Applying machine-learning and deep-learning to predict depression from brain MRI and identify depression-related brain biology

Machine Learning


  • Vos T, Lim SS, Abbafati C, Abbas KM, Abbasi M, Abbasifard M, et al. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. The Lancet. 2020;396:1204–22.

    Article 

    Google Scholar 

  • Herrman H, Patel V, Kieling C, Berk M, Buchweitz C, Cuijpers P, et al. Time for united action on depression: a lancet-world psychiatric association commission. The Lancet. 2022;399:957–1022.

    Article 

    Google Scholar 

  • Howard DM, Adams MJ, Clarke TK, Hafferty JD, Gibson J, Shirali M, et al. Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions. Nat Neurosci. 2019;22:343–52.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Dusi N, Barlati S, Vita A, Brambilla P. Brain structural effects of antidepressant treatment in major depression. Curr Neuropharmacol. 2015;13:458–65.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Patel MJ, Khalaf A, Aizenstein HJ. Studying depression using imaging and machine learning methods. NeuroImage: Clinical. 2016;10:115–23.

    Article 
    PubMed 

    Google Scholar 

  • Winter NR, Leenings R, Ernsting J, Sarink K, Fisch L, Emden D, et al. Quantifying deviations of brain structure and function in major depressive disorder across neuroimaging modalities. JAMA Psychiatry. 2022;79:879–88.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Schmaal L, Pozzi E, C. Ho T, van Velzen LS, Veer IM, Opel N, et al. ENIGMA MDD: seven years of global neuroimaging studies of major depression through worldwide data sharing. Transl Psychiatry. 2020;10:172.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Goya-Maldonado R, Erwin-Grabner T, Zeng L-L, Ching CRK, Aleman A, Amod AR, et al. Classification of major depressive disorder using vertex-wise brain sulcal depth, curvature, and thickness with a deep and a shallow learning model. Mol Psychiatry. 2025.

  • Chen X, Lu B, Li H-X, Li X-Y, Wang Y-W, Castellanos FX, et al. The DIRECT consortium and the REST-meta-MDD project: towards neuroimaging biomarkers of major depressive disorder. Psychoradiology. 2022;2:32–42.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Harris MA, Cox SR, de Nooij L, Barbu MC, Adams MJ, Shen X, et al. Structural neuroimaging measures and lifetime depression across levels of phenotyping in UK biobank. Transl Psychiatry. 2022;12:157.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Couvy-Duchesne B, Strike LT, Zhang F, Holtz Y, Zheng Z, Kemper KE, et al. A unified framework for association and prediction from vertex-wise grey-matter structure. Hum Brain Mapp. 2020;41:4062–76.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Fürtjes AE, Cole JH, Couvy-Duchesne B, Ritchie SJ. A quantified comparison of cortical atlases on the basis of trait morphometricity. Cortex. 2023;158:110–26.

    Article 
    PubMed 

    Google Scholar 

  • Belov V, Erwin-Grabner T, Aghajani M, Aleman A, Amod AR, Basgoze Z, et al. Multi-site benchmark classification of major depressive disorder using machine learning on cortical and subcortical measures. Sci Rep. 2024;14:1084.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Winter NR, Blanke J, Leenings R, Ernsting J, Fisch L, Sarink K, et al. A systematic evaluation of machine learning–based biomarkers for major depressive disorder. JAMA Psychiatry. 2024;81:386–95.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cao B, Yang E, Wang L, Mo Z, Steffens DC, Zhang H, et al. Brain morphometric features predict depression symptom phenotypes in late-life depression using a deep learning model. Front Neurosci. 2023;17:1209906.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bycroft C, Freeman C, Petkova D, Band G, Elliott LT, Sharp K, et al. The UK Biobank resource with deep phenotyping and genomic data. Nature. 2018;562:203–9.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Smith SM, Alfaro-Almagro F, Miller KL. UK Biobank brain imaging documentation version 1.10. Oxford Centre for Functional MRI of the Brain (FMRIB/WIN), Oxford University on behalf of UK Biobank; 2024.

  • Alfaro-Almagro F, Jenkinson M, Bangerter NK, Andersson JLR, Griffanti L, Douaud G, et al. Image processing and quality control for the first 10,000 brain imaging datasets from UK Biobank. Neuroimage. 2018;166:400–24.

    Article 
    PubMed 

    Google Scholar 

  • Yengo L, Sidorenko J, Kemper KE, Zheng Z, Wood AR, Weedon MN, et al. Meta-analysis of genome-wide association studies for height and body mass index in 700000 individuals of European ancestry. Hum Mol Genet. 2018;27:3641–9.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Routier A, Burgos N, Díaz M, Bacci M, Bottani S, El-Rifai O, et al. Clinica: an open-source software platform for reproducible clinical neuroscience studies. Front Neuroinform. 2021;15.

