Given the high prevalence of early life stress (ELS) and the potential physiological dysregulation such experiences can lead to, this meta-analysis tested the relationship between ELS and cortisol. ...Search terms related to ELS and cortisol were entered in to PsycINFO and PubMed. Effect sizes were extracted for four outcomes variables: cortisol awakening response (CAR), baseline cortisol (cortisol at one time point), non-stressed cortisol over time (cortisol captured at two or more time points), and cortisol reactivity to an acute stressor. The articles were additionally coded for potential confounding variables, population-related, ELS-related and cortisol-related moderators. There was no significant relationship between ELS and the CAR (g=0.19, p=0.268), ELS and baseline cortisol (g=−0.072, p=0.328), ELS and non-stressed cortisol over time (g=0.09, p=0.292) or ELS and cortisol reactivity (g=−0.089, p=0.363). However, there was a significant amount of heterogeneity amongst relationships. Within the ELS-CAR relationship, in those who had experienced ELS that was sexually, physically or emotionally abusive, the CAR was heightened. Within the ELS-Baseline relationship, if blood samples were collected the ELS was associated with a blunting effect of cortisol. The non-significant main effects challenge the commonly held belief in the literature that ELS affects cortisol later in life. However, the high degree of heterogeneity uncovered by this analysis and significant moderators suggest that the literature may benefit from consistent operationalizations of ELS and standardized methods of how cortisol is measured.
•The association between early life stress and cortisol was assessed.•No significant relationship was seen between ELS and our four cortisol measures.•Abuse, particularly sexual abuse, was associated with heightened CAR.•Blood samples in ELS groups were associate with blunted baseline cortisol.•Future literature may benefit from standardization of measurement methods.
Our society is experiencing more stress than ever before, leading to both negative psychiatric and physical outcomes. Chronic stress is linked to negative long-term health consequences, raising the ...possibility that stress is related to accelerated aging. In this study, we examine whether resilience factors affect stress-associated biological age acceleration. Recently developed "epigenetic clocks" such as GrimAge have shown utility in predicting biological age and mortality. Here, we assessed the impact of cumulative stress, stress physiology, and resilience on accelerated aging in a community sample (N = 444). Cumulative stress was associated with accelerated GrimAge (P = 0.0388) and stress-related physiologic measures of adrenal sensitivity (Cortisol/ACTH ratio) and insulin resistance (HOMA). After controlling for demographic and behavioral factors, HOMA correlated with accelerated GrimAge (P = 0.0186). Remarkably, psychological resilience factors of emotion regulation and self-control moderated these relationships. Emotion regulation moderated the association between stress and aging (P = 8.82e-4) such that with worse emotion regulation, there was greater stress-related age acceleration, while stronger emotion regulation prevented any significant effect of stress on GrimAge. Self-control moderated the relationship between stress and insulin resistance (P = 0.00732), with high self-control blunting this relationship. In the final model, in those with poor emotion regulation, cumulative stress continued to predict additional GrimAge Acceleration even while accounting for demographic, physiologic, and behavioral covariates. These results demonstrate that cumulative stress is associated with epigenetic aging in a healthy population, and these associations are modified by biobehavioral resilience factors.
Early life stress (ELS) is a widely studied concept due to both its prevalent nature and its (presumed) detrimental consequences. In this review, we discuss the relationship between ELS and its ...underlying physiology spanning the sympathetic nervous system, hypothalamic-pituitary-adrenal axis, and markers of inflammation related to immune function in both human and animal literature. We also consider the potential role of genetic and epigenetic factors on the ELS-health outcome relationship. We conclude with recommendations to overcome identified shortcomings in a field that seeks to address the health consequences of ELS.
Acute psychological stress has long been known to decrease host fitness to inflammation in a wide variety of diseases, but how this occurs is incompletely understood. Using mouse models, we show that ...interleukin-6 (IL-6) is the dominant cytokine inducible upon acute stress alone. Stress-inducible IL-6 is produced from brown adipocytes in a beta-3-adrenergic-receptor-dependent fashion. During stress, endocrine IL-6 is the required instructive signal for mediating hyperglycemia through hepatic gluconeogenesis, which is necessary for anticipating and fueling “fight or flight” responses. This adaptation comes at the cost of enhancing mortality to a subsequent inflammatory challenge. These findings provide a mechanistic understanding of the ontogeny and adaptive purpose of IL-6 as a bona fide stress hormone coordinating systemic immunometabolic reprogramming. This brain-brown fat-liver axis might provide new insights into brown adipose tissue as a stress-responsive endocrine organ and mechanistic insight into targeting this axis in the treatment of inflammatory and neuropsychiatric diseases.
