Whole blood transcriptional signatures associated with rapid antidepressant response to ketamine in patients with treatment resistant depression.
Journal
Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664
Informations de publication
Date de publication:
10 01 2022
10 01 2022
Historique:
received:
20
08
2020
accepted:
22
10
2021
revised:
22
09
2021
entrez:
11
1
2022
pubmed:
12
1
2022
medline:
1
2
2022
Statut:
epublish
Résumé
Ketamine has rapid and sustained antidepressant effects in patients with treatment-resistant depression (TRD). However, the underlying mechanisms of action are not well understood. There is increasing evidence that TRD is associated with a pro-inflammatory state and that ketamine may inhibit inflammatory processes. We thus investigated whole blood transcriptional profiles related to TRD and gene expression changes associated with treatment response to ketamine. Whole blood was collected at baseline (21 healthy controls [HC], 26 patients with TRD) and then again in patients with TRD 24 hours following a single intravenous infusion of ketamine (0.5 mg/kg). We performed RNA-sequencing and analyzed (a) baseline transcriptional profiles between patients with TRD and HC, (b) responders vs. non-responders before ketamine treatment, and (c) gene expression signatures associated with clinical improvement. At baseline, patients with TRD compared to HC showed a gene expression signature indicative of interferon signaling pathway activation. Prior to ketamine administration, the metabotropic glutamate receptor gene GRM2 and the ionotropic glutamate receptor gene GRIN2D were upregulated in responders compared to non-responders. Response to ketamine was associated with a distinct transcriptional signature, however, we did not observe gene expression changes indicative of an anti-inflammatory effect. Future studies are needed to determine the role of the peripheral immune system in the antidepressant effect of ketamine.
Identifiants
pubmed: 35013133
doi: 10.1038/s41398-021-01712-0
pii: 10.1038/s41398-021-01712-0
pmc: PMC8748646
doi:
Substances chimiques
Antidepressive Agents
0
Ketamine
690G0D6V8H
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12Subventions
Organisme : NIMH NIH HHS
ID : P50 MH096890
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH051399
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH104559
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH127820
Pays : United States
Informations de copyright
© 2021. The Author(s).
Références
Greenberg PE, Fournier AA, Sisitsky T, Pike CT, Kessler RC. The economic burden of adults with major depressive disorder in the United States (2005 and 2010). The. J Clin Psychiatry. 2015;76:155–62.
pubmed: 25742202
doi: 10.4088/JCP.14m09298
Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163:1905–17.
pubmed: 17074942
doi: 10.1176/ajp.2006.163.11.1905
Sackeim HA. The definition and meaning of treatment-resistant depression. J Clin Psychiatry. 2001;62:10–7.
pubmed: 11480879
Berlim MT, Turecki G. Definition, assessment, and staging of treatment-resistant refractory major depression: a review of current concepts and methods. Can J Psychiatry Rev canadienne de Psychiatr. 2007;52:46–54.
Akil H, Gordon J, Hen R, Javitch J, Mayberg H, McEwen B, et al. Treatment resistant depression: a multi-scale, systems biology approach. Neurosci Biobehav Rev. 2018;84:272–88.
pubmed: 28859997
doi: 10.1016/j.neubiorev.2017.08.019
Voineskos D, Daskalakis ZJ, Blumberger DM. Management of treatment-resistant depression: challenges and strategies. Neuropsychiatr Dis Treat. 2020;16:221–34.
pubmed: 32021216
pmcid: 6982454
doi: 10.2147/NDT.S198774
Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000;47:351–4.
pubmed: 10686270
doi: 10.1016/S0006-3223(99)00230-9
Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006;63:856–64.
pubmed: 16894061
doi: 10.1001/archpsyc.63.8.856
Price RB, Iosifescu DV, Murrough JW, Chang LC, Al Jurdi RK, Iqbal SZ, et al. Effects of ketamine on explicit and implicit suicidal cognition: a randomized controlled trial in treatment-resistant depression. Depression Anxiety. 2014;31:335–43.
pubmed: 24668760
doi: 10.1002/da.22253
Ibrahim L, Diazgranados N, Franco-Chaves J, Brutsche N, Henter ID, Kronstein P, et al. Course of improvement in depressive symptoms to a single intravenous infusion of ketamine vs add-on riluzole: results from a 4-week, double-blind, placebo-controlled study. Neuropsychopharmacology. 2012;37:1526–33.
pubmed: 22298121
pmcid: 3327857
doi: 10.1038/npp.2011.338
Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Green CE, Perez AM, et al. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry. 2013;170:1134–42.
