The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Increased excitotoxicity and neuroinflammatory markers in postmortem frontal cortex from bipolar disorder patients
Open accessAbstract
Reports of cognitive decline, symptom worsening and brain atrophy in bipolar disorder (BD) suggest that the disease progresses over time. The worsening neuropathology may involve excitotoxicity and neuroinflammation. We determined protein and mRNA levels of excitotoxicity and neuroinflammatory markers in postmortem frontal cortex from 10 BD patients and 10 age-matched controls. The brain tissue was matched for age, postmortem interval and pH. The results indicated statistically significant lower protein and mRNA levels of the N-methyl-D-aspartate receptors, NR-1 and NR-3A, but significantly higher protein and mRNA levels of interleukin (IL)-1beta, the IL-1 receptor (IL-1R), myeloid differentiation factor 88, nuclear factor-kappa B subunits, and astroglial and microglial markers (glial fibrillary acidic protein, inducible nitric oxide synthase, c-fos and CD11b) in postmortem frontal cortex from BD compared with control subjects. There was no significant difference in mRNA levels of tumor necrosis factor alpha or neuronal nitric oxide synthase in the same region. These data show the presence of excitotoxicity and neuroinflammation in BD frontal cortex, with particular activation of the IL-R cascade. The changes may account for reported evidence of disease progression in BD and be a target for future therapy.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“evidence of microglial and astroglial activation in several brain regions including frontal cortex, anterior cingulate cortex (ACC) and thalamus in post-mortem studies of patients with depression have been described57–59,60.”
From The role of inflammation in depression: from evolutionary imperative to modern treatment target (2016) · cites this paper as [57]
Experimental — accuracy not yet measuredIn the citing paper
“Previous work has identified differential activation of glial and neural-immune processes in brain from patients with psychiatric disorders (16, 52, 57, 66–69)”
From Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder (2018) · cites this paper as [69]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
3 retracted
Rao, J. S., Ertley, R. N., Rapoport, S. I., Bazinet, R. P., & Lee, H. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04648.x · Cited by 59
Self-citationRetractedRao, J. S., Ertley, R. N., Lee, H.-J., Rapoport, S. I., & Bazinet, R. P. (2006) · The Pharmacogenomics Journal · doi:10.1038/sj.tpj.6500391 · Cited by 40
Self-citationRetractedDecreased GRK3 but not GRK2 expression in frontal cortex from bipolar disorder patients
Rao, J. S., Rapoport, S. I., & Kim, H. (2009) · The International Journal of Neuropsychopharmacology · doi:10.1017/s146114570900025x · Cited by 22
Self-citationRetractedAnalysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860
Structure, Regulation and Function of NF-kappaB
Siebenlist, U. K., Franzoso, G., & Brown, K. D. (1994) · Annual Review of Cell Biology · doi:10.1146/annurev.cb.10.110194.002201 · Cited by 2,086
TRAF6 is a signal transducer for interleukin-1
Cao, Z., Xiong, J., Takeuchi, M., Kurama, T., & Goeddel, D. V. (1996) · Nature · doi:10.1038/383443a0 · Cited by 1,305
Ciabarra, A., Sullivan, J., Gahn, L. G., Pecht, G., Heinemann, S., & Sevarino, K. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-10-06498.1995 · Cited by 1,260
MyD88: an adapter that recruits IRAK to the IL-1 receptor complex.
Wesche, H., Henzel, W., Shillinglaw, W., Li, S., & Cao, Z.-D. (1997) · Immunity · doi:10.1016/s1074-7613(00)80402-1 · Cited by 1,247
Ninomiya‐Tsuji, J., Kishimoto, K., Hiyama, A., Inoue, J., Cao, Z., & Matsumoto, K. (1999) · Nature · doi:10.1038/18465 · Cited by 1,187
IRAK: A Kinase Associated with the Interleukin-1 Receptor
Cao, Z., Henzel, W. J., & Gao, X. (1996) · Science · doi:10.1126/science.271.5252.1128 · Cited by 898
Increased Levels of Glutamate in Brains from Patients with Mood Disorders
Hashimoto, K., Sawa, A., & Iyo, M. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.03.017 · Cited by 631
Increased NMDA current and spine density in mice lacking the NMDA receptor subunit NR3A
Das, S., Sasaki, Y., Rothe, T., Premkumar, L. S., Takasu, M. A., Crandall, J. E., Dikkes, P., Conner, D. A., Posina, V. R., Cheung, W., et al. (1998) · Nature · doi:10.1038/30748 · Cited by 618
The IL-1 family and inflammatory diseases.
