Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Transcriptional profile of pyramidal neurons in chronic schizophrenia reveals lamina-specific dysfunction of neuronal immunity

Molecular Psychiatry volume 26, pages 7699–7708 (2021)Cite this article

Subjects

Abstract

While the pathophysiology of schizophrenia has been extensively investigated using homogenized postmortem brain samples, few studies have examined changes in brain samples with techniques that may attribute perturbations to specific cell types. To fill this gap, we performed microarray assays on mRNA isolated from anterior cingulate cortex (ACC) superficial and deep pyramidal neurons from 12 schizophrenia and 12 control subjects using laser-capture microdissection. Among all the annotated genes, we identified 134 significantly increased and 130 decreased genes in superficial pyramidal neurons, while 93 significantly increased and 101 decreased genes were found in deep pyramidal neurons, in schizophrenia compared to control subjects. In these differentially expressed genes, we detected lamina-specific changes of 55 and 31 genes in superficial and deep neurons in schizophrenia, respectively. Gene set enrichment analysis (GSEA) was applied to the entire pre-ranked differential expression gene lists to gain a complete pathway analysis throughout all annotated genes. Our analysis revealed overrepresented groups of gene sets in schizophrenia, particularly in immunity and synapse-related pathways, suggesting the disruption of these pathways plays an important role in schizophrenia. We also detected other pathways previously demonstrated in schizophrenia pathophysiology, including cytokine and chemotaxis, postsynaptic signaling, and glutamatergic synapses. In addition, we observed several novel pathways, including ubiquitin-independent protein catabolic process. Considering the effects of antipsychotic treatment on gene expression, we applied a novel bioinformatics approach to compare our differential expression gene profiles with 51 antipsychotic treatment datasets, demonstrating that our results were not influenced by antipsychotic treatment. Taken together, we found pyramidal neuron-specific changes in neuronal immunity, synaptic dysfunction, and olfactory dysregulation in schizophrenia, providing new insights for the cell-subtype specific pathophysiology of chronic schizophrenia.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Distinct gene expression profiles detected in schizophrenia patients.
Fig. 2: Gene set enrichment analysis reveals pathways involved in schizophrenia pathophysiology.
Fig. 3: Our results are not influenced by antipsychotic drugs.
Fig. 4: Similarity of GSEA-based pathway analyses between our results and previously published datasets.

Similar content being viewed by others

Code availability

Computer code for AUROC analysis is listed in the Supplementary Materials Appendix 1.

References

  1. Ross CA, Margolis RL, Reading SA, Pletnikov M, Coyle JT. Neurobiology of schizophrenia. Neuron. 2006;52:139–53.

    Article  CAS  PubMed  Google Scholar 

  2. Freedman R. Schizophrenia. N Engl J Med. 2003;349:1738–49.

    Article  CAS  PubMed  Google Scholar 

  3. McCullumsmith RE, Hammond JH, Shan D, Meador-Woodruff JH. Postmortem brain: an underutilized substrate for studying severe mental illness. Neuropsychopharmacology. 2014;39:65–87.

    Article  PubMed  Google Scholar 

  4. McCullumsmith RE, Meador-Woodruff JH. Novel approaches to the study of postmortem brain in psychiatric illness: old limitations and new challenges. Biol Psychiatry. 2011;69:127–33.

    Article  PubMed  Google Scholar 

  5. McCullumsmith RE, O'donovan SM, Drummond JB, Benesh FS, Simmons M, Roberts R, et al. Cell-specific abnormalities of glutamate transporters in schizophrenia: sick astrocytes and compensating relay neurons? Mol Psychiatry. 2016;21:823–30.

    Article  CAS  PubMed  Google Scholar 

  6. O'donovan SM, Sullivan C, Koene R, Devine E, Hasselfeld K, Moody CL, et al. Cell-subtype-specific changes in adenosine pathways in schizophrenia. Neuropsychopharmacology. 2018;43:1667–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. O'donovanDonovan SM, Hasselfeld K, Bauer D, Simmons M, Roussos P, Haroutunian V, et al. Glutamate transporter splice variant expression in an enriched pyramidal cell population in schizophrenia. Transl Psychiatry. 2015;5:e579.

