It is suggested that 5-HTTLPR-related differences, when present, may be more detectable in overall post-awakening cortisol output than in baseline-relative increase, which is more detectable in overall post-awakening cortisol output than in baseline-relative increase.
Abstract
Elevated cortisol levels have been linked to major depressive disorder (MDD), but cortisol dynamics vary substantially across individuals and clinical states. Genetic variation in the serotonin transporter polymorphism (5-HTTLPR) has been proposed as one contributor to differences in hypothalamic-pituitary-adrenal axis functioning. The present study examined associations between cortisol awakening measures and 5-HTTLPR genotype groups in individuals with a history of depression compared with healthy controls, and explored whether current depressive symptom severity was related to cortisol indices. A total of 108 individuals with a history of depression were genotyped and compared with 59 healthy controls. Participants completed structured diagnostic interviews and self-reported depressive symptoms. Salivary cortisol was sampled in the evening and at five consecutive timepoints after awakening (15-min intervals). Cortisol was analyzed using a linear mixed-effects model of repeated measures and by cortisol awakening response (CAR) summary indices: area under the curve with respect to ground (AUCg) and area under the curve with respect to increase (AUCi). Cortisol changed significantly over time, but there was no evidence that genotype groups differed in the overall cortisol timecourse. In CAR summary analyses, group differences were observed for AUCg, whereas AUCi did not show corresponding group differences. Regression analyses indicated that BDI-II was not associated with AUCg or AUCi after adjustment for covariates. These findings suggest that 5-HTTLPR-related differences, when present, may be more detectable in overall post-awakening cortisol output than in baseline-relative increase.
The findings reveal a complex, sex-dependent genetic interaction that selectively influences anhedonia and anxiety, which highlights the value of considering sex-stratified genetic backgrounds and symptom specificity to advance personalised precision medicine in psychiatry.
G. L. Odierna, C. Sharpley, V. Bitsika· Brain Science· 0 citations
BACKGROUND AND AIMS
Diurnal cortisol dysregulation and daily stressor severity may jointly forecast long-term alcohol use disorder (AUD) and substance use disorder (SUD) severity, yet most evidence is cross-sectional and relies on single cortisol indices. This study examined whether three cortisol indices nonlinearly interacted with daily stressor severity to predict 9-year AUD and SUD severity.
DESIGN
Longitudinal observational study with a 9-year follow-up. Analyses were not pre-registered.
SETTING
Community-based sample in the United States of America.
PARTICIPANTS
1617 community-dwelling adults aged 33-83 years at baseline.
MEASUREMENTS
Ecological momentary assessments of salivary cortisol and daily stressor severity were collected at baseline. AUD and SUD severity were self-reported at baseline and 9-year follow-up. Cortisol indices included diurnal cortisol slope, cortisol awakening response and area under the curve (AUC).
FINDINGS
Parametric hurdle Poisson models yielded null main effects and interactions (all P > 0.050). Generalized additive models with negative binomial family revealed three statistically significant nonlinear interactions: diurnal cortisol slope × stress predicting AUD severity [effective degrees of freedom (edf) = 2.09, χ2 = 12.56, P = 0.005], cortisol awakening response × stress predicting SUD severity (edf = 2.88, χ2 = 11.60, P = 0.019) and AUC × stress predicting AUD severity (edf = 4.08, χ2 = 16.34, P = 0.006). Adjusting for age, sex, education, income and race nullified all three interactions; however, AUC × stress interaction → AUD remained statistically significant after controlling for anxiety and depression.
CONCLUSIONS
Nonlinear interactions between cortisol indices and daily stressor severity appear to predict 9-year alcohol use disorder and substance use disorder severity, with cortisol area under the curve emerging as the most robust indicator. Findings are predictive rather than causal. Cognitive-behaviorally based prevention programs targeting stress and cortisol regulation may mitigate substance use risk.
N. Zainal, Natalia Van Doren· Addiction· 0 citations
Objectives Older adults experienced measurable psychological burden during the COVID-19 pandemic. Although salivary cortisol is widely used as a biomarker of hypothalamic–pituitary–adrenal axis activity, single time-point basal measurements may show inconsistent associations with anxiety. We examined whether afternoon salivary cortisol was cross-sectionally associated with same-day state anxiety in community-dwelling older adults during the COVID-19 pandemic. Methods Community-dwelling adults aged ≥65 years were recruited between May and November 2021 in rural Japan. Afternoon salivary cortisol (15:00–16:00) was measured using enzyme-linked immunosorbent assay from stored samples. State anxiety was assessed using the State–Trait Anxiety Inventory state scale (STAI-State). Multivariable linear regression models were fitted in the overall sample and in exploratory sex-stratified analyses, adjusting for demographic, psychological, cognitive, and COVID-19–related factors. Results The analyses included 76 participants (mean age 80.8 years; 68% female). The mean (standard deviation) STAI-State score was 40.7 (10.5), and median salivary cortisol was 0.13 μg/dL. In adjusted models, salivary cortisol was not associated with STAI-State score in the overall sample or in exploratory sex-stratified analyses. Effect estimates were close to null. Conclusions In this cohort of community-dwelling older adults in Japan during the COVID-19 pandemic, a single afternoon salivary cortisol measurement was not associated with same-day state anxiety. This null finding should be interpreted in the context of the present study design and measurement approach and does not rule out an association between cortisol and anxiety under other conditions.
It is demonstrated that decreased serum BDNF levels are associated with the presence and symptom severity of anxiety disorders, and the Val66Met polymorphism does not appear to be a primary determinant of serum BDNF levels in this population, suggesting that other genetic or environmental factors may be involved.
Dicle Yilmaz Uyanik, Merve Şahin Can, O. Baykan et al.· Molecular Biology Reports· 0 citations