  • Chapter 31 – experimental design and statistical parametric mapping. In: Frackowiak RSJ, Friston KJ, Frith CD, Dolan RJ, Price CJ, Zeki S, et al., editors. Human Brain Function (Second Edition). Burlington: Academic Press; 2004. p. 599-632.

  • Diedrichsen J, Balsters JH, Flavell J, Cussans E, Ramnani N. A probabilistic MR atlas of the human cerebellum. Neuroimage. 2009;46:39–46.

    Article 
    PubMed 

    Google Scholar 

  • Makris N, Goldstein JM, Kennedy D, Hodge SM, Caviness VS, Faraone SV, et al. Decreased volume of left and total anterior insular lobule in schizophrenia. Schizophr Res. 2006;83:155–71.

    Article 
    PubMed 

    Google Scholar 

  • Frazier JA, Chiu S, Breeze JL, Makris N, Lange N, Kennedy DN, et al. Structural brain magnetic resonance imaging of limbic and thalamic volumes in pediatric bipolar disorder. Am J Psychiatry. 2005;162:1256–65.

    Article 
    PubMed 

    Google Scholar 

  • Goldstein JM, Seidman LJ, Makris N, Ahern T, O’Brien LM, Caviness VS, et al. Hypothalamic abnormalities in schizophrenia: sex effects and genetic vulnerability. Biol Psychiatry. 2007;61:935–45.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Zhang F, Chen W, Zhu Z, Zhang Q, Nabais MF, Qi T, et al. OSCA: a tool for omic-data-based complex trait analysis. Genome Biol. 2019;20:107.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Henderson CR. Best linear unbiased estimation and prediction under a selection model. Biometrics. 1975;31:423–47.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Couvy-Duchesne B, Faouzi J, Martin B, Thibeau-Sutre E, Wild A, Ansart M, et al. Ensemble learning of convolutional neural network, support vector machine, and best linear unbiased predictor for brain age prediction: ARAMIS contribution to the predictive analytics competition 2019 challenge. Front Psychiatry. 2020;11:593336.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Sabuncu MR, Ge T, Holmes AJ, Smoller JW, Buckner RL, Fischl B. Morphometricity as a measure of the neuroanatomical signature of a trait. Proc Natl Acad Sci USA. 2016;113:E5749–56.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Thibeau-Sutre E, Díaz M, Hassanaly R, Routier A, Dormont D, Colliot O, et al. ClinicaDL: An open-source deep learning software for reproducible neuroimaging processing. Comput Methods Programs Biomed. 2022;220:106818.

    Article 
    PubMed 

    Google Scholar 

  • Paszke A, Gross S, Massa F, Lerer A, Bradbury J, Chanan G, et al. PyTorch: an imperative style, high-performance deep learning library. Proceedings of the 33rd International Conference on Neural Information Processing Systems: Curran Associates Inc.; Canada: 2019. p. Article 721.

  • Robin X, Turck N, Hainard A, Tiberti N, Lisacek F, Sanchez J-C, et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics. 2011;12:77.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wray NR, Ripke S, Mattheisen M, Trzaskowski M, Byrne EM, Abdellaoui A, et al. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nat Genet. 2018;50:668–81.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Adams MJ, Streit F, Meng X, Awasthi S, Adey BN, Choi KW, et al. Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies. Cell. 2025;188:640–52.e9.

    Article 

    Google Scholar 

  • Lloyd-Jones LR, Zeng J, Sidorenko J, Yengo L, Moser G, Kemper KE, et al. Improved polygenic prediction by Bayesian multiple regression on summary statistics. Nat Commun. 2019;10:5086.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Chang CC, Chow CC, Tellier LCAM, Vattikuti S, Purcell SM, Lee JJ. Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience. 2015;4:s13742-015–0047-8.

    Article 

    Google Scholar 

  • Colle R, Segawa T, Chupin M, Tran Dong MNTK, Hardy P, Falissard B, et al. Early life adversity is associated with a smaller hippocampus in male but not female depressed in-patients: a case–control study. BMC Psychiatry. 2017;17:71.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Poirot MG, Boucherie DE, Caan MWA, Goya-Maldonado R, Belov V, Corruble E, et al. Predicting antidepressant treatment response from cortical structure on MRI: a mega-analysis from the ENIGMA-MDD working group. Hum Brain Mapp. 2025;46:e70053.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Schoenfeld TJ, Cameron HA. Adult neurogenesis and mental illness. Neuropsychopharmacology. 2015;40:113–28.

    Article 
    PubMed 

    Google Scholar 

  • Kendler KS, Gatz M, Gardner CO, Pedersen NL. A Swedish national twin study of lifetime major depression. Am J Psychiatry. 2006;163:109–14.

