Scientific studies behind the Sapiens diagnostics

Meta-analysis of 37 massage therapy studies across nine outcomes. Single applications of massage reduced state anxiety, blood pressure, and heart rate but did NOT reduce cortisol level; the largest effects were reductions in trait anxiety and depression.

This systematic review of 30 intervention studies in adult cancer survivors examined diurnal salivary cortisol sampling protocols and reporting parameters. Diurnal cortisol slope and CAR were the most commonly reported parameters, with flattened slopes, blunted CARs and elevated evening cortisol associated with poorer outcomes. The authors propose a standardized protocol sampling at key diurnal times across three or more consecutive days.

Postpartum women with long COVID were randomized to VR-enhanced mindfulness/yoga, traditional in-person sessions, or a blank control over 8 weeks, with salivary cortisol measured. The VR group showed significantly greater reductions in depression and anxiety, plus a significant decrease in salivary cortisol (p<0.001). VR-enhanced mind-body practice lowered cortisol and symptoms.

Parkinson's disease patients were randomized to 8 weeks of meditation, yoga, or usual care, with serum cortisol, IL-6 and TNF-alpha among outcomes. Both meditation and yoga significantly improved anxiety, motor symptoms and quality of life and reduced IL-6 at 6 months; cortisol was measured as a stress biomarker. Mind-body practice improved psychological and inflammatory outcomes.

Women with high perceived stress were randomized to one of four 3-week interventions (mindfulness, slow breathing/warm showers, Wim Hof Method, or HIIT), with cortisol reactivity to a lab stressor measured. All groups reduced depressive symptoms and perceived stress with no group differences, and groups were similar in cortisol reactivity pre- and post-intervention. Cortisol reactivity did not differ between interventions (null).

In this secondary analysis of an RCT, 10-week group CBSM was associated with greater reductions in cancer-related distress and PM cortisol versus psychoeducation control in breast cancer patients. Cortisol reductions occurred only among women in advantaged neighborhoods, while distress reductions occurred across neighborhoods.

In this multinational cluster-RCT, group music therapy, choir singing, and book reading each produced significant pre/post-session changes in salivary cortisol, alpha-amylase, and subjective stress in dementia care home residents. However, no significant differences were found between the study arms. Group interventions including music can positively affect stress levels.

In this RCT of women with major depressive disorder, group music therapy produced significantly stronger stress-reducing effects than a waitlist control. Significant improvements were seen in stress coping, positive thinking, daily-life stress, and diurnal salivary cortisol levels. Group music therapy is a non-invasive approach to reduce the psychobiological burden of MDD.

Phase 1b placebo-controlled RCT of seltorexant (orexin antagonist) monotherapy in major depressive disorder, with serum cortisol and cortisol waking response among biomarkers. Seltorexant 20 mg significantly improved depression scores, and the waking cortisol response decreased in the 20 mg arm but not the 40 mg or placebo arms.

Dementia patients in care homes were randomized to 6 weeks of group music therapy or control, with salivary cortisol measured. Music therapy reduced depression and lowered salivary cortisol, with benefits maintained at 3-month follow-up while controls stayed high. Group music therapy reduced cortisol and depression.

RCT of applied relaxation training versus non-intervention control in adults with elevated distress, anxiety, or depression, measuring salivary (daily AUC, CAR) and hair cortisol. Total daily salivary cortisol AUC decreased more in the relaxation group pre-to-post, but the effect became non-significant after adjustment and there was no effect on CAR or hair cortisol. Applied relaxation showed little robust effect on cortisol.

RCT of 8-week Acceptance and Commitment Therapy versus usual care in IBD patients, with hair cortisol measured at baseline and week 20. ACT significantly reduced perceived stress and depression, but hair cortisol did not change significantly in the ACT group versus control (p=0.831).

Depressed primary care patients received 12 weeks of physical exercise, internet-based CBT, or treatment as usual, with diurnal salivary cortisol measured. Physical exercise flattened the diurnal cortisol slope and reduced awakening cortisol, while ICBT and usual care had no detectable cortisol effect. Exercise lowered morning cortisol in depression.