    Article  Google Scholar 

  8. Sullivan CR, Mielnik CA, O'donovan SM, Funk AJ, Bentea E, DePasquale EA, et al. Connectivity analyses of bioenergetic changes in schizophrenia: identification of novel treatments. Mol Neurobiol. 2019;56:4492–517.

    Article  CAS  PubMed  Google Scholar 

  9. Sodhi MS, Simmons M, McCullumsmith R, Haroutunian V, Meador-Woodruff JH. Glutamatergic gene expression is specifically reduced in thalamocortical projecting relay neurons in schizophrenia. Biol Psychiatry. 2011;70:646–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sullivan CR, Koene RH, Hasselfeld K, O’Donovan SM, Ramsey A, McCullumsmith RE. Neuron-specific deficits of bioenergetic processes in the dorsolateral prefrontal cortex in schizophrenia. Mol Psychiatry. 2019;24:1319–28.

    Article  CAS  PubMed  Google Scholar 

  11. Gerfen CR, Economo MN, Chandrashekar J. Long distance projections of cortical pyramidal neurons. J Neurosci Res. 2018;96:1467–75.

    Article  CAS  PubMed  Google Scholar 

  12. Oni-Orisan A, Kristiansen LV, Haroutunian V, Meador-Woodruff JH, McCullumsmith RE. Altered vesicular glutamate transporter expression in the anterior cingulate cortex in schizophrenia. Biol Psychiatry. 2008;63:766–75.

    Article  CAS  PubMed  Google Scholar 

  13. Han W, Sestan N. Cortical projection neurons: sprung from the same root. Neuron. 2013;80:1103–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Shukla R, Prevot TD, French L, Isserlin R, Rocco BR, Banasr M, et al. The relative contributions of cell-dependent cortical microcircuit aging to cognition and anxiety. Biol Psychiatry. 2019;85:257–67.

    Article  PubMed  Google Scholar 

  15. Arion D, Huo Z, Enwright JF, Corradi JP, Tseng G, Lewis DA. Transcriptome alterations in prefrontal pyramidal cells distinguish schizophrenia from bipolar and major depressive disorders. Biol Psychiatry. 2017;82:594–600.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Arion D, Corradi JP, Tang S, Datta D, Boothe F, He A, et al. Distinctive transcriptome alterations of prefrontal pyramidal neurons in schizophrenia and schizoaffective disorder. Mol Psychiatry. 2015;20:1397–405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Beneyto M, Kristiansen LV, Oni-Orisan A, McCullumsmith RE, Meador-Woodruff JH. Abnormal glutamate receptor expression in the medial temporal lobe in schizophrenia and mood disorders. Neuropsychopharmacology. 2007;32:1888–902.

    Article  CAS  PubMed  Google Scholar 

  18. McCullumsmith RE, Meador-Woodruff JH. Striatal excitatory amino acid transporter transcript expression in schizophrenia, bipolar disorder, and major depressive disorder. Neuropsychopharmacology. 2002;26:368–75.

    Article  CAS  PubMed  Google Scholar 

  19. Schmitt A, Leonardi-Essmann F, Durrenberger PF, Wichert SP, Spanagel R, Arzberger T, et al. Structural synaptic elements are differentially regulated in superior temporal cortex of schizophrenia patients. Eur Arch Psychiatry Clin Neurosci. 2012;262:565–77.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Wu JQ, Wang X, Beveridge NJ, Tooney PA, Scott RJ, Carr VJ, et al. Transcriptome sequencing revealed significant alteration of cortical promoter usage and splicing in schizophrenia. PLoS ONE. 2012;7:e36351.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hwangwang Y, Kim J, Shin JY, Kim JI, Seo JS, Webster MJ, et al. Gene expression profiling by mRNA sequencing reveals increased expression of immune/inflammation-related genes in the hippocampus of individuals with schizophrenia. Transl Psychiatry. 2013;3:e321.