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•IL-6 is the dominant endocrine cytokine induced by acute stress in mice•Stress-inducible IL-6 is produced in brown adipocytes via ADRB3 signaling•IL-6 is required for stress hyperglycemia and adaptive “fight or flight” responses•Stress-induced IL-6 decreases tolerance to a subsequent inflammatory challenge
During acute psychological stress, brown adipocytes initiate a chain of events mediated by adrenergic signaling and IL-6 release that metabolically fuels “fight or flight” adaptive responses but at the same time comes at an inflammatory cost.
Memory for prior drinking experiences may powerfully drive later alcohol use in familiar drinking contexts, yet we know little about what patients with alcohol use disorder (AUD) remember of ...alcohol-related episodes. Although animal and theoretical models of addiction emphasize the importance of different memory systems for understanding maladaptive use, clinical research parsing what AUD patients remember from alcohol-related episodes is lacking. The current study applied a novel memory task in which moderate drinkers (N = 30) and treatment-seeking individuals with alcohol use disorder (AUD: N = 29) encoded associations between photographs of objects (alcoholic beverages and neutral items) and photographs of neutral scenes. At least 24 h later, two types of memory were assessed: item memory (object recognition) and associative memory (cued recognition of scenes associated with objects). To assess which memories predicted drinking, real-world behavior was assessed in patients with AUD at baseline and for 4 weeks following memory tests. Despite demographic differences, the results showed broadly impaired item memory in AUD compared with moderate drinkers (p < 0.001), but enhanced associative memory for scenes paired with alcohol (p = 0.015). These associative memory biases were especially pronounced for stimuli rated as more affectively salient. Furthermore, stronger but less detailed memory for alcohol-related associations (i.e., choosing the correct scene but the incorrect photograph) significantly predicted heavier baseline (p = 0.002) and higher subsequent (p = 0.01) drinking in patients with AUD. These findings reveal a novel alcohol-related memory bias in AUD, and uncover the importance of associative memory for understanding real-world heavy alcohol use.
Chronic cocaine use leads to adaptations in stress biology and in neuroactive steroid system. These adaptations are associated with high cocaine craving and increased relapse risk. This study tested ...whether potentiation of the neuroactive steroid system with the precursor pregnenolone (PREG) affects stress- and cue-induced cocaine craving, anxiety and autonomic response in individuals with cocaine use disorder (CUD). Thirty treatment-seeking individuals (21 Male, 9 Female) with CUD were randomized to placebo (PBO) or supraphysiologic PREG doses of 300 mg or 500 mg per day for 8 weeks. After 2 weeks of treatment, participants were exposed to 5-min personalized guided imagery provocation of stress, cocaine, or neutral/relaxing cues in a 3-day experiment, one condition per day on separate days, in a random, counterbalanced order. Repeated assessment of cocaine craving, anxiety, heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP) were assessed on each day. PREG significantly increased pregnenolone levels compared to PBO. Both PREG doses decreased stress- and cocaine cue-induced craving and reduced both stress- and cue-induced anxiety only in the 500 mg/day group. The 500 mg/day PREG group also displayed decreased stress-induced HR, SBP and DBP. Findings indicate that pregnenolone decreases stress- and cocaine cue-provoked craving and anxiety and reduces stress-induced autonomic arousal in individuals with CUD.
The impact of psychosocial stress on a variety of negative health outcomes is well documented, with current research efforts directed at possible mechanisms. Here, we focused on a potential mechanism ...involving differential expression of mRNA and microRNA in response to acute psychosocial stress. We utilized a validated behavioral paradigm, the Trier Social Stress Test (TSST), to induce acute psychosocial stress in a cohort of volunteers. Stress reactivity was assessed repeatedly during the TSST using saliva samples that were analyzed for levels of cortisol. Peripheral blood mononuclear cells were extracted from blood drawn at baseline and at two time points following the stress paradigm. Total RNA was extracted, and mRNA and microRNA microarrays were utilized to assess within-subject changes in gene expression between baseline and the two post-stressor time points.