    Article 
    PubMed 

    Google Scholar 

  • Lewis CM, Vassos E. Polygenic risk scores: from research tools to clinical instruments. Genome Med. 2020;12:44.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Jiang J-C, Singh K, Nitin R, Davis LK, Wray NR, Shah S. Sex-specific association between genetic risk of psychiatric disorders and cardiovascular diseases. Circ Genom Precis Med. 2024;17:e004685.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lopizzo N, Bocchio Chiavetto L, Cattane N, Plazzotta G, Tarazi FI, Pariante CM, et al. Gene–environment interaction in major depression: focus on experience-dependent biological systems. Front Psychiatry. 2015;6::68.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Colodro-Conde L, Couvy-Duchesne B, Zhu G, Coventry WL, Byrne EM, Gordon S, et al. A direct test of the diathesis–stress model for depression. Mol Psychiatry. 2018;23:1590–6.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Nolfe G, Cirillo M, Iavarone A, Negro A, Garofalo E, Cotena A, et al. Bullying at workplace and brain-imaging correlates. J Clin Med. 2018;7:200.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Crossley NA, Alliende LM, Ossandon T, Castañeda CP, González-Valderrama A, Undurraga J, et al. Imaging social and environmental factors as modulators of brain dysfunction: time to focus on developing non-western societies. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. 2019;4:8–15.

    PubMed 

    Google Scholar 

  • Mackey S, Allgaier N, Chaarani B, Spechler P, Orr C, Bunn J, et al. Mega-Analysis of gray matter volume in substance dependence: general and substance-specific regional effects. Am J Psychiatry. 2018;176:119–28.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Papagni SA, Benetti S, Arulanantham S, McCrory E, McGuire P, Mechelli A. Effects of stressful life events on human brain structure: A longitudinal voxel-based morphometry study. Stress. 2011;14:227–32.

    Article 
    PubMed 

    Google Scholar 

  • Schulz M-A, Yeo BTT, Vogelstein JT, Mourao-Miranada J, Kather JN, Kording K, et al. Different scaling of linear models and deep learning in UKBiobank brain images versus machine-learning datasets. Nat Commun. 2020;11:4238.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Mihalik A, Brudfors M, Robu M, Ferreira FS, Lin H, Rau A, et al., editors. ABCD Neurocognitive prediction challenge 2019: predicting individual fluid intelligence scores from structural MRI using probabilistic segmentation and kernel ridge regression. Adolescent Brain Cognitive Development Neurocognitive Prediction; 2019 2019//; Cham: Springer International Publishing.

  • Wen J, Thibeau-Sutre E, Diaz-Melo M, Samper-González J, Routier A, Bottani S, et al. Convolutional neural networks for classification of Alzheimer’s disease: overview and reproducible evaluation. Med Image Anal. 2020;63:101694.

    Article 
    PubMed 

    Google Scholar 

  • Antonelli M, Reinke A, Bakas S, Farahani K, Kopp-Schneider A, Landman BA, et al. The medical segmentation decathlon. Nat Commun. 2022;13:4128.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ruscio J. A probability-based measure of effect size: robustness to base rates and other factors. Psychol Methods. 2008;13:19–30.

    Article 
    PubMed 

    Google Scholar 

  • Zhou E, Wang W, Ma S, Xie X, Kang L, Xu S, et al. Prediction of anxious depression using multimodal neuroimaging and machine learning. Neuroimage. 2024;285:120499.

    Article 
    PubMed 

    Google Scholar 

  • Li J, Chen H, Fan F, Qiu J, Du L, Xiao J, et al. White-matter functional topology: a neuromarker for classification and prediction in unmedicated depression. Transl Psychiatry. 2020;10:365.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Smith SM, Douaud G, Chen W, Hanayik T, Alfaro-Almagro F, Sharp K, et al. An expanded set of genome-wide association studies of brain imaging phenotypes in UK Biobank. Nat Neurosci. 2021;24:737–45.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hasin DS, Sarvet AL, Meyers JL, Saha TD, Ruan WJ, Stohl M, et al. Epidemiology of adult DSM-5 major depressive disorder and its specifiers in the United States. JAMA Psychiatry. 2018;75:336–46.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Smith DJ, Kyle S, Forty L, Cooper C, Walters J, Russell E, et al. Differences in depressive symptom profile between males and females. J Affect Disord. 2008;108:279–84.

    Article 
    PubMed 

    Google Scholar 

  • Mohammadi S, Seyedmirzaei H, Salehi MA, Jahanshahi A, Zakavi SS, Dehghani Firouzabadi F, et al. Brain-based sex differences in depression: a systematic review of neuroimaging studies. Brain Imaging Behav. 2023;17:541–69.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zheng G, Zhou Y, Zhou J, Liang S, Li X, Xu C, et al. Abnormalities of the amygdala in schizophrenia: a real world study. BMC Psychiatry. 2023;23:615.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Stein F, Kircher T. Transdiagnostic findings across major depressive disorder, bipolar disorder and schizophrenia: a qualitative review. J Affect Disord. 2025;387:119464.

    Article 
    PubMed 

    Google Scholar 



  • Source link