Open research questions in Stress Responses and Cortisol
622 gap statements mined from Stress Responses and Cortisol papers in our 7.9M-paper local library, which holds 2,677 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.
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What the literature leaves open
However, because metabolic flux and pathway activity were not directly measured, the functional consequences of these molecular changes remain to be established. Despite these insights, certain limitations remain to be addressed in future investigations.
Lavender essential oil coordinates epidermal GABA shunt and nucleotide turnover to rescue cortisol-induced stress damage · 2026 · DOIFuture research should focus on elucidating the precise molecular and neurobiological mechanisms underlying corticosteroid-induced psychiatric effects. Special attention is warranted for paediatric and geriatric populations, patients with pre-existing psychiatric or neurological disorders, and those undergoing prolonged or high-dose corticosteroid therapies.
Corticosteroid-Induced neuropsychiatric manifestations: From pathophysiology to management · 2026 · DOITo advance the framework proposed in the present study, future research could emphasize timepoint-specific, direct comparisons of pharmacological agents across various stages of post-trauma neurobiology.
Future research is needed to investigate the possible causes of these dissimilar stress effects in a military population. Impulse control remains unaffected by the effects of heightened noradrenaline and cortisol, contributing to the inconsistent results of the effects of acute stress on inhibition.
Noradrenaline and cortisol exert differential effects on working memory and risk-taking behaviour in military personnel · 2026 · DOIThe relatively small sample size is a further limitation of this study, primarily due to the limited availability of eligible non-resilient participants within the source cohort. However, conclusions are limited by the small subsample with available HCC data.
Stress and resilience: cortisol hypo-response to acute stress in non-resilient individuals · 2026 · DOIFuture research should include additional measurement time points to assess recovery dynamics more precisely. Moreover, repeated exposure to the SECPT may allow investigation of habituation processes in relation to resilience.
Stress and resilience: cortisol hypo-response to acute stress in non-resilient individuals · 2026 · DOIA limitation of the present study is the relatively small sample size (n = 12), which may have reduced the statistical power and limited the generalizability of the findings to broader populations of athletes. A limitation of this study is its observational design, which precludes causal inferences and allows only the identification of associations between the investigated variables.
Stress Dynamics in a Basketball Game: Examining Stressors, Game-Specific Factors, and Players’ Positions · 2026 · DOIOnly a limited number of studies have examined the relationship between playing time and stress biomarkers in basketball players, with available evidence largely restricted to cortisol, while comparable data for salivary alpha-amylase remain scarce.
Stress Dynamics in a Basketball Game: Examining Stressors, Game-Specific Factors, and Players’ Positions · 2026 · DOIFuture research should investigate whether specific personality traits are associated with measurable physiological patterns across gastrointestinal and reproductive systems using standardized psychometric tools, endocrine profiling, and functional clinical assessments.
Personality beyond the brain: a new perspective on the brain-gut-gonadal axis and human fertility · 2026 · DOIThe NLRP3 inflammasome and gut microbiome are key regulators of neuroinflammation, yet their roles across distinct pubertal stress paradigms remain unclear.
Sex and stress paradigm influence behavioural, neuroimmune, and microbiome responses in pubertal CD-1 mice · 2026 · DOIAs a result, it remains uncertain whether the observed effects on oxytocin and cortisol are sustained or revert to baseline over time.
Investigating the psychophysiological effects of NaiKan Therapy: salivary oxytocin and cortisol release · 2025 · DOIHowever, little is known about patterns of combined immune/inflammatory mediator (IM) and hypothalamic-pituitary-adrenal (HPA) axis responding to acute stress in human pregnancy, let alone variations associated with maternal health risks.
Coordination of inflammatory and adrenocortical stress response during pregnancy and variation by mental health · 2025 · DOIOverall, determining the inflammatory effect of chronic stress in understudied brain regions important in mood and behavior is an important step to understanding the overall impact of stress.
While the underlying mechanisms of AD are not fully understood, differences between the sexes, genetic predispositions, hormones, and environmental factors may influence the onset and severity.
Sex and Gender Differences in Alzheimer’s Disease: Genetic, Hormonal, and Inflammation Impacts · 2024 · DOIWhether the adrenal function affects cognitive functions under chronic excess GC intervention remains unclear. Firstly, the peripheral MR/GR’s effects on the CNS have not been elucidated.
Chronic Corticosterone Administration-Induced Mood Disorders in Laboratory Rodents: Features, Mechanisms, and Research Perspectives · 2024 · DOIThe markers investigated were self-reported positive and negative affect, heart rate, electrodermal activity, salivary cortisol, and ten inflammatory markers both in capillary plasma and salivary samples, including IL-22 which has not been studied in response to acute stress in humans before.
