Machine learning multivariate pattern analysis predicts classification of posttraumatic stress disorder and its dissociative subtype: a multimodal neuroimaging approach
Abstract
Background: The field of psychiatry would benefit significantly from developing objective biomarkers that could facilitate the early identification of heterogeneous subtypes of illness. Critically, although machine learning pattern recognition methods have been applied recently to predict many psychiatric disorders, these techniques have not been utilized to predict subtypes of posttraumatic stress disorder (PTSD), including the dissociative subtype of PTSD (PTSD + DS). Methods: Using Multiclass Gaussian Process Classification within PRoNTo, we examined the classification accuracy of: (i) the mean amplitude of low-frequency fluctuations (mALFF; reflecting spontaneous neural activity during rest); and (ii) seed-based amygdala complex functional connectivity within 181 participants [PTSD ( n = 81); PTSD + DS ( n = 49); and age-matched healthy trauma-unexposed controls ( n = 51)]. We also computed mass-univariate analyses in order to observe regional group differences [false-discovery-rate (FDR)-cluster corrected p < 0.05, k = 20]. Results: We found that extracted features could predict accurately the classification of PTSD, PTSD + DS, and healthy controls, using both resting-state mALFF (91.63% balanced accuracy, p < 0.001) and amygdala complex connectivity maps (85.00% balanced accuracy, p < 0.001). These results were replicated using independent machine learning algorithms/cross-validation procedures. Moreover, areas weighted as being most important for group classification also displayed significant group differences at the univariate level. Here, whereas the PTSD + DS group displayed increased activation within emotion regulation regions, the PTSD group showed increased activation within the amygdala, globus pallidus, and motor/somatosensory regions. Conclusion: The current study has significant implications for advancing machine learning applications within the field of psychiatry, as well as for developing objective biomarkers indicative of diagnostic heterogeneity.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Resting-state brain activation analyses tentatively support the idea of an overmodulated fear network through reports of altered functional connectivity between prefrontal and subcortical areas in dissociative PTSD patients.
“Although analyses on resting-state brain activation tentatively support the idea of an overmodulated fear network (see defense cascade and shutdown models) through reports of altered functional connectivity between prefrontal and subcortical areas in dissociative PTSD patients (Nicholson et al., 2017; Nicholson et al., 2019; Rabellino et al., 2018)”
From Trauma-related dissociation and the autonomic nervous system: a systematic literature review of psychophysiological correlates of dissociative experiencing in PTSD patients (2022) · cites this paper as Nicholson et al., 2019
Cites
Etkin, A., & Wager, T. D. (2007) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2007.07030504 · Cited by 3,391 · cited 2× · see citing works
“…and is hypothesized to be related to a disruption of normal interoceptive processing (Nicholson et al ., 2016 b ), where altered insula activation has also been found between PTSD patients and controls (Etkin and Wager, 2007; Aupperle et al ., 2012; Pitman et al ., 2012; Mazza et al ., 2013).”
BackgroundEmotion Modulation in PTSD: Clinical and Neurobiological Evidence for a Dissociative Subtype
Lanius, R. A., Vermetten, E., Loewenstein, R. J., Brand, B., Schmahl, C., Bremner, J. D., & Spiegel, D. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2009.09081168 · Cited by 1,123 · cited 5× · see citing works
“the medial prefrontal cortex (mPFC) and increased bottom-up activation of the amygdala/limbic system, with concomitant hyperarousal and emotion undermodulation (Lanius et al., 2010; Hayes et al., 2012; Stevens et al., 2013; Reinders et al., 2014; Sadeh et al., 2014; Nicholson et al., 2017; Pitman, 2012).”
BackgroundResultInfluentialSelf-citationUsing Neuroscience to Help Understand Fear and Anxiety: A Two-System Framework
LeDoux, J. E., & Pine, D. S. (2016) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2016.16030353 · Cited by 1,035 · see citing works
Post-traumatic stress disorder.
Yehuda, R., Hoge, C. W., McFarlane, A. C., Vermetten, E., Lanius, R. A., Nievergelt, C. M., Hobfoll, S. E., Koenen, K. C., Neylan, T. C., & Hyman, S. E. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.57 · Cited by 870 · see citing works
Self-citationExecutive function and PTSD: disengaging from trauma.
Aupperle, R. L., Melrose, A. J., Stein, M. B., & Paulus, M. P. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.02.008 · Cited by 657 · see citing works
Kozlowska, K., Walker, P., McLean, L., & Carrive, P. (2015) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000065 · Cited by 468 · see citing works
Hopper, J. W., Frewen, P. A., van der Kolk, B. A., & Lanius, R. A. (2007) · Journal of Traumatic Stress · doi:10.1002/jts.20284 · Cited by 376 · see citing works
Self-citationAltered resting-state amygdala functional connectivity in men with posttraumatic stress disorder
Sripada, R. K., King, A. P., Garfinkel, S. N., Wang, X., Sripada, C. S., Welsh, R. C., & Liberzon, I. (2012) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.110069 · Cited by 352 · see citing works
FREWEN, P. A., & LANIUS, R. A. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1364.010 · Cited by 306 · see citing works
Self-citationThe innate alarm system in PTSD: conscious and subconscious processing of threat.
