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Current Neuropharmacology

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ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

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Clinical Trial

Baseline Plasma BDNF Levelsare Associated with Antianhedonic Effects of Repeated-Dose Intravenous Ketamine in Major Depressive Disorder

Author(s): Wei Zheng, Limei Gu, Yanling Zhou, Chengyu Wang, Xiaofeng Lan, Bin Zhang, Zezhi Li* and Yuping Ning*

Volume 21, Issue 4, 2023

Published on: 03 November, 2022

Page: [1013 - 1021] Pages: 9

DOI: 10.2174/1570159X20666220927085706

Price: $65

Abstract

Objective: Evidence has shown that brain-derived neurotrophic factor (BDNF) is associated with anhedonia symptoms in major depressive disorder (MDD) patients, while the rapid antianhedonic effects of ketamine may occur independently of depressive symptoms. To our knowledge, the relationship between plasma BDNF (pBDNF) and the effect of repeated-dose intravenous ketamine on anhedonic symptoms has not been investigated.

Methods: Seventy-five Chinese individuals with MDD received ketamine treatments. Anhedonia and pBDNF concentrations were evaluated with a subscale of the Montgomery-Åsberg Depression Rating Scale (MADRS) and enzyme-linked immunosorbent assay (ELISA) at baseline, day 13 and day 26.

Results: Baseline pBDNF levels were associated with changes in anhedonic symptoms on day 13 (r=0.30, P=0.008). Interestingly, pBDNF concentrations were associated with changes in anhedonia symptomson day 26 (r= -0.32, P=0.02). Baseline pBDNF levels were higher in antianhedonic responders than in antianhedonic nonresponders (F=4.2, P=0.04). Ketaminereduced anhedonia symptoms in antianhedonic responders compared to nonresponders on days 13 and 26 (all Ps<0.05). The baseline high BDNF group had a lower level of anhedonia than the low BDNF group on days 13 (P<0.001) and 26 (P=0.01).

Conclusion: Our study suggests that baseline pBDNF concentrations may predict the antianhedonic effect in individuals with MDD treated with repeated doses of ketamine.

