Table 2 - uploaded by Annelie Nordin Adolfsson
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Objective:
Elevated cortisol levels with aging have been associated with atrophy of the hippocampus and prefrontal cortex (PFC), as well as with impaired cognitive functions in men. However, co-existing diseases have confounded many studies examining these relationships. Studies in women are lacking. Our objective was to test whether salivary cort...
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Income and education are both elements of a person’s socioeconomic status, which is predictive of a broad range of life outcomes. The brain’s gray matter volume (GMV) is influenced by socioeconomic status and mediators related to an unhealthy life style. We here investigated two independent general population samples comprising 2838 participants (a...
Citations
... Apart from a few studies in newborns and (young) children (Blankenship et al., 2019;Buss et al., 2012;Fowler et al., 2021;Keresztes et al., 2020;Merz et al., 2019;Moog et al., 2021;Wiedenmayer et al., 2006), there mainly exist studies elaborating the interplay between basal HPA axis responses and structural brain measures. HPA axis markers thereby range from simple one-time collected salivary cortisol samples (Cho, 2001), 24-h urinary cortisol and basal adrenocorticotropic hormone levels (Wolf et al., 2002), to diurnal cortisol assessments and/or cortisol awakening responses (Dedovic et al., 2010;Ennis et al., 2019;Kremen et al., 2010;Lu et al., 2013;Lupien et al., 1998;MacLullich et al., 2005;Stomby et al., 2016;Sudheimer et al., 2014;Treadway et al., 2009), morning salivary cortisol after dexamethasone administration (Cacciaglia et al., 2017), as well as hair cortisol (R. Chen et al., 2016). In addition, two studies focused on perceived stress measures instead of cortisol responses (Blix et al., 2013;Piccolo & Noble, 2018). ...
The investigation of the relationship between neural measures of limbic structures and hypothalamic pituitary adrenal axis responses to acute stress exposure in healthy young adults has so far focused in particular on task‐based and resting state functional connectivity studies. Thus, the present study examined the association between limbic volume and thickness measures and acute cortisol responses to the psychosocial stress paradigm Scan STRESS . Using Permutation Analysis of Linear Models controlling for sex, age and total brain volume, the associations between (sex‐specific) cortisol increases and human connectome project style anatomical variables of limbic structures (i.e. volume and thickness) were investigated in 66 healthy and young (18–33 years) subjects (35 men, 31 women taking oral contraceptives). In addition, exploratory (sex‐specific) bivariate correlations between cortisol increases and structural measures were conducted. The present data provide interesting new insights into the involvement of striato‐limbic structures in psychosocial stress processing, suggesting that acute cortisol stress responses are also associated with mere structural measures of the human brain. Thus, our preliminary findings suggest that not only situation‐ and context‐dependent reactions of the limbic system (i.e. blood oxygenation level‐dependent reactions) are related to acute (sex‐specific) cortisol stress responses but also basal and somewhat more constant structural measures. Our study hereby paves the way for further analyses in this context and highlights the relevance of the topic.
... Similar to findings from animal models (36,60,62,63), some studies have linked higher cortisol levels with reduced PFC volume and thickness, with most studies having been conducted in adults (Table S4). In adults, higher salivary, hair, and serum cortisol levels have been significantly associated with reduced lateral and medial PFC and ACC gray matter (127)(128)(129)(130)(131)(132). This pattern of results has also been found in children and adolescents (133,134), but other studies have linked lower cortisol levels or reactivity to reduced PFC and ACC thickness in children (14,134). ...
