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Resting-state brain alteration after a single dose of SSRI administration predicts 8-week remission of patients with major depressive disorder

  • Y. Cheng (a1), J. Xu (a2), D. Arnone (a3), B. Nie (a4), H. Yu (a5), H. Jiang (a1), Y. Bai (a1), C. Luo (a5), R. A. A. Campbell (a6), B. Shan (a4), L. Xu (a7) and X. Xu (a1)...

Abstract

Background

The present study investigated alteration of brain resting-state activity induced by antidepressant treatment and attempted to investigate whether treatment efficacy can be predicted at an early stage of pharmacological treatment.

Method

Forty-eight first-episode medication-free patients diagnosed with major depression received treatment with escitalopram. Resting-state functional magnetic resonance imaging was administered prior to treatment, 5 h after the first dose, during the course of pharmacological treatment (week 4) and at endpoint (week 8). Resting-state activity was evaluated in the course of the 8-week treatment and in relation to clinical improvement.

Results

Escitalopram dynamically modified resting-state activity in depression during the treatment. After 5 h the antidepressant induced a significant decrease in the signal in the occipital cortex and an increase in the dorsolateral and dorsomedial prefrontal cortices and middle cingulate cortex. Furthermore, while remitters demonstrated more obvious changes following treatment, these were more modest in non-responders suggesting possible tonic and dynamic differences in the serotonergic system. Changes after 5 h in the caudate, occipital and temporal cortices were the best predictor of clinical remission at endpoint.

Conclusions

This study revealed the possibility of using the measurement of resting-state neural changes a few hours after acute administration of antidepressant to identify individuals likely to remit after a few weeks of treatment.

Copyright

Corresponding author

*Address for correspondence: X. Xu, MD, Department of Psychiatry, the First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming 650032, People's Republic of China. (Email: xfxu2004@sina.com, xuxf2012@163.com)

