hypofunction hypothesis. Neuropharmacology 62, 1401-1412, doi:10.1016/j. neuropharm.2011.03.015 (2012).
11 Kristiansen, L. V., Huerta, I., Beneyto, M. & Meador-Wood- ruff, J. H. NMDA receptors and schizophrenia. Current opinion in pharmacology 7, 48-55, doi:10.1016/j.coph.2006.08.013 (2007).
12 Lahti, A., Koffel, B., LaPorte, D. & Tamminga, C. Subanes- thetic doses of ketamine stimulate psychosis in schizophrenia. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 13, 9-19, doi:10.1016/0893- 133X(94)00131-I (1995).
13 Malhotra, A. et al. Ketamine-induced exacerbation of psychotic symptoms and cognitive impairment in neurolep- tic-free schizophrenics. Neuropsychopharmacology : officialpublication of the American College of Neuropsychopharmacolo- gy 17, 141-150, doi:10.1016/S0893-133X(97)00036-5 (1997).
14 Chartoff, E., Heusner, C. & Palmiter, R. Dopamine is not required for the hyperlocomotor response to NMDA receptor an- tagonists. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 30, 1324-1333, doi:10.1038/sj.npp.1300678 (2005).
15 Marek, G. et al. Glutamatergic (N-methyl-D-aspartate receptor) hypofrontality in schizophrenia: too little juice or a mi- swired brain? Molecular pharmacology 77, 317-326, doi:10.1124/ mol.109.059865 (2010).
16 Rowland, L. et al. Effects of ketamine on anterior cin- gulate glutamate metabolism in healthy humans: a 4-T proton MRS study. The American journal of psychiatry 162, 394-396, doi:10.1176/appi.ajp.162.2.394 (2005).
17 Beneyto, M. & Meador-Woodruff, J. Lamina-specific ab- normalities of NMDA receptor-associated postsynaptic protein transcripts in the prefrontal cortex in schizophrenia and bipolar disorder. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 33, 2175-2186, doi:10.1038/sj.npp.1301604 (2008).
18 Schmitt, A. et al. Gene expression of NMDA receptor subunits in the cerebellum of elderly patients with schizophre- nia. European archives of psychiatry and clinical neuroscience 260, 101-111, doi:10.1007/s00406-009-0017-1 (2010).
19 Akbarian, S. et al. Selective alterations in gene expres- sion for NMDA receptor subunits in prefrontal cortex of schizo- phrenics. The Journal of neuroscience : the official journal of the Society for Neuroscience 16, 19-30 (1996).
20 Timms, A. E. et al. Support for the N-methyl-D-aspartate receptor hypofunction hypothesis of schizophrenia from exome sequencing in multiplex families. JAMA psychiatry 70, 582-590, doi:10.1001/jamapsychiatry.2013.1195 (2013).
21 Titulaer, M. et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor enceph- alitis: an observational cohort study. Lancet neurology 12, 157- 165, doi:10.1016/S1474-4422(12)70310-1 (2013).
22 Gunduz-Bruce, H. The acute effects of NMDA antag- onism: from the rodent to the human brain. Brain research re-
views 60, 279-286, doi:10.1016/j.brainresrev.2008.07.006 (2009).
23 Forrest, D. et al. Targeted disruption of NMDA receptor 1 gene abolishes NMDA response and results in neonatal death. Neuron 13, 325-338, doi:10.1016/0896-6273(94)90350-6 (1994).
24 Hughes, E. G. et al. Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis. The Journal of neuroscience : the official journal of the Society for Neuroscience 30, 5866-5875, doi:10.1523/JNEUROSCI.0167-10.2010 (2010).
25 Rhoads, J., Guirgis, H., McKnight, C. & Duchemin, A.-M. Lack of anti-NMDA receptor autoantibodies in the serum of sub- jects with schizophrenia. Schizophrenia research 129, 213-214, doi:10.1016/j.schres.2010.12.018 (2011).
26 Haussleiter, I. et al. Investigation of antibodies against synaptic proteins in a cross-sectional cohort of psychotic pa- tients. Schizophrenia research 140, 258-259, doi:10.1016/j. schres.2012.05.006 (2012).
27 Masdeu, J. et al. Serum IgG antibodies against the NR1 subunit of the NMDA receptor not detected in schizophrenia. The American journal of psychiatry 169, 1120-1121, doi:10.1176/appi. ajp.2012.12050646 (2012).
28 Steiner, J. et al. Increased prevalence of diverse N-me- thyl-D-aspartate glutamate receptor antibodies in patients with an initial diagnosis of schizophrenia: specific relevance of IgG NR1a antibodies for distinction from N-methyl-D-aspartate glutamate receptor encephalitis. JAMA psychiatry 70, 271-278, doi:10.1001/2013.jamapsychiatry.86 (2013).
29 Hammer, C. et al. Neuropsychiatric disease relevance of circulating anti-NMDA receptor autoantibodies depends on blood-brain barrier integrity. Molecular psychiatry, doi:10.1038/ mp.2013.110 (2013).
30 Pollak, T. A., McCormack, R., Peakman, M., Nicholson, T. R. & David, A. S. Prevalence of anti-N-methyl-d-aspartate (NMDA) antibodies in patients with schizophrenia and related psychoses: a systematic review and meta-analysis. Psychological medicine, 1-13, doi:10.1017/S003329171300295X (2013).
31 Maneta, E. & Garcia, G. Psychiatric Manifestations of Anti-NMDA Receptor Encephalitis: Neurobiological Underpin- nings and Differential Diagnostic Implications. Psychosomatics 55, 37-44, doi:10.1016/j.psym.2013.06.002 (2014).

Downloads

Published

2015-01-01

How to Cite

Kennedy, L. (2015). Autoantibodies to the NMDA Receptor in Schizophrenia: A Literature Review. Trinity Student Medical Journal , 16(1), Page 43–48. Retrieved from https://ojs.tchpc.tcd.ie/index.php/tsmj/article/view/1874

Similar Articles

<< < 4 5 6 7 8 9 10 11 > >> 

You may also start an advanced similarity search for this article.