Salivary cortisol and prefrontal cortical thickness in middle-aged men: A twin study

Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA.
NeuroImage (Impact Factor: 6.36). 02/2010; 53:1093-1102. DOI: 10.1016/j.neuroimage.2010.02.026
Source: PubMed

ABSTRACT Although glucocorticoid receptors are highly expressed in the prefrontal cortex, the hippocampus remains the predominant focus in the literature examining relationships between cortisol and brain. We examined phenotypic and genetic associations of cortisol levels with the thickness of prefrontal and anterior cingulate cortex regions, and with hippocampal volume in a sample of 388 middle-aged male twins who were 51-59 years old. Small but significant negative phenotypic associations were found between cortisol levels and the thickness of left dorsolateral (superior frontal gyrus, left rostral middle frontal gyrus) and ventrolateral (pars opercularis, pars triangularis, pars orbitalis) prefrontal regions, and right dorsolateral (superior frontal gyrus) and medial orbital frontal cortex. Most of the associations remained significant after adjusting for general cognitive ability, cardiovascular risk factors, and depression. Bivariate genetic analyses suggested that some of the associations were primarily accounted for by shared genetic influences; that is, some of the genes that tend to result in increased cortisol levels also tend to result in reduced prefrontal cortical thickness. Aging has been associated with reduced efficiency of hypothalamic-pituitary-adrenal function, frontal lobe shrinkage, and increases in health problems, but our present data do not allow us to determine the direction of effects. Moreover, the degree or the direction of the observed associations and the extent of their shared genetic underpinnings may well change as these individuals age. Longitudinal assessments are underway to elucidate the direction of the associations and the genetic underpinnings of longitudinal phenotypes for changes in cortisol and brain morphology.