Socioeconomic disadvantage during childhood predicts an increased risk for mental health problems across the life span. Socioeconomic disadvantage shapes multiple aspects of children’s proximal environments and increases exposure to chronic stressors. Drawing from multiple literatures, we propose that childhood socioeconomic disadvantage may lead to adaptive changes in the regulation of stress response systems including the hypothalamic-pituitary-adrenal (HPA) axis. These changes, in turn, affect the development of prefrontal cortical (PFC) circuitry responsible for top-down control over cognitive and emotional processes. Translational findings indicate that chronic stress reduces dendritic complexity and spine density in the medial PFC and anterior cingulate cortex, in part through altered HPA axis regulation. Socioeconomic disadvantage has frequently been associated with reduced gray matter in the dorsolateral and ventrolateral PFC and anterior cingulate cortex and lower fractional anisotropy in the superior longitudinal fasciculus, cingulum bundle, and uncinate fasciculus during middle childhood and adolescence. Evidence of socioeconomic disparities in hair cortisol concentrations in children has accumulated, although null findings have been reported. Coupled with links between cortisol levels and reduced gray matter in the PFC and anterior cingulate cortex, these results support mechanistic roles for the HPA axis and these PFC circuits. Future longitudinal studies should simultaneously consider multiple dimensions of proximal factors, including cognitive stimulation, while focusing on epigenetic processes and genetic moderators to elucidate how socioeconomic context may influence the HPA axis and PFC circuitry involved in cognitive and emotional control. These findings, which point to modifiable factors, can be harnessed to inform policy and more effective prevention strategies.
... Being a morning person should be beneficial to our health as this suits the diurnal rhythm well, but in the present study, morningness was found to decrease the SA of the RMFG. Stomby's cross-sectional prospective study might have served an explanation with sleepless, by indicating that higher cortisol in elderly people with less sleep correlates with the decrease of SA on the RMFG (Stomby et al., 2016). However, for night people, compensatory hypertrophy could explain the increased SA of the RMFG, the same as the consequence of Li's study pointing out that patients with brain injury are discovered to have a significant increase of cortical SA and volume in the right lateral occipital gyrus . ...
Introduction
Numerous studies have suggested a connection between circadian rhythm and neurological disorders with cognitive and consciousness impairments in humans, yet little evidence stands for a causal relationship between circadian rhythm and the brain cortex.
Methods
The top 10,000 morningness-related single-nucleotide polymorphisms of the Genome-wide association study (GWAS) summary statistics were used to filter the instrumental variables. GWAS summary statistics from the ENIGMA Consortium were used to assess the causal relationship between morningness and variates like cortical thickness (TH) or surficial area (SA) on the brain cortex. The inverse-variance weighted (IVW) and weighted median (WM) were used as the major estimates whereas MR-Egger, MR Pleiotropy RESidual Sum and Outlier, leave-one-out analysis, and funnel-plot were used for heterogeneity and pleiotropy detecting.
Results
Regionally, morningness decreased SA of the rostral middle frontal gyrus with genomic control (IVW: β = −24.916 mm, 95% CI: −47.342 mm to −2.490 mm, p = 0.029. WM: β = −33.208 mm, 95% CI: −61.933 mm to −4.483 mm, p = 0.023. MR Egger: β < 0) and without genomic control (IVW: β = −24.581 mm, 95% CI: −47.552 mm to −1.609 mm, p = 0.036. WM: β = −32.310 mm, 95% CI: −60.717 mm to −3.902 mm, p = 0.026. MR Egger: β < 0) on a nominal significance, with no heterogeneity or no outliers.
Conclusions and implications
Circadian rhythm causally affects the rostral middle frontal gyrus; this sheds new light on the potential use of MRI in disease diagnosis, revealing the significance of circadian rhythm on the progression of disease, and might also suggest a fresh therapeutic approach for disorders related to the rostral middle frontal gyrus-related.
... However, the literature examining the combined effect of high basal cortisol levels and inflammation is limited. In a previous pilot study conducted in cognitively intact older people, the authors showed that higher cortisol, in conjunction with higher IL-6 and TNF-alpha, is associated with smaller hippocampal volume [42], an area critical for cognition, and long-term cognitive decline if structure or function is disturbed [43][44][45]. However, up to now, to our knowledge, no studies have examined the synergistic effect of both basal stress hormone and inflammation levels on neurocognitive indices, such as performance on executive function tests, in older people either with or without cognitive impairment. ...
