Send to

Choose Destination
Biol Psychiatry Cogn Neurosci Neuroimaging. 2019 Jun 21. pii: S2451-9022(19)30171-5. doi: 10.1016/j.bpsc.2019.05.018. [Epub ahead of print]

Toward Robust Anxiety Biomarkers: A Machine Learning Approach in a Large-Scale Sample.

Author information

Department of Psychology, New York University, New York, New York.
Department of Psychology, Yale University, New Haven, Connecticut; Department of Psychiatry, Yale University, New Haven, Connecticut.
Department of Psychology, Harvard University, Cambridge Massachusetts. Electronic address:



The field of psychiatry has long sought biomarkers that can objectively diagnose patients, predict treatment response, or identify individuals at risk of illness onset. However, reliable psychiatric biomarkers have yet to emerge. The recent application of machine learning techniques to develop neuroimaging-based biomarkers has yielded promising preliminary results. However, much of the work in this domain has not met best practice standards from the field of machine learning. This is especially true for studies of anxiety, creating uncertainty about the potential for anxiety biomarker development.


We applied machine learning tools to predict trait anxiety from neuroimaging measurements in humans. Using publicly available data from the Brain Genomics Superstruct Project, we compared a suite of neuroimaging-based machine learning models predicting anxiety within a discovery sample (n = 531, 307 women) via k-fold cross-validation, and we tested the final model (a stacked model incorporating region-to-region functional connectivity, amygdala seed-to-voxel connectivity, and volumetric and cortical thickness data) in a held-out, unseen test sample (n = 348, 209 women).


Though the best model was able to predict anxiety within the discovery sample (cross-validated R2 of .06, permutation test p < .001), the generalization test within the holdout sample failed (R2 of -.04, permutation test p > .05).


In this study, we did not find evidence of a generalizable anxiety biomarker. However, we encourage other researchers to investigate this topic, utilizing large samples and proper methodology, to clarify the potential of neuroimaging-based anxiety biomarkers.


Anxiety; Biomarker; Functional connectivity; Machine learning; Predictive modeling; fMRI


Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center