    Article  Google Scholar 

  22. Pietersen CY, Mauney SA, Kim SS, Lim MP, Rooney RJ, Goldstein JM, et al. Molecular profiles of pyramidal neurons in the superior temporal cortex in schizophrenia. J Neurogenet. 2014;28:53–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Arion D, Horvath S, Lewis DA, Mirnics K. Infragranular gene expression disturbances in the prefrontal cortex in schizophrenia: signature of altered neural development? Neurobiol Dis. 2010;37:738–46.

    Article  CAS  PubMed  Google Scholar 

  24. Beneyto M, Meador-Woodruff JH. Lamina-specific abnormalities of AMPA receptor trafficking and signaling molecule transcripts in the prefrontal cortex in schizophrenia. Synapse. 2006;60:585–98.

    Article  CAS  PubMed  Google Scholar 

  25. Korostynski M, Piechota M, Dzbek J, Mlynarski W, Szklarczyk K, Ziolkowska B, et al. Novel drug-regulated transcriptional networks in brain reveal pharmacological properties of psychotropic drugs. BMC Genomics. 2013;14:606.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Sunun W, Lee S, Zhabotynsky V, Zou F, Wright FA, Crowley JJ, et al. Transcriptome atlases of mouse brain reveals differential expression across brain regions and genetic backgrounds. G3. 2012;2:203–11.

    Article  Google Scholar 

  27. Kondoondo MA, Tajinda K, Colantuoni C, Hiyama H, Seshadri S, Huang B, et al. Unique pharmacological actions of atypical neuroleptic quetiapine: possible role in cell cycle/fate control. Transl Psychiatry. 2013;3:e243.

    Article  Google Scholar 

  28. Rizig MA, McQuillin A, Ng A, Robinson M, Harrison A, Zvelebil M, et al. A gene expression and systems pathway analysis of the effects of clozapine compared to haloperidol in the mouse brain implicates susceptibility genes for schizophrenia. J Psychopharmacol. 2012;26:1218–30.

    Article  CAS  PubMed  Google Scholar 

  29. Kim Y, Giusti-Rodriguez P, Crowley JJ, Bryois J, Nonneman RJ, Ryan AK, et al. Comparative genomic evidence for the involvement of schizophrenia risk genes in antipsychotic effects. Mol Psychiatry. 2018;23:708–12.

    Article  CAS  PubMed  Google Scholar 

  30. Wengen DF. Alternatives to flaring spreader flaps and upper lateral advancement for the internal nasal valve. HNO. 2012;60:595–6.

    Article  Google Scholar 

  31. Yamaguchi KD, Ruderman DL, Croze E, Wagner TC, Velichko S, Reder AT, et al. IFN-beta-regulated genes show abnormal expression in therapy-naive relapsing-remitting MS mononuclear cells: gene expression analysis employing all reported protein-protein interactions. J Neuroimmunol. 2008;195:116–20.

    Article  CAS  PubMed  Google Scholar 

  32. Alganem K, Shukla R, Eby H, Abel M, Zhang X, McIntyre WB, et al. Kaleidoscope: a new bioinformatics pipeline web application for in silico hypothesis exploration of omics signatures. bioRxiv. 2020. https://doi.org/10.1101/2020.05.01.070805.

  33. Katsel P, Davis KL, Gorman JM, Haroutunian V. Variations in differential gene expression patterns across multiple brain regions in schizophrenia. Schizophr Res. 2005;77:241–52.

    Article  CAS  PubMed  Google Scholar 

  34. Khandaker GM, Cousins L, Deakin J, Lennox BR, Yolken R, Jones PB. Inflammation and immunity in schizophrenia: implications for pathophysiology and treatment. Lancet Psychiatry. 2015;2:258–70.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Birnbaum R, Jaffe AE, Chen Q, Shin JH, BrainSeq C, Kleinman JE, et al. Investigating the neuroimmunogenic architecture of schizophrenia. Mol Psychiatry. 2018;23:1251–60.