pubmed: 23982301
pmcid: 3992936
doi: 10.1176/appi.ajp.2013.13030392
Zanos P, Gould TD. Mechanisms of ketamine action as an antidepressant. Mol Psychiatry. 2018;23:801–11.
pubmed: 29532791
pmcid: 5999402
doi: 10.1038/mp.2017.255
Cathomas F, Murrough JW, Nestler EJ, Han MH, Russo SJ. Neurobiology of resilience: interface between mind and body. Biol Psychiatry. 2019;86:410–20.
pubmed: 31178098
pmcid: 6717018
doi: 10.1016/j.biopsych.2019.04.011
Hodes GE, Kana V, Menard C, Merad M, Russo SJ. Neuroimmune mechanisms of depression. Nat Neurosci. 2015;18:1386–93.
pubmed: 26404713
pmcid: 4843114
doi: 10.1038/nn.4113
Köhler CA, Freitas TH, Maes M, de Andrade NQ, Liu CS, Fernandes BS, et al. Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies. Acta Psychiatr Scandinavica. 2017;135:373–87.
doi: 10.1111/acps.12698
Syed SA, Beurel E, Loewenstein DA, Lowell JA, Craighead WE, Dunlop BW, et al. Defective inflammatory pathways in never-treated depressed patients are associated with poor treatment response. Neuron 2018;99:914–24.e3.
pubmed: 30146307
pmcid: 6151182
doi: 10.1016/j.neuron.2018.08.001
Liu JJ, Wei YB, Strawbridge R, Bao Y, Chang S, Shi L, et al. Peripheral cytokine levels and response to antidepressant treatment in depression: a systematic review and meta-analysis. Mol Psychiatry. 2020;25:339–50.
pubmed: 31427752
doi: 10.1038/s41380-019-0474-5
Bhattacharya A, Drevets WC. Role of neuro-immunological factors in the pathophysiology of mood disorders: implications for novel therapeutics for treatment resistant depression. Curr Top Behav Neurosci. 2017;31:339–56.
pubmed: 27677784
doi: 10.1007/7854_2016_43
Raison CL, Rutherford RE, Woolwine BJ, Shuo C, Schettler P, Drake DF, et al. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry. 2013;70:31–41.
pubmed: 22945416
pmcid: 4015348
doi: 10.1001/2013.jamapsychiatry.4
Kiraly DD, Horn SR, Van Dam NT, Costi S, Schwartz J, Kim-Schulze S, et al. Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome. Transl Psychiatry. 2017;7:e1065.
pubmed: 28323284
pmcid: 5416674
doi: 10.1038/tp.2017.31
Tan S, Wang Y, Chen K, Long Z, Zou J. Ketamine alleviates depressive-like behaviors via down-regulating inflammatory cytokines induced by chronic restraint stress in mice. Biol Pharm Bull. 2017;40:1260–7.
pubmed: 28769008
doi: 10.1248/bpb.b17-00131
Wang N, Yu HY, Shen XF, Gao ZQ, Yang C, Yang JJ, et al. The rapid antidepressant effect of ketamine in rats is associated with down-regulation of pro-inflammatory cytokines in the hippocampus. Upsala J Med Sci. 2015;120:241–48.
pubmed: 26220286
pmcid: 4816884
doi: 10.3109/03009734.2015.1060281
Yang JJ, Wang N, Yang C, Shi JY, Yu HY, Hashimoto K. Serum interleukin-6 is a predictive biomarker for ketamine’s antidepressant effect in treatment-resistant patients with major depression. Biol Psychiatry. 2015;77:e19–20.
pubmed: 25104172
doi: 10.1016/j.biopsych.2014.06.021
Park M, Newman LE, Gold PW, Luckenbaugh DA, Yuan P, Machado-Vieira R, et al. Change in cytokine levels is not associated with rapid antidepressant response to ketamine in treatment-resistant depression. J Psychiatr Res. 2017;84:113–18.
pubmed: 27718369
doi: 10.1016/j.jpsychires.2016.09.025
American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5. 5th edn. Arlington, VA, Washington, D.C.: American Psychiatric Association; 2013.
First MB, Spitzer RL, Gibbon M, Williams JBW. Structured clinical interview for DSM-IV axis I disorders, clinician version (SCID-CV). Washington, DC: American Psychiatric Press; 1996.
