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Antidepressant-resistant depression is characterized by reduced short- and long-interval cortical inhibition

Published online by Cambridge University Press:  03 June 2019

Jia-Shyun Jeng Open the ORCID record for Jia-Shyun Jeng [Opens in a new window] ,
Cheng-Ta Li ,
Hui-Ching Lin ,
Shih-Jen Tsai ,
Ya-Mei Bai ,
Tung-Ping Su ,
Yu-Wen Chang  and
Chih-Ming Cheng
Jia-Shyun Jeng
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
Cheng-Ta Li*
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan Institute of Brain Science and Brain Research Center, National Yang-Ming University, Taipei, Taiwan Institute of Cognitive Neuroscience, National Central University, Jhongli, Taiwan
Hui-Ching Lin
Affiliation:
Department and Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan
Shih-Jen Tsai
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan
Ya-Mei Bai
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan Institute of Brain Science and Brain Research Center, National Yang-Ming University, Taipei, Taiwan
Tung-Ping Su
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan Institute of Brain Science and Brain Research Center, National Yang-Ming University, Taipei, Taiwan Department of Psychiatry, Cheng-Hsin General Hospital, Taipei, Taiwan
Yu-Wen Chang
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
Chih-Ming Cheng
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan Institute of Brain Science and Brain Research Center, National Yang-Ming University, Taipei, Taiwan Taipei Veterans General Hospital Yuan Shan branch, Yilan, Taiwan
*
Author for correspondence: Cheng-Ta Li, E-mail: on5083@msn.com; ctli2@vghtpe.gov.tw
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Abstract

Background

Major depressive disorder (MDD) is highly heterogeneous and can be classified as treatment-resistant depression (TRD) or antidepressant-responsive depression (non-TRD) based on patients' responses to antidepressant treatment. Methods for distinguishing between TRD and non-TRD are critical clinical concerns. Deficits of cortical inhibition (CI) have been reported to play an influential role in the pathophysiology of MDD. Whether TRD patients' CI is more impaired than that of non-TRD patients remains unclear.

Methods

Paired-pulse transcranial magnetic stimulation (ppTMS) was used to measure cortical inhibitory function including GABAA- and GABAB-receptor-related CI and cortical excitatory function including glutamate-receptor-related intracortical facilitation (ICF). We recruited 36 healthy controls (HC) and 36 patients with MDD (non-TRD, n = 16; TRD, n = 20). All participants received evaluations for depression severity and ppTMS examinations. Non-TRD patients received an additional ppTMS examination after 3 months of treatment with the SSRI escitalopram.

Results

Patients with TRD exhibited reduced short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition (LICI), as shown by abnormally higher estimates, than those with non-TRD or HC (F = 11.030, p < 0.001; F = 10.309, p < 0.001, respectively). After an adequate trial of escitalopram treatment, the LICI of non-TRD reduced significantly (t = − 3.628, p < 0.001), whereas the ICF remained lower than that of HC and showed no difference from pretreatment non-TRD.

Conclusions

TRD was characterized by relatively reduced CI, including both GABAA- and GABAB-receptor-mediated neurons while non-TRD preserved partial CI. In non-TRD, SSRIs may mainly modulate GABAB-receptor-related LICI. Our findings revealed distinguishable features of CI in antidepressant-resistant and responsive major depression.

Keywords

AntidepressantLICIpaired-pulse transcranial magnetic stimulation (ppTMS)SICISSRItreatment-resistant depression (TRD)
Type
Original Articles
Information
Psychological Medicine , Volume 50 , Issue 8 , June 2020 , pp. 1285 - 1291
Copyright
Copyright © Cambridge University Press 2019