In this RCT, 120 subjects either listened to Mozart, Strauss, or ABBA for 25 minutes or rested in silence, with serum cortisol, blood pressure, and heart rate measured before and after. Serum cortisol decreased in all groups, with larger reductions in the Mozart and Strauss music groups than in silence (Mozart -4.56, Strauss -4.76, silence -2.39 microg/dL). Music by Mozart and Strauss also lowered blood pressure and heart rate.

Multisite RCT comparing mindfulness-based cancer recovery (meditation and yoga), supportive-expressive group therapy, and a stress-management control in distressed breast cancer survivors, with diurnal salivary cortisol slope as a primary outcome. Both MBCR (p=0.011) and SET (p=0.002) maintained cortisol slopes over time, whereas control slopes flattened.

In 200 stroke high-risk adults aged 60-85, the Allostatic Load Index from 10 cardiovascular, metabolic and inflammatory indicators was positively associated with cognitive impairment (OR=1.27; adjusted OR=1.33). Cognitive impairment affected 50.5% of participants; waist-to-height ratio (threshold 0.55) was a key component, and a random forest model achieved AUC=0.8247.

Study of 151 patients with structural heart disease determining hair cortisol concentrations (HCC) at baseline and 12-week follow-up and their associations with physiological and psychological measures. A positive association was found between HCC and BMI, and mental health status predicted change in HCC over time.

Systematic review of 8 studies of manual therapy (chiropractic, osteopathic, massage) in children with respiratory diseases, with salivary cortisol among the outcomes assessed. Six of eight studies found benefits including in spirometry, immunologic tests, anxiety, or salivary cortisol level.

Cohort study of 2170 workers (hair from 340) followed 6 years examining associations between shift work, hair cortisol concentration (HCC), and dyslipidemia. Shift workers had higher dyslipidemia risk and higher HCC; higher HCC was associated with higher dyslipidemia incidence and mediated 16.24% of the shift work effect.

In 8,581 middle-aged adults from the 1970 British Cohort Study with activPAL-measured sedentary behavior, each additional hour/day of total sedentary time was associated with 5% higher odds of high allostatic load (OR=1.05; 95% CI 1.01-1.09), and each additional sedentary break per hour with 3% lower odds (OR=0.97; 95% CI 0.94-0.99). Mean bout duration was not significantly associated with AL.

Study of 1124 adults (hair from 598) evaluating associations of childhood trauma with perceived stress and hair cortisol concentrations (HCC) in coronary artery disease and non-CVD patients. Childhood trauma was associated with greater perceived stress but not 3-month cortisol secretion in hair.

90-day double-blind RCT of a prebiotic/beta-glucan/silymarin nutraceutical blend in overweight adults, measuring weight, gut microbiota, inflammation, sleep, and cortisol. Both blend groups showed reduced body weight, improved microbiota, and reduced cortisol levels alongside better sleep and lower inflammatory ratios. The nutraceutical/diet intervention lowered the cortisol stress biomarker.

Breast cancer survivors were randomized to yoga-based exercise, comprehensive exercise, or self-chosen activity for 6 months, with diurnal salivary cortisol slope (10 samples over 2 days) measured pre/post. All groups improved perceived stress and sleep; the comprehensive exercise group showed the most favorable cortisol slope change (-0.183) approaching significance (p=0.057), with no significant between-group cortisol differences.

Pilot RCT of an MBSR program versus usual care in Parkinson's disease patient-caregiver dyads, measuring bedtime cortisol, diurnal cortisol slope, and inflammatory markers. MBSR patients showed decreased mean bedtime cortisol and IL-1beta, and caregivers showed improved diurnal cortisol slope rhythmicity versus control. MBSR improved circadian cortisol markers in both patients and caregivers.

Double-blind RCT of 8 weeks of real versus sham acupuncture for anxiety in Parkinson disease, with serum cortisol and ACTH as secondary outcomes. Real acupuncture produced a significantly greater reduction in anxiety (HAM-A) at follow-up; cortisol/ACTH were measured as secondary endpoints.

