Scientific studies behind the Sapiens diagnostics

This meta-analysis of 50 articles quantified sex differences in cortisol parameters (including hair cortisol, basal cortisol, CAR, stress reactivity) in depression. Depressed females had significantly higher hair cortisol, higher CAR, and lower cortisol stress reactivity than depressed males.

Systematic review and meta-analysis of 17 studies (2001-2020) examining the association between high allostatic load and all-cause and cardiovascular mortality. High AL was consistently associated with increased mortality risk, though heterogeneity was high.

This systematic review and meta-analysis examined the relationship between major depressive disorder (MDD) and hair cortisol concentration (HCC). Results were contradictory across studies; a random-effects meta-analysis found no significant HCC difference between depressed patients and healthy controls.

This large meta-analysis of 146 cohorts (34,342 individuals) related hair cortisol and hair cortisone to BMI, waist circumference and waist-hip ratio across all ages. Hair glucocorticoids were consistently positively associated with all anthropometric measures, strongest for hair cortisone with waist circumference.

This systematic review synthesized research on hair cortisol, chronic stress and mental health. Chronic stress was associated with increased hair cortisol (medium-to-large effects), while depression showed increased and anxiety/PTSD decreased hair cortisol, with generally smaller effects for psychopathology.

This systematic review and meta-analysis evaluated cortisol measurement and biopsychosocial correlates in sickle cell disease (SCD); cortisol was mostly measured in serum/plasma with only one hair study. Meta-analysis found no significant difference in cortisol between SCD participants and healthy controls.

This systematic review and meta-analysis of 58 randomised controlled trials examined whether psychological stress management interventions change cortisol levels (measured in blood, saliva or hair) in non-patient groups. Interventions outperformed control conditions with a medium positive effect size (g=0.282), with mindfulness/meditation and relaxation being most effective.

This meta-analysis examined associations between chronic stress and hair cortisol concentration (HCC) in children. Chronic stress was positively associated with HCC, with effects strongest when stress was measured as stressful life events within the past six months and when HCC was measured by LC-MS/MS.

This meta-analysis of 8 studies examined the association between psychological resilience and hair cortisol concentration (HCC) in adults. Resilience and HCC were inversely correlated, with the association stronger in those aged 40 or younger.

This meta-analysis of 101 studies (>2500 women) reviewed adrenocortical hormones including cortisol (serum, urine, CSF, hair), DHEA-S and testosterone in anorexia nervosa versus healthy controls. Cortisol was significantly higher and DHEA-S and total testosterone significantly lower in anorexia nervosa patients.

This multilevel meta-analysis of 29 studies assessed the association between maternal psychological distress and hair cortisol during pregnancy and early postpartum. The overall effect was small and non-significant, but effects were stronger in pregnant (vs postpartum) samples and when distress was measured before hair cortisol.

Systematic review and meta-analysis of 17-18 studies examining associations of sleep disturbance and sleep duration with allostatic load. Effect sizes were pooled across 26,924 participants.

This meta-analysis examined the relationship between hair cortisol concentration (HCC) and anthropometry in children. Small positive correlations were found between HCC and BMI, BMI z-score, waist circumference and body fat, with sex moderating the BMI relationship.

This systematic and meta-analytic review of 18 studies found significant cross-sectional associations between higher allostatic load and poorer global cognition (r=-0.08, p<0.001) and executive function (r=-0.07, p=0.02), but not memory (r=-0.07, p=0.10). AL algorithm, biomarkers included and sample age were key moderators.

This comprehensive meta-analysis (66 studies, N=10,289) identified basic covariates and stress/mental-health determinants of hair cortisol concentration (HCC). Stress-exposed groups showed 22% higher HCC (43% when stress was ongoing), while anxiety disorders showed 17% reduced HCC; age, sex, hair washing and treatment were key covariates.

This systematic review of 13 studies examined how allostatic load has been retrospectively calculated in cancer patients, finding considerable variability in the number of biomarkers used (6 to 16), the specific biomarkers, and biosystem representation. The lack of standardization complicates retrospective AL calculation, and no gold standard exists.