Dinarello, C. A. (2002) · PubMed · Cited by 597
Sucher, N. J., Akbarian, S., Chi, C.-L., Leclerc, C., Awobuluyi, M., Deitcher, D. L., Wu, M., Yuan, J., Jones, E. G., & Lipton, S. A. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-10-06509.1995 · Cited by 420
Phospholipase A2 in the central nervous system
Sun, G. Y., Xu, J., Jensen, M. D., & Simonyi, Á. (2004) · Journal of Lipid Research · doi:10.1194/jlr.r300016-jlr200 · Cited by 391
Imbalance between pro-inflammatory and anti-inflammatory cytokines in bipolar disorder
Kim, Y.-K., Jung, H.-G., Myint, A.-M., Kim, H., & Park, S.-H. (2007) · Journal of Affective Disorders · doi:10.1016/j.jad.2007.02.018 · Cited by 375
Self-citationBuchsbaum, M. S., Wu, J. C., DeLisi, L. E., Holcomb, H. H., KESSLER, R. M., Johnson, J., King, A. C., Hazlett, E., Langston, K. C., & Post, R. M. (1986) · Journal of Affective Disorders · doi:10.1016/0165-0327(86)90036-4 · Cited by 368
Harrison, P. J., Heath, P. R., Eastwood, S. L., Burnet, P. W. J., McDonald, B., & Pearson, R. C. A. (1995) · Neuroscience Letters · doi:10.1016/0304-3940(95)12102-a · Cited by 342
Chronic neuroinflammation in rats reproduces components of the neurobiology of Alzheimer's disease
Hauss‐Wegrzyniak, B., Dobrzański, P., Stoehr, J. D., & Wenk, G. L. (1998) · Brain Research · doi:10.1016/s0006-8993(97)01215-8 · Cited by 341
The biological properties of interleukin-1.
Dinarello, C. A. (1995) · PubMed · Cited by 320
Regional prefrontal gray and white matter abnormalities in bipolar disorder
Lopez-Larson, M. P., DelBello, M. P., Zimmerman, M. E., Schwiers, M., & Strakowski, S. M. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01350-1 · Cited by 282
Frontal lobe gray matter density decreases in bipolar I disorder
Lyoo, I. K., Kim, M. J., Stoll, A. L., Demopulos, C. M., Parow, A. M., Dager, S. R., Friedman, S. D., Dunner, D. L., & Renshaw, P. F. (2004) · Biological Psychiatry · doi:10.1016/j.biopsych.2003.10.017 · Cited by 263
Decision-making in mania: a PET study
Rubinsztein, J. S. (2001) · Brain · doi:10.1093/brain/124.12.2550 · Cited by 242
Expression and Regulation of Cyclooxygenase‐2 in Rat Microglia
Bauer, M. K. A., Lieb, K., Schulze‐Osthoff, K., Berger, T., Gebicke‐Haerter, P. J., Bauer, J., & Fiebich, B. L. (1997) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1997.00726.x · Cited by 235
Huang, J., Gao, X., Li, S., & Cao, Z. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.24.12829 · Cited by 225
Webster, M. J., O’Grady, J., Kleinman, J. E., & Weickert, C. S. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.02.037 · Cited by 212
Hoeck, W. G., Ramesha, C. S., Chang, D. J., Fan, N. C., & Heller, R. A. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.10.4475 · Cited by 208
Cell pathology in bipolar disorder
Rajkowska, G. (2002) · Bipolar Disorders · doi:10.1034/j.1399-5618.2002.01149.x · Cited by 198
TNF-α as a molecular target in bipolar disorder
Brietzke, E., & Kapczinski, F. (2008) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2008.01.006 · Cited by 163
D1 dopamine receptor binding in mood disorders measured by positron emission tomography
Suhara, T., Nakayama, K., Inoue, O., Fukuda, H., Shimizu, M., Mori, A., & Tateno, Y. (1992) · Psychopharmacology · doi:10.1007/bf02253582 · Cited by 163
Decreased NR1, NR2A, and SAP102 transcript expression in the hippocampus in bipolar disorder
