Diagnosis of depression is based on clinical parameters which may be clinically reliable but lack biological validity leading to problems of differential diagnosis or treatment. Thus, there is a need for biologically relevant criteria for better diagnosis and treatment of depression. Accumulating neuroimaging studies suggest potential biomarkers such as metabolic activity and structural or functional connectivity within the limbic-cortical circuitries that may serve for this purpose. However, employment of such neuroimaging measures as biomarkers in a clinical setting still requires further investigation. While there are some converging results, a major challenge in the field is the inconsistencies across multiple studies. This is probably due to the heterogeneous patient groups used in these studies, the variety of tasks or methodologies used during neuroimaging, and the different types of treatments or problems associated with poor data quality, which require better statistical approaches. As these problems are likely addressed, neuroimaging biomarkers can be established in the future to facilitate significant improvements in the diagnosis and treatment of depression.
- Depressive disorders
- Major depressive disorder
This is a preview of subscription content, access via your institution.
Arslan A. Genes, brains, and behavior: imaging genetics for neuropsychiatric disorders. J Neuropsychiatry Clin Neurosci. 2015;27(2):81–92.
Arslan A. Imaging genetics of schizophrenia in the post-GWAS era. Prog Neuropsychopharmacol Biol Psychiatry. 2018;80(Pt B):155–65.
Banks GP, Mikell CB, Youngerman BE, Henriques B, Kelly KM, Chan AK, et al. Neuroanatomical characteristics associated with response to dorsal anterior cingulotomy for obsessivecompulsive disorder. JAMA Psychiatry. 2015;72:127–35.
Basser PJ, Mattiello J, LeBihan D. Estimation of the effective self-diffusion tensor from the NMR spin echo. J Magn Reson. 1994a;103:247–54.
Basser PJ, Mattiello J, LeBihan D. MR diffusion tensor spectroscopy and imaging. Biophys J. 1994b;66:259–67.
Belliveau JW, Kennedy DN Jr, McKinstry RC, Buchbinder BR, Weisskoff RM, Cohen MS, Vevea JM, Brady TJ, Rosen BR. Functional mapping of the human visual cortex by magnetic resonance imaging. Science. 1991;254(5032):716–9.
Bennett CM, Baird AA, Miller MB, Wolford GL. Neural correlates of interspecies perspective taking in the post-mortem Atlantic Salmon: an argument for proper multiple comparisons correction. In: 15th annual meeting of the Organization for Human Brain Mapping, San Francisco, CA; 2009.
Bhagwagar Z, Hinz R, Taylor M, Fancy S, Cowen P, Grasby P. Increased 5-HT(2A) receptor binding in euthymic, medication-free patients recovered from depression: a positron emission study with [(11)C]MDL 100, 907. Am J Psychiatry. 2006;163:1580–7.
Campbell S, Macqueen G. The role of the hippocampus in the pathophysiology of major depression. J Psychiatry Neurosci. 2004;29(6):417–26.
Chen G, Guo Y, Zhu H, Kuang W, Bi F, Ai H, Gu Z, Huang X, Lui S, Gong Q. Intrinsic disruption of white matter microarchitecture in first-episode, drug-naive major depressive disorder: a voxel-based meta-analysis of diffusion tensor imaging. Prog Neuropsychopharmacol Biol Psychiatry. 2017;76:179–87.
Chi KF, Korgaonkar M, Grieve SM. Imaging predictors of remission to anti-depressant medications in major depressive disorder. J Affect Disord. 2015;186:134–44.
Chiang MC, McMahon KL, de Zubicaray GI, Martin NG, Hickie I, Toga AW, Wright MJ, Thompson PM. Genetics of white matter development: a DTI study of 705 twins and their siblings aged 12 to 29. Neuroimage. 2011;54(3):2308–17.
Choi S, Han KM, Kang J, Won E, Chang HS, Tae WS, Son KR, Kim SJ, Lee MS, Ham BJ. Effects of a polymorphism of the neuronal amino acid transporter SLC6A15 gene on structural integrity of white matter tracts in major depressive disorder. PLoS One. 2016;11(10):e0164301.