References

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Anderson, IM, Juhasz, G, Thomas, E, Downey, D, McKie, S, Deakin, JF, Elliott, R (2011). The effect of acute citalopram on face emotion processing in remitted depression: a pharmacoMRI study. European Neuropsychopharmacology 21, 140148.
APA, (2010). Practice Guideline for the Treatment of Patients with Major Depressive Disorder, 3rd edn. American Psychiatric Association: Arlington, VA.
Arnone, D, Job, D, Selvaraj, S, Abe, O, Amico, F, Cheng, Y, Colloby, SJ, O'Brien, JT, Frodl, T, Gotlib, IH, Ham, BJ, Kim, MJ, Koolschijn, PC, Perico, CA, Salvadore, G, Thomas, AJ, Van Tol, MJ, van der Wee, NJ, Veltman, DJ, Wagner, G, McIntosh, AM (2016). Computational meta-analysis of statistical parametric maps in major depression. Human Brain Mapping 37, 13931404.
Artigas, F (1993). 5-HT and antidepressants: new views from microdialysis studies. Trends in Pharmacological Sciences 14, 262.
Bauer, M, Pfennig, A, Severus, E, Whybrow, PC, Angst, J, Möller, H-J (2013). World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders, part 1: update 2013 on the acute and continuation treatment of unipolar depressive disorders. World Journal of Biological Psychiatry 14, 334385.
Beckmann, CF, DeLuca, M, Devlin, JT, Smith, SM (2005). Investigations into resting-state connectivity using independent component analysis. Philosophical Transactions of the Royal Society pf London, Series B: Biological Sciences 360, 10011013.
Biswal, B, Zerrin Yetkin, F, Haughton, VM, Hyde, JS (1995). Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magnetic Resonance in Medicine 34, 537541.
Bozkurt, A, Zilles, K, Schleicher, A, Kamper, L, Arigita, ES, Uylings, H, Kötter, R (2005). Distributions of transmitter receptors in the macaque cingulate cortex. Neuroimage 25, 219229.
Carvalho, A, Cavalcante, J, Castelo, M, Lima, M (2007). Augmentation strategies for treatment-resistant depression: a literature review. Journal of Clinical Pharmacy and Therapeutics 32, 415428.
Celada, P, Puig, MV, Amargós-Bosch, M, Adell, A, Artigas, F (2004). The therapeutic role of 5-HT1A and 5-HT2A receptors in depression. Journal of Psychiatry and Neuroscience 29, 252.
Connolly, CG, Wu, J, Ho, TC, Hoeft, F, Wolkowitz, O, Eisendrath, S, Frank, G, Hendren, R, Max, JE, Paulus, MP (2013). Resting-state functional connectivity of subgenual anterior cingulate cortex in depressed adolescents. Biological Psychiatry 74, 898907.
Delaveau, P, Jabourian, M, Lemogne, C, Allaili, N, Choucha, W, Girault, N, Lehericy, S, Laredo, J, Fossati, P (2016). Antidepressant short-term and long-term brain effects during self-referential processing in major depression. Psychiatry Research 247, 1724.
Dichter, GS, Gibbs, D, Smoski, MJ (2015). A systematic review of relations between resting-state functional-MRI and treatment response in major depressive disorder. Journal of Affective Disorders 172, 817.
el Mestikawy, S, Fargin, A, Raymond, JR, Gozlan, H, Hnatowich, M (1991). The 5-HT1A receptor: an overview of recent advances. Neurochemical Research 16, 110.
First, MB, Spitzer, RL, Gibbon, M, Williams, JB (1996). Structured clinical Interview for DSM-IV Axis I Disorders. New York State Psychiatric Institute: New York.
Fransson, P, Skiöld, B, Horsch, S, Nordell, A, Blennow, M, Lagercrantz, H, Åden, U (2007). Resting-state networks in the infant brain. Proceedings of the National Academy of Sciences USA 104, 1553115536.
Hamilton, M (1959). The assessment of anxiety states by rating. British Journal of Medical Psychology 32, 5055.
Hamilton, M (1960). A rating scale for depression. Journal of Neurology, Neurosurgery, and Psychiatry 23, 5662.
Heller, AS, Johnstone, T, Peterson, MJ, Kolden, GG, Kalin, NH, Davidson, RJ (2013). Increased prefrontal cortex activity during negative emotion regulation as a predictor of depression symptom severity trajectory over 6 months. JAMA Psychiatry 70, 11811189.
Küblböck, M, Woletz, M, Höflich, A, Sladky, R, Kranz, GS, Hoffmann, A, Lanzenberger, R, Windischberger, C (2014). Stability of low-frequency fluctuation amplitudes in prolonged resting-state fMRI. Neuroimage 103, 249257.
Kim, JM, Kim, SY, Stewart, R, Yoo, JA, Bae, KY, Jung, SW, Lee, MS, Yim, HW, Jun, TY (2011). Improvement within 2 weeks and later treatment outcomes in patients with depressive disorders: the CRESCEND study. Journal of Affective Disorders 129, 183190.