Limited research has evaluated factors that predict variation in maternal and offspring toddler hair cortisol, which is important since hair cortisol represents different dynamics of hypothalamic pituitary adrenal (HPA)-axis function than more common salivary or serum measures.
Previous studies have suggested that maternal childhood trauma (MCT) may influence infant temperament, but the underlying physiological mechanisms remain unclear.
Infant Temperament Is Associated With Milk Cortisol but Not With Maternal Childhood Trauma · 2024 · DOINevertheless, personality-related biological variability may represent an underexplored factor in reproductive physiology and unexplained infertility.
Personality beyond the brain: a new perspective on the brain-gut-gonadal axis and human fertility · 2026 · DOICurrent treatments primarily target symptom relief, and the biological mechanisms underlying GWI remain poorly understood.
Multi-omic analysis reveals brain–blood concordance and persistent neuroimmune reprogramming with stress and toxicant exposure in a mouse model of Gulf War Illness · 2026 · DOIEarly caregiving relationships shape the coordination of stress and immune systems, yet their biological correlates in early infancy remain insufficiently understood.
While research on the HPA axis is growing, few studies have examined whether different types of stressors affect HPA functioning differently, and none have done so in small‐scale subsistence populations.
Not All Stress Is the Same: Variable Associations Between Psychosocial Stressors and Urinary Cortisol Rhythms in a Small‐Scale Subsistence Society · 2026 · DOISeventh, neuronal density analysis was limited to the CA1 subregion of the hippocampus.
Severity-dependent changes in hippocampal necroptosis markers and neuronal loss in a PTSD-like mouse model: potential involvement of nitric oxide signaling · 2026 · DOIAccurate measurement of cortisol levels in dogs - Influence of environmental factors on cortisol levels - Clinical and behavioral implications of abnormal cortisol levels - Need for careful consideration of individual variability and acute stressors when interpreting cortisol…
Limited understanding of cortisol's effects on canine health and stress management - Need for a comprehensive review of cortisol measurement methods - Gap in knowledge on the influence of environmental factors on cortisol…
Most-cited papers in Stress Responses and Cortisol
- Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene · Science · 2003 · 6,157 citations
- Protective and Damaging Effects of Stress Mediators · New England Journal of Medicine · 1998 · 5,020 citations
- The Concepts of Stress and Stress System Disorders · JAMA · 1992 · 4,703 citations
- The Stress Process · Journal of Health and Social Behavior · 1981 · 4,553 citations
- Acute Stressors and Cortisol Responses: A Theoretical Integration and Synthesis of Laboratory Research. · Psychological Bulletin · 2004 · 4,419 citations
- Stress and the individual. Mechanisms leading to disease · Archives of Internal Medicine · 1993 · 4,299 citations
- Stress, Adaptation, and Disease: Allostasis and Allostatic Load · Annals of the New York Academy of Sciences · 1998 · 3,978 citations
- Stress and the Individual · Archives of Internal Medicine · 1993 · 3,920 citations
- The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis · JAMA · 1992 · 3,610 citations
- Maternal Care, Hippocampal Glucocorticoid Receptors, and Hypothalamic-Pituitary-Adrenal Responses to Stress · Science · 1997 · 2,514 citations
Most recent work
- Spirituality Moderates The Relationship of Stress-Linked Psychosocial Factors To Cortisol Homeostasis and Allostatic Load Among Afro-Caribbean Women · PubMed · 2026
- Endocrine and metabolic determinants of cardiometabolic risk in mild autonomous cortisol secretion · EBioMedicine · 2026
- Central neurons encode interleukin-1β signals and mediate stress-induced inflammation · The Journal of Experimental Medicine · 2026
- Neuroendocrine signature of ME/CFS: Meta-analytic evidence for bioactive cortisol deficit and exaggerated feedback sensitivity · Molecular Psychiatry · 2026
- Socioeconomic Status and Subdivisions of the Amygdala and Hippocampus in Children and Adolescents · bioRxiv · 2026
- Ferroplasticity drives social isolation-induced anxiety via a ventral hippocampal iron-α-synuclein axis · Cell Metabolism · 2026
- Allostatic load, personality traits, and cancer risk: A prospective cohort study · Psychological Medicine · 2026
- Metabolic effects of metyrapone treatment in patients with mild autonomous cortisol secretion: a prospective proof-of-concept trial · EClinicalMedicine · 2026
- Beyond the HPA axis: Synaptic circuits of PVNCRH neurons in stress-related psychiatric disorders · Pharmacological Research · 2026
- Epigenetic Basis of Stress-Induced Central Nervous System Disorders: Therapeutic Approaches · Biology · 2026
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