Skip to main content Accessibility help
×
Home

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

  • L. Wang (a1) (a2), K. Li (a3), Q. Zhang (a4), Y. Zeng (a3), W. Dai (a1) (a2), Y. Su (a1) (a2), G. Wang (a4), Y. Tan (a5), Z. Jin (a3), X. Yu (a1) (a2) and T. Si (a1) (a2)...

Abstract

Background

Most knowledge regarding the effects of antidepressant drugs is at the receptor level, distal from the nervous system effects that mediate their clinical efficacy. Using functional magnetic resonance imaging (fMRI), this study investigated the effects of escitalopram, a selective serotonin reuptake inhibitor (SSRI), on resting-state brain function in patients with major depressive disorder (MDD).

Method

Fourteen first-episode drug-naive MDD patients completed two fMRI scans before and after 8 weeks of escitalopram therapy. Scans were also acquired in 14 matched healthy subjects. Data were analyzed using the regional homogeneity (ReHo) approach.

Results

Compared to controls, MDD patients before treatment demonstrated decreased ReHo in the frontal (right superior frontal gyrus), temporal (left middle and right inferior temporal gyri), parietal (right precuneus) and occipital (left superior occipital gyrus and right cuneus) cortices, and increased ReHo in the left dorsal medial prefrontal gyrus and left anterior lobe of the cerebellum. Compared to the unmedicated state, ReHo in the patients after treatment was decreased in the left dorsal medial prefrontal gyrus, the right insula and the bilateral thalamus, and increased in the right superior frontal gyrus. Compared to controls, patients after treatment displayed a ReHo decrease in the right precuneus and a ReHo increase in the left anterior lobe of the cerebellum.

Conclusions

Successful treatment with escitalopram may be associated with modulation of resting-state brain activity in regions within the fronto-limbic circuit. This study provides new insight into the effects of antidepressants on functional brain systems in MDD.

Copyright

Corresponding author

* Address for correspondence: Dr T. Si, Clinical Psychopharmacology Division, Institute of Mental Health, Peking University, No. 51 Hua Yuan Bei Road, Hai Dian District, China. (Email: si.tian-mei@163.com)

