ArticlePsychoneuroendocrinology2017
Hypothalamic-pituitary-adrenal axis genetic variation and early stress moderates amygdala function.
Article in Psychoneuroendocrinology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The role of SKA2 on affective disorder, post-traumatic stress disorder and suicide behavior: systematic review and in silico analysis.Metabolic brain disease · 2024Pooled it
- Prenatal Internal Exposure to Polycyclic Aromatic Hydrocarbons, Maternal Genetic Susceptibility, and Child Growth Trajectories: Evidence from a Prospective Cohort Study.Environmental science & technology · 2026Article
- Molecular Mechanisms of Depression: The Interplay Between Genes and Receptors.International journal of molecular sciences · 2025Review
- Independent, Multiplicative, and Cumulative Effects of Recent Stressful Life Events and Adverse Childhood Events on Depressive Symptoms among College Students: Moderation by the HPA-axis Multilocus Genetic Variation.Journal of youth and adolescence · 2025Article
- Peripheral DNA Methylation of Cortisol- and Serotonin-Related Genes Predicts Hippocampal Volume in a Pediatric Population.Biological psychiatry global open science · 2025Article
- Examining hypothalamic-pituitary-adrenal axis genetic variation on cortisol and alpha-amylase reactivity during an explicit negative-evaluative stress induction.Stress and health : journal of the International Society for the Investigation of Stress · 2024Article
- The Interaction of Polygenic Susceptibility to Stress and Childhood Adversity Dimensions Predicts Longitudinal Trajectories of Stress-Sensitivity.Stress and health : journal of the International Society for the Investigation of Stress · 2024Article
- Allostasis, health, and development in Latin America.Neuroscience and biobehavioral reviews · 2024Review
- Hypothalamic-Pituitary-Adrenal Axis and Epilepsy.Journal of clinical neurology (Seoul, Korea) · 2024Review
- Acupressure: a possible therapeutic strategy for anxiety related to COVID-19: a meta-analysis of randomized controlled trials.Frontiers in medicine · 2024Review
- Stress-related cellular pathophysiology as a crosstalk risk factor for neurocognitive and psychiatric disorders.BMC neuroscience · 2023Review
- Implementing Core Genes and an Omnigenic Model for Behaviour Traits Prediction in Genomics.Genes · 2023Review
- Article
- Borderline Personality Disorder: Risk Factors and Early Detection.Diagnostics (Basel, Switzerland) · 2021Review
- Neural Responses to Fluoxetine in Youths with Disruptive Behavior and Trauma Exposure: A Pilot Study.Journal of child and adolescent psychopharmacology · 2021Article
- HPA-axis multilocus genetic profile score moderates the association between maternal prenatal perceived stress and offspring depression in early adulthood.Development and psychopathology · 2021Article
- Maltreatment timing, HPA axis functioning, multigenic risk, and depressive symptoms in African American youth: Differential associations without moderated mediation.Development and psychopathology · 2020Article
- Effects ofJournal of neurology, neurosurgery, and psychiatry · 2020Article
- [Moderated mediation analysis for symptoms of attention deficit/hyperactivity disorder with the symptoms of anxiety in children].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2020Article
- Finding intestinal fortitude: Integrating the microbiome into a holistic view of depression mechanisms, treatment, and resilience.Neurobiology of disease · 2020Review
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Authors and funding
7 authors.
Funding
Abstract
Early life stress may precipitate psychopathology, at least in part, by influencing amygdala function. Converging evidence across species suggests that links between childhood stress and amygdala function may be dependent upon hypothalamic-pituitary-adrenal (HPA) axis function. Using data from college-attending non-Hispanic European-Americans (n=308) who completed the Duke Neurogenetics Study, we examined whether early life stress (ELS) and HPA axis genetic variation interact to predict threat-related amygdala function as well as psychopathology symptoms. A biologically-informed multilocus profile score (BIMPS) captured HPA axis genetic variation (FKBP5 rs1360780, CRHR1 rs110402; NR3C2 rs5522/rs4635799) previously associated with its function (higher BIMPS are reflective of higher HPA axis activity). BOLD fMRI data were acquired while participants completed an emotional face matching task. ELS and depression and anxiety symptoms were measured using the childhood trauma questionnaire and the mood and anxiety symptom questionnaire, respectively. The interaction between HPA axis BIMPS and ELS was associated with right amygdala reactivity to threat-related stimuli, after accounting for multiple testing (empirical-p=0.016). Among individuals with higher BIMPS (i.e., the upper 21.4%), ELS was positively coupled with threat-related amygdala reactivity, which was absent among those with average or low BIMPS. Further, higher BIMPS were associated with greater self-reported anxious arousal, though there was no evidence that amygdala function mediated this relationship. Polygenic variation linked to HPA axis function may moderate the effects of early life stress on threat-related amygdala function and confer risk for anxiety symptomatology. However, what, if any, neural mechanisms may mediate the relationship between HPA axis BIMPS and anxiety symptomatology remains unclear.
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