The DOI matches its Crossref record; 116 of the 117 references it cites were found in a registry or an index.
Pretreatment Rostral Anterior Cingulate Cortex Theta Activity in Relation to Symptom Improvement in Depression: A Randomized Clinical Trial
Open accessAbstract
Importance: Major depressive disorder (MDD) remains challenging to treat. Although several clinical and demographic variables have been found to predict poor antidepressant response, these markers have not been robustly replicated to warrant implementation in clinical care. Increased pretreatment rostral anterior cingulate cortex (rACC) theta activity has been linked to better antidepressant outcomes. However, no prior study has evaluated whether this marker has incremental predictive validity over clinical and demographic measures. Objective: To determine whether increased pretreatment rACC theta activity would predict symptom improvement regardless of randomization arm. Design, Setting, and Participants: A multicenter randomized clinical trial enrolled outpatients without psychosis and with chronic or recurrent MDD between July 29, 2011, and December 15, 2015 (Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care [EMBARC]). Patients were consecutively recruited from 4 university hospitals: 634 patients were screened, 296 were randomized to receive sertraline hydrochloride or placebo, 266 had electroencephalographic (EEG) recordings, and 248 had usable EEG data. Resting EEG data were recorded at baseline and 1 week after trial onset, and rACC theta activity was extracted using source localization. Intent-to-treat analysis was conducted. Data analysis was performed from October 7, 2016, to January 19, 2018. Interventions: An 8-week course of sertraline or placebo. Main Outcomes and Measures: The 17-item Hamilton Rating Scale for Depression score (assessed at baseline and weeks 1, 2, 3, 4, 6, and 8). Results: The 248 participants (160 [64.5%] women, 88 [35.5%] men) with usable EEG data had a mean (SD) age of 36.75 (13.15) years. Higher rACC theta activity at both baseline (b = -1.05; 95% CI, -1.77 to -0.34; P = .004) and week 1 (b = -0.83; 95% CI, -1.60 to -0.06; P < .04) predicted greater depressive symptom improvement, even when controlling for clinical and demographic variables previously linked with treatment outcome. These effects were not moderated by treatment arm. The rACC theta marker, in combination with clinical and demographic variables, accounted for an estimated 39.6% of the variance in symptom change (with 8.5% of the variance uniquely attributable to the rACC theta marker). Conclusions and Relevance: Increased pretreatment rACC theta activity represents a nonspecific prognostic marker of treatment outcome. This is the first study to date to demonstrate that rACC theta activity has incremental predictive validity. Trial Registration: clinicaltrials.gov Identifier: NCT01407094.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“In both MDD and TRD, region-specific normalization of GABA concentrations in the occipital cortex (OCC), ACC, and DMN have repeatedly been observed in response to all successful antidepressant therapies [19,22,23,63].”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [22]
Experimental — accuracy not yet measuredIn the citing paper
“An imbalance between two primary central nervous system (CNS) neurotransmitters, L-glutamate and γ-aminobutyric acid (GABA), has emerged as having a key role in the pathophysiology of TRD.”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [22]
In the citing paper
“Glutamatergic and GABAergic dysfunction in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) has been extensively implicated in both MDD and TRD [16,17,18,19,20,21,22,23,24,25].”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [22]
In the citing paper
“In contrast, higher baseline ACC activity is associated with improved outcomes [22].”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [22]
In the citing paper
“In TRD specifically, rostral ACC function may mediate the balance between negative rumination and constructive self-evaluation, both facilitated by the DMN [17,22], suggesting that ACC dysfunction plays a role in excessive negative rumination.”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [22]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Hamilton, M. (1960) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.23.1.56 · Cited by 32,817
A new depression scale designed to be sensitive to change
Montgomery, S. A., & Åsberg, M. (1979) · British Journal of Psychiatry · doi:10.1192/bjp.134.4.382 · Cited by 13,962
Applied Longitudinal Data Analysis: Modeling Change and Event Occurrence
Singer, J. D., & Willett, J. B. (2003) · doi:10.1093/acprof:oso/9780195152968.001.0001 · Cited by 10,647
The Brain's Default Network: Anatomy, Function, and Relevance to Disease
Buckner, R. L., Andrews‐Hanna, J. R., & Schacter, D. L. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1440.011 · Cited by 9,761
Development of a Rating Scale for Primary Depressive Illness
Hamilton, M. (1967) · British Journal of Social and Clinical Psychology · doi:10.1111/j.2044-8260.1967.tb00530.x · Cited by 8,410
Development and validation of a brief screening version of the Childhood Trauma Questionnaire