For microarray gene expression analysis, we focused on 12 participants who showed a robust cortisol response to the task, as an indicator of robust HPA-axis activation. We discovered a set of mRNAs and miRNAs that exhibited dynamic expression change in response to the TSST in peripheral blood mononuclear cells, further characterizing the link between psychosocial stress and cellular response mechanisms.
Cortisol is a significant driver of the biological stress response that is potently activated by acute alcohol intake and increased with binge drinking. Binge drinking is associated with negative ...social and health consequences and risk of developing alcohol use disorder (AUD). Both cortisol levels and AUD are also associated with changes in hippocampal and prefrontal regions. However, no previous research has assessed structural gray matter volume (GMV) and cortisol concurrently to examine BD effects on hippocampal and prefrontal GMV and cortisol, and their prospective relationship to future alcohol intake.
Individuals who reported binge drinking (BD: N = 55) and demographically matched non-binge moderate drinkers (MD: N = 58) were enrolled and scanned using high-resolution structural MRI. Whole brain voxel-based morphometry was used to quantify regional GMV. In a second phase, 65% of the sample volunteered to participate in prospective daily assessment of alcohol intake for 30 days post-scanning.
Relative to MD, BD showed significantly higher cortisol and smaller GMV in regions including hippocampus, dorsal lateral prefrontal cortex (dlPFC), prefrontal and supplementary motor, primary sensory and posterior parietal cortex (FWE, p < 0.05). GMV in bilateral dlPFC and motor cortices were negatively associated with cortisol levels, and smaller GMV in multiple PFC regions was associated with more subsequent drinking days in BD.
These findings indicate neuroendocrine and structural dysregulation associated with BD relative to MD. Notably, BD-associated lower GMV regions were those involved in stress, memory and cognitive control, with lower GMV in cognitive control and motor regions also predicting higher levels of future alcohol intake in BD.
Physical activity, and likely the motivation for it, varies throughout the day. The aim of this investigation was to create a short assessment (CRAVE: Cravings for Rest and Volitional Energy ...Expenditure) to measure motivation states (wants, desires, urges) for physical activity and sedentary behaviors. Five studies were conducted to develop and evaluate the construct validity and reliability of the scale, with 1,035 participants completing the scale a total of 1,697 times. In Study 1, 402 university students completed a questionnaire inquiring about the want or desire to perform behaviors "at the present moment (right now)." Items related to physical activity (e.g., "move my body") and sedentary behaviors (e.g., "do nothing active"). An exploratory structural equation model (ESEM) revealed that 10 items should be retained, loading onto two factors (5 each for Move and Rest). In Study 2, an independent sample (
= 444) confirmed these results and found that Move and Rest desires were associated with stage-of-change for exercise behavior. In Study 3, 127 community-residing participants completed the CRAVE at 6-month intervals over two years- two times each session. Across-session interclass correlations (ICC) for Move (ICC = 0.72-0.95) and Rest (ICC = 0.69-0.88) were higher than when they were measured across 24-months (Move: ICC = 0.53; Rest: ICC = 0.49), indicating wants/desires have state-like qualities. In Study 4, a maximal treadmill test was completed by 21 university students. The CRAVE was completed immediately pre and post. Move desires decreased 26% and Rest increased 74%. Changes in Move and Rest desires were moderately associated with changes in perceived physical fatigue and energy. In Study 5, 41 university students sat quietly during a 50-min lecture. They completed the CRAVE at 3 time points. Move increased 19.6% and Rest decreased 16.7%. Small correlations were detected between move and both perceived energy and tiredness, but not calmness or tension. In conclusion, the CRAVE scale has good psychometric properties. These data also support tenets of the WANT model of motivation states for movement and rest (Stults-Kolehmainen et al., 2020a). Future studies need to explore how desires to move/rest relate to dynamic changes in physical activity and sedentarism.
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