Keywords: Ketamine, BDNF, antianhedonic effect, major depressive disorder

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[1]
Trøstheim, M.; Eikemo, M.; Meir, R.; Hansen, I.; Paul, E.; Kroll, S.L.; Garland, E.L.; Leknes, S. Assessment of anhedonia in adults with and without mental illness: A systematic review and meta-analysis. JAMA Netw. Open, 2020, 3(8), e2013233.
[http://dx.doi.org/10.1001/jamanetworkopen.2020.13233] [PMID: 32789515]
[2]
Pelizza, L.; Ferrari, A. Anhedonia in schizophrenia and major depression: State or trait? Ann. Gen. Psychiatry, 2009, 8(1), 22.
[http://dx.doi.org/10.1186/1744-859X-8-22] [PMID: 19811665]
[3]
Ducasse, D.; Loas, G.; Dassa, D.; Gramaglia, C.; Zeppegno, P.; Guillaume, S.; Olié, E.; Courtet, P. Anhedonia is associated with suicidal ideation independently of depression: A meta-analysis. Depress. Anxiety, 2018, 35(5), 382-392.
[http://dx.doi.org/10.1002/da.22709] [PMID: 29232491]
[4]
Vrieze, E.; Demyttenaere, K.; Bruffaerts, R.; Hermans, D.; Pizzagalli, D.A.; Sienaert, P.; Hompes, T.; de Boer, P.; Schmidt, M.; Claes, S. Dimensions in major depressive disorder and their relevance for treatment outcome. J. Affect. Disord., 2014, 155, 35-41.
[http://dx.doi.org/10.1016/j.jad.2013.10.020] [PMID: 24210628]
[5]
McCabe, C.; Cowen, P.J.; Harmer, C.J. Neural representation of reward in recovered depressed patients. Psychopharmacology (Berl.), 2009, 205(4), 667-677.
[http://dx.doi.org/10.1007/s00213-009-1573-9] [PMID: 19529923]
[6]
Young, C.B.; Chen, T.; Nusslock, R.; Keller, J.; Schatzberg, A.F.; Menon, V. Anhedonia and general distress show dissociable ventromedial prefrontal cortex connectivity in major depressive disorder. Transl. Psychiatry, 2016, 6(5), e810.
[http://dx.doi.org/10.1038/tp.2016.80] [PMID: 27187232]
[7]
Rodrigues, N.B.; McIntyre, R.S.; Lipsitz, O.; Cha, D.S.; Lee, Y.; Gill, H.; Majeed, A.; Phan, L.; Nasri, F.; Ho, R.; Lin, K.; Subramaniapillai, M.; Kratiuk, K.; Mansur, R.B.; Rosenblat, J.D. Changes in symptoms of anhedonia in adults with major depressive or bipolar disorder receiving IV ketamine: Results from the Canadian rapid treatment center of excellence. J. Affect. Disord., 2020, 276, 570-575.
[http://dx.doi.org/10.1016/j.jad.2020.07.083] [PMID: 32871688]
[8]
Kishimoto, T.; Chawla, J.M.; Hagi, K.; Zarate, C.A., Jr; Kane, J.M.; Bauer, M.; Correll, C.U. Single-dose infusion ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists for unipolar and bipolar depression: A meta-analysis of efficacy, safety and time trajectories. Psychol. Med., 2016, 46(7), 1459-1472.
[http://dx.doi.org/10.1017/S0033291716000064] [PMID: 26867988]
[9]
Zheng, W.; Zhou, Y.L.; Liu, W.J.; Wang, C.Y.; Zhan, Y.N.; Li, H.Q.; Chen, L.J.; Li, M.D.; Ning, Y.P. Investigation of medical effect of multiple ketamine infusions on patients with major depressive disorder. J. Psychopharmacol., 2019, 33(4), 494-501.
[http://dx.doi.org/10.1177/0269881119827811]
[10]
Tomasetti, C.; Montemitro, C.; Fiengo, A.L.C.; Santone, C.; Orsolini, L.; Valchera, A.; Carano, A.; Pompili, M.; Serafini, G.; Perna, G.; Vellante, F.; Martinotti, G.; Giannantonio, M.D.; Kim, Y.K.; Nicola, M.D.; Bellomo, A.; Ventriglio, A.; Fornaro, M.; Berardis, D.D. Novel pathways in the treatment of major depression: Focus on the glutamatergic system. Curr. Pharm. Des., 2019, 25(4), 381-387.
[http://dx.doi.org/10.2174/1381612825666190312102444] [PMID: 30864501]
[11]
De Berardis, D.; Fornaro, M.; Valchera, A.; Cavuto, M.; Perna, G.; Di Nicola, M.; Serafini, G.; Carano, A.; Pompili, M.; Vellante, F.; Orsolini, L.; Fiengo, A.; Ventriglio, A.; Yong-Ku, K.; Martinotti, G.; Di Giannantonio, M.; Tomasetti, C. Eradicating suicide at its roots: Preclinical bases and clinical evidence of the efficacy of ketamine in the treatment of suicidal behaviors. Int. J. Mol. Sci., 2018, 19(10), E2888.