Bernstein, D. P., Stein, J. A., Newcomb, M. D., Walker, E., Pogge, D., Ahluvalia, T., Stokes, J., Handelsman, L., Medrano, M., Desmond, D., et al. (2003) · Child Abuse & Neglect · doi:10.1016/s0145-2134(02)00541-0 · Cited by 6,419
Rush, A. J., Trivedi, M. H., Wisniewski, S. R., Nierenberg, A. A., Stewart, J. W., Warden, D., Niederehe, G., Thase, M. E., Lavori, P. W., Lebowitz, B. D., et al. (2006) · American Journal of Psychiatry · doi:10.1176/ajp.2006.163.11.1905 · Cited by 5,643
Self-citationSmall sample inference for fixed effects from restricted maximum likelihood
Kenward, M. G., & Roger, J. H. (1997) · Biometrics · doi:10.2307/2533558 · Cited by 4,552
Trivedi, M. H., Rush, A. J., Wisniewski, S. R., Nierenberg, A. A., Warden, D., Ritz, L., Norquist, G., Howland, R. H., Lebowitz, B., McGrath, P. J., et al. (2006) · American Journal of Psychiatry · doi:10.1176/appi.ajp.163.1.28 · Cited by 3,879
Self-citationRush, A. J., Trivedi, M. H., Ibrahim, H. M., Carmody, T. J., Arnow, B., Klein, D. N., Markowitz, J. C., Ninan, P. T., Kornstein, S., Manber, R., et al. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01866-8 · Cited by 3,829
Self-citation
Research works printed but not linked: 1
- First, 2002, Structured Clinical Interview for DSM-IV-TR Axis I Disorders-Non-Patient Edition (SCID-I/NP, 11/2002 revision)
Cited by
Sorted by citations
Mental health before and during the COVID-19 pandemic in two longitudinal UK population cohorts
Kwong, A. S. F., Pearson, R. M., Adams, M. J., Northstone, K., Tilling, K. M., Major‐Smith, D., Fawns‐Ritchie, C., Bould, H., Warne, N., Zammit, S., et al. (2020) · The British Journal of Psychiatry · doi:10.1192/bjp.2020.242 · Cited by 543
Prognosis and improved outcomes in major depression: a review
Kraus, C., Kadriu, B., Lanzenberger, R., Zarate, C. A., & Kasper, S. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0460-3 · Cited by 482
Candidate biomarkers in psychiatric disorders: state of the field
Abi‐Dargham, A., Moeller, S. J., Ali, F., DeLorenzo, C., Domschke, K., Horga, G., Jutla, A., Kotov, R., Paulus, M. P., Rubio, J. M., et al. (2023) · World Psychiatry · doi:10.1002/wps.21078 · Cited by 421
An electroencephalographic signature predicts antidepressant response in major depression
Wu, W., Zhang, Y., Jiang, J., Lucas, M. V., Fonzo, G. A., Rolle, C. E., Cooper, C., Chin-Fatt, C., Krepel, N., Cornelssen, C. A., et al. (2020) · Nature Biotechnology · doi:10.1038/s41587-019-0397-3 · Cited by 302
Self-citationDissecting diagnostic heterogeneity in depression by integrating neuroimaging and genetics
Buch, A. M., & Liston, C. M. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-020-00789-3 · Cited by 289
Metadata
- Authors
- Pizzagalli, D. A., Webb, C. A., Dillon, D. G., Tenke, C. E., Kayser, J., Goer, F., Fava, M., McGrath, P., Weissman, M., Parsey, R., Adams, P., Trombello, J., Cooper, C., Deldin, P., Oquendo, M. A., McInnis, M. G., Carmody, T., Bruder, G., & Trivedi, M. H.
- Affiliations
- Harvard University (US)
- New York State Psychiatric Institute (US)
- Department of Psychiatry, New York State Psychiatric Institute & Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York
- Department of Psychiatry, Harvard Medical School, Massachusetts General Hospital, Boston
- Stony Brook University (US)
- The University of Texas Southwestern Medical Center (US)
- University of Michigan (US)
- Department of Psychiatry, University of Pennsylvania, Perelman School of Medicine, Philadelphia
- Corresponding author
- Pizzagalli, Diego A.
- ORCID
- Venue
- JAMA Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2018-06-01
- Volume
- 75
- Issue
- 6
- Pages
- 547
- ISSN
- 2168-622X (ISSN-L)
- PMC
- PMC6083825
- OpenAlex
- W2797156514
- Cited by
- 189
- References
- 117
- Citations by year
- 2026: 19 · 2025: 16 · 2024: 18 · 2023: 19 · 2022: 16 · 2021: 41 · 2020: 25 · 2019: 27 · 2018: 8
- FWCI
- 16.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Psychiatry (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- John Templeton Foundation
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Novartis
- Sanofi
- Teva Pharmaceutical Industries
- Sunovion
- National Alliance for Research on Schizophrenia and Depression
- Vanda Pharmaceuticals
- Arcadia Fund
- Avanir Pharmaceuticals
- Cerecor
- Supernus Pharmaceuticals
- American Society of Clinical Psychopharmacology
- Usona Institute
- Otsuka America
- Belvoir Media Group
- Vistagen Therapeutics
- University of Oxford
- Servier
- H. Lundbeck A/S
- Agency for Healthcare Research and Quality
- Allergan
- National Institute of Mental Health (R00MH094438, U01MH092250, K23MH108752, U01MH092221)
- National Institute of Diabetes and Digestive and Kidney Diseases
- Janssen Research and Development
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- major depressive disorder, rostral anterior cingulate cortex, theta activity, resting-state EEG, antidepressant response prediction, sertraline, source localization, Hamilton Depression Rating Scale, incremental predictive validity
- MeSH terms
- Adult, Antidepressive Agents, Depressive Disorder, Major, Major Depressive Disorder, Electroencephalography, Female, Gyrus Cinguli, Humans, Male, Middle Aged, Prognosis, Theta Rhythm, Treatment Outcome, Sertraline, 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