Chronic low back pain patients were randomized to a 9-session MBSR program or control, with blood cortisol and cytokines measured. The mindfulness program halted the rise in cortisol and reduced IL-1beta, while decreasing depression, stress, and pain and improving function and sleep. MBSR stabilized cortisol and lowered inflammation.

Advanced lung cancer patients were randomized to 12 weeks of aerobic exercise, tai chi, or self-management, with salivary cortisol assessed as a circadian-rhythm outcome. Interventions were feasible but effect-related outcomes, including salivary cortisol, showed no statistically significant changes in any group. Results were null for the biomarker.

In this RCT, a 3-day mindfulness retreat reduced perceived stress and anxiety and improved inflammatory cytokine balance (lower IL-6, IL-8; higher IL-10) versus active control. Salivary cortisol correlated strongly with anxiety and perceived stress at endpoint. The retreat improved key mediators of stress and inflammation.

RCT of a 12-week Paleolithic diet with or without added structured exercise in type 2 diabetes, measuring urinary glucocorticoid metabolites and cortisone-to-cortisol conversion (hepatic 11beta-HSD1 activity). Both groups lost weight and improved insulin sensitivity, with increased conversion of cortisone to cortisol reflecting altered hepatic cortisol metabolism. Weight loss changed tissue-specific cortisol metabolism rather than lowering systemic cortisol.

Pilot RCT of 10 acupressure sessions versus sham for postpartum low back pain, with salivary cortisol as a biomarker outcome. Acupressure reduced pain, activity limitations, and depression, but there was no significant between-group difference in salivary cortisol.

RCT of 4-week mindfulness-based focused attention training versus progressive muscle relaxation in remitted depressed patients, with seven daily salivary cortisol samples pre/post. No group differences in CAR or slope; total cortisol rose across groups, but mindfulness buffered this increase in patients showing marked reductions in negative affect and rumination.

Open-label RCT of an 8-week mindfulness-based program versus no intervention in infertile women, measuring chronic stress symptoms, depression, well-being, hair cortisol, and serum BDNF. The program significantly reduced stress and depressive symptoms and improved well-being, but hair cortisol and BDNF did not change significantly. Mindfulness reduced subjective stress without a significant hair-cortisol effect.

RCT comparing 8 weeks of Inner Resources mindfulness meditation and mantra versus psychoeducation and telephone support in female dementia caregivers, with diurnal cortisol slope as a primary outcome. The meditation group showed statistically significant improvement in diurnal cortisol slope and life satisfaction versus control. Meditation improved the diurnal cortisol rhythm.

Healthy volunteers were randomized to a 10-day training in meditation, breathing techniques and cold exposure or no training, then underwent experimental endotoxemia, with cortisol measured. The trained group showed increased epinephrine and higher cortisol during the practice, with greater anti-inflammatory IL-10 and lower pro-inflammatory cytokines. The mind-body training raised cortisol and suppressed the innate immune response.

Dementia caregivers were randomized to mindfulness meditation, education, or respite-only over 7 weeks, with salivary cortisol among secondary outcomes. Both active interventions reduced self-rated caregiver stress versus respite-only, but most secondary measures including salivary cortisol were not significantly affected. Cortisol results were null.

Using NHANES 2003-2010 linked to mortality files, participants in the highest allostatic load index tertile (T3) had a 52% increased probability of all-cause mortality versus T1 (OR 1.52, 95% CI 1.28-1.76). As a continuous variable, ALI was also associated with cardiac mortality (OR 1.14), though not cancer-specific mortality.

In a French military cohort deployed to Afghanistan, four allostatic load markers (urinary and blood cortisol, BDNF, 8-iso-PGF2alpha) measured pre-deployment in medically fit, symptom-free personnel were tested as predictors of partial/full PTSD after 6-month deployment. After controlling for age, baseline PCLS and number of missions, elevated pre-deployment nocturnal urinary cortisol predicted partial/full PTSD.