This systematic review of 25 studies examined the association between adverse childhood experiences (maltreatment, abuse, poverty, discrimination) and allostatic load. Overall, ACEs were associated with elevated AL and poorer adult health, with health risk behaviors, social support and coping resources moderating or mediating the association.

This systematic review of 13 studies examined associations of the allostatic load index with brain structure and function in adults. All studies confirmed associations between higher AL and alterations in brain areas including the hippocampus, white and gray matter volume in older adults, and cortical thinning in overweight subjects and schizophrenia.

This PRISMA systematic review and meta-analysis of five studies examined perceived discrimination and allostatic load in Black adults aged 40+. Meta-analysis of four studies found a small, non-significant pooled effect (Hedges's g=0.132; 95% CI -0.338 to 0.602; p=0.582) with high heterogeneity (I-squared=94.24%), though four studies individually reported significant discrimination-AL associations.

This three-level meta-analysis synthesized studies on maternal hair cortisol concentration (HCC) before and during pregnancy and spontaneous preterm birth (PTB). No evidence of a significant HCC difference between preterm and term groups was found; effects were small, imprecise and non-significant.

This meta-analysis of 28 studies assessed the association between adverse experiences and hair cortisol levels. The overall effect was small but significant and positive, with a subgroup of studies showing negative associations; effects were moderated by adversity type/timing and sample characteristics.

This systematic review of 44 studies (8,370 children) examined associations between social adversity indicators and hair cortisol in young children (birth-8 years). Evidence was limited and inconsistent, with 70% of the 142 examined associations being null.

This systematic review of 25 studies identified variations in allostatic load measures across adolescent populations. Biomarkers ranged from 1 to 14, with the most common index consisting of 6 biomarkers (cortisol, epinephrine, norepinephrine, systolic and diastolic blood pressure, and BMI).

Systematic review of 267 original investigations summarizing knowledge on allostatic load and overload and their clinical implications across general population and clinical settings. Findings link AL/overload to poorer physical and mental health outcomes.

This systematic review of 36 studies assessed determinants of hair cortisol concentration (HCC) in children and adolescents. Higher HCC was associated with male sex and anthropometry (BMI, waist circumference), while hair wash frequency and hair products did not affect HCC when proximal segments were used.

This meta-analysis of 18 RCTs found cognitive-behavioral stress management decreased serum cortisol, anxiety, depression, and negative mood in breast cancer patients. It increased relaxation, benefit finding, and positive affect. No effect was seen on overall stress or mood disturbance.

Meta-analysis of 18 RCTs of massage for breast cancer-related symptoms, including cortisol among outcomes. Massage significantly reduced anger and fatigue, but showed no significant effect on cortisol, depression, anxiety, pain, or quality of life.

This meta-analysis of longitudinal studies examined sleep and non-sleep circadian disorders as predictors of subsequent depression. Among circadian markers, a heightened cortisol awakening response at baseline was associated with higher risk of incident depression. Various sleep disorders and circadian disruptions were confirmed as risk factors for later depression.

This systematic review and meta-analysis of 179 associations from 80 studies examined links between diurnal cortisol slopes and health outcomes. Flatter diurnal cortisol slopes were significantly associated with poorer health overall (r=0.147), with the largest effect for immune/inflammation outcomes (r=0.288).

In 1,021 US adults aged 50+ from NHANES 1999-2002 (follow-up through 2019), each 1-point increase in allostatic load of glucose homeostasis was associated with a 9.5% higher risk of all-cause death (HR=1.095; 95% CI 1.016-1.181) and 15.8% higher cardiovascular death (HR=1.158; 95% CI 1.010-1.327). Epigenetic age biomarkers HorvathAge and PhenoAge mediated 7.53% and 18.00% of the AL-mortality association.

Systematic review and meta-analysis of 27 RCTs of auricular stimulation (transauricular vagus nerve stimulation, auricular acupuncture/acupressure) on inflammatory and stress biomarkers. Auricular stimulation reduced CRP, TNF-alpha, IL-6, and IL-10, but cortisol did not change significantly (while salivary amylase increased).