McCullumsmith, R. E., Kristiansen, L. V., Beneyto, M., Scarr, E., Dean, B., & Meador‐Woodruff, J. H. (2006) · Brain Research · doi:10.1016/j.brainres.2006.09.011 · Cited by 156
Cytokines: Influence on Glial Cell Gene Expression and Function
Benveniste, E. N. (1997) · KARGER eBooks · doi:10.1159/000058653 · Cited by 147
Fatemi, S. H., Laurence, J. A., Araghi‐Niknam, M., Stary, J. M., Schulz, S. C., Lee, S. S., & Gottesman, I. I. (2003) · Schizophrenia Research · doi:10.1016/j.schres.2003.08.014 · Cited by 141
NR3A NMDA receptor subunit mRNA expression in schizophrenia, depression and bipolar disorder
Mueller, H. T., & Meador‐Woodruff, J. H. (2004) · Schizophrenia Research · doi:10.1016/j.schres.2004.02.016 · Cited by 139
Martucci, L., Wong, A. H. C., Luca, V. D., Likhodi, O., Wong, G. W. H., King, N. A., & Kennedy, J. L. (2006) · Schizophrenia Research · doi:10.1016/j.schres.2006.02.001 · Cited by 137
Basselin, M., Chang, L., Bell, J. M., & Rapoport, S. I. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300920 · Cited by 114
Self-citationExpression of neuronal nitric oxide synthase in the hippocampal formation in affective disorders
de Oliveira, R. M. W., Guimarães, F. S., & Deakin, J. F. W. (2008) · Brazilian Journal of Medical and Biological Research · doi:10.1590/s0100-879x2008000400012 · Cited by 113
Mundo, E., Tharmalingham, S., Neves-Pereira, M., Dalton, E. J., Macciardi, F. M., Parikh, S. V., Bolonna, A. A., Kerwin, R. W., Arranz, M. J., MAKOFF, A. J., et al. (2003) · Molecular Psychiatry · doi:10.1038/sj.mp.4001218 · Cited by 105
Gascón, S., Deogracias, R., Sobrado, M., Roda, J. M., Renart, J., Rodríguez‐Peña, A., & Díaz‐Guerra, M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504108200 · Cited by 78
Chang, Y. C., Kim, H., Rapoport, S. I., & Rao, J. S. (2008) · Neurochemical Research · doi:10.1007/s11064-008-9731-8 · Cited by 76
Self-citationPharmacology of Interleukin-1 Actions in the Brain
Rothwell, N. J., & Luheshi, G. N. (1994) · Advances in pharmacology · doi:10.1016/s1054-3589(08)60428-7 · Cited by 73
Spriggs, D. R., Sherman, M., Imamura, K., Mohri, M., Rodriguez, C., Robbins, G., & Kufe, D. W. (1990) · PubMed · Cited by 72
Itokawa, M., Yamada, K., Iwayama‐Shigeno, Y., Ishitsuka, Y., Detera‐Wadleigh, S. D., & Yoshikawa, T. (2003) · Neuroscience Letters · doi:10.1016/s0304-3940(03)00501-9 · Cited by 70
Basselin, M., Villacreses, N. E., Lee, H., Bell, J. M., & Rapoport, S. I. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04593.x · Cited by 56
Self-citationBasselin, M., Chang, L., Chen, M., Bell, J. M., & Rapoport, S. I. (2008) · Neurochemical Research · doi:10.1007/s11064-008-9700-2 · Cited by 55
Self-citationBenes, F. M. (2007) · Schizophrenia Bulletin · doi:10.1093/schbul/sbm064 · Cited by 53
Acarín, L., Peluffo, H., González, B., & Castellano, B. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10261 · Cited by 51
Jupp, O. J., Vandenabeele, P., & MacEwan, D. J. (2003) · Biochemical Journal · doi:10.1042/bj20030705 · Cited by 47
Shan, Y., Carlock, L. R., & Walker, P. D. (1997) · Experimental Neurology · doi:10.1006/exnr.1997.6427 · Cited by 38
Basselin, M., Villacreses, N. E., Chen, M., Bell, J. M., & Rapoport, S. I. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.04.021 · Cited by 33
Self-citationActivation of ERK1/2 and cPLA2 by the p55 TNF Receptor Occurs Independently of FAN
Lüschen, S., Adam, D., Ussat, S., Kreder, D. E., Schneider‐Brachert, W., Krönke, M., & Adam‐Klages, S. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3173 · Cited by 30