Lanius, R. A., Rabellino, D., Boyd, J. E., Harricharan, S., Frewen, P. A., & McKinnon, M. C. (2017) · Current Opinion in Psychology · doi:10.1016/j.copsyc.2016.11.006 · Cited by 120 · see citing works
Self-citationPosttraumatic stress disorder: a theoretical model of the hyperarousal subtype
Weston, C. S. E. (2014) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2014.00037 · Cited by 114 · see citing works
Reinders, A. A. T. S., Willemsen, A. T. M., den Boer, J. A., Vos, H. P. J., Veltman, D. J., & Loewenstein, R. J. (2014) · Psychiatry Research: Neuroimaging · doi:10.1016/j.pscychresns.2014.05.005 · Cited by 96 · see citing works
McKinnon, M. C., Boyd, J. E., Frewen, P. A., Lanius, U. F., Jetly, R., Richardson, J. D., & Lanius, R. A. (2016) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2016.07.017 · Cited by 94 · cited 2× · see citing works
“…top-down emotion regulation signals from multiple areas of the PFC and ACC, thereby blunting bottom-up defense/fear generation from the amygdala and mid-brain (Lanius et al ., 2010; Åhs et al ., 2015; Etkin et al ., 2015; Ledoux, 2016; McKinnon et al ., 2016; Nicholson et al ., 2017; pitman, 2012).”
BackgroundSelf-citationWolf, E. J., Rasmusson, A. M., Mitchell, K. S., Logue, M. W., Baldwin, C. T., & Miller, M. W. (2014) · Depression and Anxiety · doi:10.1002/da.22260 · Cited by 75 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Biomarkers of Pathological Dissociation: A Systematic Review
Roydeva, M. I., & Reinders, A. A. T. S. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.11.019 · Cited by 116 · see citing works
Harricharan, S., Nicholson, A. A., Thome, J., Densmore, M., McKinnon, M. C., Théberge, J., Frewen, P. A., Neufeld, R. W. J., & Lanius, R. A. (2020) · Psychophysiology · doi:10.1111/psyp.13472 · Cited by 94 · see citing works
Self-citationThe use of machine learning techniques in trauma-related disorders: a systematic review
Ramos-Lima, L. F., Waikamp, V., Antonelli-Salgado, T., Passos, I. C., & Freitas, L. H. M. (2020) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2019.12.001 · Cited by 98 · see citing works
Beutler, S., Mertens, Y. L., Ladner, L., Schellong, J., Croy, I., & Daniels, J. K. (2022) · European Journal of Psychotraumatology · doi:10.1080/20008066.2022.2132599 · Cited by 64 · see citing works
“…overmodulated fear network (see defense cascade and shutdown models) through reports of altered functional connectivity between prefrontal and subcortical areas in dissociative PTSD patients (Nicholson et al., 2017; Nicholson et al., 2019; Rabellino et al., 2018), experimental studies are lacking.”
BackgroundLotfinia, S., Soorgi, Z., Mertens, Y., & Daniels, J. (2020) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2020.05.006 · Cited by 53 · see citing works
Toward Robust Anxiety Biomarkers: A Machine Learning Approach in a Large-Scale Sample
Boeke, E. A., Holmes, A. J., & Phelps, E. A. (2020) · Biological Psychiatry: Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2019.05.018 · Cited by 50 · see citing works
Chen, Z., Liu, X., Yang, Q., Wang, Y.-J., Miao, K., Gong, Z., Yu, Y., Leonov, A., Liu, C., Feng, Z., et al. (2023) · JAMA Network Open · doi:10.1001/jamanetworkopen.2023.1671 · Cited by 43 · see citing works
Systematic review of machine learning in PTSD studies for automated diagnosis evaluation
Wu, Y., Mao, K., Dennett, L., Zhang, Y., & Chen, J. (2023) · npj Mental Health Research · doi:10.1038/s44184-023-00035-w · Cited by 30 · see citing works
Neurobiological and genetic correlates of the dissociative subtype of posttraumatic stress disorder.
Wolf, E. J., Hawn, S. E., Sullivan, D. R., Miller, M. W., Sanborn, V., Brown, E., Neale, Z., Fein-Schaffer, D., Zhao, X., Logue, M. W., et al. (2023) · Journal of Psychopathology and Clinical Science · doi:10.1037/abn0000795 · Cited by 23 · see citing works
- Authors
- Nicholson, A. A., Densmore, M., McKinnon, M. C., Neufeld, R. W. J., Frewen, P. A., Théberge, J., Jetly, R., Richardson, J. D., & Lanius, R. A.
- Affiliations
- Western University (CA)
- Homewood Research Institute (CA)
- Canadian Armed Forces (CA)
- Corresponding author
- Nicholson, Andrew A.
- ORCID
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2018-10-11
- Volume
- 49
- Issue
- 12
- Pages
- 2049-2059
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- OpenAlex
- W2897587989
- Cited by
- 79
- References
- 14
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 13 · 2023: 14 · 2022: 12 · 2021: 8 · 2020: 13 · 2019: 5
- FWCI
- 7.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- General Dynamics Land Systems
- Canadian Institutes of Health Research
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Keywords
- post-traumatic stress disorder, dissociative subtype of PTSD, multivariate pattern analysis, seed-based functional connectivity, biomarkers, diagnostic classification, emotion regulation, globus pallidus
- MeSH terms
- Machine Learning, Adult, Amygdala, Brain Mapping, Dissociative Disorders, Emotions, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Rest, Stress Disorders, Post-Traumatic, Multivariate Analysis, Case-Control Studies, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