This systematic review of 28 studies (16 in meta-analysis) found individuals with psychiatric disorders had elevated allostatic load versus healthy controls. AL was significantly higher in schizophrenia and first-episode psychosis (SMD 0.97, 95% CI 0.76-1.18) but not in major depressive disorder (SMD 0.07, 95% CI -0.23 to 0.37).

This individual participant meta-analysis of four UK cohorts tested whether diurnal cortisol measures predict later mental well-being. Well-being was not associated with morning cortisol, diurnal slope, or CAR, though a borderline association with higher evening cortisol and lower well-being was found and attenuated after adjustment.

Systematic review and meta-analysis of 16 RCTs (music, guided relaxation, mindfulness, breathing/muscle relaxation) in lactating individuals, with milk macronutrients/cortisol and stress/anxiety outcomes. Relaxation increased milk quantity and infant weight gain and slightly reduced stress and anxiety; milk cortisol was a prespecified outcome.

This meta-analysis of 35 RCTs (46 interventions) found stress-management interventions reduced anxiety, depression, distress, and fatigue and improved quality of life in HIV+ adults. However, no significant effects were found on hormonal outcomes including cortisol and DHEA-S. The null hormonal result may reflect limited assessment windows.

Retrospective NHANES cohort (1988-2010) of US men linked to National Death Index examined the joint association of allostatic load (9-biomarker score) and educational attainment with cancer mortality. High AL was defined as a score of 3 or more, calculated from abnormal biomarkers and health measures.

Retrospective cohort of breast, lung, and colorectal cancer patients modeled AL as ordinal (0-11) and used competing-risk and time-varying Cox regression to estimate 2-year MACE. AL before and after cancer diagnosis was examined.

This systematic review and meta-analysis of 11 studies (879 participants) examined the cortisol awakening response in psychosis. CAR was attenuated in patients with psychosis versus healthy controls (g=-0.426), with flattened CAR in schizophrenia and first-episode psychosis but not at-risk mental states.

This systematic review of 22 studies compared hair cortisol concentrations (HCC) in patients with mental disorders versus healthy controls. Depression patients tended toward higher HCC while PTSD patients tended toward lower HCC, with sampling timing and sample heterogeneity influencing results.

In 6,806 US Health and Retirement Study participants aged 56+, AL was constructed from neuroendocrine, immune, metabolic and cardiovascular biomarkers. Over 5 years, incident dementia was higher in the highest versus lowest AL quartile (HR=1.96, 95% CI 1.37-2.80), attenuating to HR=1.59 after adjustment. Race/ethnicity did not modify the association.

Cohort of stage I-III breast cancer patients examined how neighborhood opportunity relates to allostatic load and all-cause mortality. Logistic and Cox models tested associations and interactions between neighborhood opportunity and AL.

Cohort of stage I-III breast cancer patients computed AL as a quartile-based biomarker summary and examined its association with all-cause mortality using Cox models. High AL was defined as above the median.

Systematic review and meta-analysis of 17 studies (including 4 RCTs) examining balneotherapy effects on serum and salivary cortisol. Evidence indicated a significant short-term cortisol reduction in stressed healthy individuals, though the pooled mud-balneotherapy meta-analysis effect did not reach significance (g=-0.11, 95% CI -0.30 to 0.08).

In 245,683 UK Biobank participants (median 13.5-year follow-up), high allostatic load was associated with increased overall cancer risk (HR 1.06, 95% CI 1.04-1.09) and several site-specific cancers (HR 1.08-1.43). A synergistic interaction was found between high AL and 'nervous-dominant' personality, strongest for liver cancer (HR 1.58).

Systematic review of 12 studies consolidating the operationalization, antecedents, and outcomes of allostatic load in cancer. A mini meta-analysis pooled the association between AL and cancer-specific mortality despite heterogeneity in AL measurement.

RCT of 8-week MBSR (meditation and yoga) versus waitlist in perimenopausal women, examining depressive symptoms with the cortisol awakening response among endocrine moderators. MBSR reduced depressive symptoms, stress, and anxiety and improved sleep; baseline endocrine sensitivity moderated benefit, though cortisol was analyzed as a moderator rather than a changed outcome.