References

Hide All
Anand, A, Li, Y, Wang, Y, Wu, J, Gao, S, Bukhari, L, Mathews, VP, Kalnin, A, Lowe, MJ (2005). Activity and connectivity of brain mood regulating circuit in depression: a functional magnetic resonance study. Biological Psychiatry 57, 10791088.
APA (2000). Diagnostic and Statistical Manual of Mental Disorders, 4th edn. American Psychiatric Press: Washington, DC.
Bruhl, AB, Kaffenberger, T, Herwig, U (2010). Serotonergic and noradrenergic modulation of emotion processing by single dose antidepressants. Neuropsychopharmacology 35, 521533.
Chao-Gan, Y, Yu-Feng, Z (2010). DPARSF: a MATLAB toolbox for ‘pipeline’ data analysis of resting-state fMRI. Frontiers in Systems Neuroscience 4, 13.
Cheng, W, Ji, X, Zhang, J, Feng, J (2012). Individual classification of ADHD patients by integrating multiscale neuroimaging markers and advanced pattern recognition techniques. Frontiers in Systems Neuroscience 6, 58.
Disner, SG, Beevers, CG, Haigh, EA, Beck, AT (2011). Neural mechanisms of the cognitive model of depression. Nature Reviews Neuroscience 12, 467477.
Drevets, WC (2000). Functional anatomical abnormalities in limbic and prefrontal cortical structures in major depression. Progress in Brain Research 126, 413431.
Fales, CL, Barch, DM, Rundle, MM, Mintun, MA, Snyder, AZ, Cohen, JD, Mathews, J, Sheline, YI (2008). Altered emotional interference processing in affective and cognitive-control brain circuitry in major depression. Biological Psychiatry 63, 377384.
Fox, MD, Raichle, ME (2007). Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nature Reviews Neuroscience 8, 700711.
Fu, CH, Steiner, H, Costafreda, SG (2013). Predictive neural biomarkers of clinical response in depression: a meta-analysis of functional and structural neuroimaging studies of pharmacological and psychological therapies. Neurobiology of Disease 52, 7583.
Fu, CH, Williams, SC, Cleare, AJ, Brammer, MJ, Walsh, ND, Kim, J, Andrew, CM, Pich, EM, Williams, PM, Reed, LJ, Mitterschiffthaler, MT, Suckling, J, Bullmore, ET (2004). Attenuation of the neural response to sad faces in major depression by antidepressant treatment: a prospective, event-related functional magnetic resonance imaging study. Archives of General Psychiatry 61, 877889.
Guo, WB, Liu, F, Xue, ZM, Xu, XJ, Wu, RR, Ma, CQ, Wooderson, SC, Tan, CL, Sun, XL, Chen, JD, Liu, ZN, Xiao, CQ, Chen, HF, Zhao, JP (2012). Alterations of the amplitude of low-frequency fluctuations in treatment-resistant and treatment-response depression: a resting-state fMRI study. Progress in Neuro-Psychopharmacology and Biological Psychiatry 37, 153160.
Guo, WB, Liu, F, Xue, ZM, Yu, Y, Ma, CQ, Tan, CL, Sun, XL, Chen, JD, Liu, ZN, Xiao, CQ, Chen, HF, Zhao, JP (2011 a). Abnormal neural activities in first-episode, treatment-naive, short-illness-duration, and treatment-response patients with major depressive disorder: a resting-state fMRI study. Journal of Affective Disorders 135, 326331.
Guo, WB, Sun, XL, Liu, L, Xu, Q, Wu, RR, Liu, ZN, Tan, CL, Chen, HF, Zhao, JP (2011 b). Disrupted regional homogeneity in treatment-resistant depression: a resting-state fMRI study. Progress in Neuro-Psychopharmacology and Biological Psychiatry 35, 12971302.
Hamilton, M (1967). Development of a rating scale for primary depressive illness. British Journal of Social and Clinical Psychology 6, 278296.
Harmer, CJ, Mackay, CE, Reid, CB, Cowen, PJ, Goodwin, GM (2006). Antidepressant drug treatment modifies the neural processing of nonconscious threat cues. Biological Psychiatry 59, 816820.
Hashioka, S (2011). Antidepressants and neuroinflammation: can antidepressants calm glial rage down? Mini Reviews in Medicinal Chemistry 11, 555564.