Klomp, A, van Wingen, G, de Ruiter, MB, Caan, MW, Denys, D, Reneman, L (2013). Test–retest reliability of task-related pharmacological MRI with a single-dose oral citalopram challenge. Neuroimage 75, 108116.
Komulainen, E, Heikkila, R, Meskanen, K, Raij, TT, Nummenmaa, L, Lahti, J, Jylha, P, Melartin, T, Harmer, CJ, Isometsa, E, Ekelund, J (2016). A single dose of mirtazapine attenuates neural responses to self-referential processing. Journal of Psychopharmacology 30, 2332.
Kraus, C, Ganger, S, Losak, J, Hahn, A, Savli, M, Kranz, GS, Baldinger, P, Windischberger, C, Kasper, S, Lanzenberger, R (2014). Gray matter and intrinsic network changes in the posterior cingulate cortex after selective serotonin reuptake inhibitor intake. Neuroimage 84, 236244.
Labuschagne, I, Croft, RJ, Phan, KL, Nathan, PJ (2010). Augmenting serotonin neurotransmission with citalopram modulates emotional expression decoding but not structural encoding of moderate intensity sad facial emotional stimuli: an event-related potential (ERP) investigation. Journal of Psychopharmacology 24, 11531164.
Larsen, RS, Smith, IT, Miriyala, J, Han, JE, Corlew, RJ, Smith, SL, Philpot, BD (2014). Synapse-specific control of experience-dependent plasticity by presynaptic NMDA receptors. Neuron 83, 879893.
Liu, F, Guo, W, Liu, L, Long, Z, Ma, C, Xue, Z, Wang, Y, Li, J, Hu, M, Zhang, J (2013). Abnormal amplitude low-frequency oscillations in medication-naive, first-episode patients with major depressive disorder: a resting-state fMRI study. Journal of Affective Disorders 146, 401406.
Liu, J, Ren, L, Womer, FY, Wang, J, Fan, G, Jiang, W, Blumberg, HP, Tang, Y, Xu, K, Wang, F (2014). Alterations in amplitude of low frequency fluctuation in treatment-naïve major depressive disorder measured with resting-state fMRI. Human Brain Mapping 35, 49794988.
Logothetis, NK, Pauls, J, Augath, M, Trinath, T, Oeltermann, A (2001). Neurophysiological investigation of the basis of the fMRI signal. Nature 412, 150157.
Mantini, D, Perrucci, MG, Del Gratta, C, Romani, GL, Corbetta, M (2007). Electrophysiological signatures of resting state networks in the human brain. Proceedings of the National Academy of Sciences USA 104, 1317013175.
Mayberg, HS (1997). Limbic-cortical dysregulation: a proposed model of depression. Journal of Neuropsychiatry and Clinical Neurosciences 9, 471–81.
Mayberg, HS, Silva, JA, Brannan, SK, Tekell, JL, Mahurin, RK, McGinnis, S, Jerabek, PA (2002). The functional neuroanatomy of the placebo effect. American Journal of Psychiatry 159, 728737.
McBean, DE, Ritchie, IM, Olverman, HJ, Kelly, PA (1999). Effects of the specific serotonin reuptake inhibitor, citalopram, upon local cerebral blood flow and glucose utilisation in the rat. Brain Research 847, 8084.
Owens, MJ, Rosenbaum, JF (2002). Escitalopram: a second-generation SSRI. CNS Spectrums 7, 3439.
Palmer, SM, Crewther, SG, Carey, LM (2015). A meta-analysis of changes in brain activity in clinical depression. Frontiers in Human Neuroscience 8, 1045.
Perkins, AM, Arnone, D, Smallwood, J, Mobbs, D (2015). Thinking too much: self-generated thought as the engine of neuroticism. Trends in Cognitive Science 19, 492498.
Phillips, ML, Drevets, WC, Rauch, SL, Lane, R (2003). Neurobiology of emotion perception II: implications for major psychiatric disorders. Biological Psychiatry 54, 515528.
Posner, J, Hellerstein, DJ, Gat, I, Mechling, A, Klahr, K, Wang, Z, McGrath, PJ, Stewart, JW, Peterson, BS (2013). Antidepressants normalize the default mode network in patients with dysthymia. JAMA Psychiatry 70, 373382.
Price, JL, Drevets, WC (2010). Neurocircuitry of mood disorders. Neuropsychopharmacology 35, 192216.
Pytliak, M, Vargova, V, Mechirova, V, Felsoci, M (2011). Serotonin receptors - from molecular biology to clinical applications. Physiological Research 60, 1525.
Qi, R, Zhang, L, Wu, S, Zhong, J, Zhang, Z, Zhong, Y, Ni, L, Zhang, Z, Li, K, Jiao, Q (2012). Altered resting-state brain activity at functional MR imaging during the progression of hepatic encephalopathy. Radiology 264, 187195.
Quirk, GJ, Beer, JS (2006). Prefrontal involvement in the regulation of emotion: convergence of rat and human studies. Current Opinion in Neurobiology 16, 723727.
Rauch, A, Rainer, G, Logothetis, NK (2008). The effect of a serotonin-induced dissociation between spiking and perisynaptic activity on BOLD functional MRI. Proceedings of the National Academy of Sciences USA 105, 67596764.
Rive, MM, van Rooijen, G, Veltman, DJ, Phillips, ML, Schene, AH, Ruhe, HG (2013). Neural correlates of dysfunctional emotion regulation in major depressive disorder. A systematic review of neuroimaging studies. Neuroscience & Biobehavioral Reviews 37, 25292553.
