Evidence map›Paper›PMID 25824424›Full record

Trial reportNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2015

Amygdala Reactivity to Emotional Faces in the Prediction of General and Medication-Specific Responses to Antidepressant Treatment in the Randomized iSPOT-D Trial.

Leanne M Williams, Mayuresh S Korgaonkar, Yun C Song, Rebecca Paton, Sarah Eagles, Andrea Goldstein-Piekarski, Stuart M Grieve, Anthony W F Harris, Tim Usherwood, Amit Etkin

Registry-linked trialOpen access · bronzeAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04342299 (The Antidepressant Advisor), which is not on this map. Cited by 91 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed, 4 pooled it
15.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04342299 completednot on this mapstarted 2018, after this paper: background citation

The Antidepressant Advisor: A Decision Support System for UK Primary Care - a Feasibility Study: Study 3

TypeobservationalSponsorKing's College LondonRan2018 to 2021Enrolled45ConditionsMajor Depressive Disorder
3 · Its place in the literature

Who cites it

91 citing papers in PubMed, 4 syntheses or guidelines pooled it, 198 citations in OpenAlex.

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  5. Examining fronto-limbic brain and sleep mechanisms of antidepressant effects in cognitive-behavioral therapy for insomnia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
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31 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

Leanne M Williams1] Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA [2] Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC) Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA [3] The Brain Dynamics Center, Sydney Medical School, University of Sydney and Westmead Millennium Institute, Sydney, NSW, Australia.
Mayuresh S Korgaonkar1] The Brain Dynamics Center, Sydney Medical School, University of Sydney and Westmead Millennium Institute, Sydney, NSW, Australia [2] Discipline of Psychiatry, Sydney Medical School, University of Sydney, Westmead Hospital, Sydney, NSW, Australia.
Yun C SongThe Brain Dynamics Center, Sydney Medical School, University of Sydney and Westmead Millennium Institute, Sydney, NSW, Australia.
Rebecca PatonThe Brain Dynamics Center, Sydney Medical School, University of Sydney and Westmead Millennium Institute, Sydney, NSW, Australia.
Sarah EaglesThe Brain Dynamics Center, Sydney Medical School, University of Sydney and Westmead Millennium Institute, Sydney, NSW, Australia.
Andrea Goldstein-Piekarski1] Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA [2] Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC) Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.
Stuart M Grieve1] The Brain Dynamics Center, Sydney Medical School, University of Sydney and Westmead Millennium Institute, Sydney, NSW, Australia [2] Discipline of Psychiatry, Sydney Medical School, University of Sydney, Westmead Hospital, Sydney, NSW, Australia [3] Sydney Translational Imaging Laboratory, Sydney Medical School, Sydney, NSW, Australia.
Anthony W F Harris1] The Brain Dynamics Center, Sydney Medical School, University of Sydney and Westmead Millennium Institute, Sydney, NSW, Australia [2] Discipline of Psychiatry, Sydney Medical School, University of Sydney, Westmead Hospital, Sydney, NSW, Australia.
Tim UsherwoodDepartment of General Practice, Sydney Medical School Westmead, University of Sydney, Sydney, NSW, Australia.
Amit Etkin1] Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA [2] Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC) Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.
University of Sydney · AUMental Illness Research, Education and Clinical Centers · USStanford University · USVA Palo Alto Health Care System · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Although the cost of poor treatment outcomes of depression is staggering, we do not yet have clinically useful methods for selecting the most effective antidepressant for each depressed person. Emotional brain activation is altered in major depressive disorder (MDD) and implicated in treatment response. Identifying which aspects of emotional brain activation are predictive of general and specific responses to antidepressants may help clinicians and patients when making treatment decisions. We examined whether amygdala activation probed by emotion stimuli is a general or differential predictor of response to three commonly prescribed antidepressants, using functional magnetic resonance imaging (fMRI). A test-retest design was used to assess patients with MDD in an academic setting as part of the International Study to Predict Optimized Treatment in Depression. A total of 80 MDD outpatients were scanned prior to treatment and 8 weeks after randomization to the selective serotonin reuptake inhibitors escitalopram and sertraline and the serotonin-norepinephrine reuptake inhibitor, venlafaxine-extended release (XR). A total of 34 matched controls were scanned at the same timepoints. We quantified the blood oxygen level-dependent signal of the amygdala during subliminal and supraliminal viewing of facial expressions of emotion. Response to treatment was defined by ⩾50% symptom improvement on the 17-item Hamilton Depression Rating Scale. Pre-treatment amygdala hypo-reactivity to subliminal happy and threat was a general predictor of treatment response, regardless of medication type (Cohen's d effect size 0.63 to 0.77; classification accuracy, 75%). Responders showed hypo-reactivity compared to controls at baseline, and an increase toward 'normalization' post-treatment. Pre-treatment amygdala reactivity to subliminal sadness was a differential moderator of non-response to venlafaxine-XR (Cohen's d effect size 1.5; classification accuracy, 81%). Non-responders to venlafaxine-XR showed pre-treatment hyper-reactivity, which progressed to hypo-reactivity rather than normalization post-treatment, and hypo-reactivity post-treatment was abnormal compared to controls. Impaired amygdala activation has not previously been highlighted in the general vs differential prediction of antidepressant outcomes. Amygdala hypo-reactivity to emotions signaling reward and threat predicts the general capacity to respond to antidepressants. Amygdala hyper-reactivity to sad emotion is involved in a specific non-response to a serotonin-norepinephrine reuptake inhibitor. The findings suggest amygdala probes may help inform the personal selection of antidepressant treatments.

Indexed as

EmotionsAdultAmygdalaAntidepressive AgentsCase-Control StudiesCitalopramFacial ExpressionFemaleHumansImage Processing, Computer-AssistedMajor Depressive DisorderMaleMiddle AgedOxygenPhotic StimulationPredictive Value of TestsAntidepressive AgentsCitalopramOxygenVenlafaxine Hydrochloride

Identifiers

PMID25824424
PMCPMC4538354
OpenAlexW2026088841

What OpenQuestion holds

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Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.