[http://dx.doi.org/10.3390/ijms19102888] [PMID: 30249029]
[12]
Li, Z.; Ruan, M.; Chen, J.; Fang, Y. Major depressive disorder: Advances in neuroscience research and translational applications. Neurosci. Bull., 2021, 37(6), 863-880.
[http://dx.doi.org/10.1007/s12264-021-00638-3] [PMID: 33582959]
[13]
Zheng, W.; Zhou, Y.L.; Liu, W.J.; Wang, C.Y.; Zhan, Y.N.; Lan, X.F.; Zhang, B.; Ning, Y.P. A preliminary study of adjunctive ketamine for treatment-resistant bipolar depression. J. Affect. Disord., 2020, 275, 38-43.
[http://dx.doi.org/10.1016/j.jad.2020.06.020] [PMID: 32658821]
[14]
Xiong, J.; Lipsitz, O.; Chen-Li, D.; Rosenblat, J.D.; Rodrigues, N.B.; Carvalho, I.; Lui, L.M.W.; Gill, H.; Narsi, F.; Mansur, R.B.; Lee, Y.; McIntyre, R.S. The acute antisuicidal effects of single-dose intravenous ketamine and intranasal esketamine in individuals with major depression and bipolar disorders: A systematic review and meta-analysis. J. Psychiatr. Res., 2021, 134, 57-68.
[http://dx.doi.org/10.1016/j.jpsychires.2020.12.038] [PMID: 33360864]
[15]
De Berardis, D.; Tomasetti, C.; Pompili, M.; Serafini, G.; Vellante, F.; Fornaro, M.; Valchera, A.; Perna, G.; Volpe, U.; Martinotti, G.; Fraticelli, S.; Di Giannantonio, M.; Kim, Y.K.; Orsolini, L. An update on glutamatergic system in suicidal depression and on the role of esketamine. Curr. Top. Med. Chem., 2020, 20(7), 554-584.
[http://dx.doi.org/10.2174/1568026620666200131100316] [PMID: 32003691]
[16]
Lally, N.; Nugent, A.C.; Luckenbaugh, D.A.; Ameli, R.; Roiser, J.P.; Zarate, C.A. Anti-anhedonic effect of ketamine and its neural correlates in treatment-resistant bipolar depression. Transl. Psychiatry, 2014, 4(10), e469.
[http://dx.doi.org/10.1038/tp.2014.105] [PMID: 25313512]
[17]
Lally, N.; Nugent, A.C.; Luckenbaugh, D.A.; Niciu, M.J.; Roiser, J.P.; Zarate, C.A., Jr Neural correlates of change in major depressive disorder anhedonia following open-label ketamine. J. Psychopharmacol., 2015, 29(5), 596-607.
[http://dx.doi.org/10.1177/0269881114568041] [PMID: 25691504]
[18]
Zheng, W.; Gu, L.M.; Sun, C.H.; Zhou, Y.L.; Wang, C.Y.; Lan, X.F.; Zhang, B.; Ning, Y.P. Comparative effectiveness of repeated ketamine infusions in treating anhedonia in bipolar and unipolar depression. J. Affect. Disord., 2022, 300, 109-113.
[http://dx.doi.org/10.1016/j.jad.2021.12.105] [PMID: 34965393]
[19]
Papp, C.; Pak, K.; Erdei, T.; Juhasz, B.; Seres, I.; Szentpéteri, A.; Kardos, L.; Szilasi, M.; Gesztelyi, R.; Zsuga, J. Alteration of the irisin-brain-derived neurotrophic factor axis contributes to disturbance of mood in COPD patients. Int. J. Chron. Obstruct. Pulmon. Dis., 2017, 12, 2023-2033.
[http://dx.doi.org/10.2147/COPD.S135701] [PMID: 28744117]
[20]
Wu, C.; Lu, J.; Lu, S.; Huang, M.; Xu, Y. Increased ratio of mature BDNF to precursor-BDNF in patients with major depressive disorder with severe anhedonia. J. Psychiatr. Res., 2020, 126, 92-97.
[http://dx.doi.org/10.1016/j.jpsychires.2020.05.010] [PMID: 32428748]
[21]
Yan, Q.S.; Feng, M.J.; Yan, S.E. Different expression of brain-derived neurotrophic factor in the nucleus accumbens of alcohol-preferring (P) and -nonpreferring (NP) rats. Brain Res., 2005, 1035(2), 215-218.
[http://dx.doi.org/10.1016/j.brainres.2004.12.039] [PMID: 15722062]
[22]
Hamani, C.; Machado, D.C.; Hipólide, D.C.; Dubiela, F.P.; Suchecki, D.; Macedo, C.E.; Tescarollo, F.; Martins, U.; Covolan, L.; Nobrega, J.N. Deep brain stimulation reverses anhedonic-like behavior in a chronic model of depression: Role of serotonin and brain derived neurotrophic factor. Biol. Psychiatry, 2012, 71(1), 30-35.
[http://dx.doi.org/10.1016/j.biopsych.2011.08.025] [PMID: 22000731]
[23]