Systematic review and meta-analysis of 33 RCTs of acupuncture-combined anesthesia in pulmonary resection surgery, including stress markers cortisol and adrenaline. Combined acupuncture anesthesia reduced anesthetic use and postoperative pain and decreased TNF-alpha, adrenaline, and cortisol levels (p<0.05).

This prospective cohort of 1090 KORA-F3 participants assessed salivary cortisol and cardiovascular mortality over ~11 years. A more pronounced CAR and greater peak-to-bedtime ratio predicted lower cardiovascular mortality, while higher late-night cortisol predicted higher cardiovascular mortality and stroke risk.

This MIDUS study of 1735 US adults tested whether daily negative affect and diurnal cortisol explain the link between socioeconomic status and all-cause mortality 13 years later. Higher SES was linked to lower mortality sequentially through lower daily depressive affect and a steeper (healthier) diurnal cortisol slope.

Using 12-year panel data from 8,291 English Longitudinal Study of Ageing participants, between-person differences in allostatic load were associated with depressive symptoms (coefficient 0.02, 95% CI 0.01-0.04), but within-individual changes in AL were not. Most of the association was driven by differences between individuals rather than changes over time.

This systematic review and meta-analysis assessed associations between hair cortisol concentration (HCC) and blood pressure. Small positive associations were found between HCC and systolic and diastolic BP, and HCC was strongly positively associated with hypertension status.

This systematic review and meta-analysis examined associations between hair, salivary, serum and urinary cortisol and adiposity indicators in children. Hair cortisol concentration was significantly associated with fat mass index and BMI/BMI z-score, whereas salivary and serum cortisol were not associated with adiposity.

Systematic review and meta-analysis comparing cortisol awakening response (state) and hair cortisol concentration (trait) associations with obesity and fat distribution. Adiposity indices were not associated with CAR but correlated significantly and positively with hair cortisol concentration.

This scoping review across five databases characterised cortisol levels, cortisol rhythm and CAR in shiftworkers. Shiftwork, especially night shift, significantly disrupts cortisol production, the diurnal rhythm and CAR, with irregular schedules producing greater disruption. The literature lacks methodological consistency and focuses on acute rather than chronic effects.

This systematic review of 58 articles (1997-2012) examined the allostatic load construct, its antecedents and health outcomes, finding considerable heterogeneity in AL operationalization and biomarkers. The literature demonstrated associations between AL and socioeconomic status, race/ethnicity, gender, stress exposure, and physical and mental health and all-cause mortality.

This PRISMA-ScR scoping review mapped 19 post-2018 studies of biological biomarkers assessed alongside validated burnout measures in emergency/acute-care healthcare workers. Biomarker selection clustered around HPA-axis cortisol (10/19), with fewer autonomic or immune-inflammatory studies. Associations were heterogeneous and confounder adjustment was low (3/19), so no single reproducible burnout biomarker was supported, pointing instead to multi-system dysregulation.

Systematic review of 31 studies re-evaluating a two-staged model of hair cortisol concentrations (HCC) in lifetime trauma exposure and PTSD. Predictions of cortisol hypersecretion during recent/ongoing traumatic stress were largely confirmed, while assumed hyposecretion distal to trauma was more ambiguous. Prognostic and intervention-related evidence for HCC remains sparse.

PRISMA-compliant review of 14 publications (1,916 participants) examining hair cortisol concentration (HCC) as a predictive or outcome parameter in psychological and neuropsychiatric interventions. Effects of relaxation, mental training, CBT, and PTSD therapy on HCC were equivocal, though baseline HCC showed predictive value for treatment response.

PRISMA systematic review of 9 observational studies investigating hair cortisol concentration differences between obese and non-obese minors. Findings were inconclusive: five studies found higher HCC in obese youth, while four found no significant difference.

Systematic review of 21 studies (N=10,666) examining associations between primary allostatic load mediators (cortisol, DHEAS, urinary catecholamines) and metabolic syndrome. Hair cortisol was associated with MetS in 100% of the studies assessing it, and lower DHEAS tended to associate with MetS.