There is growing evidence that high basal cortisol levels and systemic inflammation independently contribute to cognitive decline among older people without dementia. The present cross-sectional study examined (a) the potential synergistic effect of cortisol levels and systemic inflammation on executive function and (b) whether this effect is more prominent among older people with mild cognitive impairment (MCI). A sub-sample of 99 patients with MCI and 84 older people without cognitive impairment (CNI) (aged 73.8 ± 7.0 years) were recruited from a large population-based cohort in Crete, Greece, and underwent comprehensive neuropsychiatric and neuropsychological evaluation and a single morning measurement of cortisol and IL-6 plasma levels. Using moderated regression models, we found that the relation between cortisol and executive function in the total sample was moderated by IL-6 levels (b = −0.994, p = 0.044) and diagnostic group separately (b = −0.632, p < 0.001). Moreover, the interaction between cortisol and IL-6 levels was significant only among persons with MCI (b = −0.562, p < 0.001). The synergistic effect of stress hormones and systemic inflammation on cognitive status appears to be stronger among older people who already display signs of cognitive decline. Targeting hypercortisolemia and inflammation may be a promising strategy toward improving the course of cognitive decline.
... Animal studies have shown that both pre-and postnatal disturbances in cortisol affect neuronal growth, dendritic arborization, and long-term potentiation, although the effects depend on GC dose, brain region, and developmental time-window (Shirazi et al. 2015). For example, GCs might impair neurogenesis when given in high doses while stimulating neurogenesis at intermediate doses (Shirazi et al. 2015;Stomby et al. 2016;Morsi et al. 2018). The hippocampus and the prefrontal cortex are particularly sensitive to f luctuations in GC levels due to their high glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) density (Reul and de Kloet 1985;Lupien et al. 1999;McEwen and Magarinos 2001;Joëls 2008;Madalena and Lerch 2017). ...
... The question remains whether these differences might be clinically relevant, and whether they ref lect a maladaptive process, or are part of a compensatory mechanism. High doses of cortisol have been associated with impaired neurogenesis, which may explain the potential mild atrophy in patients on relatively higher doses (Shirazi et al. 2015;Stomby et al. 2016;Morsi et al. 2018). However, in our cohort, a higher medication dose was associated with "better" performance on a visuospatial working memory task. ...
Long-term disturbances in cortisol levels might affect brain structure in individuals with autoimmune Addison's disease (AAD). This study investigated gray and white matter brain structure in a cohort of young adults with AAD. T1- and diffusion-weighted images were acquired for 52 individuals with AAD and 70 healthy controls, aged 19-43 years, using magnetic resonance imaging. Groups were compared on cortical thickness, surface area, cortical gray matter volume, subcortical volume (FreeSurfer), and white matter microstructure (FSL tract-based spatial statistics). Individuals with AAD had 4.3% smaller total brain volume. Correcting for head size, we did not find any regional structural differences, apart from reduced volume of the right superior parietal cortex in males with AAD. Within the patient group, a higher glucocorticoid (GC) replacement dose was associated with smaller total brain volume and smaller volume of the left lingual gyrus, left rostral anterior cingulate cortex, and right supramarginal gyrus. With the exception of smaller total brain volume and potential sensitivity of the parietal cortex to GC disturbances in men, brain structure seems relatively unaffected in young adults with AAD. However, the association between GC replacement dose and reduced brain volume may be reason for concern and requires follow-up study.
... As these reports show, the association between cortisol and the hippocampus and cognitive function has been clarified. There are also reports on the association between cortisol levels and brain volume [18][19][20][21][22]. Additionally, high cortisol levels are associated with smaller hippocampal volumes [23]. ...
