ReviewComprehensive Physiology2016
Regulation of the Hypothalamic-Pituitary-Adrenocortical Stress Response.
Review in Comprehensive Physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,087 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1,087 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,770 citations in OpenAlex.
- The association between posttraumatic stress disorder and migraine: A systematic review.Headache · 2026Pooled it
- Biomarker evidence for the pathophysiological mechanisms of insomnia: a systematic review and meta-analysis.Frontiers in immunology · 2026Pooled it
- Critical illness-related corticosteroid insufficiency after acute brain hemorrhage surgery: a prospective cohort study with a randomized trial of hydrocortisone : HYdrocortisone theraPy in nEurocRitical illness; HYPER study.Critical care (London, England) · 2026Trial
- Trial
- Voluntary versus forced exercise modulates anxiety‑like behaviors and hippocampal inflammation gene expression following traumatic stress in rats.IBRO neuroscience reports · 2026Article
- Association of Vitamin B6 and Homocysteine-ACTH Coupling With Depressive and Anxiety Symptoms in Burning Mouth Syndrome: An Exploratory Case-Control Study.Journal of oral rehabilitation · 2026Article
- Transcutaneous auricular vagus nerve stimulation for anxiety symptoms across fear, trauma, and disease contexts: a narrative review of clinical evidence and mechanisms.European archives of psychiatry and clinical neuroscience · 2026Review
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- Chronic Pre-Trauma Corticosterone Attenuates Trauma Memory Formation and Alters Gene Expression in Glucocorticoid Signalling Pathways.Genes, brain, and behavior · 2026Article
- Early life experiences, the neural epigenome and affective disorder risk.Nature reviews. Neuroscience · 2026Review
- Stress, needs, and behaviour: understanding chronic stress in pet domestic dogs (Canis lupus familiaris) from the prism of needs.Biological reviews of the Cambridge Philosophical Society · 2026Review
- Chronic stress and myeloid immunosuppression in cancer: A neuroimmune link to behavioral dysfunction.Brain, behavior, & immunity - health · 2026Review
- Impact of environmental enrichment and allostatic load induced by repeated mixing on the transcriptome of three porcine brain tissues.Molecular brain · 2026Article
- Is cold exposure a viable lifestyle intervention for mental health? Reviewing evidence and mechanisms.Molecular psychiatry · 2026Review
- Impact of Short-term Rehabilitation on Chronic Stress-induced Brain Alterations and Associated Cognitive Deficits.Annals of neurosciences · 2026Article
- Article
- Hypothalamic c-Fos expression changes during late chicken embryonic development and increases following experimental stimulation.Scientific reports · 2026Article
- From Cellular Stress to Systemic Adaptation: The Circadian Clock and Stress Response at Cellular and Systemic Levels.International journal of molecular sciences · 2026Review
- The Adolescent Microbiome-Gut-Brain Axis: Development, Mechanisms, and Translational Perspectives.Nutrients · 2026Review
1,027 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The hypothalamo-pituitary-adrenocortical (HPA) axis is required for stress adaptation. Activation of the HPA axis causes secretion of glucocorticoids, which act on multiple organ systems to redirect energy resources to meet real or anticipated demand. The HPA stress response is driven primarily by neural mechanisms, invoking corticotrophin releasing hormone (CRH) release from hypothalamic paraventricular nucleus (PVN) neurons. Pathways activating CRH release are stressor dependent: reactive responses to homeostatic disruption frequently involve direct noradrenergic or peptidergic drive of PVN neurons by sensory relays, whereas anticipatory responses use oligosynaptic pathways originating in upstream limbic structures. Anticipatory responses are driven largely by disinhibition, mediated by trans-synaptic silencing of tonic PVN inhibition via GABAergic neurons in the amygdala. Stress responses are inhibited by negative feedback mechanisms, whereby glucocorticoids act to diminish drive (brainstem) and promote transsynaptic inhibition by limbic structures (e.g., hippocampus). Glucocorticoids also act at the PVN to rapidly inhibit CRH neuronal activity via membrane glucocorticoid receptors. Chronic stress-induced activation of the HPA axis takes many forms (chronic basal hypersecretion, sensitized stress responses, and even adrenal exhaustion), with manifestation dependent upon factors such as stressor chronicity, intensity, frequency, and modality. Neural mechanisms driving chronic stress responses can be distinct from those controlling acute reactions, including recruitment of novel limbic, hypothalamic, and brainstem circuits. Importantly, an individual's response to acute or chronic stress is determined by numerous factors, including genetics, early life experience, environmental conditions, sex, and age. The context in which stressors occur will determine whether an individual's acute or chronic stress responses are adaptive or maladaptive (pathological).
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.