Busner J, Targum SD. The clinical global impressions scale: applying a research tool in clinical practice. Psychiatry. 2007;4:28–37.
pubmed: 20526405
pmcid: 2880930
Conway CR, George MS, Sackeim HA. Toward an evidence-based, operational definition of treatment-resistant depression: when enough is enough. JAMA Psychiatry. 2017;74:9–10.
pubmed: 27784055
doi: 10.1001/jamapsychiatry.2016.2586
Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382–9.
pubmed: 444788
doi: 10.1192/bjp.134.4.382
S A FastQC: A quality control tool for high throughput sequence data. 2010; http://www.bioinformaticsbabrahamacuk/projects/fastqc/ .
Krueger F. “Trim galore.” A wrapper tool around Cutadapt FastQC to consistently apply quality and adapter trimming to FastQ files. 2015;516:517.
Kim D, Langmead B, Salzberg SL. HISAT: a fast spliced aligner with low memory requirements. Nat methods. 2015;12:357–60.
pubmed: 25751142
pmcid: 4655817
doi: 10.1038/nmeth.3317
Anders S, Pyl PT, Huber W. HTSeq-a Python framework to work with high-throughput sequencing data. Bioinformatics. 2015;31:166–9.
pubmed: 25260700
doi: 10.1093/bioinformatics/btu638
Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550.
pubmed: 25516281
pmcid: 4302049
doi: 10.1186/s13059-014-0550-8
Hoffman GE, Schadt EE. variancePartition: interpreting drivers of variation in complex gene expression studies. BMC Bioinforma. 2016;17:483.
doi: 10.1186/s12859-016-1323-z
Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinforma. 2008;9:559.
doi: 10.1186/1471-2105-9-559
Smyth G LIMMA: Linear models for microarray data. 2005. p. 397–420.
Huang da W, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009;37:1–13.
pubmed: 19033363
doi: 10.1093/nar/gkn923
Huang da W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4:44–57.
pubmed: 19131956
doi: 10.1038/nprot.2008.211
Kramer A, Green J, Pollard J Jr, Tugendreich S. Causal analysis approaches in Ingenuity Pathway Analysis. Bioinformatics. 2014;30:523–30.
pubmed: 24336805
doi: 10.1093/bioinformatics/btt703
Mostafavi S, Battle A, Zhu X, Potash JB, Weissman MM, Shi J, et al. Type I interferon signaling genes in recurrent major depression: increased expression detected by whole-blood RNA sequencing. Mol Psychiatry. 2014;19:1267–74.
pubmed: 24296977
doi: 10.1038/mp.2013.161
Leday GGR, Vértes PE, Richardson S, Greene JR, Regan T, Khan S, et al. Replicable and coupled changes in innate and adaptive immune gene expression in two case-control studies of blood microarrays in major depressive disorder. Biol Psychiatry. 2018;83:70–80.
pubmed: 28688579
pmcid: 5720346
doi: 10.1016/j.biopsych.2017.01.021
Jansen R, Penninx BWJH, Madar V, Xia K, Milaneschi Y, Hottenga JJ, et al. Gene expression in major depressive disorder. Mol Psychiatry. 2016;21:339–47.
Guilloux JP, Bassi S, Ding Y, Walsh C, Turecki G, Tseng G, et al. Testing the predictive value of peripheral gene expression for nonremission following citalopram treatment for major depression. Neuropsychopharmacology. 2015;40:701–10.
pubmed: 25176167
doi: 10.1038/npp.2014.226
Liu Z, Li X, Sun N, Xu Y, Meng Y, Yang C, et al. Microarray profiling and co-expression network analysis of circulating lncRNAs and mRNAs associated with major depressive disorder. PLoS ONE. 2014;9:e93388–e88.
pubmed: 24676134
pmcid: 3968145
doi: 10.1371/journal.pone.0093388
Belzeaux R, Bergon A, Jeanjean V, Loriod B, Formisano-Tréziny C, Verrier L, et al. Responder and nonresponder patients exhibit different peripheral transcriptional signatures during major depressive episode. Transl Psychiatry. 2012;2:e185–e85.
pubmed: 23149449
pmcid: 3565773
doi: 10.1038/tp.2012.112
Chen K, Liu J, Cao X. Regulation of type I interferon signaling in immunity and inflammation: a comprehensive review. J Autoimmun. 2017;83:1–11.
pubmed: 28330758
doi: 10.1016/j.jaut.2017.03.008
Le Page C, Genin P, Baines MG, Hiscott J. Interferon activation and innate immunity. Rev Immunogenet. 2000;2:374–86.