Background:
Identifying peripheral biomarkers related to modifiable risk factors to prevent dementia at an early stage will be extremely beneficial. We have been studying how older adults can maintain their mental health and continue to live in a familiar community. The aim of this study is to investigate the association between serum cortisol levels and brain volume among older adults in rural Japan.
Methods:
This was a longitudinal study conducted in Kurokawa-cho, Imari, Saga Prefecture, Japan, among people aged 65 years and above, as reported previously. We conducted a survey twice. The first survey was conducted from October 2009 to March 2011 (Timepoint 1) and the second was conducted from November 2016 to September 2017 (Timepoint 2). Blood samples for serum cortisol levels analysis were collected from participants at Timepoint 1. Serum cortisol levels were measured using the enzyme-linked immunosorbent assay. The participants underwent brain MRI examinations, and Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) for cognitive function assessment at Timepoint 1 and Timepoint 2. We obtained 70 participants (16 men, mean age 72.69 ± 3.18 years; 54 women, mean age 72.69 ± 4.60 years, at Timepoint 1) for analysis. Correlation analysis was performed between serum cortisol levels at baseline (Timepoint 1) and brain volume (Timepoint 1, Timepoint 2, and Timepoint 1-Timepoint 2 difference) using voxel-based morphometry method.
Results:
There was no significant difference in serum cortisol levels between men (72.32 ± 17.30 ng/ml) and women (76.60 ± 21.12 ng/ml) at baseline. Additionally, no effect of blood collection time on cortisol levels was observed in these participants. Small volume correction analysis at the cluster level by applying multiple comparison corrections (family-wise error; P < 0.05) showed a negative correlation between serum cortisol levels (Timepoint 1) and brain volume (Timepoint 2) within the region containing the left hippocampus.
Conclusions:
Serum cortisol levels may serve as a peripheral biomarker of age-related volume changes involving the hippocampus in older adults aged 65 years and above.
... Elevated basal cortisol levels have been linked to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which is related to excessive exposure to physical or psychosocial stressors, and aging [8][9][10][11][12][13]. Furthermore, increased basal cortisol levels have been associated with a reduced volume of the hippocampus and prefrontal cortex in older adults, crucial brain anatomic structures for memory and executive functions [8,[14][15][16][17]. Several studies in older adults have revealed negative associations between basal cortisol levels, memory performance, and executive functions [18][19][20]. ...
Background:
Mild cognitive impairment (MCI) is frequent in elderly and a risk factor for dementia. Both insomnia and increased cortisol levels are risk factors for MCI.
Objective:
We examined cross-sectionally whether increased cortisol levels are associated with short sleep duration (SSD) and/or the insomnia short sleep duration (ISS) phenotype, in elderly with MCI.
Methods:
One hundred twenty-four participants with MCI and 84 cognitively non-impaired controls (CNI)≥60 years underwent medical history, physical examination, neuropsychiatric evaluation, neuropsychological testing, 3-day actigraphy, assessment of subjective insomnia symptoms, and a single morning plasma cortisol level. The short sleep phenotypes were defined by sleep efficiency below the median of the entire sample (i.e.,≤81%) with at least one insomnia symptom (ISS) or without (SSD). ANOVA models were used to compare the various sleep phenotypes to those who did not present either short sleep or insomnia symptoms [non-insomnia (NI)].
Results:
MCI participants had higher cortisol levels compared to the CNI group (p = 0.009). MCI participants with insomnia (n = 44) or SSD (n = 38) had higher cortisol levels compared to the NI group (n = 42; p = 0.014 and p = 0.045, respectively). Furthermore, MCI participants with ISS phenotype but not those with insomnia with normal sleep duration had higher cortisol levels compared to NI (p = 0.011 and p = 0.4, respectively). Both linear trend analyses showed that cortisol reached the highest levels in the ISS phenotype.
Conclusion:
The ISS and SSD phenotypes are associated with increased cortisol levels in elderly with MCI. Improving sleep quality and duration and decreasing cortisol levels may delay further cognitive decline.
