Developmental change in amygdala reactivity during adolescence: effects of family history of depression and stressful life events
Open accessAbstract
OBJECTIVE: Although heightened amygdala reactivity is observed in patients with major depression, two critical gaps in our knowledge remain. First, it is unclear whether heightened amygdala reactivity is a premorbid vulnerability or a consequence of the disorder. Second, it is unknown how and when this neural phenotype develops. The authors sought to address these gaps by evaluating developmental change in threat-related amygdala reactivity in adolescents at high or low risk for depression based on family history, before onset of disorder. METHOD: At baseline and again 2 years later, adolescents (initially 11-15 years of age) participated in a functional MRI paradigm that elicited threat-related amygdala reactivity. After quality control, data were available for 232 adolescents at wave 1 and 197 adolescents at wave 2; longitudinal data meeting quality control at both waves were available for 157 of these participants. Change in amygdala reactivity was assessed as a function of family history of depression and severity of stressful life events. RESULTS: Threat-related amygdala reactivity increased with age in participants with a positive family history regardless of the severity of life stress reported, and it increased in adolescents with a negative family history who reported relatively severe life stress. These changes in amygdala reactivity with age occurred in the absence of clinical disorder or increases in depressive symptoms. CONCLUSIONS: These results suggest that heightened amygdala reactivity emerges during adolescence, prior to the development of depression, as a function of familial risk or, in the absence of familial risk, stressful life events.
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ELS/CT is repeatedly associated with facial threat- or negative-emotion-related amygdala hyper-responsiveness.
“However, findings are conclusive concerning amygdala responsiveness, as ELS/CT has been repeatedly associated with facial threat- or negative-emotion-related amygdala hyper-responsiveness (416, 417, 447, 448).”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [448]
The Results (Hypothesis 2; page unavailable) link higher stressful-life-event severity to increasing left-amygdala reactivity to fearful faces with age in low-risk adolescents. The Discussion (page unavailable) says childhood emotional neglect had no significant effect on amygdala development. This single study therefore supports a qualified association with life stress, not the broader claim that early-life stress or childhood trauma is repeatedly and conclusively associated with hyper-responsiveness across negative emotions. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe relation between ELS/CT and risk for adult depression is mediated by preceding amygdala hyperactivity.
“In addition, some studies even suggested that the relation between ELS/CT and risk for adult depression is actually mediated by this preceding amygdala hyperactivity (448, 449).”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [448]
The Results (Hypothesis 2; page not provided) link greater stressful life events to increasing amygdala reactivity during adolescence in adolescents without familial risk. The Discussion says this reactivity may increase later vulnerability, but the authors had not yet tested whether it mediates the link between early stress or childhood trauma and adult depression. (LLM, conf=0.87)
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“However, findings are conclusive concerning amygdala responsiveness, as ELS/CT has been repeatedly associated with facial threat- or negative-emotion-related amygdala hyper-responsiveness (416, 417, 447, 448).”
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- Authors
- Swartz, J. R., Williamson, D. E., & Hariri, A. R.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Venue
- American Journal of Psychiatry
- Published
- 2015-03-01
- Volume
- 172
- Issue
- 3
- Pages
- 276-283
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC4452289
- OpenAlex
- W2100880539
- Semantic Scholar
- 8bed70061139a5f8e411a05ffaa58b6bb2681e8b
- Cited by
- 144
- References
- 42
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 5 · 2023: 13 · 2022: 9 · 2021: 9 · 2020: 9 · 2019: 25 · 2018: 12 · 2017: 17 · 2016: 24 · 2015: 9
- FWCI
- 9.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (R01AA016274)
- National Institute on Drug Abuse (R01DA033369, R21DA022569, R01DA031579)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007376)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Keywords
- amygdala reactivity, adolescence, family history of depression, life events, developmental changes, major depressive disorder, neural phenotypes, longitudinal neuroimaging
- MeSH terms
- Adolescent, Amygdala, Depressive Disorder, Family, Female, Humans, Life Change Events, Magnetic Resonance Imaging, Male, Psychological Techniques, Psychopathology, Risk Factors, Stress, Psychological, Risk Assessment
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