Study of 1822 pregnant women in Lima, Peru, extracting cortisol and cortisone from 6-cm hair samples (3-cm proximal reflecting early pregnancy) to examine associations of child abuse and intimate partner violence with hair corticosteroid levels. Women who experienced child abuse had higher cortisol and cortisone across pregnancy.

This meta-analysis of 25 studies found higher allostatic load risk with older age (OR 1.05), low education (OR 1.25) and low physical activity (OR 1.44), and lower AL risk with high income (OR 0.77) and female sex (OR 0.80). Older, male, low-income, low-education and physically inactive people were more likely to have high AL.

Predominantly Latino adolescents were cluster-randomized to control, lifestyle, stress-reduction guided imagery, or lifestyle-behavior guided imagery (LBGI) over 12 weeks, with diurnal salivary cortisol measured. LBGI produced a small increase in the cortisol awakening response versus control (d=0.24), with no significant changes in diurnal slope or perceived stress overall. Guided imagery modestly raised CAR.

Healthy stressed adults were randomized to 6-week MBSR, CBT, or waitlist, then completed repeated laboratory stressors with salivary cortisol sampled to index habituation. Both MBSR and CBT produced greater cortisol habituation than control, though neither reduced overall cortisol output.

In 3281 Whitehall II participants, six saliva samples yielded the daytime cortisol slope and bedtime level, related to carotid-femoral pulse wave velocity over five years. Among women, a shallower cortisol slope and higher bedtime cortisol at baseline predicted greater five-year increases in aortic stiffness. HPA-axis dysregulation predicted progression of aortic stiffness in women.

This meta-analysis of 19 RCTs found stress-specific interventions benefited cancer patients' subjective cognition but had uncertain effects on morning cortisol and TNF-alpha, and no effect on cortisol at other times or on IL-10, IL-8, IL-6, IL-1, or CRP. Effects on executive function were uncertain. More rigorous studies are needed.

This systematic review of reviews analyzed 18 synthesis reviews (representing 238 studies, 1995-2020) to identify commonly used allostatic load biomarkers and measurement approaches. The original ten biomarkers were most often used, with body mass index and C-reactive protein increasingly added, and the review highlights a gap in geographic considerations for neighborhood AL research.

This systematic review identified potential physiological biomarkers of chronic stress across 37 studies. Cortisol (including hair cortisol), ACTH, BDNF, catecholamines, glucose, HbA1c, lipids, DHEA-S, CRP and interleukins were highlighted as potential diagnostic biomarkers of chronic stress.

This integrative review of 11 studies (8 cross-sectional, 3 longitudinal) examined the association between discrimination and allostatic load in adults. Nine studies found a significant positive association, with lifetime, childhood racial, everyday and weight discrimination positively associated with AL.

This scoping review of 14 studies mapped evidence on neighborhood socioeconomic deprivation and allostatic load, with most studies from the USA, cross-sectional, and using a mode of eight biomarkers. Twelve of 14 studies reported a significant association between neighborhood deprivation and AL, with stronger associations among Black individuals, men and those with poor social support.

This systematic review of 16 studies (2003-2013) summarized measurement and methodological challenges of the Allostatic Load Index in occupational settings. Substantial heterogeneity was observed, with 39 different variables used across studies and primary mediators rarely included; consensus on ALI measurement in working populations is limited.

This meta-analysis of twelve studies pooled correlations between antenatal depression and cortisol rhythmicity including CAR, diurnal slope and total output (AUCg). Antenatal depression showed significant negative associations with both CAR (r=-0.33) and diurnal slope (r=-0.31), indicating a blunted CAR and flattened slope, but no association with AUCg. Findings suggest a dynamic HPA-axis dysregulation without altered total output.

Using NHANES 2005-2018 (26,480 adults for AL analysis), allostatic load was associated with all-cause mortality (HR=1.25; 95% CI 1.11-1.41), strengthening in adults aged <70 (HR=1.44; 95% CI 1.21-1.70). Circadian syndrome showed a stronger association with mortality than metabolic syndrome or AL across both sexes.

Meta-analysis of RCTs of aerobic, resistance, yoga and tai chi interventions on sleep and circadian rhythm in cancer survivors. Exercise significantly reduced salivary cortisol (MD -0.09 mg/dL) and improved sleep quality and wake-after-sleep-onset. Exercise lowered circadian salivary cortisol in cancer survivors.

