Predicting treatment response in social anxiety disorder from functional magnetic resonance imaging.
Open accessAbstract
CONTEXT: Current behavioral measures poorly predict treatment outcome in social anxiety disorder (SAD). To our knowledge, this is the first study to examine neuroimaging-based treatment prediction in SAD. OBJECTIVE: To measure brain activation in patients with SAD as a biomarker to predict subsequent response to cognitive behavioral therapy (CBT). DESIGN: Functional magnetic resonance imaging (fMRI) data were collected prior to CBT intervention. Changes in clinical status were regressed on brain responses and tested for selectivity for social stimuli. SETTING: Patients were treated with protocol-based CBT at anxiety disorder programs at Boston University or Massachusetts General Hospital and underwent neuroimaging data collection at Massachusetts Institute of Technology. PATIENTS: Thirty-nine medication-free patients meeting DSM-IV criteria for the generalized subtype of SAD. INTERVENTIONS: Brain responses to angry vs neutral faces or emotional vs neutral scenes were examined with fMRI prior to initiation of CBT. MAIN OUTCOME MEASURES: Whole-brain regression analyses with differential fMRI responses for angry vs neutral faces and changes in Liebowitz Social Anxiety Scale score as the treatment outcome measure. RESULTS: Pretreatment responses significantly predicted subsequent treatment outcome of patients selectively for social stimuli and particularly in regions of higher-order visual cortex. Combining the brain measures with information on clinical severity accounted for more than 40% of the variance in treatment response and substantially exceeded predictions based on clinical measures at baseline. Prediction success was unaffected by testing for potential confounding factors such as depression severity at baseline. CONCLUSIONS: The results suggest that brain imaging can provide biomarkers that substantially improve predictions for the success of cognitive behavioral interventions and more generally suggest that such biomarkers may offer evidence-based, personalized medicine approaches for optimally selecting among treatment options for a patient.
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Pre-treatment neural activity in amygdala, dACC, prefrontal, occipital, and temporal regions during simple perceptual matching tasks has predicted CBT responses in SAD participants.
“A handful of emerging studies have found that pre-treatment neural activity in amygdala, dACC, prefrontal, occipital, and temporal regions during simple perceptual matching tasks has predicted responses to CBT in SAD participants (Doehrmann et al., 2013; Klumpp et al., 2013, 2014).”
From Neural responses to social threat and predictors of cognitive behavioral therapy and acceptance and commitment therapy in social anxiety disorder (2017) · cites this paper as Doehrmann et al., 2013
The Comment reports that pretreatment responses to angry versus neutral faces in two occipitotemporal regions predicted CBT outcome in patients with SAD. The Results say prefrontal correlations did not survive correction for multiple comparisons, and found no predictive association in the amygdala; this paper does not establish the claimed dACC prediction. The Methods describe a simple 1-back repetition task during scanning. (LLM, conf=0.88)
Experimental — accuracy not yet measuredGreater symptom reduction following cognitive behavioral therapy is associated with greater pre-treatment neural responses to emotional stimuli within anterior cingulate cortex, dorsomedial/ventromedial prefrontal cortex, and occipital and parietal areas.
“greater symptom reduction following CBT was associated with greater pre-treatment neural responses to emotional stimuli (emotional faces or rejecting statements) within the anterior cingulate cortex (ACC), dm/vmPFC and areas of occipital and parietal lobe (dACC and dmPFC; Burklund et al., 2017; Doehrmann et al., 2013; Klumpp et al., 2014; Klumpp et al., 2013)”
From Neural connectivity during affect labeling predicts treatment response to psychological therapies for social anxiety disorder. (2019) · cites this paper as Doehrmann et al., 2013
The Results (Regression Analyses With Brain Responses; page unavailable) report that greater pretreatment responses to angry versus neutral faces in two occipitotemporal clusters correlated with greater CBT response. They do not report the claimed association in anterior cingulate, dorsomedial or ventromedial prefrontal, or parietal regions. Other prefrontal correlations did not survive correction for multiple comparisons. (LLM, conf=0.88)
Experimental — accuracy not yet measuredFacial expressions have been shown to predict vulnerability to developing mental disorders and treatment response in SAD.
“They have proven to be a powerful research tool with the ability to predict important outcomes including vulnerability to developing mental disorders (e.g., Pezawas et al., 2005) and even treatment response in SAD (e.g., Doehrmann et al., 2013).”
From Neural responses to social threat and predictors of cognitive behavioral therapy and acceptance and commitment therapy in social anxiety disorder (2017) · cites this paper as Doehrmann et al., 2013
The primary limitation of this work was the sample size, although it is consistent with prior studies in this field.
“The primary limitation of this work was the sample size, although it is consistent with prior studies in this field (Doehrmann et al., 2013; Whitfield-Gabrieli et al., 2016).”
From Neural connectivity during affect labeling predicts treatment response to psychological therapies for social anxiety disorder. (2019) · cites this paper as Doehrmann et al., 2013
Most studies have instead examined baseline neural predictors of short-term clinical outcomes in SAD.
“Instead, by far the majority of studies have evaluated baseline neural predictors of short-term clinical outcomes in SAD (Burklund, Torre, Lieberman, Taylor, & Craske, 2017; Doehrmann et al., 2013; Klumpp et al., 2017; Young et al., 2018).”