Colle R, Cury C, Chupin M, Deflesselle E, Hardy P, Nasser G, Falissard B, Ducreux D, Colliot O, Corruble E. Hippocampal volume predicts antidepressant efficacy in depressed patients without incomplete hippocampal inversion. Neuroimage Clin. 2016;12:949–55. eCollection 2016
Connolly CG, Ho TC, Blom EH, LeWinn KZ, Sacchet MD, Tymofiyeva O, Simmons AN, Yang TT. Resting-state functional connectivity of the amygdala and longitudinal changes in depression severity in adolescent depression. J Affect Disord. 2017;207:86–94.
Crane NA, Jenkins LM, Bhaumik R, Dion C, Gowins JR, Mickey BJ, Zubieta JK, Langenecker SA. Multidimensional prediction of treatment response to antidepressants with cognitive control and functional MRI. Brain. 2017;140(Pt 2):472–86.
Diksic M, Sako K, Feindel W, Kato A, Yamamoto YL, Farrokhzad S, Thompson C. Pharmacokinetics of positron-labeled 1,3-bis(2-chloroethyl)nitrosourea in human brain tumors using positron emission tomography. Cancer Res. 1984;44(7):3120–4.
Drevets WC, Frank E, Price JC, Kupfer DJ, Holt D, Greer PJ, Huang Y, Gautier C, Mathis C. PET imaging of serotonin 1A receptor binding in depression. Biol Psychiatry. 1999;46:1375–87.
Drysdale AT, Grosenick L, Downar J, Dunlop K, Mansouri F, Meng Y, Fetcho RN, Zebley B, Oathes DJ, Etkin A, Schatzberg AF, Sudheimer K, Keller J, Mayberg HS, Gunning FM, Alexopoulos GS, Fox MD, Pascual-Leone A, Voss HU, Casey BJ, Dubin MJ, Liston C. Resting-state connectivity biomarkers define neurophysiological subtypes of depression. Nat Med. 2017;23(1):28–38.
Dubin MJ, Liston C, Avissar MA, Ilieva I, Gunning FM. Network-guided transcranial magnetic stimulation for depression. Curr Behav Neurosci Rep. 2017;4(1):70–7.
Dunlop BW, Kelley ME, McGrath CL, Craighead WE, Mayberg HS. Preliminary findings supporting insula metabolic activity as a predictor of outcome to psychotherapy and medication treatments for depression. J Neuropsychiatry Clin Neurosci. 2015;27(3):237–9.
Dunlop BW, Rajendra JK, Craighead WE, Kelley ME, McGrath CL, Choi KS, Kinkead B, Nemeroff CB, Mayberg HS. Functional connectivity of the subcallosal cingulate cortex and differential outcomes to treatment with cognitive-behavioral therapy or antidepressant medication for major depressive disorder. Am J Psychiatry. 2017;174:533–45.
Dyster TG, Mikell CB, Sheth SA. The co-evolution of neuroimaging and psychiatric neurosurgery. Front Neuroanat. 2016;10:68.
Ebert D, Feistel H, Barocka A. Effects of sleep deprivation on the limbic system and the frontal lobes in affective disorders: a study with Tc-99m-HMPAO SPECT. Psychiatry Res. 1991;40(4):247–51.
Finnema SJ, Nabulsi NB, Eid T, Detyniecki K, Lin SF, Chen MK, et al. Imaging synaptic density in the living human brain. Sci Transl Med. 2016;8:348ra96.
Fischl B, Dale AM. Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proc Natl Acad Sci U S A. 2000;97(20):11050–5.
Fox MD, Raichle ME. Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci. 2007;8:700–11.
Frodl T, Jager M, Smajstrlova I, et al. Effect of hippocampal and amygdala volumes on clinical outcomes in major depression: a 3-year prospective magnetic resonance imaging study. J Psychiatry Neurosci. 2008;33:423–30.
Frodl T, Scheuerecker J, Schoepf V, et al. Different effects of mirtazapine and venlafaxine on brain activation: an open randomized controlled f MRI study. J Clin Psychiatry. 2011;72:448–57.
Fu CH, Mourao-Miranda J, Costafreda SG, Khanna A, Marquand AF, Williams SC, Brammer MJ. Pattern classification of sad facial processing: toward the development of neurobiological markers in depression. Biol Psychiatry. 2008;63(7):656–62.
Fu CH, Steiner H, Costafreda SG. Predictive neural biomarkers of clinical response in depression: a meta-analysis of functional and structural neuroimaging studies of pharmacological and psychological therapies. Neurobiol Dis. 2013;52:75–83.
Garnett S, Firnau G, Nahmias C, Chirakal R. Striatal dopamine metabolism in living monkeys examined by positron emission tomography. Brain Res. 1983;280(1):169–71.
Glasser MF, Rilling JK. DTI tractography of the human brain’s language pathways. Cereb Cortex. 2008;18:2471–82.
Glasser MF, Coalson TS, Robinson EC, Hacker CD, Harwell J, Yacoub E, Ugurbil K, Anderson J, Beckmann DF, Jenkinson M, Smith SM, Van Essen D. A multi-modal parcellation of human cerebral cortex. Nature. 2016;536:171–8.
Goodwin GM. Innovation translates into antidepressant effectiveness. J Psychopharmacol. 2008;22(7 Suppl):9–12.
Grieve SM, Korgaonkar MS, Gordon E, Williams LM, Rush AJ. Prediction of nonremission to antidepressant therapy using diffusion tensor imaging. J Clin Psychiatry. 2016;77(4):e436–43.
Handwerker DA, Bandettini PA. Hemodynamic signals not predicted? Not so: a comment on Sirotin and Das (2009). Neuroimage. 2011;55(4):1409–12.
Insel T, Cuthbert B, Garvey M, Heinssen R, Pine DS, Quinn K. Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am J Psychiatry. 2010;167(7):748–51.
Jahanshad N, Lee AD, Barysheva M, et al. Genetic influences on brain asymmetry: a DTI study of 374 twins and siblings. Neuroimage. 2010;52:455–69.
Kaufman J, Sullivan GM, Yang J, Ogden RT, Miller JM, Oquendo MA, Mann JJ, Parsey RV, DeLorenzo C. Quantification of the serotonin 1A receptor using PET: identification of a potential biomarker of major depression in males. Neuropsychopharmacology. 2015;40(7):1692–9.
Kempton MJ, Salvador Z, Munafò MR, Geddes JR, Simmons A, Frangou S, Williams SC. Structural neuroimaging studies in major depressive disorder. Meta-analysis and comparison with bipolar disorder. Arch Gen Psychiatry. 2011;68(7):675–90.
Keedwell PA, Andrew C, Williams SC, Brammer MJ, Phillips ML. The neural correlates of anhedonia in major depressive disorder. Biol Psychiatry. 2005;58(11):843–53.
Kleinschmidt A, Müller NG. The blind, the lame, and the poor signals of brain function—a comment on Sirotin and Das (2009). Neuroimage. 2010;50(2):622–5.
Korgaonkar MS, Fornito A, Williams LM, Grieve SM. Abnormal structural networks characterize major depressive disorder: a connectome analysis. Biol Psychiatry. 2014;76(7):567–74.
Krishnan V, Nestler EJ. Linking molecules to mood: new insight into the biology of depression. Am J Psychiatry. 2010;167:1305–20.
Lai CH, Wu YT. Alterations in white matter micro-integrity of the superior longitudinal fasciculus and anterior thalamic radiation of young adult patients with depression. Psychol Med. 2014;44:2825–32.
Lan MJ, Chhetry BT, Oquendo MA, Sublette ME, Sullivan G, Mann JJ, Parsey RV. Cortical thickness differences between bipolar depression and major depressive disorder. Bipolar Disord. 2014;16(4):378–88.
Li C-T, Bai Y-M, Huang Y-L, Chen Y-S, Chen T-J, Cheng J-Y, et al. Association between antidepressant resistance in unipolar depression and subsequent bipolar disorder: cohort study. Br J Psychiatry. 2012;200:45–51.
Liao Y, Huang X, Wu Q, Yang C, Kuang W, Du M, Lui S, Yue Q, Chan RC, Kemp GJ, Gong Q. Is depression a disconnection syndrome? Meta-analysis of diffusion tensor imaging studies in patients with MDD. J Psychiatry Neurosci. 2013;38(1):49–56.
Light SN, Heller AS, Johnstone T, et al. Reduced right ventrolateral prefrontal cortex activity while inhibiting positive affect is associated with improvement in hedonic capacity after 8 weeks of antidepressant treatment in major depressive disorder. Biol Psychiatry. 2011;70:962–8.
Little JT, Ketter TA, Kimbrell TA, et al. Bupropion and venlafaxine responded differ in pretreatment regional cerebral metabolism in unipolar depression. Biol Psychiatry. 2005;57:220–8.
Lorenzetti V, Allen NB, Fornito A, Yucel M. Structural brain abnormalities in major depressive disorder: a selective review of recent MRI studies. J Affect Disord. 2009;117:1–17.
MacQueen GM, Yucel K, Taylor VH, Macdonald K, Joffe R. Posterior hippocampal volumes are associated with remission rates in patients with major depressive disorder. Biol Psychiatry. 2008;64:880–3.
Mayberg HS. Limbic-cortical dysregulation: a proposed model of depression. J Neuropsychiatry Clin Neurosci. 1997;9:471–81. https://doi.org/10.1176/jnp.9.3.471.
Mayberg HS. Targeted electrode-based modulation of neural circuits for depression. J Clin Invest. 2009;119:717–25.
McGrath CL, Kelley ME, Holtzheimer PE, Dunlop BW, Craighead WE, Franco AR, Craddock RC, Mayberg HS. Toward a neuroimaging treatment selection biomarker for major depressive disorder. JAMA Psychiat. 2013;70(8):821–9.
McGrath CL, Kelley ME, Dunlop BW, Holtzheimer PE 3rd, Craighead WE, Mayberg HS. Pretreatment brain states identify likely nonresponse to standard treatments for depression. Biol Psychiatry. 2014;76(7):527–35.
Meyer JH, McMain S, Kennedy SH, Korman L, Brown GM, DaSilva JN, Wilson AA, Blak T, Eynan-Harvey R, Goulding VS, Houle S, Links P. Dysfunctional attitudes and 5-HT2 receptors during depression and self-harm. Am J Psychiatry. 2003;160:90–9.
Myung W, Han CE, Fava M, Mischoulon D, Papakostas GI, Heo JY, Kim KW, Kim ST, Kim DJ, Kim DK, Seo SW, Seong JK, Jeon HJ. Reduced frontal-subcortical white matter connectivity in association with suicidal ideation in major depressive disorder. Transl Psychiatry. 2016;6(6):e835.
O’Donnell LJ, Westin CF. An introduction to diffusion tensor image analysis. Neurosurg Clin N Am. 2011;22(2):185–96.
Ogawa S, Tank DW, Menon R, Ellermann JM, Kim SG, Merkle H, Ugurbil K. Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. Proc Natl Acad Sci U S A. 1992;89(13):5951–5.
Patel MJ, Khalaf A, Aizenstein HJ. Studying depression using imaging and machine learning methods. Neuroimage Clin. 2016;10:115–23.
Petrovska J, Coynel D, Fastenrath M, Milnik A, Auschra B, Egli T, Gschwind L, Hartmann F, Loos E, Sifalakis K, Vogler C, de Quervain DJ, Papassotiropoulos A, Heck A. The NCAM1 gene set is linked to depressive symptoms and their brain structural correlates in healthy individuals. J Psychiatr Res. 2017;91:116–23.
Phillips ML, Chase HW, Sheline YI, Etkin A, Almeida JR, Deckersbach T, Trivedi MH. Identifying predictors, moderators, and mediators of antidepressant response in major depressive disorder: neuroimaging approaches. Am J Psychiatry. 2015;172(2):124–38.
Pizzagalli DA. Frontocingulate dysfunction in depression: toward biomarkers of treatment response. Neuropsychopharmacology. 2011;36:183–206.
Price J, Cole V, Goodwin GM. Emotional side-effects of selective serotonin reuptake inhibitors: qualitative study. Br J Psychiatry. 2009;195(3):211–7.
Qin J, Wei M, Liu H, Chen J, Yan R, Hua L, Zhao K, Yao Z, Lu Q. Abnormal hubs of white matter networks in the frontal-parieto circuit contribute to depression discrimination via pattern classification. Magn Reson Imaging. 2014;32:1314–20.
Repple J, Meinert S, Grotegerd D, Kugel H, Redlich R, Dohm K, Zaremba D, Opel N, Buerger C, Förster K, Nick T, Arolt V, Heindel W, Deppe M, Dannlowski U. A voxel-based diffusion tensor imaging study in unipolar and bipolar depression. Bipolar Disord. 2017;19(1):23–31.
Salvadore G, Cornwell BR, Colon-Rosario V, et al. Increased anterior cingulate cortical activity in response to fearful faces: a neurophysiological biomarker that predicts rapid antidepressant response to ketamine. Biol Psychiatry. 2009;65:289–95.
Sankar A, Zhang T, Gaonkar B, Doshi J, Erus G, Costafreda SG, Marangell L, Davatzikos C, Fu CH. Diagnostic potential of structural neuroimaging for depression from a multi-ethnic community sample. BJPsych Open. 2016;2(4):247–54.
Sargent PA, Kjaer KH, Bench CJ, Rabiner EA, Messa C, Meyer J, Gunn RN, Grasby PM, Cowen PJ. Brain serotonin 1A receptor binding measured by positron emission tomography with [11C]WAY-100635: effects of depression and antidepressant treatment. Arch Gen Psychiatry. 2000;57:174–80.
Savitz JB, Drevets WC. Imaging phenotypes of major depressive disorder: genetic correlates. Neuroscience. 2009;164:300–30.
Schotten MT, Ffytche DH, Bizzi A, et al. Atlasing location, asymmetry and inter-subject variability of white matter tracts in the human brain with MR diffusion tractography. Neuroimage. 2011;54:49–59.
Siegle GJ, Carter CS, Thase ME. Use of fMRI to predict recovery from unipolar depression with cognitive behavior therapy. Am J Psychiatry. 2006;163:735–8.
Sirotin YB, Das A. Anticipatory haemodynamic signals in sensory cortex not predicted by local neuronal activity. Nature. 2009;457(7228):475–9.
Smith DF, Jakobsen S. Molecular tools for assessing human depression by positron emission tomography. Eur Neuropsychopharmacol. 2009;19:611–28.
Song YJ, Korgaonkar MS, Armstrong LV, Eagles S, Williams LM, Grieve SM. Tractography of the brainstem in major depressive disorder using diffusion tensor imaging. PLoS One. 2014;9:e84825.
Su L, Cai Y, Xu Y, Dutt A, Shi S, Bramon E. Cerebral metabolism in major depressive disorder: a voxel-based meta-analysis of positron emission tomography studies. BMC Psychiatry. 2014;14:321.
Takeuchi H, Taki Y, Sekiguchi A, Nouchi R, Kotozaki Y, Nakagawa S, Miyauchi CM, Iizuka K, Yokoyama R, Shinada T, Yamamoto Y, Hanawa S, Araki T, Kunitoki K, Sassa Y, Kawashima R. Mean diffusivity of basal ganglia and thalamus specifically associated with motivational states among mood states. Brain Struct Funct. 2017;222(2):1027–37.
Tatham EL, Hall GB, Clark D, Foster J, Ramasubbu R. The 5-HTTLPR and BDNF polymorphisms moderate the association between uncinate fasciculus connectivity and antidepressants treatment response in major depression. Eur Arch Psychiatry Clin Neurosci. 2017;267(2):135–47.
Taylor WD, Kuchibhatla M, Payne ME, et al. Frontal white matter anisotropy and antidepressant remission in late-life depression. PLoS One. 2008;3:e3267.
Trivedi MH, McGrath PJ, Fava M, Parsey RV, Kurian BT, Phillips ML, Oquendo MA, Bruder G, Pizzagalli D, Toups M, Cooper C, Adams P, Weyandt S, Morris DW, Grannemann BD, Ogden RT, Buckner R, McInnis M, Kraemer HC, Petkova E, Carmody TJ, Weissman MM. Establishing moderators and biosignatures of antidepressant response in clinical care (EMBARC): rationale and design. J Psychiatr Res. 2016;78:11–23.
Tymofiyeva O, Connolly CG, Ho TC, Sacchet MD, Henje Blom E, LeWinn KZ, Xu D, Yang TT. DTI-based connectome analysis of adolescents with major depressive disorder reveals hypoconnectivity of the right caudate. J Affect Disord. 2017;207:18–25.
Uğurbil K. The road to functional imaging and ultrahigh fields. Neuroimage. 2012;62(2):726–35. https://doi.org/10.1016/j.neuroimage.2012.01.134.
Vakili K, Pillay SS, Lafer B, Fava M, Renshaw PF, Bonello-Cintron CM, Yurgelun-Todd DA. Hippocampal volume in primary unipolar major depression: a magnetic resonance imaging study. Biol Psychiatry. 2000;47(12):1087–90.
Vul E, Harris C, Winkielman P, Pashler H. Puzzlingly high correlations in fMRI studies of emotion, personality, and social cognition. Perspect Psychol Sci. 2009;4(3):274–90.
Wagner G, Koch K, Schachtzabel C, et al. Differential effects of serotonergic and noradrenergic antidepressants on brain activity during a cognitive control task and neurofunctional prediction of treatment outcome in patients with depression. J Psychiatry Neurosci. 2010;35:247–57.
Walsh ND, Williams SC, Brammer MJ, et al. A longitudinal functional magnetic resonance imaging study of verbal working memory in depression after antidepressant therapy. Biol Psychiatry. 2007;62:1236–43.
WHO. Depression fact sheet. 2017. http://www.who.int/mediacentre/factsheets/fs369/en.
Williams LM. Defining biotypes for depression and anxiety based on large-scale circuit dysfunction: a theoretical review of the evidence and future directions for clinical translation. Depress Anxiety. 2017;34(1):9–24.
Won E, Choi S, Kang J, Kim A, Han KM, Chang HS, Tae WS, Son KR, Joe SH, Lee MS, Ham BJ. Association between reduced white matter integrity in the corpus callosum and serotonin transporter gene DNA methylation in medication-naive patients with major depressive disorder. Transl Psychiatry. 2016;6(8):e866.
Wu J, Buchsbaum MS, Gillin JC, Tang C, Cadwell S, Wiegand M, Najafi A, Klein E, Hazen K, Bunney WE Jr, Fallon JH, Keator D. Prediction of antidepressant effects of sleep deprivation by metabolic rates in the ventral anterior cingulated and medial prefrontal cortex. Am J Psychiatry. 1999;156(8):1149–58.
Zuo XN, Anderson JS, Bellec P, et al. An open science resource for establishing reliability and reproducibility in functional connectomics. Sci Data. 2014;1:140049.
Editors and Affiliations
Rights and permissions
© 2018 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Arslan, A. (2018). Application of Neuroimaging in the Diagnosis and Treatment of Depression. In: Kim, YK. (eds) Understanding Depression. Springer, Singapore. https://doi.org/10.1007/978-981-10-6577-4_5
Publisher Name: Springer, Singapore
Print ISBN: 978-981-10-6576-7
Online ISBN: 978-981-10-6577-4
eBook Packages: MedicineMedicine (R0)