    Article  CAS  PubMed  Google Scholar 

  36. Cai HQ, Catts VS, Webster MJ, Galletly C, Liu D, O’Donnell M, et al. Increased macrophages and changed brain endothelial cell gene expression in the frontal cortex of people with schizophrenia displaying inflammation. Mol Psychiatry. 2020;25:761–75.

    Article  CAS  PubMed  Google Scholar 

  37. Mowry BJ, Gratten J. The emerging spectrum of allelic variation in schizophrenia: current evidence and strategies for the identification and functional characterization of common and rare variants. Mol Psychiatry. 2013;18:38–52.

    Article  CAS  PubMed  Google Scholar 

  38. Pandey GN, Rizavi HS, Zhang H, Ren X. Abnormal gene and protein expression of inflammatory cytokines in the postmortem brain of schizophrenia patients. Schizophr Res. 2018;192:247–54.

    Article  PubMed  Google Scholar 

  39. Reale M, Patruno A, De Lutiis MA, Pesce M, Felaco M, Di Giannantonio M, et al. Dysregulation of chemo-cytokine production in schizophrenic patients versus healthy controls. BMC Neurosci. 2011;12:13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Lesh TA, Careaga M, Rose DR, McAllister AK, Van de Water J, Carter CS, et al. Cytokine alterations in first-episode schizophrenia and bipolar disorder: relationships to brain structure and symptoms. J Neuroinflammation. 2018;15:165.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Maxeiner HG, Marion Schneider E, Kurfiss ST, Brettschneider J, Tumani H, Bechter K. Cerebrospinal fluid and serum cytokine profiling to detect immune control of infectious and inflammatory neurological and psychiatric diseases. Cytokine. 2014;69:62–7.

    Article  CAS  PubMed  Google Scholar 

  42. Wang AK, Miller BJ. Meta-analysis of cerebrospinal fluid cytokine and tryptophan catabolite alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder, and depression. Schizophr Bull. 2018;44:75–83.

    Article  PubMed  Google Scholar 

  43. Söderlund J, Schröder J, Nordin C, Samuelsson M, Walther-Jallow L, Karlsson H, et al. Activation of brain interleukin-1beta in schizophrenia. Mol Psychiatry. 2009;14:1069–71.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Altamura AC, Pozzoli S, Fiorentini A, Dell’osso B. Neurodevelopment and inflammatory patterns in schizophrenia in relation to pathophysiology. Prog Neuropsychopharmacol Biol Psychiatry. 2013;42:63–70.

    Article  CAS  PubMed  Google Scholar 

  45. Garver DL, Tamas RL, Holcomb JA. Elevated interleukin-6 in the cerebrospinal fluid of a previously delineated schizophrenia subtype. Neuropsychopharmacology. 2003;28:1515–20.

    Article  CAS  PubMed  Google Scholar 

  46. Hayes LN, Severance EG, Leek JT, Gressitt KL, Rohleder C, Coughlin JM, et al. Inflammatory molecular signature associated with infectious agents in psychosis. Schizophr Bull. 2014;40:963–72.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Mittleman BB, Castellanos FX, Jacobsen LK, Rapoport JL, Swedo SE, Shearer GM. Cerebrospinal fluid cytokines in pediatric neuropsychiatric disease. J Immunol. 1997;159:2994–9.

    Article  CAS  PubMed  Google Scholar 

  48. Stefansson H, Ophoff RA, Steinberg S, Andreassen OA, Cichon S, Rujescu D, et al. Common variants conferring risk of schizophrenia. Nature. 2009;460:744–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Osimo EF, Beck K, Reis Marques T, Howes OD. Synaptic loss in schizophrenia: a meta-analysis and systematic review of synaptic protein and mRNA measures. Mol Psychiatry. 2019;24:549–61.

