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Mapping the effect of escitalopram treatment on amplitude of low-frequency fluctuations in patients with depression: a resting-state fMRI study

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Abstract

Antidepressant medications represent the most common treatment option for major depressive disorder (MDD), but the neuro-psychological mechanisms by which antidepressants act to improve depressive symptoms remain under-specified. We designed this study to assess the effects of escitalopram treatment on spontaneous brain activity of MDD patients using functional magnetic resonance imaging (fMRI). Twenty first-episode drug-naive MDD patients received resting-state fMRI scans before and after 8 weeks of treatment with a selective serotonin reuptake inhibitor - escitalopram. Twenty age- and gender-matched healthy controls were also scanned twice with an 8-week interval. The fractional amplitude of low-frequency fluctuation (fALFF) was used to characterize the spontaneous brain activity. The analysis of covariance (ANCOVA) was performed to determine treatment-related changes in fALFF. The symptoms were significantly improved in MDD patients after treatment. We observed significant group-by-time interaction on fALFF in the left dorsomedial prefrontal cortex, the right middle frontal gyrus, and the left putamen. Post-hoc analyses showed that the fALFF values in these regions were significantly higher in the MDD patients compared to healthy controls at baseline and were reduced after treatment. The findings suggest that abnormalities in the brain areas involved in emotional processing and regulation could be normalized by effective antidepressant treatment with escitalopram in the MDD patients and free of a task situation.

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References

  • Anand A, Li Y, Wang Y, et al. (2005) Antidepressant effect on connectivity of the mood-regulating circuit: an FMRI study. Neuropsychopharmacology 30:1334–1344

    CAS  PubMed  Google Scholar 

  • Arnone D, McKie S, Elliott R, Thomas EJ, et al. (2012) Increased amygdale responses to sad but not fearful faces in major depression: relation to mood state and pharmacological treatment. Am J Psychiatry 169:841–850

    Article  PubMed  Google Scholar 

  • Beauregard M, Paquette V, Lévesque J (2006) Dysfunction in the neural circuitry of emotional selfregulation in major depressive disorder. NeuroReport 17:843–846

    Article  PubMed  Google Scholar 

  • Bigos KL, Pollock BG, Aizenstein HJ, et al. (2008) Acute 5-HT reuptake blockade potentiates human amygdala reactivity. Neuropsychopharmacology 33:3221–3225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Biswal B, Yetkin FZ, Haughton VM, et al. (1995) Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med 34:537–541

    Article  CAS  PubMed  Google Scholar 

  • Buckner RL, Sepulcre J, Talukdar T, et al. (2009) Cortical hubs revealed by intrinsic functional connectivity: mapping, assessment of stability, and relation to Alzheimer's disease. J Neurosci 29:1860–1873

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chao-Gan Y, Yu-Feng Z (2010) DPARSF: a MATLAB toolbox for "pipe0line" data analysis of resting-state fMRI. Front Syst Neurosci 4:13

    PubMed  PubMed Central  Google Scholar 

  • Del-Ben CM, Deakin JF, Mckie S, et al. (2005) The effect of citalopram pretreatment on neuronal responses to neuropsychological tasks in normal volunteers: an fMRI study. Neuropsychopharmacology 30:1724–1734

    Article  CAS  PubMed  Google Scholar 

  • Delaveau P, Jabourian M, Lemogne C, et al. (2011) Brain effects of antidepressants in major depression: a meta-analysis of emotionalprocessing studies. J Affect Disord 130:66–74

    Article  CAS  PubMed  Google Scholar 

  • Epstein J, Pan H, Kocsis JH, et al. (2006) Lack of ventral striatal response to positive stimuli in depressed versus normal subjects. Am J Psychiatry 163:1784–1790

    Article  PubMed  Google Scholar 

  • Fox MD, Raichle ME (2007) Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci 8:700–711

    Article  CAS  PubMed  Google Scholar 

  • Fu CH, Williams SC, Cleare AJ, et al. (2004) Attenuation of the neural response to sad faces in major depression by antidepressant treatment: a prospective, event-related functional magnetic resonance imaging study. Arch Gen Psychiatry 61:877–889

    Article  PubMed  Google Scholar 

  • Gyurak A, Patenaude B, Korgaonkar MS, et al (2016) Frontoparietal activation during response inhibition predicts remission to antidepressants in patients with major depression. Biol Psychiatry 79:274–281