In UK Biobank participants aged 40-69 (median follow-up 15.4 years, 39,804 deaths), higher allostatic load (12-metric score) was associated with all-cause and cause-specific mortality in a dose-response manner. Per 1-point AL rise, associations were strongest for digestive (sHR=1.25) and cardiovascular (sHR=1.20) mortality, versus cancer (sHR=1.08) and respiratory (sHR=1.11), and were more pronounced for premature deaths.

CHARLS cohort of Chinese adults aged 45+ examined baseline AL and longitudinal AL changes against incident CVD and all-cause mortality over 7 years. Cox models assessed hazard ratios by AL category and per-unit AL change.

Among 27,393 postmenopausal women in the Women's Health Initiative (median 17.2-year follow-up), high allostatic load was associated with increased invasive breast cancer risk (HR 1.36, 95% CI 1.20-1.54 for highest vs lowest tertile). The association was strongest for hormone-receptor-positive, HER2-negative breast cancer (HR 1.54).

In the population-based AGES-Reykjavik Study, latent profile analysis of allostatic load markers identified a 'Multisystem dysregulation' profile associated with increased risk of all-cause dementia (HR 1.72), Alzheimer's disease (HR 1.75) and non-AD dementias (HR 1.87) over 12 years. AL profiles and depressive symptoms were independently related to dementia, with additive interaction for the multisystem profile.

In multiple myeloma patients enrolled in the E1A11 trial, a 1-unit increase in baseline allostatic load was associated with greater odds of high fatigue (OR 1.21) and worse overall survival (adjusted HR 1.21, 95% CI 1.06-1.37). There was no association between AL and progression-free survival or induction therapy non-completion.

Prospective study of 89 outpatients with depression and anxiety disorders testing whether pretreatment 3-month hair cortisol predicts psychological therapy response. Non-responders had lower pretreatment hair cortisol and reported more childhood trauma than responders.

Among 1,444 UK Biobank breast cancer survivors (plus 1,444 age-matched controls), AL derived from 11 biomarkers was associated with poorer sleep (beta=0.18), greater fatigue (beta=0.23), functional limitation (beta=0.28), depression (beta=0.15) and anxiety (beta=0.12), but not cognitive function. AL partially mediated 6-15% of income and 8-9% of education associations with outcomes.

Using SWAN data on 1,185 perimenopausal women aged 42-52, group-based dual trajectory modeling showed AL and depression were interactively associated: high AL trajectories increased the likelihood of high depression trajectories (14.65%) and high depression trajectories increased the likelihood of high AL trajectories (41.2%). Age, race, income, social support and vasomotor symptoms were common influences.

In 5,885 LEAD cohort participants aged 25-82, allostatic load score from 14 cardiovascular, metabolic and body-composition parameters was linked to higher odds of pre-frailty/frailty at baseline (OR=1.11, 95% CI 1.08-1.15) and to transitioning from robust to pre-frail/frail (RRR=1.06). Depressive symptoms mediated 35% of the cross-sectional and 17% of the longitudinal AL-frailty association.

Using two waves of the Tromso Study (8,117 individuals, 10 biomarkers) linked to mortality through 2022, higher biological health score (based on allostatic load theory) predicted mortality. Tromso6-BHS HR=1.20 (0.99-1.45) and Tromso7-BHS HR=1.26 (1.05-1.52); the longitudinal BHS showed the strongest 7-year mortality risk (HR=1.30; 1.09-1.56) and lowered median survival by up to 1.84 years.

In 4,989 CHARLS participants (median 9.0-year follow-up), high allostatic load (HR 3.22, 95% CI 2.39-4.33) and depressive symptoms (HR 1.82) were each associated with increased cardiometabolic multimorbidity risk. Participants with both high AL and depressive symptoms had the highest risk (HR 4.98, 95% CI 3.20-7.75).

In 3,336 Health and Retirement Study participants, allostatic load (five biomarkers) in 2012 was significantly associated with incidence of multimorbidity (2+ chronic conditions) in 2016 (estimate 0.10, 95% CI 0.07-0.14). Wealth and education were indirectly associated with multimorbidity through allostatic load and behaviours.