Robinson, OJ, Overstreet, C, Allen, PS, Letkiewicz, A, Vytal, K, Pine, DS, Grillon, C (2013). The role of serotonin in the neurocircuitry of negative affective bias: serotonergic modulation of the dorsal medial prefrontal-amygdala ‘aversive amplification'circuit. Neuroimage 78, 217223.
Rush, A, Trivedi, M, Wisniewski, S, Nierenberg, A, Stewart, J, Warden, D, Niederehe, G, Thase, M, Lavori, P, Lebowitz, B (2006). Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR* D report. American Journal of Psychiatry 163, 19051917.
Schölvinck, ML, Maier, A, Frank, QY, Duyn, JH, Leopold, DA (2010). Neural basis of global resting-state fMRI activity. Proceedings of the National Academy of Sciences USA 107, 1023810243.
Schwarz, AJ, Gozzi, A, Reese, T, Bifone, A (2007). In vivo mapping of functional connectivity in neurotransmitter systems using pharmacological MRI. Neuroimage 34, 16271636.
Sheline, YI, Barch, DM, Price, JL, Rundle, MM, Vaishnavi, SN, Snyder, AZ, Mintun, MA, Wang, S, Coalson, RS, Raichle, ME (2009). The default mode network and self-referential processes in depression. Proceedings of the National Academy of Sciences USA 106, 19421947.
Späti, J, Hänggi, J, Doerig, N, Ernst, J, Sambataro, F, Brakowski, J, Jäncke, L, grosse Holtforth, M, Seifritz, E, Spinelli, S (2015). Prefrontal thinning affects functional connectivity and regional homogeneity of the anterior cingulate cortex in depression. Neuropsychopharmacology 40, 16401648.
Taylor, MJ, Freemantle, N, Geddes, JR, Bhagwagar, Z (2006). Early onset of selective serotonin reuptake inhibitor antidepressant action: systematic review and meta-analysis. Archives of General Psychiatry 63, 12171223.
van de Ven, V, Wingen, M, Kuypers, KP, Ramaekers, JG, Formisano, E (2013). Escitalopram decreases cross-regional functional connectivity within the default-mode network. PLoS ONE 8, e68355.
Wang, L, Li, K, Zhang, Q, Zeng, Y, Dai, W, Su, Y, Wang, G, Tan, Y, Jin, Z, Yu, X (2014 a). Short-term effects of escitalopram on regional brain function in first-episode drug-naive patients with major depressive disorder assessed by resting-state functional magnetic resonance imaging. Psychological Medicine 44, 14171426.
Wang, LJ, Kuang, WH, Xu, JJ, Lei, D, Yang, YC (2014 b). Resting-state brain activation correlates with short-time antidepressant treatment outcome in drug-naive patients with major depressive disorder. Journal of International Medical Research 42, 966975.
Wise, T, Radua, J, Via, E, Cardoner, N, Abe, O, Adams, TM, Amico, F, Cheng, Y, Cole, JH, de Azevedo Marques Perico, C, Dickstein, DP, Farrow, TF, Frodl, T, Wagner, G, Gotlib, IH, Gruber, O, Ham, BJ, Job, DE, Kempton, MJ, Kim, MJ, Koolschijn, PC, Malhi, GS, Mataix-Cols, D, McIntosh, AM, Nugent, AC, O'Brien, JT, Pezzoli, S, Phillips, ML, Sachdev, PS, Salvadore, G, Selvaraj, S, Stanfield, AC, Thomas, AJ, van Tol, MJ, van der Wee, NJ, Veltman, DJ, Young, AH, Fu, CH, Cleare, AJ, Arnone, D (in press). Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: evidence from voxel-based meta-analysis. Molecular Psychiatry.
Wong, JJ, O'Daly, O, Mehta, MA, Young, AH, Stone, JM (2016). Ketamine modulates subgenual cingulate connectivity with the memory-related neural circuit-a mechanism of relevance to resistant depression? PeerJ 4, e1710.
Yamamura, T, Okamoto, Y, Okada, G, Takaishi, Y, Takamura, M, Mantani, A, Kurata, A, Otagaki, Y, Yamashita, H, Yamawaki, S (2016). Association of thalamic hyperactivity with treatment-resistant depression and poor response in early treatment for major depression: a resting-state fMRI study using fractional amplitude of low-frequency fluctuations. Translational Psychiatry 6, e754.
Yu-Feng, Z, Yong, H, Chao-Zhe, Z, Qing-Jiu, C, Man-Qiu, S, Meng, L, Li-Xia, T, Tian-Zi, J, Yu-Feng, W (2007). Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI. Brain and Development 29, 8391.
Zhou, Y, Wang, K, Liu, Y, Song, M, Song, SW, Jiang, T (2010). Spontaneous brain activity observed with functional magnetic resonance imaging as a potential biomarker in neuropsychiatric disorders. Cognitive Neurodynamics 4, 275294.
Zou, QH, Zhu, CZ, Yang, Y, Zuo, XN, Long, XY, Cao, QJ, Wang, YF, Zang, YF (2008). An improved approach to detection of amplitude of low-frequency fluctuation (ALFF) for resting-state fMRI: fractional ALFF. Journal of Neuroscience Methods 172, 137141.

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