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Available from: Larry J Seidman, Sep 28, 2015
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    • "For example, animal models demonstrate a relationship between experimentally-induced stress and hippocampal damage [Sapolsky et al., 1985]. Human studies indicate that psychological stress may disrupt hypothalamic-pituitary-adrenal axis activity, resulting in altered cortisol levels and cellular damage or tissue volume reductions in various brain regions [Kremen et al., 2010; Lupien et al., 1998; Lupien et al., 2005]. Taken together, these findings raise the question of whether the apoE genotype may influence susceptibility to PTSD following trauma. "
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    ABSTRACT: Factors determining who develops PTSD following trauma are not well understood. The €4 allele of the apolipoprotein E (apoE) gene is associated with dementia and unfavorable outcome following brain insult. PTSD is also associated with dementia. Given evidence that psychological trauma adversely affects the brain, we hypothesized that the apoE genotype moderates effects of psychological trauma on PTSD pathogenesis. To investigate the moderation of the relationship between PTSD symptoms and combat exposure, we used 172 participants with combat trauma sustained during the Vietnam War. PTSD symptoms were the dependent variable and number of combat experiences, apoE genotype, and the combat experiences × apoE genotype interaction were predictors. We also examined the outcome of a diagnosis of PTSD (n = 39) versus no PTSD diagnosis (n = 131). The combat × apoE genotype interaction was significant for both PTSD symptoms (P = .014) and PTSD diagnosis (P = .009). ApoE genotype moderates the relationship between combat exposure and PTSD symptoms. Although the pathophysiology of PTSD is not well understood, the €4 allele is related to reduced resilience of the brain to insult. Our results are consistent with the €4 allele influencing the effects of psychological trauma on the brain, thereby affecting the risk of PTSD. © 2013 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 10/2013; 162(7):762-9. DOI:10.1002/ajmg.b.32154 · 3.42 Impact Factor
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    • "In a small cohort of 13 young subjects, higher morning cortisol levels were associated with larger hippocampal volumes (Pruessner et al., 2007). By contrast, two studies in large, middle-aged cohorts (N> 380) did not find such a relationship (Knoops et al., 2010; Kremen et al., 2010) but one of these reported that smaller hippocampal volumes were correlated with higher evening cortisol levels, as well as with higher morning cortisol levels after dexamethasone administration (Knoops et al., 2010). Another study found that smaller hippocampi were associated with higher morning adrenocorticotropin levels and higher 24-hour urine cortisol levels (Wolf et al., 2002). "
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    ABSTRACT: It is well-established that prolonged high levels of cortisol have adverse effects on hippocampal neurons and glial cells. Morphometric studies linking hippocampus volume to basal HPA-axis activity, however, have yielded less consistent results. Asymmetry may also be considered, since there is growing evidence for hemispheric lateralization in brain systems regulating arousal and emotion. Here we tested the hypotheses that individual variations in basal morning and afternoon/evening cortisol levels would be associated with the degree of hemispheric asymmetry in hippocampal microstructure. Fifty healthy adults aged 19 to 86 years were included in the analyses. Diffusion-weighted imaging was acquired from all subjects. Hippocampal mean diffusivity (MD) and volume was extracted. Cortisol measures were based on 5 morning and 3 afternoon/evening saliva samples. Higher left relative to right hippocampus MD was associated with higher basal cortisol levels. Associations were anatomically specific and not attributable to hippocampal volume asymmetry. No correlation between hippocampal volume and MD was observed, suggesting that MD and volume index distinct biological properties of the hippocampus. Observed associations raise a number of possibilities, among them an asymmetric role of the hippocampus on HPA-axis regulation, or conversely, that individual variations in secreted cortisol, perhaps associated with stress, may have lateralized effects on hippocampal microstructure. Our results point to an important relationship between the limbic system and neuroendocrine function in terms of left-right asymmetries, raising additional questions about how the limbic system is related to neuroendocrine functions.
    NeuroImage 07/2012; 63(1):95-103. DOI:10.1016/j.neuroimage.2012.06.071 · 6.36 Impact Factor
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    • "Details of the sample can be found in the study by Kremen et al. (2006, 2010a). Participants were 474 individuals with analyzable magnetic resonance imaging (MRI) data who are part of a sample of 1237 twins who participated in wave 1 of the Vietnam Era Twin Study of Aging (VETSA); there were 404 paired twins [110 monozygotic (MZ) and 92 dizygotic (DZ) pairs] and 70 unpaired twins. "
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    ABSTRACT: The estimation of cortical thickness is in part dependent on the degree of contrast in T1 signal intensity between white matter and gray matter along the cortical mantle. The ratio of white matter to gray matter signal (WM/GM contrast) has been found to vary as a function of age and Alzheimer's disease status, suggesting a biological component to what might otherwise be labeled as a nuisance variable. The aim of the present study was to determine if measures of WM/GM contrast are genetically influenced, as well as the degree to which this phenotype may be related to the genetic and environment determinants of cortical thickness. Participants were 514 male twins (130 monozygotic, 97 dizygotic pairs, and 60 unpaired individuals) from the Vietnam Era Twin Study of Aging. Ages ranged from 51 to 59 years. Measures of WM/GM contrast and cortical thickness were derived for 66 cortical regions of interest (ROI) using FreeSurfer-based methods. Univariate and bivariate twin analyses were used in order to estimate the heritability of WM/GM contrast, as well as the degree of shared genetic and environmental variance between WM/GM contrast and cortical thickness. WM/GM contrast was found to be significantly heritable in the majority of ROIs. The average heritability across individual ROIs was highest in the occipital lobe (.50), and lowest in the cingulate cortex (.24). Significant phenotypic correlations between WM/GM contrast and cortical thickness were observed for most of the ROIs. The majority of the phenotypic correlations were negative, ranging from ?.11 to ?.54. Of the 66 associations, only 17 significant genetic correlations were found, ranging from ?.16 to ?.34, indicating small amounts of shared genetic variance. The majority of the phenotypic correlations were accounted for by small unique environmental effects common between WM/GM contrast and cortical thickness. These findings demonstrate that like cortical thickness, WM/GM contrast is a genetically influenced brain structure phenotype. The lack of significant genetic correlations with cortical thickness suggests that this measure potentially represents a unique source of genetic variance, one that has yet to be explored by the field of imaging genetics.
    NeuroImage 04/2012; 60(3):1686-95. DOI:10.1016/j.neuroimage.2012.01.122 · 6.36 Impact Factor
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