Using Health and Retirement Study data (2010-2016, n=3,246), severe chronic work discrimination (RRR 1.61) and high allostatic load (RRR 1.49) were each associated with elevated HbA1c, a marker of glucose control and type 2 diabetes risk. AL did not moderate the discrimination-HbA1c association; Black participants had the highest rates of elevated HbA1c and AL.

In 1,921 middle-aged and older CHARLS participants, having 2+ adverse childhood experiences (OR 1.78) and 2+ adverse adulthood experiences (OR 1.82) were associated with worse depression symptom trajectories. Increasing inflammatory allostatic load over time (OR 1.60) was associated with worse trajectories, while decreasing metabolic AL (OR 0.63) was associated with lower depression.

Using data from a phase III RCT of omega-3 supplementation in pediatric MDD, hair AEA and cortisol were measured in 110 youth with MDD across four timepoints and 127 healthy controls. Children and adolescents with MDD showed lower baseline hair cortisol and AEA than controls. Hair cortisol was negatively associated with depressive symptoms longitudinally.

This systematic review of 20 studies synthesised neuroendocrine correlates of grief and bereavement, with cortisol as the most common outcome. Bereaved subjects showed elevated mean cortisol, flattened diurnal cortisol slopes and higher morning cortisol, moderated by grief severity, depressive symptoms and individual differences. The authors call for broader neuroendocrine assessment and longitudinal designs to inform interventions.

This systematic review of burnout's medical features covers its pathophysiology and HPA axis involvement, noting that severe burnout is associated with a lower or smaller increase in the cortisol awakening response. It argues salivary cortisol evaluation can help predict and differentiate burnout from depression and anxiety.

Case-control study of 56 women (25 Parkinson's disease, 31 controls) examining hair cortisol and cortisone in relation to PD diagnosis, clinical features, and metabolic syndrome. Hair cortisone (not cortisol) was significantly higher in PD patients (d=0.87) and positively associated with mood and anxiety symptoms.

18-month RCT randomizing participants to healthy dietary guidelines, Mediterranean, or high-polyphenol green-Mediterranean diet, measuring fasting morning cortisol. Both Mediterranean diets reduced fasting cortisol by ~1.6-1.8% at 18 months, with the green-MED reduction significant versus healthy-guidelines controls. Long-term Mediterranean, especially green-MED, diet lowered fasting morning cortisol independent of weight loss.

This study of 126 overweight nondiabetic adults measured insulin resistance via insulin suppression test alongside cognitive and neuropsychiatric measures. Insulin resistance was associated with weaker fine motor performance (Purdue Pegboard) and increased subclinical depression symptoms.

This selective review of RCTs disentangled mindfulness components (attention monitoring vs experiential acceptance) affecting stress physiology including HPA-axis/cortisol activity. Monitoring plus acceptance benefited acute-challenge physiological stress, whereas monitoring alone buffered basal physiological stress with longer practice. Effects were state- and outcome-specific.

This systematic review of 59 RCTs compared music and non-music sound interventions on ICU patient outcomes, including cortisol regulation. Both slow-tempo music and sound interventions significantly regulated cortisol levels, decreased pain, improved sleep, and reduced stress/anxiety versus standard care. Music interventions had more evidence for effects on stress biomarkers than non-music sound.

This systematic review of 14 RCTs identified 18 stress biomarkers in music interventions, most commonly plasma cortisol, salivary cortisol, and salivary alpha-amylase. Of five studies reporting p-values for both biomarkers and psychological outcomes, four found significant reductions in both stress biomarkers and psychological stress in music groups. Music interventions may reduce stress biomarker levels in acute situations.

This review of 35 human trials found 25 reported significant decreases in stress and/or anxiety with yoga regimens. Of 14 studies measuring biochemical/physiological markers including cortisol, support for yoga was inconsistent. Evidence is suggestive of benefit but limited by small samples and weak designs.

This randomized controlled trial applied non-pharmacological interventions to phase-advance the sleep-wake timing of late-chronotype 'night owls', using the peak time of the cortisol awakening response as a circadian phase marker. Participants advanced their circadian timing by about 2 hours, with improvements in depression, stress, and cognitive and physical performance.

