Cited by 106Functional Brain Connectivity StudiesMental Health Research TopicsNeural and Behavioral Psychology Studies

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Parsing Heterogeneity in the Brain Connectivity of Depressed and Healthy Adults During Positive Mood

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Price, Rebecca B., Lane, Stephanie, Gates, Kathleen, Kraynak, Thomas E., Horner, Michelle S., Thase, Michael E., Siegle, Greg J.·2017·Biological Psychiatry

DOI 10.1016/j.biopsych.2016.06.023PMC PMC5215983

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Abstract

Background There is well-known heterogeneity in affective mechanisms in depression that may extend to positive affect. We used data-driven parsing of neural connectivity to reveal subgroups present across depressed and healthy individuals during positive processing, informing targets for mechanistic intervention.Methods Ninety-two individuals (68 depressed patients, 24 never-depressed control subjects) completed a sustained positive mood induction during functional magnetic resonance imaging. Directed functional connectivity paths within a depression-relevant network were characterized using Group Iterative Multiple Model Estimation (GIMME), a method shown to accurately recover the direction and presence of connectivity paths in individual participants. During model selection, individuals were clustered using community detection on neural connectivity estimates. Subgroups were externally tested across multiple levels of analysis.Results Two connectivity-based subgroups emerged: subgroup A, characterized by weaker connectivity overall, and subgroup B, exhibiting hyperconnectivity (relative to subgroup A), particularly among ventral affective regions. Subgroup predicted diagnostic status (subgroup B contained 81% of patients; 50% of control subjects; χ 2 = 8.6, p = .003) and default mode network connectivity during a separate resting-state task. Among patients, subgroup B members had higher self-reported symptoms, lower sustained positive mood during the induction, and higher negative bias on a reaction-time task. Symptom-based depression subgroups did not predict these external variables.Conclusions Neural connectivity-based categorization travels with diagnostic category and is clinically predictive, but not clinically deterministic. Both patients and control subjects showed heterogeneous, and overlapping, profiles. The larger and more severely affected patient subgroup was characterized by ventrally driven hyperconnectivity during positive processing. Data-driven parsing suggests heterogeneous substrates of depression and possible resilience in control subjects in spite of biological overlap.

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Authors: Price, R. B., Lane, S., Gates, K., Kraynak, T. E., Horner, M. S., Thase, M. E., & Siegle, G. J.
Affiliations: University of Pittsburgh (US)
University of North Carolina at Chapel Hill (US)
Philadelphia VA Medical Center (US)
Corresponding author: Price, Rebecca B.
ORCID: Price, Rebecca B.
Lane, Stephanie
Gates, Kathleen
Kraynak, Thomas E.
Thase, Michael E.
Siegle, Greg J.
Venue: Biological Psychiatry
Publisher: Elsevier BV
Published: 2017-02
Volume: 81
Issue: 4
Pages: 347-357
ISSN: 0006-3223 (ISSN-L)
DOI: 10.1016/j.biopsych.2016.06.023
PMC: PMC5215983
OpenAlex: W2463383187
Cited by: 106
References: 56
Citations by year: 2026: 5 · 2025: 6 · 2024: 7 · 2023: 15 · 2022: 9 · 2021: 18 · 2020: 17 · 2019: 9 · 2018: 10 · 2017: 8
FWCI: 6.15
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biological Psychiatry (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Heart, Lung, and Blood Institute (T32HL007560)
National Institute of Mental Health (R01MH069618, K02MH082998, R01MH058397, K23MH100259, R01MH074807, R01MH058356)
National Institute of Biomedical Imaging and Bioengineering (R21EB015573)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
Social Sciences › Psychology › Experimental and Cognitive Psychology › Mental Health Research Topics
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords: depression, positive mood, neuronal heterogeneity, directed functional connectivity, GIMME, community detection, default mode network, mood induction, negative bias, resilience
MeSH terms: Adult, Affect, Brain, Brain Mapping, Depressive Disorder, Major, Major Depressive Disorder, Female, Humans, Magnetic Resonance Imaging, Male, Neural Pathways, Psychiatric Status Rating Scales, Resilience, Psychological

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Parsing Heterogeneity in the Brain Connectivity of Depressed and Healthy Adults During Positive Mood

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