  • Hamilton M (1967) Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 6:278–296

    Article  CAS  PubMed  Google Scholar 

  • Hasler G, Drevets WC, Husseini KM, et al. (2004) Discovering endophenotypes for major depression. Neuropsychopharmacol 29:1765–1781

    Article  CAS  Google Scholar 

  • He Y, Wang J, Wang L, et al. (2009) Uncovering intrinsic modular organization of spontaneous brain activity in humans. PLoS One 4:e5226

    Article  PubMed  PubMed Central  Google Scholar 

  • Heller AS, Johnstone T, Peterson MJ, et al. (2013) Increased prefrontal cortex activity during negative emotion regulation as a predictor of depression symptom severity trajectory over 6 months. JAMA Psychiatry 70:1181–1119

    Article  CAS  PubMed  Google Scholar 

  • Keedwell PA, Andrew C, Williams SC, et al. (2005) A double dissociation of ventromedial prefrontal cortical responses to sad and happy stimuli in depressed and healthy individuals. Biol Psychiatry 58:495–503

    Article  PubMed  Google Scholar 

  • Kennedy SH, Evans KR, Krüger S, et al. (2001) Changes in regional brain glucose metabolism measured with positron emission tomography after paroxetine treatment of major depression. Am J Psychiatry 158:899–905

    Article  CAS  PubMed  Google Scholar 

  • Koenigs M, Grafman J (2009) The functional neuroanatomy of depression: distinct roles for ventromedial and dorsolateral prefrontalcortex. Behav Brain Res 201:239–243

    Article  PubMed  PubMed Central  Google Scholar 

  • Kupfer DJ, Frank E, Phillips ML (2012) Major depressive disorder: new clinical, neurobiological, and treatment perspectives. Lancet 379:1045–1055

    Article  PubMed  Google Scholar 

  • Lanzenberger R, Kranz GS, Haeusler D, et al. (2012) Prediction of SSRI treatment response in major depression based on serotonin transporter interplay between median raphe nucleus and projection areas. NeuroImage 63:874–881

    Article  CAS  PubMed  Google Scholar 

  • Ledberg A, Akerman S, Roland PE (1998) Estimation of the probabilities of 3D clusters in functional brain images. NeuroImage 8:113–128

    Article  CAS  PubMed  Google Scholar 

  • Lepine JP, Briley M (2011) The increasing burden of depression. Neuropsychiatr Dis Treat 7:3–7

    PubMed  PubMed Central  Google Scholar 

  • Liu Y, Du L, Li Y, et al. (2015) Antidepressant effects of electroconvulsive therapy correlate with subgenual anterior cingulate activity and connectivity in depression. Medicine (Baltimore) 94:e2033

    Article  CAS  Google Scholar 

  • Ma Y (2015) Neuropsychological mechanism underlying antidepressant effect: a systematic meta-analysis. Mol Psychiatry 20:311–319

    Article  CAS  PubMed  Google Scholar 

  • Maier W, Buller R, Philipp M, et al. (1988) The Hamilton anxiety scale: reliability, validity and sensitivity to change in anxiety and depressive disorders. J Affect Disord 14:61–68

    Article  CAS  PubMed  Google Scholar 

  • Mayberg HS, Liotti M, Brannan SK, et al. (1999) Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. Am J Psychiatry 156:675–682

    CAS  PubMed  Google Scholar 

  • McCabe C, Mishor Z (2011) Antidepressant medications reduce subcortical-cortical resting-state functional connectivity in healthy volunteers. NeuroImage 57:1317–1323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McCabe C, Mishor Z, Filippini N, et al. (2011) SSRI administration reduces resting state functional connectivity in dorso-medial prefrontal cortex. Mol Psychiatry 16:592–594

    Article  CAS  PubMed  Google Scholar 

  • O’Doherty J, Dayan P, Schultz J, et al. (2004) Dissociable roles of ventral and dorsal striatum in instrumental conditioning. Science 304:452–454

    Article  PubMed  Google Scholar 

  • Perrin JS, Merz S, Bennett DM, et al. (2012) Electroconvulsive therapy reduces frontal cortical connectivity in severe depressive disorder. Proc Natl Acad Sci U S A 109:5464–5468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pizzagalli DA, Holmes AJ, Dillon DG, et al. (2009) Reduced caudate and nucleus accumbens response to rewards in unmedicated individuals with major depressive disorder. Am J Psychiatry 166:702–710