Study of 107 parent-preschooler dyads examining whether elevated baseline hair cortisol moderated effects of a 14-week mindful eating intervention on anthropometric, blood pressure, and eating behavior outcomes. Elevated child and parent hair cortisol were associated with smaller intervention benefits (e.g., less body fat reduction, less decline in emotional eating).

This ALSPAC cohort study collected salivary cortisol at four daily time points in 841 fifteen-year-olds and tested whether the cortisol awakening response predicted depression at age 18. No association was found between salivary cortisol (CAR, diurnal drop, or AUC) and subsequent depression.

In a longitudinal study of 208 Mexican-origin individuals, perceived discrimination in adolescence significantly predicted higher depression at age 26 (beta=0.09, p=0.045), and age-26 depression moderated the association between adolescent economic hardship and age-26 allostatic load. Findings indicate intersectional effects of adolescent adversity on later mental and physical health.

In 117 adolescents, resting-state fMRI measured allostatic-interoceptive system (AIS) global efficiency and depressive symptoms were assessed ~2 years later. Emotional attention moderated the AIS-depression link: for adolescents with low emotional attention, greater AIS integration predicted lower prospective depression, whereas for those with high emotional attention it predicted greater prospective depression.

In 485 low-SES Chinese adolescents assessed over one year, composite depression-anxiety scores differed minimally between high- and low-AL groups, but network structure differed. Anxiety symptoms showed stronger prospective associations with depression in the high-AL group, and somatic/gastrointestinal symptoms were more prominent bridge nodes in the high-AL network.

In 164 women (45.6% with confirmed child sexual abuse), HPA-axis attenuation was estimated from morning cortisol intercepts and slopes reflecting cumulative allostatic load, and four PTSS trajectories were identified via growth mixture modeling. Greater HPA attenuation was linked to chronic symptoms: each 1-SD decrease in cortisol slope tripled odds of the High Stable PTSS trajectory (OR=2.97, 95% CI 1.40-6.31).

Using the Midlife in Japan survey and biomarker projects (152 participants), work-to-family conflict at baseline was significantly associated with increased allostatic load index over four years (count ratio 1.15, 95% CI 1.03-1.28), whereas family-to-work conflict was not. Allostatic load is presented as a biological mechanism linking work stress to cardiovascular disease.

Memory clinic patients from the Co-STAR study underwent AL measurement (multi-system blood markers), CSF sampling for Alzheimer biomarkers, and neuropsychological testing with 3-year follow-up. Linear regressions tested AL against AD biomarkers and cognition.

This meta-analysis examined associations between physical activity and diurnal HPA axis regulation, specifically the diurnal cortisol slope and the cortisol awakening response. Higher physical activity was associated with a slightly steeper diurnal cortisol slope (r=-0.043), but the cortisol awakening response did not differ by activity level.

In this RCT, 42 care-home residents with mild-to-moderate cognitive decline received 16 weeks of one-to-one music therapy versus an active storytelling control, with salivary cortisol/DHEA ratio measured as a stress biomarker. The music therapy group showed cognitive, behavioral, and physiological benefits, with biomarker changes suggested as underlying mechanisms. Directional cortisol/DHEA effect sizes were not numerically reported.

Three-arm RCT testing lavender aromatherapy via inhalation and foot massage on blood pressure and stress in essential hypertension patients. Lavender oil reduced blood pressure, heart rate, serum cortisol, and subjective anxiety.

Pilot RCT randomizing amnestic MCI older adults to an 8-week mindfulness-based intervention or psychoeducation, with cortisol awakening response measured pre/post. MBI participants who practiced meditation most at home showed a slight reduction in CAR, while the psychoeducation group showed reduced perceived stress.

Path-analysis study of 203 acute myocardial infarction patients and 3,134 population controls testing whether standard modifiable risk factors mediate the association between hair cortisol concentration (HCC) and coronary artery disease. CAD patients had elevated HCC, and 80% of the HCC-CAD association was mediated by diabetes, hyperlipidemia, and hypertension.

