Evidence map›Paper›PMID 34492429›Full record

Observational studyJournal of affective disorders2021

Greater baseline connectivity of the salience and negative affect circuits are associated with natural improvements in anxiety over time in untreated participants.

Bailey Holt-Gosselin, Arielle S Keller, Megan Chesnut, Ruth Ling, Katherine A Grisanzio, Leanne M Williams

Abstract readObservational Study
In one paragraph

Observational study in Journal of affective disorders, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact, top 89% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. MedComm · 2025
    Article
  2. Article
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

6 authors at 3 institutions in 1 country.

Bailey Holt-GosselinDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States; Interdepartmental Neuroscience Graduate Program, Yale University, New Haven, CT, United States.
Arielle S KellerDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States; Neurosciences PhD Program, Stanford University, Stanford CA, United States.
Megan ChesnutDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States.
Ruth LingDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States.
Katherine A GrisanzioDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States.
Leanne M WilliamsDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States; Mental Illness Research, Education and Clinical Center, Palo Alto VA Healthcare System, Palo Alto, CA, United States. Electronic address: leawilliams@stanford.edu.
Stanford University · USVA Palo Alto Health Care System · USYale University · US

Funding

Mapping connectomes for disordered emotional statesU01MH109985 · NIMH · STANFORD UNIVERSITY · PI WILLIAMS, LEANNE · 2017 to 2020
$3.1M
Neural Dimensions of Threat Reactivity and Regulation for Understanding AnxietyR01MH101496 · NIMH · STANFORD UNIVERSITY · PI WILLIAMS, LEANNE · 2013 to 2016
$2.3M
NIMH NIH HHS R01 MH101496NIMH NIH HHS U01 MH109985
6 · The paper itself

Abstract

backgroundThere is limited research examining the natural trajectories of depression and anxiety, how these trajectories relate to baseline neural circuit function, and how symptom trajectory-circuit relationships are impacted by engagement in lifestyle activities including exercise, hobbies, and social interactions. To address these gaps, we assessed these relations over three months in untreated participants.

methods262 adults (59.5% female, mean age 35) with symptoms of anxiety and depression, untreated with pharmacotherapy or behavioral therapy, completed the DASS-42, WHOQOL, and custom surveys at baseline and follow-up to assess symptoms, psychosocial function, and lifestyle activity engagement. At baseline, participants underwent fMRI under task-free and task-evoked conditions. We quantified six circuits implicated in these symptoms: default mode, salience, negative and positive affect, attention, and cognitive control.

resultsFrom baseline to 3 months, some participants demonstrated a natural improvement in anxiety (24%) and depression (26%) symptoms. Greater baseline salience circuit connectivity (pFDR=0.045), specifically between the left and right insula (pFDR=0.045), and greater negative affect circuit connectivity elicited by sad faces (pFDR=0.030) were associated with anxiety symptom improvement. While engagement in lifestyle activities were not associated with anxiety improvements, engagement in hobbies moderated the association between negative affect circuit connectivity and anxiety symptom improvement (p = 0.048). LIMITATIONS: The observational design limits causal inference.

conclusionsOur findings highlight the role of the salience and negative affect circuits as potential circuit markers of natural anxiety symptom improvements over time. Future studies that identify biomarkers associated with symptom improvements are critical for the development of personalized treatment targets.

Indexed as

AnxietyAnxiety DisordersAdultCerebral CortexFemaleHumansMagnetic Resonance ImagingMaleAnxietyfMRIFunctional connectivityLongitudinal studyNegative affect circuitUntreated

Identifiers

PMID34492429
PMCPMC11890217
OpenAlexW3198512848

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.