Réus, G.Z.; Abelaira, H.M.; Stringari, R.B.; Fries, G.R.; Kapczinski, F.; Quevedo, J. Memantine treatment reverses anhedonia, normalizes corticosterone levels and increases BDNF levels in the prefrontal cortex induced by chronic mild stress in rats. Metab. Brain Dis., 2012, 27(2), 175-182.
[http://dx.doi.org/10.1007/s11011-012-9281-2] [PMID: 22327556]
[24]
Machado-Vieira, R.; Yuan, P.; Brutsche, N. DiazGranados, N.; Luckenbaugh, D.; Manji, H.K.; Zarate, C.A., Jr Brain-derived neurotrophic factor and initial antidepressant response to an N-methyl-D-aspartate antagonist. J. Clin. Psychiatry, 2009, 70(12), 1662-1666.
[http://dx.doi.org/10.4088/JCP.08m04659] [PMID: 19744406]
[25]
Medeiros, G.C.; Greenstein, D.; Kadriu, B.; Yuan, P.; Park, L.T.; Gould, T.D.; Zarate, C.A., Jr Treatment of depression with ketamine does not change plasma levels of brain-derived neurotrophic factor or vascular endothelial growth factor. J Affect Disord, 2021, 280(Pt A), 136-139.
[http://dx.doi.org/10.1016/j.jad.2020.11.011]
[26]
Zheng, W.; Zhou, Y.L.; Wang, C.Y.; Lan, X.F.; Zhang, B.; Zhou, S.M.; Yan, S.; Ning, Y.P. Plasma BDNF concentrations and the antidepressant effects of six ketamine infusions in unipolar and bipolar depression. PeerJ, 2021, 9, e10989.
[http://dx.doi.org/10.7717/peerj.10989] [PMID: 33850645]
[27]
Zheng, W.; Zhou, Y.L.; Wang, C.Y.; Lan, X.F.; Zhang, B.; Zhou, S.M.; Yan, S.; Yang, M.Z.; Nie, S.; Ning, Y.P. Association between plasma levels of BDNF and the antisuicidal effects of repeated ketamine infusions in depression with suicidal ideation. Ther. Adv. Psychopharmacol., 2020, 10, 2045125320973794.
[http://dx.doi.org/10.1177/2045125320973794] [PMID: 33282177]
[28]
Hamilton, M. A rating scale for depression. J. Neurol. Neurosurg. Psychiatry, 1960, 23(1), 56-62.
[http://dx.doi.org/10.1136/jnnp.23.1.56] [PMID: 14399272]
[29]
Xie, G.R.; Shen, Q.J. Use of the Chinese version of the hamilton rating scale for depression in general population and patients with major depression. Chinese Journal of Nervous and Mental Diseases, 1984, 10, 364.
[30]
Beck, A.T.; Kovacs, M.; Weissman, A. Assessment of suicidal intention: The scale for suicide ideation. J. Consult. Clin. Psychol., 1979, 47(2), 343-352.
[http://dx.doi.org/10.1037/0022-006X.47.2.343] [PMID: 469082]
[31]
Montgomery, S.A.; Asberg, M. A new depression scale designed to be sensitive to change. Br. J. Psychiatry, 1979, 134(4), 382-389.
[http://dx.doi.org/10.1192/bjp.134.4.382] [PMID: 444788]
[32]
Cao, B.; Park, C.; Subramaniapillai, M.; Lee, Y.; Iacobucci, M.; Mansur, R.B.; Zuckerman, H.; Phan, L.; McIntyre, R.S. The efficacy of vortioxetine on anhedonia in patients with major depressive disorder. Front. Psychiatry, 2019, 10, 17.
[http://dx.doi.org/10.3389/fpsyt.2019.00017] [PMID: 30766492]
[33]
McIntyre, R.S.; Loft, H.; Christensen, M.C. Efficacy of vortioxetine on anhedonia: Results from a pooled analysis of short-term studies in patients with major depressive disorder. Neuropsychiatr. Dis. Treat., 2021, 17, 575-585.
[http://dx.doi.org/10.2147/NDT.S296451] [PMID: 33654400]
[34]
Zheng, W.; Gu, L.M.; Zhou, Y.L.; Wang, C.Y.; Lan, X.F.; Zhang, B.; Shi, H.S.; Wang, D.F.; Ning, Y.P. Association of VEGF with antianhedonic effects of repeated-dose intravenous ketamine in treatment-refractory depression. Front. Psychiatry, 2021, 12, 780975.
[http://dx.doi.org/10.3389/fpsyt.2021.780975] [PMID: 34925104]
[35]
Zheng, W.; Zhou, Y.L.; Liu, W.J.; Wang, C.Y.; Zhan, Y.N.; Li, H.Q.; Chen, L.J.; Li, M.D.; Ning, Y.P. Rapid and longer-term antidepressant effects of repeated-dose intravenous ketamine for patients with unipolar and bipolar depression. J. Psychiatr. Res., 2018, 106, 61-68.
[http://dx.doi.org/10.1016/j.jpsychires.2018.09.013] [PMID: 30278319]
[36]