From Changes in functional connectivity with cognitive behavioral therapy for social anxiety disorder predict outcomes at follow-up (2020) · cites this paper as Doehrmann et al., 2013
fMRI studies of pretreatment brain predictors have reported that lesser rostral anterior cingulate cortex and lesser left DLPFC activity during reappraisal of negative images, inverse connectivity between amygdala and right VLPFC during affect labeling, greater occipitotemporal activation to angry vs neutral faces, and dorsal ACC activation during self-referential criticism are associated with响应
“fMRI studies of pretreatment brain predictors have reported that lesser rostral anterior cingulate cortex and lesser left DLPFC activity during reappraisal of negative images, 42,43 inverse connectivity between amygdala and right VLPFC during affect labeling, 44 greater occipitotemporal activation to angry vs neutral faces, 45 and dorsal ACC activation 46 during self-referential criticism are”
Some recent studies suggest that fMRI can accurately predict treatment outcome.
“some recent studies do, in fact, suggest that some of these methods, such as fMRI, can accurately predict treatment outcome (Doehrmann, Ghosh, Polli, Reynolds, Whitfield-Gabrieli, Hofmann, Pollack, & Gabrieli, 2013)”
From Toward a Cognitive-Behavioral Classification System for Mental Disorders (2014) · cites this paper as Doehrmann et al., 2013
The authors' own research suggests that brain imaging can predict treatment outcome.
“Our own research suggests that brain imaging can predict treatment outcome (Anteraper, Triantafyllou, Sawyer, Hofmann, Gabrieli, & Whitfield-Gabrieli, 2014; Doehrmann, Ghosh, Polli, Reynolds, Whitfield-Gabrieli, Hofmann, Pollack, & Gabrieli, 2013; Hofmann, 2013)”
From A process-based approach to psychological diagnosis and treatment:The conceptual and treatment utility of an extended evolutionary meta model (2020) · cites this paper as Doehrmann et al., 2013
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Toward a Cognitive-Behavioral Classification System for Mental Disorders
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“…2010; Buchheim et al., 2012; De Greck et al., 2011) and numerous investigations of cognitive behavioral types of treatments (e.g., Bor et al., 2011; Doehrmann et al., 2012; Hauner et al., 2012; Kircher et al., 2013; Klumpp, Fitzgerald, & Phan, 2013; Ritchey, Dolcos, Eddington, Strauman, & Cabeza,…”
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Amygdala–cingulate intrinsic connectivity is associated with degree of social inhibition
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A review of machine learning prediction methods for anxiety disorders
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Single-case experimental research designs.
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“Together, this would suggest a ‘building on strengths’ model (Engebretson et al., 1989; Rude and Rehm, 1991), such that individuals with greater capacity to implicitly regulate their emotions may benefit more from psychological treatment.”
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“Instead, by far the majority of studies have evaluated baseline neural predictors of short-term clinical outcomes in SAD (Burklund, Torre, Lieberman, Taylor, and Craske, 2017; Doehrmann et al., 2013; Klumpp et al., 2017; Young et al., 2018).”
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Bridging the theory-practice gap by getting even bolder with the boulder model
Hofmann, S. G. (2013) · Behavior Therapy · doi:10.1016/j.beth.2013.04.006 · Cited by 13 · see citing works
“In my opinion, some of the most promising and excitingwork comes from studies that examine predictors and mechanisms of CBT using modern neuroscience methods (Doehrmann et al., 2013; Siegle, Carter, & Thase, 2006) and other translational research strategies (e.”
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Can fMRI be used to predict the course of treatment for social anxiety disorder?
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Self-citationThe future of cognitive behavioral therapy
Hofmann, S. (2015) · Verhaltenstherapie · doi:10.1159/000375272 · Cited by 3 · see citing works
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Self-citation
- Authors
- Doehrmann, O., Ghosh, S. S., Polli, F. E., Reynolds, G. O., Horn, F., Keshavan, A., Triantafyllou, C., Saygin, Z. M., Whitfield-Gabrieli, S., Hofmann, S. G., Pollack, M., & Gabrieli, J. D.
- Affiliations
- McGovern Institute for Brain Research (US)
- Boston University (US)
- ORCID
- Venue
- JAMA Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2013-01-01
- Volume
- 70
- Issue
- 1
- Pages
- 87
- ISSN
- 2168-622X (ISSN-L)
- PMC
- PMC3844518
- OpenAlex
- W2073814621
- Semantic Scholar
- 54595b86b8827c37283e56a7e672105602f14d4a
- Cited by
- 262
- References
- 63
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 12 · 2023: 11 · 2022: 13 · 2021: 32 · 2020: 16 · 2019: 16 · 2018: 19 · 2017: 21 · 2016: 21 · 2015: 25 · 2014: 34 · 2013: 24 · 2012: 2
- FWCI
- 36.41
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- JAMA Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- PMC
- Funders
- National Institute of Mental Health (R01MH075889, MH078308., MH075889, R01MH078308)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- social anxiety disorder, treatment response prediction, cognitive behavioral therapy, neuroimaging biomarkers, brain activation, personalized medicine, clinical severity
- MeSH terms
- Adult, Anxiety Disorders, Brain, Female, Humans, Magnetic Resonance Imaging, Male, Phobic Disorders, Predictive Value of Tests, Psychotherapy, Group, Biomarkers, Cognitive Behavioral Therapy, Treatment Outcome
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.
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