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Cited by 44Child and Adolescent Psychosocial and Emotional DevelopmentNeural and Behavioral Psychology StudiesTreatment of Major Depression

Anterior Insula Volume and Guilt: Neurobehavioral Markers of Recurrence After Early Childhood Major Depressive Disorder

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Belden, Andy C., Barch, Deanna M., Oakberg, Timothy J., April, Laura M., Harms, Michael P., Botteron, Kelly N., Luby, Joan L.·2015·JAMA Psychiatry
DOI 10.1001/jamapsychiatry.2014.1604PMC PMC5103694
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Abstract

IMPORTANCE: This is the first study to date to examine volumetric alterations in the anterior insula (AI) as a potential biomarker for the course of childhood major depressive disorder (MDD). OBJECTIVES: To examine whether children with a history of preschool-onset (PO) MDD show reduced AI volume, whether a specific symptom of PO MDD (pathological guilt) is related to AI volume reduction (given the known relationship between AI and guilt processing), and whether AI volumes predict subsequent likelihood of having an episode of MDD. DESIGN, SETTING, AND PARTICIPANTS: In a prospective longitudinal study, 306 children (age range, 3.00-5.11 years) and caregivers completed DSM diagnostic assessments at 6 annual time points during 10 years as part of the Preschool Depression Study. Magnetic resonance imaging was completed on a subset of 145 school-age children (age range, 6.11-12.11 years). MAIN OUTCOMES AND MEASURES: Whole-brain-adjusted AI volume measured using magnetic resonance imaging at school age and children's diagnosis of MDD any time after their imaging. RESULTS: Compared with children without a history of PO MDD, school-age children previously diagnosed as having PO MDD had smaller left and right AI volumes (Wilks Λ = 0.94, F2,124 = 3.37, P = .04, Cohen d = 0.23). However, the effect of PO MDD on reduced AI volumes was better explained by children's experience of pathological guilt during preschool (Λ = 0.91, F2,120 = 6.17, P = .003, d = .30). When covarying for children's lifetime history of MDD episodes, their experience of pathological guilt during preschool, as well as their sex and age at the time of imaging, schoolchildren's right-side AI volume was a significant predictor of being diagnosed as having an MDD episode after imaging (odds ratio, 0.96; 95% CI, 0.01-0.75; P = .03). CONCLUSIONS AND RELEVANCE: These results provide evidence that structural abnormalities in AI volume are related to the neurobiology of depressive disorders starting in early childhood. The present findings are consistent with mounting research in adult MDD suggesting that insula function and structure may be a target biomarker for major depression.

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  • Reduced bilateral anterior insula volumes have been associated with pathological guilt in preschool depression and the risk for major depressive disorder later in life.

    “reduced bilateral anterior insula volumes have been associated with pathological guilt in preschool depression ant the risk for MDD later in life (Belden et al., 2015).”

    From Social functioning in major depressive disorder (2016) · cites this paper as Belden et al., 2015

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  1. [21]Weiss J Sampson H Mount Zion Psychotherapy Research Group The Psychoanalytic Process: Theory, Clinical Observation, and Empirical Research New York, NY Guilford Press 1986
  2. [28]Gangemi A Mancini F Guilt and Guilts: Re-constructing Emotional Spaces: From Experience to Regulation Prague, Czechoslovakia Prague College of Psychosocial Studies Press 2011 169 188

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Authors
Belden, A. C., Barch, D. M., Oakberg, T. J., April, L. M., Harms, M. P., Botteron, K. N., & Luby, J. L.
Affiliations
Washington University in St. Louis (US)
ORCID
Venue
JAMA Psychiatry
Publisher
American Medical Association (AMA)
Published
2015-01-01
Volume
72
Issue
1
Pages
40
ISSN
2168-622X (ISSN-L)
DOI
10.1001/jamapsychiatry.2014.1604
PMC
PMC5103694
OpenAlex
W2138836774
Cited by
44
References
68
Citations by year
2026: 1 · 2025: 5 · 2024: 5 · 2023: 2 · 2022: 4 · 2021: 1 · 2020: 3 · 2019: 7 · 2017: 5 · 2016: 4 · 2015: 6 · 2014: 1
FWCI
6.30
Type
journal article
Language
en
Open access
Locations
  • JAMA Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Public Health Service (PA-07-070 NIMH R01)
  • National Institute of Mental Health (K01MH090515, L40 MH087187, R01MH064769, R01MH090786, T32MH100019)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
anterior insula, brain volume, early childhood depression
MeSH terms
Adult, Cerebral Cortex, Child, Child, Preschool, Major Depressive Disorder, Female, Humans, Image Processing, Computer-Assisted, Life Change Events, Longitudinal Studies, Magnetic Resonance Imaging, Male, Missouri, Organ Size, Prospective Studies, Psychiatric Status Rating Scales, Recurrence, Statistics as Topic, Caregivers, Age of Onset

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