    Article  CAS  PubMed  Google Scholar 

  50. Glantz LA, Lewis DA. Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Arch Gen Psychiatry. 2000;57:65–73.

    Article  CAS  PubMed  Google Scholar 

  51. Bauer D, Gupta D, Harotunian V, Meador-Woodruff JH, McCullumsmith RE. Abnormal expression of glutamate transporter and transporter interacting molecules in prefrontal cortex in elderly patients with schizophrenia. Schizophr Res. 2008;104:108–20.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Harrison PJ, Law AJ, Eastwood SL. Glutamate receptors and transporters in the hippocampus in schizophrenia. Ann N Y Acad Sci. 2003;1003:94–101.

    Article  CAS  PubMed  Google Scholar 

  53. Berlekom AB, Muflihah CH, Snijders GJLJ, MacGillavry HD, Middeldorp J, Hol EM, et al. Synapse pathology in schizophrenia: a meta-analysis of postsynaptic elements in postmortem brain studies. Schizophr Bull. 2020;46:374–86.

  54. Bousman CA, Chana G, Glatt SJ, Chandler SD, Lucero GR, Tatro E, et al. Preliminary evidence of ubiquitin proteasome system dysregulation in schizophrenia and bipolar disorder: convergent pathway analysis findings from two independent samples. Am J Med Genet B Neuropsychiatr Genet. 2010;153B:494–502.

    Article  CAS  PubMed  Google Scholar 

  55. Liuiu C, Bousman CA, Pantelis C, Skafidas E, Zhang D, Yue W, et al. Pathway-wide association study identifies five shared pathways associated with schizophrenia in three ancestral distinct populations. Transl Psychiatry. 2017;7:e1037.

    Article  Google Scholar 

  56. Rubio MD, Wood K, Haroutunian V, Meador-Woodruff JH. Dysfunction of the ubiquitin proteasome and ubiquitin-like systems in schizophrenia. Neuropsychopharmacology. 2013;38:1910–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. McCurdy RD, Féron F, Perry C, Chant DC, McLean D, Matigian N, et al. Cell cycle alterations in biopsied olfactory neuroepithelium in schizophrenia and bipolar I disorder using cell culture and gene expression analyses. Schizophr Res. 2006;82:163–73.

    Article  PubMed  Google Scholar 

  58. Schiffer M, von Gersdorff G, Bitzer M, Susztak K, Bottinger EP. Smad proteins and transforming growth factor-beta signaling. Kidney Int Suppl. 2000;77:S45–52.

    Article  CAS  PubMed  Google Scholar 

  59. Horiuchioriuchi Y, Kondo MA, Okada K, Takayanagi Y, Tanaka T, Ho T, et al. Molecular signatures associated with cognitive deficits in schizophrenia: a study of biopsied olfactory neural epithelium. Transl Psychiatry. 2016;6:e915.

    Article  Google Scholar 

  60. Kiparizoska S, Ikuta T. Disrupted olfactory integration in schizophrenia: functional connectivity study. Int J Neuropsychopharmacol. 2017;20:740–6.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Turetsky BI, Moberg PJ, Roalf DR, Arnold SE, Gur RE. Decrements in volume of anterior ventromedial temporal lobe and olfactory dysfunction in schizophrenia. Arch Gen Psychiatry. 2003;60:1193–200.

    Article  PubMed  Google Scholar 

  62. Egbujo CN, Sinclair D, Borgmann-Winter KE, Arnold SE, Turetsky BI, Hahn CG. Molecular evidence for decreased synaptic efficacy in the postmortem olfactory bulb of individuals with schizophrenia. Schizophr Res. 2015;168:554–62.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Pantazopoulos H, Boyer-Boiteau A, Holbrook EH, Jang W, Hahn CG, Arnold SE, et al. Proteoglycan abnormalities in olfactory epithelium tissue from subjects diagnosed with schizophrenia. Schizophr Res. 2013;150:366–72.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Borgmann-Winter KE, Wang HY, Ray R, Willis BR, Moberg PJ, Rawson NE, et al. Altered G protein coupling in olfactory neuroepithelial cells from patients with schizophrenia. Schizophr Bull. 2016;42:377–85.