In 12,934 participants of the Canadian Longitudinal Study on Aging, UGT2B17/UGT2B28 gene deletions showed sex-specific associations with aging outcomes including allostatic-load-based physiological dysregulation, which was more prevalent in males. Among males aged 65+, UGT2B28 deficiency was associated with reduced high dysregulation (40.0% vs 53.0%, p=0.05) while UGT2B17 deficiency with higher (60.4% vs 53.0%, p=0.03); no significant association with all-cause mortality was observed.

Using NHANES 2009-2016 data on 15,571 participants, allostatic load was significantly associated with mortality (HR 1.16, 95% CI 1.09-1.23), with larger effects in women and those aged 40-49. Depression mediated approximately 10.45% of the AL-mortality relationship.

Among 40,520 colorectal cancer surgery patients in the Epic Cosmos database, 7.1% had high allostatic load, which increased stepwise with social vulnerability. High AL was associated with a 48% increased risk of postoperative complications (OR 1.48), 79% increased risk of extended stay (OR 1.79), and a two-fold increase in 30-day mortality (OR 2.13).

Among 34,253 hepatopancreatobiliary cancer surgery patients, 13.8% had high allostatic load, which rose stepwise with social vulnerability. High AL was associated with a 44% increased risk of Clavien-Dindo grade IV complications (OR 1.44), 85% increased risk of failure to rescue (OR 1.85), and roughly two-fold higher 30-day mortality (OR 1.92).

Meta-analysis of 21 studies quantifying acute exercise effects on salivary cortisol in men. Standardized mean differences for post-exercise salivary cortisol were large for aerobic (3.04), and moderate for resistance (0.77) and power (1.20) exercise. Acute exercise consistently elevated salivary cortisol, with effect sizes strongly influenced by study design and sampling.

Meta-analysis of massage therapy studies computing between-group effect sizes for cortisol change. Effects were almost all small and nonsignificant (d=0.05-0.30), except a larger multiple-dose effect in children (d=0.52), concluding massage's cortisol effect is generally very small and often indistinguishable from zero.

RCT of digital CBT for insomnia (SleepCare) versus psychoeducation in 74 nurses with shift work sleep disorder, with hair cortisol as a secondary endpoint. The intervention reduced insomnia severity, and reduced hair cortisol was observed post-intervention in the SleepCare group.

RCT of an 8-week mindfulness program versus wait-list in 30 university workers with high stress, measuring hair cortisol alongside psychometric stress and anxiety. Hair cortisol, perceived stress, and anxiety significantly decreased in the intervention group but not controls.

Fifty-five pregnant women with a depressive episode provided saliva at awakening, +30 and +60 minutes to compute CAR measures (AUCg, AUCi, peak reactivity), with depression measured to two months postpartum. Higher AUCi and peak cortisol reactivity during pregnancy were associated with less postpartum symptom reduction, while total output (AUCg) was not predictive. Heightened cortisol reactivity to awakening may indicate persistent stress vulnerability in peripartum depression.

Thirty-eight participants with mild-to-moderate depression collected saliva across an internet-based intervention to assess the cortisol awakening response, total diurnal output and diurnal slope alongside hair cortisol. Treatment response on depression or chronic stress was not associated with changes in any cortisol parameter. Exploratory analysis suggested non-responders had a steeper pre-intervention alpha-amylase slope.

In a longitudinal pregnancy cohort, salivary diurnal cortisol was collected at five daily timepoints each trimester alongside affective symptoms and life events. Individual differences in diurnal slope and total output showed modest stability, with total output increasing across pregnancy. Elevated depressive symptoms and major life events were associated with higher morning awakening cortisol and a flatter diurnal slope across trimesters.

In head and neck cancer patient-caregiver dyads, caregiver diurnal cortisol slope was assessed from saliva at radiation start and five weeks into treatment. Caregiver cortisol slope became significantly flatter during treatment, with greater schedule burden and lower patient and caregiver quality of life each associated with flatter slopes. Results suggest a mind-body interaction and cortisol dysregulation in cancer caregivers.

In pregnant women in Pakistan assessed at early-mid and mid-late gestation, 50 anxiety, depression and stress symptoms were mapped to six peripheral biomarkers and a composite allostatic load score. Somatic anxiety was the most central symptom node and the network strengthened across gestation. At the later timepoint the Depression cluster exhibited the highest CRP and allostatic load.