In 4,552 All of Us participants with traumatic brain injury, pre-injury allostatic load (pALI) was derived from anthropometric and laboratory biomarkers. Higher pALI was associated with increased post-TBI mortality (adjusted HR=1.71, 95% CI 1.36-2.14) and greater incidence of PTSD (HR=1.28, 95% CI 1.10-1.50) and sleep disorder (HR=1.42, 95% CI 1.29-1.57).

In UK Biobank participants free of severe mental illness at baseline, AL was measured from 10 metabolic, cardiovascular and inflammatory biomarkers over a median 13.7-year follow-up. High AL combined with unhealthy sleep carried the highest risk (schizophrenia HR=2.44, 95% CI 1.01-5.88; bipolar disorder HR=6.94, 95% CI 4.22-11.22). AL amplified genetic susceptibility, with an additive interaction for schizophrenia.

In the UK Biobank, participants in the highest allostatic load quintile had increased kidney cancer incidence (HR 1.70, 95% CI 1.38-2.10) and, among patients, increased mortality (HR 3.10, 95% CI 1.51-6.36) over a mean 13.2-year follow-up. Inflammatory and metabolic proteins (notably HAVCR1) mediated the AL-kidney cancer associations.

In 304,959 UK Biobank adults, higher allostatic load quartiles were associated with progressively increased colorectal cancer risk (20-43% across Q2-Q4). Among 1,794 CRC patients, the highest AL quartile was associated with increased all-cause mortality (HR 1.71, 95% CI 1.16-2.50) in a dose-response manner.

This UK Biobank prospective study of 361,920 adults estimated allostatic load from 10 biomarkers and followed dementia over a median 12.88 years. High AL was associated with increased risk of all-cause dementia (HR 1.269, 95% CI 1.159-1.390) and especially vascular dementia (HR 1.934, 95% CI 1.569-2.384).

In 333,017 adults followed a median 13 years, high allostatic load was associated with increased risk of depression (HR 1.389), anxiety (HR 1.304) and suicide (HR 1.433). Women and younger individuals with high AL were especially vulnerable to depression and anxiety.

This RCT randomized 204 older adults with mild dementia to dance movement therapy, physical exercise, or waitlist, measuring salivary cortisol and psychosocial outcomes over more than a year. The dance movement therapy group showed reduced depression and loneliness and improved diurnal cortisol slope (d=0.30), effects that persisted at one-year follow-up, whereas exercise showed no significant effects.

In a retrospective cohort of 126 men with newly diagnosed metastatic prostate cancer, each 1-point increase in allostatic load (0-9 scale) was associated with increased hazard of death (HR=1.25; 95% CI 1.02-1.53; p=0.029) after adjustment. Associations strengthened when body composition measures replaced BMI (e.g., low muscle mass HR=1.59; 95% CI 1.26-2.00), and AL was also associated with disease progression (HR=1.25; p=0.018).

Prospective cohort of 320 children from low-income households evaluating cumulative environmental stress, hair cortisol, and cardiometabolic risk in middle childhood. Cumulative stress was associated with higher cardiometabolic risk and higher hair cortisol, but hair cortisol did not mediate the stress-cardiometabolic risk association.

12-week RCT comparing a low-calorie MIND diet versus a standard low-calorie diet in type 2 diabetic women with insomnia, measuring serum cortisol and BDNF. The MIND diet group showed a significant reduction in cortisol levels and increase in BDNF versus control, alongside improved sleep, depression, and anxiety. Diet meaningfully lowered the cortisol stress biomarker.

Prospective Danish cohort (Lolland-Falster Health Study) combined 10 biomarkers across cardiovascular, inflammatory, and metabolic systems into a summary AL index and followed participants for mortality (mean 2.6 years). Cox regression compared AL index against individual biomarkers.

In 8,775 Austrian LEAD cohort participants (mean follow-up 7.7 years), allostatic load with lung function parameters was associated with all-cause mortality (HR=1.19; 95% CI 1.14-1.24) versus AL without lung function (HR=1.16; 95% CI 1.11-1.21). High AL (categorical) carried >2-fold mortality risk, and models incorporating lung function showed superior predictive performance.