He, Y, Wang, L, Zang, Y, Tian, L, Zhang, X, Li, K, Jiang, T (2007). Regional coherence changes in the early stages of Alzheimer's disease: a combined structural and resting-state functional MRI study. NeuroImage 35, 488500.
Kalin, NH, Davidson, RJ, Irwin, W, Warner, G, Orendi, JL, Sutton, SK, Mock, BJ, Sorenson, JA, Lowe, M, Turski, PA (1997). Functional magnetic resonance imaging studies of emotional processing in normal and depressed patients: effects of venlafaxine. Journal of Clinical Psychiatry 58 (Suppl. 16), 3239.
Kendall, MG, Gibbons, JD (1990). Rank Correlation Methods, 5th edn. Oxford University Press: New York.
Kennedy, SH, Evans, KR, Kruger, S, Mayberg, HS, Meyer, JH, McCann, S, Arifuzzman, AI, Houle, S, Vaccarino, FJ (2001). Changes in regional brain glucose metabolism measured with positron emission tomography after paroxetine treatment of major depression. American Journal of Psychiatry 158, 899905.
Kimbrell, TA, Ketter, TA, George, MS, Little, JT, Benson, BE, Willis, MW, Herscovitch, P, Post, RM (2002). Regional cerebral glucose utilization in patients with a range of severities of unipolar depression. Biological Psychiatry 51, 237252.
Kiviniemi, V (2008). Endogenous brain fluctuations and diagnostic imaging. Human Brain Mapping 29, 810817.
Lanzenberger, R, Kranz, GS, Haeusler, D, Akimova, E, Savli, M, Hahn, A, Mitterhauser, M, Spindelegger, C, Philippe, C, Fink, M, Wadsak, W, Karanikas, G, Kasper, S (2012). Prediction of SSRI treatment response in major depression based on serotonin transporter interplay between median raphe nucleus and projection areas. NeuroImage 63, 874881.
Lee, BH, Kim, YK (2010). The roles of BDNF in the pathophysiology of major depression and in antidepressant treatment. Psychiatry Investigation 7, 231235.
Li, Z, Kadivar, A, Pluta, J, Dunlop, J, Wang, Z (2012). Test-retest stability analysis of resting brain activity revealed by blood oxygen level-dependent functional MRI. Journal of Magnetic Resonance Imaging 36, 344354.
Liu, F, Hu, M, Wang, S, Guo, W, Zhao, J, Li, J, Xun, G, Long, Z, Zhang, J, Wang, Y, Zeng, L, Gao, Q, Wooderson, SC, Chen, J, Chen, H (2012). Abnormal regional spontaneous neural activity in first-episode, treatment-naive patients with late-life depression: a resting-state fMRI study. Progress in Neuro-Psychopharmacology and Biological Psychiatry 39, 326331.
Liu, Y, Liang, M, Zhou, Y, He, Y, Hao, Y, Song, M, Yu, C, Liu, H, Liu, Z, Jiang, T (2008). Disrupted small-world networks in schizophrenia. Brain 131, 945961.
Liu, Z, Xu, C, Xu, Y, Wang, Y, Zhao, B, Lv, Y, Cao, X, Zhang, K, Du, C (2010). Decreased regional homogeneity in insula and cerebellum: a resting-state fMRI study in patients with major depression and subjects at high risk for major depression. Psychiatry Research 182, 211215.
Manev, H, Uz, T, Manev, R (2003). Glia as a putative target for antidepressant treatments. Journal of Affective Disorders 75, 5964.
Mayberg, HS (1997). Limbic-cortical dysregulation: a proposed model of depression. Journal of Neuropsychiatry and Clinical Neurosciences 9, 471481.
Mayberg, HS (2003). Modulating dysfunctional limbic-cortical circuits in depression: towards development of brain-based algorithms for diagnosis and optimised treatment. British Medical Bulletin 65, 193207.
Mayberg, HS, Brannan, SK, Tekell, JL, Silva, JA, Mahurin, RK, McGinnis, S, Jerabek, PA (2000). Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response. Biological Psychiatry 48, 830843.
Mayberg, HS, Liotti, M, Brannan, SK, McGinnis, S, Mahurin, RK, Jerabek, PA, Silva, JA, Tekell, JL, Martin, CC, Lancaster, JL, Fox, PT (1999). Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. American Journal of Psychiatry 156, 675682.