... Elevated basal cortisol levels have been associated with dysregulation of the hypothalamic-pituitaryadrenal (HPA) axis, responsible for the endogenous cortisol circulation, and attributed to excessive exposure to physical or psychosocial stressors, such as chronic inflammation, malnutrition, or traumatic experiences (Lupien et al., 1998;Sapolsky et al., 1986;Vgontzas et al., 2003). Furthermore, HPA dysregulation and increased basal cortisol levels have been linked to atrophy or damage of the hippocampus and prefrontal cortex in older adults (Lupien et al., 1998(Lupien et al., , 2009Huang et al., 2009;Arnsten, 2009;Stomby et al., 2016). Such associations are typically documented among persons who suffer from affective disorders and/or cognitive impairment. ...
... However, HPA axis dysregulation may also be found among elders who do not meet formal criteria for psychiatric or cognitive disorders [mild cognitive impairment (MCI), or dementia]. Both hippocampus and prefrontal cortex are critical for cognition, and therefore disturbances in their function and/or structure may have longterm consequences on cognitive ability and resilience (Cabeza & Nyberg, 2000;Lupien et al., 1998;Stomby et al., 2016). In sum, individual variability in basal cortisol levels among older adults may account for significant variance in the impact of aging on cognition. ...
Elevated basal cortisol levels in elderly may indicate dysregulation of the internal stress-related system, as well as dysfunction and structural alterations in brain structures necessary for cognition, such as hippocampus and prefrontal cortex. Because of the close relation of executive functions and episodic memory processing, in this study we explored whether the association of elevated cortisol levels on episodic memory could be partly attributed to cortisol effects on executive functions. In this cross-sectional study we analyzed data from a sample of 236 community-dwelling older adults from the Cretan Aging Cohort aged 75.56 ± 7.21 years [53 with dementia due to probable Alzheimer’s disease, 99 with Mild Cognitive Impairment (MCI) and 84 cognitively non-impaired participants (NI)]. Morning serum cortisol levels were higher in the probable AD as compared to the NI group (p = .031). Mediated regression models in the total sample supported the hypothesis that the negative association of basal cortisol levels with delayed memory was fully mediated by the relation of basal cortisol levels with executive functions and immediate memory (adjusted for age and self-reported depression symptoms). Moderated mediation regression models revealed that the direct effect of cortisol on executive function and the effect of executive function on delayed memory performance were statistically significant among participants diagnosed with MCI, while the immediate memory effect on delayed memory was more pronounced in AD patients, as compared to the NI group. The current findings corroborate neuroimaging research highlighting cortisol effects on executive functions and immediate memory and further suggest that dysregulation of systems involved in these functions may account for the purported detrimental long-term effects of high cortisol levels on delayed memory.
... The authors concluded widespread neuronal effects of sex and stress hormones and suggested future studies to widen the range of researched brain regions, e.g. on cortical thickness (Gray et al., 2017). Stomby et al. (2016) reported small sex-dependent associations between area under curve saliva cortisol concentrations and cortical thickness of the caudal middle frontal gyrus and the right pars opercularis in 200 elderlies (>54 years). Although the interaction effects did not stand the adjustment for multiple testing, a positive association between cortisol concentrations and cortical thickness was observed in post-hoc analyses in healthy women but not in men (Stomby et al., 2016). ...
... Stomby et al. (2016) reported small sex-dependent associations between area under curve saliva cortisol concentrations and cortical thickness of the caudal middle frontal gyrus and the right pars opercularis in 200 elderlies (>54 years). Although the interaction effects did not stand the adjustment for multiple testing, a positive association between cortisol concentrations and cortical thickness was observed in post-hoc analyses in healthy women but not in men (Stomby et al., 2016). ...