In 7,299 Hispanic adults from NHANES 1999-2010 linked to mortality data, 33.4% had high allostatic load. Among those aged 60+, US citizenship (with low or high AL) conferred >3-fold cancer mortality risk, and >10 years US residence ~6-fold risk, but cancer mortality was driven primarily by age and nativity factors rather than AL itself.

In 3,069 stage I-III breast cancer patients (median 55.4-month follow-up), high allostatic load (>3) was associated with increased mortality (HR 1.26-1.53 across models). The association was strongest among rural Black patients (HR per 1-unit AL 3.33, 95% CI 1.27-8.77), though AL's contribution to racial and rural disparities was not statistically significant.

In 9,936 UK Biobank participants with prior depression, AL (from 10 biomarkers) and frailty were assessed over a median 13.19-year follow-up. Compared with low AL, medium (HR=1.25) and high AL (HR=1.42, 95% CI 1.26-1.60) increased depression recurrence risk; frailty and prefrailty likewise raised risk (HR up to 1.72). Frailty mediated 22.42% of AL's effect and AL mediated 12.27% of frailty's effect.

Prospective Lifelines cohort study analyzing 6341 hair samples for cortisol and cortisone and associating them with incident cardiovascular disease over 5-7 years. Hair cortisone was independently associated with incident CVD, particularly in younger individuals, and with immune parameters.

Cohort of prostate cancer patients modeled AL as an ordinal variable (0-11) and used competing-risk and time-varying Cox regression to assess 2-year major adverse cardiac events (MACE). AL before and after diagnosis was examined.

Using English Longitudinal Study of Ageing data (N=4,399, aged 50+, 6-year follow-up), this study examined longitudinal associations of hair cortisol and cortisone with verbal memory, time orientation and dementia. Unadjusted associations with worse cognition were seen, but after full adjustment neither hair cortisol nor cortisone was associated with cognition or dementia.

Jackson Heart Study of African Americans examined whether resilience modifies the association between allostatic load (metabolic, cardiovascular, immune markers) and CVD outcomes (stroke, CHD, heart failure). Sex-stratified Cox regression was used.

Prospective cohort of Chinese adults aged 60+ from the CLHLS examined AL burden (0-9 score) and all-cause mortality, analyzed separately by sex. Cox models adjusted for demographics and lifestyle.

NHANES III cohort of adults aged 40-65 examined church attendance, a 10-marker allostatic load score, and all-cause mortality over up to 18 years. Cox models adjusted for socioeconomic, health, and behavioral covariates.

In 1,089 patients with type 2 diabetes (28.0% with coronary artery disease), both allostatic load (10-biomarker index) and type D personality showed stronger associations with CAD than most traditional risk factors. AL mediated 16.67% of the type D-CAD association; adjusted odds ratios for CAD were 1.68 for type D alone, 1.87 for high AL alone, and 2.74 for both combined.

This systematic review and meta-analysis of 19 studies examined associations between social cognition and cortisol in the general population. Better emotion control was associated with higher cortisol (r=0.083), but there was no evidence of association between social cognition and diurnal cortisol slope or the cortisol awakening response.

This systematic review and meta-analysis of 147 studies examined associations between the cortisol awakening response and psychosocial factors, analyzing the awakening increase (CARi) and total waking output (CARauc) separately. Job and general life stress were positively associated with CARi, while fatigue, burnout, and exhaustion were negatively associated.

Among 181,455 women in the UK Biobank followed 2006-2020, higher allostatic load was associated with increased breast cancer risk (HR 1.05 per unit; multivariate HR 1.05, 95% CI 1.03-1.07). Women in the high AL group (3-11) had a 1.17-fold increased risk versus the low AL group, independent of known breast cancer risk factors.

Systematic review of 22 studies (8 meta-analyzed) on forest bathing and cortisol. Salivary cortisol was significantly lower in forest groups than urban groups both before (MD -0.08 ug/dl) and after intervention (MD -0.05 ug/dl). Forest bathing produced short-term cortisol reductions consistent with stress relief.