McCabe, C, Mishor, Z, Filippini, N, Cowen, PJ, Taylor, MJ, Harmer, CJ (2011). SSRI administration reduces resting state functional connectivity in dorso-medial prefrontal cortex. Molecular Psychiatry 16, 592594.
Oldfield, RC (1971). The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9, 97113.
Peng, DH, Shen, T, Zhang, J, Huang, J, Liu, J, Liu, SY, Jiang, KD, Xu, YF, Fang, YR (2012). Abnormal functional connectivity with mood regulating circuit in unmedicated individual with major depression: a resting-state functional magnetic resonance study. Chinese Medical Journal 125, 37013706.
Pringle, A, Browning, M, Cowen, PJ, Harmer, CJ (2011). A cognitive neuropsychological model of antidepressant drug action. Progress in Neuro-Psychopharmacology and Biological Psychiatry 35, 15861592.
Roiser, JP, Elliott, R, Sahakian, BJ (2012). Cognitive mechanisms of treatment in depression. Neuropsychopharmacology 37, 117136.
Sato, JR, Hoexter, MQ, Fujita, A, Rohde, LA (2012). Evaluation of pattern recognition and feature extraction methods in ADHD prediction. Frontiers in Systems Neuroscience 6, 68.
Seminowicz, DA, Mayberg, HS, McIntosh, AR, Goldapple, K, Kennedy, S, Segal, Z, Rafi-Tari, S (2004). Limbic-frontal circuitry in major depression: a path modeling metanalysis. NeuroImage 22, 409418.
Sheehan, DV, Lecrubier, Y, Sheehan, KH, Amorim, P, Janavs, J, Weiller, E, Hergueta, T, Baker, R, Dunbar, GC (1998). The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. Journal of Clinical Psychiatry 59 (Suppl. 20), 2233.
Shehzad, Z, Kelly, AM, Reiss, PT, Gee, DG, Gotimer, K, Uddin, LQ, Lee, SH, Margulies, DS, Roy, AK, Biswal, BB, Petkova, E, Castellanos, FX, Milham, MP (2009). The resting brain: unconstrained yet reliable. Cerebral Cortex 19, 22092229.
Sheline, YI, Price, JL, Yan, Z, Mintun, MA (2010). Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus. Proceedings of the National Academy of Sciences USA 107, 1102011025.
Song, XW, Dong, ZY, Long, XY, Li, SF, Zuo, XN, Zhu, CZ, He, Y, Yan, CG, Zang, YF (2011). REST: a toolkit for resting-state functional magnetic resonance imaging data processing. PLoS One 6, e25031.
Takahashi, H, Yahata, N, Koeda, M, Takano, A, Asai, K, Suhara, T, Okubo, Y (2005). Effects of dopaminergic and serotonergic manipulation on emotional processing: a pharmacological fMRI study. NeuroImage 27, 9911001.
Tao, H, Guo, S, Ge, T, Kendrick, KM, Xue, Z, Liu, Z, Feng, J (2013). Depression uncouples brain hate circuit. Molecular Psychiatry 18, 101111.
Tomasi, D, Volkow, ND (2012). Abnormal functional connectivity in children with attention-deficit/hyperactivity disorder. Biological Psychiatry 71, 443450.
Wu, QZ, Li, DM, Kuang, WH, Zhang, TJ, Lui, S, Huang, XQ, Chan, RC, Kemp, GJ, Gong, QY (2011). Abnormal regional spontaneous neural activity in treatment-refractory depression revealed by resting-state fMRI. Human Brain Mapping 32, 12901299.
Yao, Z, Wang, L, Lu, Q, Liu, H, Teng, G (2009). Regional homogeneity in depression and its relationship with separate depressive symptom clusters: a resting-state fMRI study. Journal of Affective Disorders 115, 430438.
Yu, R, Hsieh, MH, Wang, HL, Liu, CM, Liu, CC, Hwang, TJ, Chien, YL, Hwu, HG, Tseng, WY (2013). Frequency dependent alterations in regional homogeneity of baseline brain activity in schizophrenia. PLoS One 8, e57516.
Zang, Y, Jiang, T, Lu, Y, He, Y, Tian, L (2004). Regional homogeneity approach to fMRI data analysis. NeuroImage 22, 394400.
Zhao, X, Liu, Y, Wang, X, Liu, B, Xi, Q, Guo, Q, Jiang, H, Jiang, T, Wang, P (2012). Disrupted small-world brain networks in moderate Alzheimer's disease: a resting-state FMRI study. PLoS One 7, e33540.

Keywords

Type Description Title
WORD
Supplementary materials

Wang Supplementary Material
Table

 Word (42 KB)
42 KB

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed