Neuroimaging-Based Biomarkers in Psychiatry: Clinical Opportunities of a Paradigm Shift

Article

Fu, C. and Costafreda, Sergi G. 2013. Neuroimaging-Based Biomarkers in Psychiatry: Clinical Opportunities of a Paradigm Shift. Canadian Journal of Psychiatry. 58 (9), pp. 499-508.
AuthorsFu, C. and Costafreda, Sergi G.
Abstract

Neuroimaging research has substantiated the functional and structural abnormalities
underlying psychiatric disorders but has, thus far, failed to have a significant impact on
clinical practice. Recently, neuroimaging-based diagnoses and clinical predictions derived
from machine learning analysis have shown significant potential for clinical translation.
This review introduces the key concepts of this approach, including how the multivariate
integration of patterns of brain abnormalities is a crucial component. We survey recent
findings that have potential application for diagnosis, in particular early and differential
diagnoses in Alzheimer disease and schizophrenia, and the prediction of clinical response
to treatment in depression. We discuss the specific clinical opportunities and the challenges
for developing biomarkers for psychiatry in the absence of a diagnostic gold standard. We
propose that longitudinal outcomes, such as early diagnosis and prediction of treatment
response, offer definite opportunities for progress. We propose that efforts should be
directed toward clinically challenging predictions in which neuroimaging may have added
value, compared with the existing standard assessment. We conclude that diagnostic and
prognostic biomarkers will be developed through the joint application of expert psychiatric
knowledge in addition to advanced methods of analysis.

JournalCanadian Journal of Psychiatry
Journal citation58 (9), pp. 499-508
ISSN1497-0015
Year2013
PublisherCanadian Psychiatric Association
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CC BY-ND
Web address (URL)http://publications.cpa-apc.org/media.php?mid=1708
Publication dates
PrintSep 2013
Publication process dates
Deposited05 Aug 2014
FunderHigher Education Funding Council of England
Medical Research Council
National Institute for Health Research
Copyright information© Canadian Psychiatric Association. First published in the Canadian Journal of Psychiatry, 58(9), September 2013. Authors are granted permission to archive PDFs of the final printed versions of their articles in their institutions’ archive 6 months after publication.
Additional information

The Canadian Psychiatric Association proudly supports the
In Review series by providing an honorarium to the authors

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Lorenzetti, V., Costafreda, S. G., Rimmer, R., Rasenick, M. M., Marangell, L. B. and Fu, C. 2020. Brain-derived neurotrophic factor association with amygdala response in major depressive disorder. Journal of Affective Disorders. 267, pp. 103-106. https://doi.org/10.1016/j.jad.2020.01.159
The Neuroscience of Sadness: A Multidisciplinary Synthesis and Collaborative Review for the Human Affectome Project
Arias, J. A., Williams, C., Raghvani, R., Aghajani, M., Baez, S., Belzung, C., Booij, L., Busatto, G., Chiarella, J., Fu, C., Ibanez, A., Liddell, B. J., Lowe, L., Penninx, B. W. J. H., Rosa, P. and Kemp, A. H. 2020. The Neuroscience of Sadness: A Multidisciplinary Synthesis and Collaborative Review for the Human Affectome Project. Neuroscience & Biobehavioral Reviews. 111, pp. 199-228. https://doi.org/10.1016/j.neubiorev.2020.01.006
Addressing heterogeneity (and homogeneity) in treatment mechanisms in depression and the potential to develop diagnostic and predictive biomarkers
Fu, C., Fan, Y. and Davatzikos, C. 2019. Addressing heterogeneity (and homogeneity) in treatment mechanisms in depression and the potential to develop diagnostic and predictive biomarkers. NeuroImage: Clinical. 24 (Art.101997). https://doi.org/10.1016/j.nicl.2019.101997
Comparative efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults: systematic review and network meta-analysis
Mutz, Julian, Vipulananthan, Vijeinika, Carter, Ben, Hurlemann, René, Fu, C. and Young, Allan H. 2019. Comparative efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults: systematic review and network meta-analysis. BMJ. 364, p. Art. l1079. https://doi.org/10.1136/bmj.l1079
A systematic review and meta-analysis of the neural correlates of psychological therapies in major depression
Sankar, Anjali, Melin, Alice, Lorenzetti, Valentina, Horton, Paul, Costafreda, Sergi G. and Fu, C. 2018. A systematic review and meta-analysis of the neural correlates of psychological therapies in major depression. Psychiatry Research: Neuroimaging. 279, pp. 31-39. https://doi.org/10.1016/j.pscychresns.2018.07.002
Efficacy and acceptability of non-invasive brain stimulation for the treatment of adult unipolar and bipolar depression: A systematic review and meta-analysis of randomised sham-controlled trials
Mutz, Julian, Edgcumbe, Daniel R., Brunoni, Andre R. and Fu, C. 2018. Efficacy and acceptability of non-invasive brain stimulation for the treatment of adult unipolar and bipolar depression: A systematic review and meta-analysis of randomised sham-controlled trials. Neuroscience & Biobehavioral Reviews. 92, pp. 291-303. https://doi.org/10.1016/j.neubiorev.2018.05.015
Predictors of amygdala activation during the processing of emotional stimuli: A meta-analysis of 385 PET and fMRI studies
Costafreda, Sergi G., Brammer, Michael J., David, Anthony S. and Fu, C. 2007. Predictors of amygdala activation during the processing of emotional stimuli: A meta-analysis of 385 PET and fMRI studies. Brain Research Reviews. 58 (1), pp. 57-70. https://doi.org/10.1016/j.brainresrev.2007.10.012
Neural basis of the emotional Stroop interference effect in major depression
Mitterschiffthaler, M. T., Williams, S. C. R., Walsh, N. D., Cleare, A. J., Donaldson, C., Scott, J. and Fu, C. 2008. Neural basis of the emotional Stroop interference effect in major depression. Psychological Medicine. 38 (02), pp. 247-256. https://doi.org/10.1017/S0033291707001523
Pattern Classification of Sad Facial Processing: Toward the Development of Neurobiological Markers in Depression
Fu, C., Mourao-Miranda, Janaina, Costafreda, Sergi G., Khanna, Akash, Marquand, Andre F., Williams, Steve C.R. and Brammer, Michael J. 2008. Pattern Classification of Sad Facial Processing: Toward the Development of Neurobiological Markers in Depression. Biological Psychiatry. 63 (7), pp. 656-662. https://doi.org/10.1016/j.biopsych.2007.08.020
Neural Responses to Sad Facial Expressions in Major Depression Following Cognitive Behavioral Therapy
Fu, C., Williams, Steven C.R., Cleare, Anthony J., Scott, Jan, Mitterschiffthaler, Martina T., Walsh, Nicholas D., Donaldson, Catherine, Suckling, John, Andrew, Chris, Steiner, Herbert and Murray, Robin M. 2008. Neural Responses to Sad Facial Expressions in Major Depression Following Cognitive Behavioral Therapy. Biological Psychiatry. 64 (6), pp. 505-512. https://doi.org/10.1016/j.biopsych.2008.04.033
Neuroanatomy of verbal working memory as a diagnostic biomarker for depression
Marquand, Andre F., Mourão-Miranda, Janaina, Brammer, Michael J., Cleare, Anthony J. and Fu, C. 2008. Neuroanatomy of verbal working memory as a diagnostic biomarker for depression. NeuroReport. 19 (15), pp. 1507-1511. https://doi.org/10.1097/WNR.0b013e328310425e
Neural correlates of sad faces predict clinical remission to cognitive behavioural therapy in depression
Costafreda, Sergi G., Khanna, Akash, Mourao-Miranda, Janaina and Fu, C. 2009. Neural correlates of sad faces predict clinical remission to cognitive behavioural therapy in depression. NeuroReport. 20 (7), pp. 637-641. https://doi.org/10.1097/WNR.0b013e3283294159
Amygdala activation to masked happy facial expressions
Juruena, Mario F., Giampietro, Vincent P., Smith, Stephen D., Surguladze, Simon A., Dalton, Jeffrey A., Benson, Philip J., Cleare, Anthony J. and Fu, C. 2010. Amygdala activation to masked happy facial expressions. Journal of the International Neuropsychological Society. 16 (02), pp. 383-387. https://doi.org/10.1017/S1355617709991172
Subregional hippocampal deformations in major depressive disorder
Cole, James, Toga, Arthur W., Hojatkashani, Cornelius, Thompson, Paul, Costafreda, Sergi G., Cleare, Anthony J., Williams, Steven C.R., Bullmore, Edward T., Scott, Jan L., Mitterschiffthaler, Martina T., Walsh, Nicholas D., Donaldson, Catherine, Mirza, Mubeena, Marquand, Andre, Nosarti, Chiara, McGuffin, Peter and Fu, C. 2010. Subregional hippocampal deformations in major depressive disorder. Journal of Affective Disorders. 126 (1-2), pp. 272-277. https://doi.org/10.1016/j.jad.2010.03.004
Ketamine-Induced Disruption of Verbal Self-Monitoring Linked to Superior Temporal Activation
Stone, J. M., Abel, K. M., Allen, M.P.G., van Haren, N., Matsumoto, K., McGuire, P. K. and Fu, C. 2010. Ketamine-Induced Disruption of Verbal Self-Monitoring Linked to Superior Temporal Activation. Pharmacopsychiatry. 44 (1), pp. 33-48. https://doi.org/10.1055/s-0030-1267942
Machine learning classification with confidence: Application of transductive conformal predictors to MRI-based diagnostic and prognostic markers in depression
Nouretdinov, Ilia, Costafreda, Sergi G., Gammerman, Alexander, Chervonenkis, Alexey, Vovk, Vladimir, Vapnik, Vladimir and Fu, C. 2011. Machine learning classification with confidence: Application of transductive conformal predictors to MRI-based diagnostic and prognostic markers in depression. NeuroImage. 56 (2), pp. 809-813. https://doi.org/10.1016/j.neuroimage.2010.05.023
Cortisol responses to serial MRI scans in healthy adults and in depression
Peters, Sabine, Cleare, Anthony J., Papadopoulos, Andrew and Fu, C. 2011. Cortisol responses to serial MRI scans in healthy adults and in depression. Psychoneuroendocrinology. 36 (5), pp. 737-741. https://doi.org/10.1016/j.psyneuen.2010.10.009
No effect of 5HTTLPR or BDNF Val66Met polymorphism on hippocampal morphology in major depression
Cole, J., Weinberger, D. R., Mattay, V. S., Cheng, X., Toga, A. W., Thompson, P. M., Powell-Smith, G., Cohen-Woods, S., Simmons, A., McGuffin, P. and Fu, C. 2011. No effect of 5HTTLPR or BDNF Val66Met polymorphism on hippocampal morphology in major depression. Genes, Brain and Behavior. 10 (7), pp. 756-764. https://doi.org/10.1111/j.1601-183X.2011.00714.x
Hippocampal atrophy in first episode depression: A meta-analysis of magnetic resonance imaging studies
Cole, James, Costafreda, Sergi G., McGuffin, Peter and Fu, C. 2011. Hippocampal atrophy in first episode depression: A meta-analysis of magnetic resonance imaging studies. Journal of Affective Disorders. 134 (1-3), pp. 483-487. https://doi.org/10.1016/j.jad.2011.05.057
Interaction between effects of genes coding for dopamine and glutamate transmission on striatal and parahippocampal function
Pauli, Andreina, Prata, Diana P., Mechelli, Andrea, Picchioni, Marco, Fu, C., Chaddock, Christopher A., Kane, Fergus, Kalidindi, Sridevi, McDonald, Colm, Kravariti, Eugenia, Toulopoulou, Timothea, Bramon, Elvira, Walshe, Muriel, Ehlert, Natascha, Georgiades, Anna, Murray, Robin, Collier, David A. and McGuire, Philip 2012. Interaction between effects of genes coding for dopamine and glutamate transmission on striatal and parahippocampal function. Human Brain Mapping. 34 (9), pp. 2244-2258. https://doi.org/10.1002/hbm.22061
White matter abnormalities and illness severity in major depressive disorder
Cole, James, Chaddock, Christopher A., Farmer, Anne E., Aitchison, Katherine J., Simmons, Andrew, McGuffin, Peter and Fu, C. 2012. White matter abnormalities and illness severity in major depressive disorder. British Journal of Psychiatry. 201 (01), pp. 33-39. https://doi.org/10.1192/bjp.bp.111.100594
Predictive neural biomarkers of clinical response in depression: A meta-analysis of functional and structural neuroimaging studies of pharmacological and psychological therapies
Fu, C., Steiner, Herbert and Costafreda, Sergi G. 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, pp. 75-83. https://doi.org/10.1016/j.nbd.2012.05.008
Modulation of amygdala response and connectivity in depression by serotonin transporter polymorphism and diagnosis
Costafreda, Sergi G., McCann, Peter, Saker, Pascal, Cole, James H., Cohen-Woods, Sarah, Farmer, Anne E., Aitchison, Katherine J., McGuffin, Peter and Fu, C. 2013. Modulation of amygdala response and connectivity in depression by serotonin transporter polymorphism and diagnosis. Journal of Affective Disorders. 150 (1), pp. 96-103. https://doi.org/10.1016/j.jad.2013.02.028
Modafinil Augmentation Therapy in Unipolar and Bipolar Depression
Goss, Alexander J., Kaser, Muzaffer, Costafreda, Sergi G., Sahakian, Barbara J. and Fu, C. 2013. Modafinil Augmentation Therapy in Unipolar and Bipolar Depression. The Journal of Clinical Psychiatry. 74 (11), pp. 1101-1107. https://doi.org/10.4088/JCP.13r08560
Other race effect on amygdala response during affective facial processing in major depression
Sankar, Anjali, Costafreda, Sergi G., Marangell, Lauren B. and Fu, C. 2018. Other race effect on amygdala response during affective facial processing in major depression. Neuroscience Letters. 662, pp. 381-384. https://doi.org/10.1016/j.neulet.2017.10.043
The effect of psychosis associated CACNA1C, and its epistasis with ZNF804A, on brain function
Tecelão, Diogo, Mendes, Ana, Martins, Daniel, Fu, C., Chaddock, Christopher A, Picchioni, Marco M, McDonald, Colm, Kalidindi, Sridevi, Murray, Robin and Prata, Diana P 2018. The effect of psychosis associated CACNA1C, and its epistasis with ZNF804A, on brain function. Genes, Brain and Behavior. 18 (4), p. e12510. https://doi.org/10.1111/gbb.12510
Unravelling the GSK3β-related genotypic interaction network influencing hippocampal volume in recurrent major depressive disorder
Inkster, Becky, Simmons, Andy, Cole, James, Schoof, Erwin, Linding, Rune, Nichols, Tom, Muglia, Pierandrea, Holsboer, Florian, Saemann, Philipp, McGuffin, Peter, Fu, C., Miskowiak, Kamilla, Matthews, Paul M., Zai, Gwyneth and Nicodemus, Kristin 2018. Unravelling the GSK3β-related genotypic interaction network influencing hippocampal volume in recurrent major depressive disorder. Psychiatric Genetics. 28 (5), pp. 77-84. https://doi.org/10.1097/YPG.0000000000000203
Associations between polygenic risk scores for four psychiatric illnesses and brain structure using multivariate pattern recognition
Ranlund, Siri, Rosa, Maria Joao, de Jong, Simone, Cole, James H., Kyriakopoulos, Marinos, Fu, C., Mehta, Mitul A. and Dima, Danai 2018. Associations between polygenic risk scores for four psychiatric illnesses and brain structure using multivariate pattern recognition. NeuroImage: Clinical. 20, pp. 1026-1036. https://doi.org/10.1016/j.nicl.2018.10.008
Anodal transcranial direct current stimulation over the right dorsolateral prefrontal cortex enhances reflective judgment & decision-making
Edgcumbe, Daniel R., Thoma, V., Rivolta, Davide, Nitsche, Michael A. and Fu, C. 2018. Anodal transcranial direct current stimulation over the right dorsolateral prefrontal cortex enhances reflective judgment & decision-making. Brain Stimulation. 12 (3), pp. 652-658. https://doi.org/10.1016/j.brs.2018.12.003
Effects of antidepressant therapy on neural components of verbal working memory in depression
Sankar, Anjali, Adams, Tracey M, Costafreda, Sergi G. and Fu, C. 2017. Effects of antidepressant therapy on neural components of verbal working memory in depression. Journal of Psychopharmacology. 31 (9), pp. 1176-1183. https://doi.org/10.1177/0269881117724594
Body mass index, but not FTO genotype or major depressive disorder, influences brain structure
Cole, J.H., Boyle, C.P., Simmons, A., Cohen-Woods, S., Rivera, M., McGuffin, P., Thompson, P.M. and Fu, C. 2013. Body mass index, but not FTO genotype or major depressive disorder, influences brain structure. Neuroscience. 252 (Nov.), pp. 109-117. https://doi.org/10.1016/j.neuroscience.2013.07.015
Classification of Major Depressive Disorder via Multi-Site Weighted LASSO Model
Zhu, Dajiang, Riedel, Brandalyn C., Jahanshad, Neda, Groenewold, Nynke A., Stein, Dan J., Gotlib, Ian H., Dima, Danai, Cole, James H., Fu, C., Walter, Henrik, Veer, Ilya M., Frodl, Thomas, Schmaal, Lianne, Veltman, Dick J. and Thompson, Paul M. 2017. Classification of Major Depressive Disorder via Multi-Site Weighted LASSO Model. in: Descoteaux, Maxime, Maier-Hein, Lena, Franz, Alfred, Jannin, Pierre, Collins, D. Louis and Duchesne, Simon (ed.) Medical Image Computing and Computer-Assisted Intervention − MICCAI 2017 Springer, Cham.
Recent Advances in Neuroimaging of Mood Disorders: Structural and Functional Neural Correlates of Depression, Changes with Therapy, and Potential for Clinical Biomarkers
Atkinson, Lauren, Sankar, Anjali, Adams, Tracey M. and Fu, C. 2014. Recent Advances in Neuroimaging of Mood Disorders: Structural and Functional Neural Correlates of Depression, Changes with Therapy, and Potential for Clinical Biomarkers. Current Treatment Options in Psychiatry. 1 (3), pp. 278-293. https://doi.org/10.1007/s40501-014-0022-5
Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: evidence from voxel-based meta-analysis
Wise, T., Radua, J., Via, E., Cardoner, N., Abe, O., Adams, T. M., Amico, F., Cheng, Y., Cole, J. H., de Azevedo Marques Périco, C., Dickstein, D. P., Farrow, T. F. D., Frodl, T., Wagner, G., Gotlib, I. H., Gruber, O., Ham, B. J., Job, D. E., Kempton, M. J., Kim, M. J., Koolschijn, P. C. M. P., Malhi, G. S., Mataix-Cols, D., McIntosh, A. M., Nugent, A. C., O'Brien, J. T.., Pezzoli, S, Phillips, M. L., Sachdev, P. S., Salvadore, G., Selvaraj, S., Stanfield, A. C., Thomas, A. J., van Tol, M. J., van der Wee, N. J. A., Veltman, D. J., Young, A. H., Fu, C., Cleare, A. J. and Arnone, D. 2016. Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: evidence from voxel-based meta-analysis. Molecular Psychiatry. https://doi.org/10.1038/mp.2016.72
Diagnostic potential of structural neuroimaging for depression from a multi-ethnic community sample
Sankar, Anjali, Zhang, Tianhao, Gaonkar, Bilwaj, Doshi, Jimit, Erus, Guray, Costafreda, Sergi G., Marangell, Lauren, Davatzikos, Christos and Fu, C. 2016. Diagnostic potential of structural neuroimaging for depression from a multi-ethnic community sample. BJPsych Open. 2 (4), pp. 247-254. https://doi.org/10.1192/bjpo.bp.115.002493
Meta-analyses of structural regional cerebral effects in type 1 and type 2 diabetes
Moulton, Calum D., Costafreda, Sergi G., Horton, Paul, Ismail, Khalida and Fu, C. 2015. Meta-analyses of structural regional cerebral effects in type 1 and type 2 diabetes. Brain Imaging and Behavior. 9 (4), pp. 651-662.
A systematic review of the neurophysiology of mindfulness on EEG oscillations
Lomas, T., Ivtzan, I. and Fu, C. 2015. A systematic review of the neurophysiology of mindfulness on EEG oscillations. Neuroscience & Biobehavioral Reviews. 57, pp. 401-410.
Multimodal functional and structural neuroimaging investigation of major depressive disorder following treatment with duloxetine
Fu, C., Costafreda, Sergi G, Sankar, Anjali, Adams, Tracey M, Rasenick, Mark M, Liu, Peng, Donati, Robert, Maglanoc, Luigi A, Horton, Paul and Marangell, Lauren B 2015. Multimodal functional and structural neuroimaging investigation of major depressive disorder following treatment with duloxetine. BMC Psychiatry. 15 (1).
Neural effects of cognitive–behavioural therapy on dysfunctional attitudes in depression
Sankar, A., Scott, J., Paszkiewicz, A., Giampietro, V. P., Steiner, H. and Fu, C. 2014. Neural effects of cognitive–behavioural therapy on dysfunctional attitudes in depression. Psychological Medicine. 45 (7), pp. 1425-1433.
Modulatory effects of brain-derived neurotrophic factor Val66Met polymorphism on prefrontal regions in major depressive disorder
Legge, R. M., Sendi, S., Cole, J. H., Cohen-Woods, S., Costafreda, S. G., Simmons, A., Farmer, A. E., Aitchison, K. J., McGuffin, P. and Fu, C. 2015. Modulatory effects of brain-derived neurotrophic factor Val66Met polymorphism on prefrontal regions in major depressive disorder. The British Journal of Psychiatry. 206 (5), pp. 379-384.
Prognostic and Diagnostic Potential of the Structural Neuroanatomy of Depression
Domschke, Katharina, Costafreda, Sergi G., Chu, Carlton, Ashburner, John and Fu, C. 2009. Prognostic and Diagnostic Potential of the Structural Neuroanatomy of Depression. PLoS ONE. 4 (7), p. e6353.
Pattern of neural responses to verbal fluency shows diagnostic specificity for schizophrenia and bipolar disorder
Costafreda, Sergi G, Fu, C., Picchioni, Marco, Toulopoulou, Timothea, McDonald, Colm, Kravariti, Eugenia, Walshe, Muriel, Prata, Diana, Murray, Robin M and McGuire, Philip K 2011. Pattern of neural responses to verbal fluency shows diagnostic specificity for schizophrenia and bipolar disorder. BMC Psychiatry. 11 (1), p. 18.