    Article  PubMed  PubMed Central  Google Scholar 

  • Posner J, Hellerstein DJ, Gat I, et al. (2013) Antidepressants normalize the default mode network in patients with dysthymia. JAMA Psychiatry 70:373–382

    Article  PubMed  PubMed Central  Google Scholar 

  • Power JD, Barnes KA, Snyder AZ, et al. (2012) Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. NeuroImage 59:2142–2154

    Article  PubMed  Google Scholar 

  • Rosenblau G, Sterzer P, Stoy M, et al. (2012) Functional neuroanatomy of emotion processing in major depressive disorder is altered after successful antidepressant therapy. J Psychopharmacol 26:1424–1433

    Article  PubMed  Google Scholar 

  • Schaefer HS, Putnam KM, Benca RM, et al. (2006) Event-related functional magnetic resonance imaging measures of neural activity to positive social stimuli in pre- and post-treatment depression. Biol Psychiatry 60:974–986

    Article  PubMed  Google Scholar 

  • Sheehan DV, Lecrubier Y, Sheehan KH, et al. (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. J Clin Psychiatry 59:22–33

    PubMed  Google Scholar 

  • Sheline YI, Price JL, Yan Z, et al. (2010) Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus. Proc Natl Acad Sci U S A 107:11020–11025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song XW, Dong ZY, Long XY, et al. (2011) REST: a toolkit for resting-state functional magnetic resonance imaging data processing. PLoS One 6:e25031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stuhrmann A, Suslow T, Dannlowski U (2011) Facial emotion processing in major depression: a systematic review of neuroimaging findings. Biol Mood Anxiety Disord 1:10

    Article  PubMed  PubMed Central  Google Scholar 

  • Surguladze S, Brammer MJ, Keedwell P, et al. (2005) A differential pattern of neural response toward sad versus happy facial expressions in major depressive disorder. Biol Psychiatry 57:201–209

    Article  PubMed  Google Scholar 

  • Tahmasian M, Knight DC, Manoliu A, et al. (2013) Aberrant intrinsic connectivity of hippocampus and amygdala overlap in the fronto-insular and dorsomedial-prefrontal cortex in major depressive disorder. Front Hum Neurosci 7:639

    Article  PubMed  PubMed Central  Google Scholar 

  • Tremblay LK, Naranjo CA, Graham SJ (2005) Functional neuroanatomical substrates of altered reward processing in major depressive disorder revealed by a dopaminergic probe. Arch Gen Psychiatry 62:1228–1236

    Article  PubMed  Google Scholar 

  • Wang Z, Yan C, Zhao C, et al. (2011) Spatial patterns of intrinsic brain activity in mild cognitive impairment and Alzheimer’s disease: a resting-state functional MRI study. Hum Brain Mapp 32:1720–1740

    Article  PubMed  Google Scholar 

  • Wang L, Dai Z, Peng H, et al. (2014) Overlapping and segregated resting-state functional connectivity in patients with major depressive disorder with and without childhood neglect. Hum Brain Mapp 35:1154–1166

    Article  PubMed  Google Scholar 

  • Woodward LJ, Clark CA, Bora S, et al. (2012) Neonatal white matter abnormalities an important predictor of neurocognitive outcome for very preterm children. PLoS One 7:e51879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zang YF, He Y, Zhu CZ, et al. (2007) Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI. Brain Dev 29:83–91

    Article  PubMed  Google Scholar 

  • Zou QH, Zhu CZ, Yang Y, et al. (2008) An improved approach to detection of amplitude of low-frequency fluctuation (ALFF) for resting-state fMRI: fractional ALFF. J Neurosci Methods 172:137–141

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We thank the funding from National Key Technology R&D Program (2015BAI13B01), National Key Basic Research Program of China (973 Program) (2013CB531305; 2012CB720704) and research grants from the “12th Five-year-plan” of National Key Technologies R&D Program of China (2011ZX09302-004).

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Correspondence to Qingmei Kong or Tianmei Si.

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The authors report no conflict of interest in conducting this study and preparing the manuscript.

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Li Wang, Xueni Li contributed equally to the paper.

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Wang, L., Li, X., Li, K. et al. Mapping the effect of escitalopram treatment on amplitude of low-frequency fluctuations in patients with depression: a resting-state fMRI study. Metab Brain Dis 32, 147–154 (2017). https://doi.org/10.1007/s11011-016-9871-5

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