Using NHANES 1988-2010 linked to the National Death Index, high allostatic load was associated with a 23% increased risk of cancer death overall (adjusted sHR 1.23, 95% CI 1.06-1.43). The risk was highest among obese adults (sHR 1.39) and overweight adults (sHR 1.31) but attenuated in healthy-weight individuals.

Among 161,964 men in the UK Biobank, allostatic load was higher in prostate cancer cases than controls (3.47 vs 3.35), and each 1-unit AL increase was associated with 5% increased prostate cancer risk (HR 1.05, 95% CI 1.03-1.06). The significant association was observed only among men younger than 58, with a more-than-additive joint effect between AL and polygenic risk score.

Cohort study of 1784 workers (hair cortisol in 423) examining relationships between changing occupational stress, hair cortisol concentration (HCC), and hypertension over follow-up. Increased occupational stress raised hypertension risk, high HCC increased hypertension risk, and HCC mediated 36.83% of the stress-hypertension effect.

In 4,632 NHANES 2005-2018 participants aged 20+, both CONUT and allostatic load were positively correlated with heart failure (AL OR=1.23 in Model 1; OR=1.14 in Model 2). Depressive status moderated the CONUT-HF association (p-interaction=0.035), and AL showed limited predictive performance for HF in the depressive subgroup (AUC=0.6048).

In this nationally representative CHARLS sample, cumulative stressful life events were associated with higher prevalence of cardiometabolic multimorbidity (P-trend <0.001), with functional disability (OR 1.93) and marital problems (OR 1.49) as notable events. Allostatic load significantly mediated 16.7% of the association between accumulated stressful life events and cardiometabolic multimorbidity.

In an online study of 3,590 Chinese subjects post-COVID-19, medical and nonmedical workers had similar allostatic load (15.8% vs 17.8%). Anxiety, depression, somatization, hostility and abnormal illness behavior were positively associated with AL, while social support and global well-being were negatively associated.

In 60 Ukrainian refugees and 50 matched controls, AL index from biomarkers, cognitive biases and psychotic-like experiences (PLEs) were assessed. Refugees showed higher AL, PLEs and belief inflexibility. AL index and belief inflexibility were each positively associated with PLEs and amplified by refugee status, but their interaction was negative, suggesting cognitive rigidity weakened AL's direct impact on PLEs.

Case-control study of 73 acute coronary syndrome (ACS) patients and 93 healthy controls measuring hair and fingernail cortisol as retrospective indices. ACS patients had significantly higher hair and fingernail cortisol, and high levels were associated with two- to three-fold increased ACS risk after adjustment.

This study developed and validated ProAL50, a proteomics-based allostatic load measure from 50 circulating proteins, using UK Biobank data with external validation in CARDIA. ProAL50 mirrored traditional AL in construct validity but showed stronger associations with incident chronic diseases (all cancers, type 2 diabetes, ischemic heart disease, chronic lung and kidney disease) and with all-cause and cause-specific mortality; proteins clustered in lipid-metabolic and immune-inflammatory pathways.

In this RCT, 362 participants were assigned to short or long Yoga Nidra meditation, active control or waitlist, with psychological outcomes and diurnal salivary cortisol assessed pre-post over two months. Regular practice was associated with reductions in total cortisol and steeper diurnal slopes, and the long form produced a flatter cortisol wake-up reaction. Small but significant psychological and cortisol effects were observed for the meditation.

This 3-year longitudinal study of 358 Dutch adolescents tested whether the cortisol awakening response moderates the link between depressive symptoms and violent outcomes. When CAR was low, depressive symptoms were positively associated with violence, whereas the association reversed when CAR was high.

This study compared morning and evening salivary cortisol/DHEAS ratios of 187 remitted recurrent depression patients with 72 controls and followed them over 10 years. Remitted patients showed a flatter diurnal profile of the cortisol/DHEAS ratio, and higher morning ratio predicted shorter time to recurrence, suggesting a trait vulnerability marker.