pubmed: 11256746
McNab F, Mayer-Barber K, Sher A, Wack A, O’Garra A. Type I interferons in infectious disease. Nat Rev Immunol. 2015;15:87–103.
pubmed: 25614319
pmcid: 7162685
doi: 10.1038/nri3787
Bonaccorso S, Marino V, Biondi M, Grimaldi F, Ippoliti F, Maes M. Depression induced by treatment with interferon-alpha in patients affected by hepatitis C virus. J Affect Disord. 2002;72:237–41.
pubmed: 12450640
doi: 10.1016/S0165-0327(02)00264-1
Udina M, Castellví P, Moreno-España J, Navinés R, Valdés M, Forns X, et al. Interferon-induced depression in chronic hepatitis C: a systematic review and meta-analysis. J Clin Psychiatry. 2012;73:1128–38.
pubmed: 22967776
doi: 10.4088/JCP.12r07694
Zanos P, Highland JN, Stewart BW, Georgiou P, Jenne CE, Lovett J, et al. (2 R,6 R)-hydroxynorketamine exerts mGlu2 receptor-dependent antidepressant actions. Proc Natl Acad Sci USA. 2019;116:6441–50.
pubmed: 30867285
pmcid: 6442605
doi: 10.1073/pnas.1819540116
Li D, Yuan H, Ortiz-Gonzalez XR, Marsh ED, Tian L, McCormick EM, et al. GRIN2D recurrent de novo dominant mutation causes a severe epileptic encephalopathy treatable with NMDA receptor channel blockers. Am J Hum Genet. 2016;99:802–16.
pubmed: 27616483
pmcid: 5065652
doi: 10.1016/j.ajhg.2016.07.013
Zanos P, Thompson SM, Duman RS, Zarate CA Jr, Gould TD. Convergent mechanisms underlying rapid antidepressant action. CNS Drugs. 2018;32:197–227.
pubmed: 29516301
pmcid: 6005380
doi: 10.1007/s40263-018-0492-x
Monyer H, Burnashev N, Laurie DJ, Sakmann B, Seeburg PH. Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron. 1994;12:529–40.
pubmed: 7512349
doi: 10.1016/0896-6273(94)90210-0
Khlestova E, Johnson JW, Krystal JH, Lisman J. The role of GluN2C-containing NMDA receptors in Ketamine’s psychotogenic action and in schizophrenia models. J Neurosci. 2016;36:11151–7.
pubmed: 27807157
pmcid: 5148234
doi: 10.1523/JNEUROSCI.1203-16.2016
Sullivan PF, Fan C, Perou CM. Evaluating the comparability of gene expression in blood and brain. Am J Med Genet Part B, Neuropsychiatr Genet. 2006;141b:261–8.
doi: 10.1002/ajmg.b.30272
Boldyrev AA, Carpenter DO, Johnson P. Emerging evidence for a similar role of glutamate receptors in the nervous and immune systems. J Neurochem. 2005;95:913–8.
pubmed: 16271044
doi: 10.1111/j.1471-4159.2005.03456.x
Bhandage AK, Jin Z, Hellgren C, Korol SV, Nowak K, Williamsson L, et al. AMPA, NMDA and kainate glutamate receptor subunits are expressed in human peripheral blood mononuclear cells (PBMCs) where the expression of GluK4 is altered by pregnancy and GluN2D by depression in pregnant women. J Neuroimmunol. 2017;305:51–58.
pubmed: 28284346
doi: 10.1016/j.jneuroim.2017.01.013
Haile CN, Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Foulkes A, et al. Plasma brain derived neurotrophic factor (BDNF) and response to ketamine in treatment-resistant depression. Int J Neuropsychopharmacol. 2014;17:331–6.
pubmed: 24103211
doi: 10.1017/S1461145713001119
Laje G, Lally N, Mathews D, Brutsche N, Chemerinski A, Akula N, et al. Brain-derived neurotrophic factor Val66Met polymorphism and antidepressant efficacy of ketamine in depressed patients. Biol Psychiatry. 2012;72:e27–8.
pubmed: 22771240
pmcid: 3786174
doi: 10.1016/j.biopsych.2012.05.031
Dunner DL, Rush AJ, Russell JM, Burke M, Woodard S, Wingard P, et al. Prospective, long-term, multicenter study of the naturalistic outcomes of patients with treatment-resistant depression. J Clin Psychiatry. 2006;67:688–95.
pubmed: 16841617
doi: 10.4088/JCP.v67n0501