c-fos mRNA Expression in Rat Cortical Neurons During Glutamate-Mediated Excitotoxicity
Rogers, A. (2004) · Toxicological Sciences · doi:10.1093/toxsci/kfh279 · Cited by 29
Tong, W., Shah, D., Xu, J., Diehl, J. A., Hans, A., Hannink, M., & Sun, G. Y. (1999) · Journal of Molecular Neuroscience · doi:10.1007/bf02736923 · Cited by 19
Rogers, A., Schmuck, G., Scholz, G., Griffiths, R., Meredith, C., Schousboe, A., Campiani, G., & Williams, D. C. (2004) · Archives of Toxicology · doi:10.1007/s00204-004-0617-5 · Cited by 11
Flagged first, then by citations
Cited by
Sorted by citations
The role of inflammation in depression: from evolutionary imperative to modern treatment target
Miller, A. H., & Raison, C. L. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2015.5 · Cited by 3,942
Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder
Gandal, M. J., Zhang, P., Hadjimichael, E., Walker, R. L., Chen, C., Liu, S., Won, H., van Bakel, H., Varghese, M., Wang, Y., et al. (2018) · Science · doi:10.1126/science.aat8127 · Cited by 1,247
Berk, M., Kapczinski, F., Andreazza, A. C., Dean, O. M., Giorlando, F., Maes, M., Yücel, M., Gama, C. S., Dodd, S., Dean, B., et al. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.10.001 · Cited by 1,178
Neuroinflammation and psychiatric illness
Najjar, S., Pearlman, D. M., Alper, K., Najjar, A., & Devinsky, O. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-43 · Cited by 733
The role of inflammation and microglial activation in the pathophysiology of psychiatric disorders
Réus, G. Z., Fries, G. R., Stertz, L., Badawy, M., Passos, I. C., Barichello, T., Kapczinski, F., & Quevedo, J. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.05.018 · Cited by 594
Metadata
- Authors
- Rao, J. S., Harry, G. J., Rapoport, S. I., & Kim, H. W.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Rao, J S
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2009-06-02
- Volume
- 15
- Issue
- 4
- Pages
- 384-392
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC2844920
- OpenAlex
- W2014858274
- Cited by
- 432
- References
- 54
- Citations by year
- 2026: 12 · 2025: 10 · 2024: 18 · 2023: 20 · 2022: 23 · 2021: 35 · 2020: 31 · 2019: 26 · 2018: 26 · 2017: 29 · 2016: 38 · 2015: 48 · 2014: 25 · 2013: 25 · 2012: 26
- FWCI
- 13.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99 AG999999)
- National Institute on Aging
- National Institute of Mental Health (R24MH068855)
- National Cancer Institute
- National Institute of Environmental Health Sciences
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- bipolar disorder, excitotoxicity, neuroinflammation, frontal cortex, NMDA receptor, NR1, IL-1β, IL-1 receptor, myeloid differentiation factor 88, NF-κB, microglia, astrocytes, glial fibrillary acidic protein, inducible nitric oxide synthase, c-fos, CD11b, disease progression, postmortem brain
- MeSH terms
- Adult, Bipolar Disorder, Female, Frontal Lobe, Gene Expression Regulation, Humans, Male, Middle Aged, Nerve Tissue Proteins, Nuclear Proteins, Postmortem Changes, RNA, Messenger, Statistics as Topic, Case-Control Studies, Receptors, N-Methyl-D-Aspartate, Proto-Oncogene Proteins c-fos, Receptors, Interleukin-1, Inflammation Mediators, CD11b Antigen, Interleukin-1beta, Myeloid Differentiation Factor 88
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