Wu, Z.W.; Shi, H.; Chen, D.C.; Chen, S.; Xiu, M.H.; Zhang, X.Y. BDNF serum levels and cognitive improvement in drug-naive first episode patients with schizophrenia: A prospective 12-week longitudinal study. Psychoneuroendocrinology, 2020, 122, 104879.
[http://dx.doi.org/10.1016/j.psyneuen.2020.104879] [PMID: 33049658]
[37]
Garcia, L.S.; Comim, C.M.; Valvassori, S.S.; Réus, G.Z.; Stertz, L.; Kapczinski, F.; Gavioli, E.C.; Quevedo, J. Ketamine treatment reverses behavioral and physiological alterations induced by chronic mild stress in rats. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2009, 33(3), 450-455.
[http://dx.doi.org/10.1016/j.pnpbp.2009.01.004] [PMID: 19439250]
[38]
Allen, A.P.; Naughton, M.; Dowling, J.; Walsh, A.; Ismail, F.; Shorten, G.; Scott, L.; McLoughlin, D.M.; Cryan, J.F.; Dinan, T.G.; Clarke, G. Serum BDNF as a peripheral biomarker of treatment-resistant depression and the rapid antidepressant response: A comparison of ketamine and ECT. J. Affect. Disord., 2015, 186, 306-311.
[http://dx.doi.org/10.1016/j.jad.2015.06.033] [PMID: 26275358]
[39]
Grunebaum, M.F.; Ellis, S.P.; Keilp, J.G.; Moitra, V.K.; Cooper, T.B.; Marver, J.E.; Burke, A.K.; Milak, M.S.; Sublette, M.E.; Oquendo, M.A.; Mann, J.J. Ketamine versus midazolam in bipolar depression with suicidal thoughts: A pilot midazolam-controlled randomized clinical trial. Bipolar Disord., 2017, 19(3), 176-183.
[http://dx.doi.org/10.1111/bdi.12487] [PMID: 28452409]
[40]
Haile, C.N.; Murrough, J.W.; Iosifescu, D.V.; Chang, L.C.; Al Jurdi, R.K.; Foulkes, A.; Iqbal, S.; Mahoney, J.J., III; De La Garza, R., II; Charney, D.S.; Newton, T.F.; Mathew, S.J. Plasma brain derived neurotrophic factor (BDNF) and response to ketamine in treatment-resistant depression. Int. J. Neuropsychopharmacol., 2014, 17(2), 331-336.
[http://dx.doi.org/10.1017/S1461145713001119] [PMID: 24103211]
[41]
Rybakowski, J.K.; Permoda-Osip, A.; Skibinska, M.; Adamski, R.; Bartkowska-Sniatkowska, A. Single ketamine infusion in bipolar depression resistant to antidepressants: Are neurotrophins involved? Hum. Psychopharmacol., 2013, 28(1), 87-90.
[http://dx.doi.org/10.1002/hup.2271] [PMID: 23124710]
[42]
van Zutphen, E.M.; Rhebergen, D.; van Exel, E.; Oudega, M.L.; Bouckaert, F.; Sienaert, P.; Vandenbulcke, M.; Stek, M.; Dols, A. Brain-derived neurotrophic factor as a possible predictor of electroconvulsive therapy outcome. Transl. Psychiatry, 2019, 9(1), 155.
[http://dx.doi.org/10.1038/s41398-019-0491-9] [PMID: 31127089]
[43]
Mikoteit, T.; Beck, J.; Eckert, A.; Hemmeter, U.; Brand, S.; Bischof, R.; Holsboer-Trachsler, E.; Delini-Stula, A. High baseline BDNF serum levels and early psychopathological improvement are predictive of treatment outcome in major depression. Psychopharmacology (Berl.), 2014, 231(15), 2955-2965.
[http://dx.doi.org/10.1007/s00213-014-3475-8] [PMID: 24562062]
[44]
Denk, M.C.; Rewerts, C.; Holsboer, F.; Erhardt-Lehmann, A.; Turck, C.W. Monitoring ketamine treatment response in a depressed patient via peripheral mammalian target of rapamycin activation. Am. J. Psychiatry, 2011, 168(7), 751-752.
[http://dx.doi.org/10.1176/appi.ajp.2011.11010128] [PMID: 21724677]
[45]
Kokane, S.S.; Armant, R.J.; Bolaños-Guzmán, C.A.; Perrotti, L.I. Overlap in the neural circuitry and molecular mechanisms underlying ketamine abuse and its use as an antidepressant. Behav. Brain Res., 2020, 384, 112548.
[http://dx.doi.org/10.1016/j.bbr.2020.112548] [PMID: 32061748]
[46]
Levy, M.J.F.; Boulle, F.; Steinbusch, H.W.; van den Hove, D.L.A.; Kenis, G.; Lanfumey, L. Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression. Psychopharmacology (Berl.), 2018, 235(8), 2195-2220.
[http://dx.doi.org/10.1007/s00213-018-4950-4] [PMID: 29961124]

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