... Integrating the well-described interaction of the HPA and HPG axis (Gray et al., 2017;Bourke et al., 2012;Hertel et al., 2017;Baker and Driver, 2007;Cumming et al., 1983), we further expected sex differences in these cortisol-cortical thickness associations. Although the results of Stomby et al. (2017) (Stomby et al., 2016) were based on a smaller elderly sample, we assumed stronger associations between cortisol concentrations and cortical thickness in women. In support of the validity of the cortical thickness analyses in our sample, we aimed to replicate previously reported sex differences in our basal serum cortisol concentrations as well as inverse associations of the basal cortisol concentrations with depressive symptoms and childhood maltreatment (Fogelman and Canli, 2018;Heim et al., 2008). ...
Background
Basal cortisol concentrations vary between men and women. Likewise, previous findings suggest stress-related cortical thickness alterations. Thus, we aimed at elucidating sex differences in the association between serum cortisol concentrations and cortical thickness.
Methods
Data of 2594 participants (55.55% male; mean age = 53.55 years ± 13.17 years) of the general population were used to investigate sex differences in basal serum cortisol concentrations and associations of serum cortisol concentrations with global and regional cortical thickness. The validity of the results was tested by including sex hormone concentrations as a biological and childhood maltreatment and depressive symptoms as a psychological confounder.
Results
Basal serum cortisol concentrations were higher in men than in women (β = −0.158, t(2575) = -6.852, p = 9.056e-12). Sex differences in serum cortisol concentrations were diminished by including serum concentrations of testosterone, estrone, or estradiol in the models. In men but not in women, serum cortisol concentrations were inversely associated with the global cortical thickness (men: β = −0.064, t(1412) = -3.010, p = .003; women: β = −0.016, t(1131) = -0.607, p = .544). Additionally, these effects were observed in eleven cortical regions after adjusting for multiple testing. The associations were independent of childhood maltreatment and depressive symptoms.
Conclusion
Sex differences in serum cortisol concentrations and the association between serum cortisol concentrations and cortical thickness suggest important sex-specific effects of stress on the brain. Future studies should integrate the interaction between the hypothalamic-pituitary-adrenal (HPA) axis and hypothalamic-pituitary-gonadal (HPG) axis in sex-stratified analyses.
... 49 Preclinical studies have reported corticosterone-induced dendritic atrophy in the hippocampus 53 and MPFC. 54 The relationship between elevated cortisol levels and prefrontal, 55 temporal and parietal atrophy 56 have been reported in healthy individuals. A meta-analysis reported the relationship between increased cortisol levels and hippocampal atrophy in patients with late-life depression. ...
Psychotic major depression (PMD) is hypothesized to be a distinct clinical entity from nonpsychotic major depression (NPMD). However, neurobiological evidence supporting this notion is scarce. The aim of this study is to identify gray matter volume (GMV) differences between PMD and NPMD and their longitudinal change following electroconvulsive therapy (ECT). Structural magnetic resonance imaging (MRI) data from 8 independent sites in the Global ECT-MRI Research Collaboration (GEMRIC) database (n = 108; 56 PMD and 52 NPMD; mean age 71.7 in PMD and 70.2 in NPMD) were analyzed. All participants underwent MRI before and after ECT. First, cross-sectional whole-brain voxel-wise GMV comparisons between PMD and NPMD were conducted at both time points. Second, in a flexible factorial model, a main effect of time and a group-by-time interaction were examined to identify longitudinal effects of ECT on GMV and longitudinal differential effects of ECT between PMD and NPMD, respectively. Compared with NPMD, PMD showed lower GMV in the prefrontal, temporal and parietal cortex before ECT; PMD showed lower GMV in the medial prefrontal cortex (MPFC) after ECT. Although there was a significant main effect of time on GMV in several brain regions in both PMD and NPMD, there was no significant group-by-time interaction. Lower GMV in the MPFC was consistently identified in PMD, suggesting this may be a trait-like neural substrate of PMD. Longitudinal effect of ECT on GMV may not explain superior ECT response in PMD, and further investigation is needed.