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References

Abdallah, CG, Jackowski, A, Sato, JR, Mao, X, Kang, G, Cheema, R, Coplan, JD, Mathew, SJ and Shungu, DC (2015) Prefrontal cortical GABA abnormalities are associated with reduced hippocampal volume in major depressive disorder. European Neuropsychopharmacology 25, 1082–1090.CrossRefGoogle ScholarPubMed
Arnone, D, Mumuni, AN, Jauhar, S, Condon, B and Cavanagh, J (2015) Indirect evidence of selective glial involvement in glutamate-based mechanisms of mood regulation in depression: meta-analysis of absolute prefrontal neuro-metabolic concentrations. European Neuropsychopharmacology 25, 1109–1117.CrossRefGoogle ScholarPubMed
Asaoka, N, Nishitani, N, Kinoshita, H, Kawai, H, Shibui, N, Nagayasu, K, Shirakawa, H, Nakagawa, T and Kaneko, S (2017) Chronic antidepressant potentiates spontaneous activity of dorsal raphe serotonergic neurons by decreasing GABA B receptor-mediated inhibition of L-type calcium channels. Scientific Reports 7, 13609.CrossRefGoogle Scholar
Association, AP (2013) Diagnostic and Statistical Manual of Mental Disorders (DSM-5®). Arlington, VA: American Psychiatric Pub.CrossRefGoogle Scholar
Bajbouj, M, Lisanby, SH, Lang, UE, Danker-Hopfe, H, Heuser, I and Neu, P (2006) Evidence for impaired cortical inhibition in patients with unipolar major depression. Biological Psychiatry 59, 395–400.CrossRefGoogle ScholarPubMed
Brennan, BP, Admon, R, Perriello, C, Laflamme, EM, Athey, AJ, Pizzagalli, DA, Hudson, JI, Pope, HG and Jensen, JE (2017) Acute change in anterior cingulate cortex GABA, but not glutamine/glutamate, mediates antidepressant response to citalopram. Psychiatry Research: Neuroimaging 269, 9–16.CrossRefGoogle Scholar
Cornelisse, LN, Van Der Harst, JE, Lodder, JC, Baarendse, PJ, Timmerman, A, Mansvelder, HD, Spruijt, BM and Brussaard, AB (2007) Reduced 5-HT1A-and GABAB receptor function in dorsal raphe neurons upon chronic fluoxetine treatment of socially stressed rats. Journal of Neurophysiology 98, 196–204.CrossRefGoogle ScholarPubMed
Croarkin, PE, Levinson, AJ and Daskalakis, ZJ (2011) Evidence for GABAergic inhibitory deficits in major depressive disorder. Neuroscience & Biobehavioral Reviews 35, 818–825.CrossRefGoogle ScholarPubMed
Croarkin, PE, Nakonezny, PA, Husain, MM, Melton, T, Buyukdura, JS, Kennard, BD, Emslie, GJ, Kozel, FA and Daskalakis, ZJ (2013) Evidence for increased glutamatergic cortical facilitation in children and adolescents with major depressive disorder. Jama Psychiatry 70, 291–299.CrossRefGoogle ScholarPubMed
Croarkin, PE, Nakonezny, PA, Husain, MM, Port, JD, Melton, T, Kennard, BD, Emslie, GJ, Kozel, FA and Daskalakis, ZJ (2014) Evidence for pretreatment LICI deficits among depressed children and adolescents with nonresponse to fluoxetine. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 7, 243–251.CrossRefGoogle ScholarPubMed
Daskalakis, ZJ, Fitzgerald, PB and Christensen, BK (2007) The role of cortical inhibition in the pathophysiology and treatment of schizophrenia. Brain Research Reviews 56, 427–442.CrossRefGoogle ScholarPubMed
Di Lazzaro, V, Oliviero, A, Meglio, M, Cioni, B, Tamburrini, G, Tonali, P and Rothwell, J (2000) Direct demonstration of the effect of lorazepam on the excitability of the human motor cortex. Clinical Neurophysiology 111, 794–799.CrossRefGoogle ScholarPubMed
Farmer, A, Redman, K, Harris, T, Webb, R, Mahmood, A, Sadler, S and McGuffin, P (2001) The Cardiff sib-pair study: suicidal ideation in depressed and healthy subjects and their siblings. Crisis 22, 71–73.CrossRefGoogle ScholarPubMed
Fitzgerald, PB, Brown, TL, Marston, NA, Daskalakis, ZJ, De Castella, A, Bradshaw, JL and Kulkarni, J (2004) Motor cortical excitability and clinical response to rTMS in depression. Journal of Affective Disorders 82, 71–76.CrossRefGoogle ScholarPubMed
Hamilton, M (1960) A rating scale for depression. Journal of Neurology, Neurosurgery, and Psychiatry 23, 56.CrossRefGoogle ScholarPubMed
Inghilleri, M, Berardelli, A, Cruccu, G and Manfredi, M (1993) Silent period evoked by transcranial stimulation of the human cortex and cervicomedullary junction. The Journal of Physiology 466, 521–534.Google ScholarPubMed