    Article  PubMed  Google Scholar 

  65. Bychkov ER, Ahmed MR, Gurevich VV, Benovic JL, Gurevich EV. Reduced expression of G protein-coupled receptor kinases in schizophrenia but not in schizoaffective disorder. Neurobiol Dis. 2011;44:248–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. McCullumsmith RE, Stincic TL, Agrawal SM, Meador-Woodruff JH. Differential effects of antipsychotics on haloperidol-induced vacuous chewing movements and subcortical gene expression in the rat. Eur J Pharmacol. 2003;477:101–12.

    Article  CAS  PubMed  Google Scholar 

  67. Funk AJ, Rumbaugh G, Harotunian V, McCullumsmith RE, Meador-Woodruff JH. Decreased expression of NMDA receptor-associated proteins in frontal cortex of elderly patients with schizophrenia. Neuroreport. 2009;20:1019–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Shi Y, He M. Differential gene expression identified by RNA-Seq and qPCR in two sizes of pearl oyster (Pinctada fucata). Gene. 2014;538:313–22.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We acknowledge Brett Mcintyre, Jiwon Lee, and Roshni Panda from Institute of Medical Sciences, University of Toronto, and Center for Addiction and Mental Health, Toronto, Ontario, Canada, for their contribution in curating the antipsychotic datasets and providing guidance. Grant support: R01 MH107487, R01 AG05759, R01 MH121102, R01 MH094445, R21 MH107916, and RC1 MH088752.

Author information

Author notes

  1. These authors contributed equally: Xiaojun Wu, Rammohan Shukla.

Authors and Affiliations

  1. Department of Neurosciences, University of Toledo College of Medicine, Toledo, OH, USA

    Xiaojun Wu, Rammohan Shukla, Khaled Alganem, Xiaolu Zhang, Hunter M. Eby, Emily A. Devine & Robert E. McCullumsmith

  2. Department of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Erica Depasquale, James Reigle & Jarek Meller

  3. Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA

    Micah Simmons & James Meador-Woodruff

  4. Centre for Addiction and Mental Health, Toronto, ON, Canada

    Margaret K. Hahn, Christy Au-Yeung & Roshanak Asgariroozbehani

  5. Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada

    Margaret K. Hahn & Roshanak Asgariroozbehani

  6. Department of Psychiatry, Vickie & Jack Farber Institute for Neuroscience, Jefferson University Hospitals, Philadelphia, PA, USA

    Chang-Gyu Hahn

  7. Departments of Psychiatry and Neuroscience, The Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Vahram Haroutunian

  8. James J. Peters VA Medical Center, Mental Illness Research Education and Clinical Center (MIRECC), Bronx, NY, USA

    Vahram Haroutunian

  9. Neurosciences Institute, ProMedica, Toledo, OH, USA

    Robert E. McCullumsmith

Authors
  1. Xiaojun Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rammohan Shukla
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Khaled Alganem
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaolu Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hunter M. Eby
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Emily A. Devine
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Erica Depasquale
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. James Reigle
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Micah Simmons
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Margaret K. Hahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Christy Au-Yeung
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Roshanak Asgariroozbehani
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Chang-Gyu Hahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Vahram Haroutunian
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Jarek Meller
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. James Meador-Woodruff
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Robert E. McCullumsmith
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert E. McCullumsmith.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, X., Shukla, R., Alganem, K. et al. Transcriptional profile of pyramidal neurons in chronic schizophrenia reveals lamina-specific dysfunction of neuronal immunity. Mol Psychiatry 26, 7699–7708 (2021). https://doi.org/10.1038/s41380-021-01205-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41380-021-01205-y

This article is cited by

Search

Advanced search

Quick links