Innis, RB, Nestler, EJ and Aghajanian, GK (1988) Evidence for G protein mediation of serotonin-and GABAB-induced hyperpolarization of rat dorsal raphe neurons. Brain Research 459, 27–36.CrossRefGoogle Scholar
Küçükibrahimoğlu, E, Saygın, MZ, Çalışkan, M, Kaplan, OK, Ünsal, C and Gren, MZ (2009) The change in plasma GABA, glutamine and glutamate levels in fluoxetine-or S-citalopram-treated female patients with major depression. European Journal of Clinical Pharmacology 65, 571–577.CrossRefGoogle ScholarPubMed
Kujirai, T, Caramia, M, Rothwell, JC, Day, B, Thompson, P, Ferbert, A, Wroe, S, Asselman, P and Marsden, CD (1993) Corticocortical inhibition in human motor cortex. The Journal of Physiology 471, 501–519.CrossRefGoogle ScholarPubMed
Lam, RW, Mcintosh, D, Wang, J, Enns, MW, Kolivakis, T, Michalak, EE, Sareen, J, Song, W-Y, Kennedy, SH and Macqueen, GM (2016) Canadian network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 1. Disease burden and principles of care. The Canadian Journal of Psychiatry 61, 510–523.CrossRefGoogle ScholarPubMed
Lefaucheur, J, Lucas, B, Andraud, F, Hogrel, J, Bellivier, F, Del Cul, A, Rousseva, A, Leboyer, M and Paillere-Martinot, M (2008) Inter-hemispheric asymmetry of motor corticospinal excitability in major depression studied by transcranial magnetic stimulation. Journal of Psychiatric Research 42, 389–398.CrossRefGoogle ScholarPubMed
Levinson, AJ, Fitzgerald, PB, Favalli, G, Blumberger, DM, Daigle, M and Daskalakis, ZJ (2010) Evidence of cortical inhibitory deficits in major depressive disorder. Biological Psychiatry 67, 458–464.CrossRefGoogle ScholarPubMed
Lewis, CP, Nakonezny, PA, Blacker, CJ, Voort, JLV, Port, JD, Worrell, GA, Jo, HJ, Daskalakis, ZJ and Croarkin, PE (2018) Cortical inhibitory markers of lifetime suicidal behavior in depressed adolescents. Neuropsychopharmacology 43, 1822–1831.CrossRefGoogle ScholarPubMed
Li, CT, Chen, MH, Lin, WC, Hong, CJ, Yang, BH, Liu, RS, Tu, PC and Su, TP (2016) The effects of low-dose ketamine on the prefrontal cortex and amygdala in treatment-resistant depression: a randomized controlled study. Human Brain Mapping 37, 1080–1090.CrossRefGoogle ScholarPubMed
Li, CT, Lu, CF, Lin, HC, Huang, YZ, Juan, CH, Su, TP, Bai, YM, Chen, MH and Lin, WC (2017) Cortical inhibitory and excitatory function in drug-naive generalized anxiety disorder. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 10, 604–608.CrossRefGoogle ScholarPubMed
Li, CT, Yang, KC and Lin, WC (2018) Glutamatergic dysfunction and glutamatergic compounds for major psychiatric disorders: evidence from clinical neuroimaging studies. Frontiers in Psychiatry 9, 1–11.Google ScholarPubMed
Liepert, J, Schwenkreis, P, Tegenthoff, M and Malin, J-P (1997) The glutamate antagonist riluzole suppresses intracortical facilitation. Journal of Neural Transmission 104, 1207–1214.CrossRefGoogle ScholarPubMed
Little, A (2009) Treatment-resistant depression. American Family Physician 80, 167–172.Google ScholarPubMed
Mcdonnell, MN, Orekhov, Y and Ziemann, U (2006) The role of GABA B receptors in intracortical inhibition in the human motor cortex. Experimental Brain Research 173, 86–93.CrossRefGoogle ScholarPubMed
Milev, RV, Giacobbe, P, Kennedy, SH, Blumberger, DM, Daskalakis, ZJ, Downar, J, Modirrousta, M, Patry, S, Vila-Rodriguez, F and Lam, RW (2016) Canadian network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 4. Neurostimulation treatments. The Canadian Journal of Psychiatry 61, 561–575.CrossRefGoogle ScholarPubMed
Moussavi, S, Chatterji, S, Verdes, E, Tandon, A, Patel, V and Ustun, B (2007) Depression, chronic diseases, and decrements in health: results from the World Health Surveys. The Lancet 370, 851–858.CrossRefGoogle ScholarPubMed
Nakamura, H, Kitagawa, H, Kawaguchi, Y and Tsuji, H (1997) Intracortical facilitation and inhibition after transcranial magnetic stimulation in conscious humans. The Journal of Physiology 498, 817–823.CrossRefGoogle ScholarPubMed
Nemeroff, CB (2007) Prevalence and management of treatment-resistant depression. Journal of Clinical Psychiatry 68, 17.Google ScholarPubMed
Oldfield, RC (1971) The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9, 97–113.CrossRefGoogle ScholarPubMed
Pehrson, AL and Sanchez, C (2015) Altered γ-aminobutyric acid neurotransmission in major depressive disorder: a critical review of the supporting evidence and the influence of serotonergic antidepressants. Drug Design, Development and Therapy 9, 603.CrossRefGoogle ScholarPubMed
Price, RB, Shungu, DC, Mao, X, Nestadt, P, Kelly, C, Collins, KA, Murrough, JW, Charney, DS and Mathew, SJ (2009) Amino acid neurotransmitters assessed by proton magnetic resonance spectroscopy: relationship to treatment resistance in major depressive disorder. Biological Psychiatry 65, 792–800.CrossRefGoogle ScholarPubMed
Radhu, N, De Jesus, DR, Ravindran, LN, Zanjani, A, Fitzgerald, PB and Daskalakis, ZJ (2013) A meta-analysis of cortical inhibition and excitability using transcranial magnetic stimulation in psychiatric disorders. Clinical Neurophysiology 124, 1309–1320.CrossRefGoogle ScholarPubMed
Rajkowska, G, O'Dwyer, G, Teleki, Z, Stockmeier, CA and Miguel-Hidalgo, JJ (2007) GABAergic neurons immunoreactive for calcium binding proteins are reduced in the prefrontal cortex in major depression. Neuropsychopharmacology 32, 471.CrossRefGoogle ScholarPubMed
Roick, H, Von Giesen, H, Benecke, R (1993) On the origin of the postexcitatory inhibition seen after transcranial magnetic brain stimulation in awake human subjects. Experimental Brain Research 94, 489–498.CrossRefGoogle ScholarPubMed
Sanacora, G, Mason, GF, Rothman, DL and Krystal, JH (2002) Increased occipital cortex GABA concentrations in depressed patients after therapy with selective serotonin reuptake inhibitors. American Journal of Psychiatry 159, 663–665.CrossRefGoogle ScholarPubMed
Sanger, TD, Garg, RR and Chen, R (2001) Interactions between two different inhibitory systems in the human motor cortex. The Journal of Physiology 530, 307–317.CrossRefGoogle ScholarPubMed
Serrats, J, Artigas, F, Mengod, G and CortS,R S,R (2003) GABAB receptor mRNA in the raphe nuclei: co-expression with serotonin transporter and glutamic acid decarboxylase. Journal of Neurochemistry 84, 743–752.CrossRefGoogle ScholarPubMed
Slattery, DA, Desrayaud, S and Cryan, JF (2005) GABAB receptor antagonist-mediated antidepressant-like behavior is serotonin-dependent. Journal of Pharmacology and Experimental Therapeutics 312, 290–296.CrossRefGoogle ScholarPubMed
Tremblay, S, Beaul, V, Proulx, S, De Beaumont, L, Marjańska, M, Doyon, J, Pascual-Leone, A, Lassonde, M and Th Oret, H (2012) Relationship between transcranial magnetic stimulation measures of intracortical inhibition and spectroscopy measures of GABA and glutamate + glutamine. Journal of Neurophysiology 109, 1343–1349.CrossRefGoogle ScholarPubMed
Trivedi, MH, Morris, DW, Wisniewski, SR, Nierenberg, AA, Gaynes, BN, Kurian, BT, Warden, D, Stegman, D, Shores-Wilson, K, Rush, A (2013) Clinical and sociodemographic characteristics associated with suicidal ideation in depressed outpatients. The Canadian Journal of Psychiatry 58, 113–122.CrossRefGoogle ScholarPubMed
Valls-Solé, J, Pascual-Leone, A, Wassermann, EM and Hallett, M (1992) Human motor evoked responses to paired transcranial magnetic stimuli. Electroencephalography and Clinical Neurophysiology/Evoked Potentials Section 85, 355–364.CrossRefGoogle ScholarPubMed
Wang, HY, Kuo, ZC, Fu, YS, Chen, RF, Min, MY and Yang, HW (2015) GABAB receptor-mediated tonic inhibition regulates the spontaneous firing of locus coeruleus neurons in developing rats and in citalopram-treated rats. The Journal of Physiology 593, 161–180.CrossRefGoogle ScholarPubMed
Werhahn, KJ, Kunesch, E, Noachtar, S, Benecke, R and Classen, J (1999) Differential effects on motorcortical inhibition induced by blockade of GABA uptake in humans. The Journal of Physiology 517, 591–597.CrossRefGoogle ScholarPubMed
Williams, JB and Kobak, KA (2008) Development and reliability of a structured interview guide for the Montgomery-Åsberg Depression Rating Scale (SIGMA). The British Journal of Psychiatry 192, 52–58.CrossRefGoogle Scholar
Ziemann, U, Lnnecker, S, Steinhoff, BJ and Paulus, W (1996) The effect of lorazepam on the motor cortical excitability in man. Experimental Brain Research 109, 127–135.CrossRefGoogle ScholarPubMed
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