Acute psychosocial stress alters thalamic network centrality.

Acute stress triggers a broad psychophysiological response that is adaptive if rapidly activated and terminated. While the brain controls the stress response, it is strongly affected by it. Previous research of stress effects on brain activation and connectivity has mainly focused on pre-defined brain regions or networks, potentially missing changes in the rest of the brain. We here investigated how both stress reactivity and stress recovery are reflected in whole-brain network topology and how changes in functional connectivity relate to other stress measures. Healthy young males (n = 67) completed the Trier Social Stress Test or a control task. From 60 min before until 105 min after stress onset, blocks of resting-state fMRI were acquired. Subjective, autonomic, and endocrine measures of the stress response were assessed throughout the experiment. Whole-brain network topology was quantified using Eigenvector centrality (EC) mapping, which detects central hubs of a network. Stress influenced subjective affect, autonomic activity, and endocrine measures. EC differences between groups as well as before and after stress exposure were found in the thalamus, due to widespread connectivity changes in the brain. Stress-driven EC increases in the thalamus were significantly correlated with subjective stress ratings and showed non-significant trends for a correlation with heart rate variability and saliva cortisol. Furthermore, increases in thalamic EC and in saliva cortisol persisted until 105 min after stress onset. We conclude that thalamic areas are central for information processing after stress exposure and may provide an interface for the stress response in the rest of the body and in the mind.

Calcitonin measurement in pediatrics: reference ranges are gender-dependent, validation in medullary thyroid cancer and thyroid diseases.

BACKGROUND: There is only limited information on serum reference ranges of calcitonin (CT) in infants, children and adolescents. This gap hampers valid diagnostics in patients with multiple endocrine neoplasia type 2 (MEN 2) and planned prophylactic thyroidectomy. In addition, age-dependent reference ranges for CT are necessary to define a cure in medullary thyroid carcinoma (MTC). We asked whether the reference ranges for CT levels were age- and gender-dependent in the serum of a pediatric cohort. METHODS: A total of 6090 serum samples of 2639 subjects of the LIFE-Child cohort aged between 1 month and 17.9 years were analyzed by the CT electrochemiluminescence immunoassay (ECLIA). Reference intervals were estimated using the LMS method. For clinical validation the serum of 28 patients (61 samples) with MEN 2 and 106 patients (136 samples) with thyroid diseases were analyzed. RESULTS: CT levels showed a clear age- and gender-dependence with significantly higher values in boys (p<0.01). An accelerated decline of CT levels from newborn to children at the age of 4 and 5 years was observed for both sexes. A cure for MTC was demonstrated in 71% of MEN 2 patients after thyroidectomy, whereas 5 patients remained suspicious for micrometastasis or relapse. Only 1.5% of our patients with thyroid diseases revealed increased CT levels. CONCLUSIONS: This is the largest study to establish novel pediatric reference ranges from the CT values of healthy subjects. It allows a precise laboratory monitoring of CT in pediatric patients with MEN 2. Thyroid diseases did not have a relevant influence on CT levels in our pediatric cohort.

Stress-related hormones in association with periodontal condition in adolescents-results of the epidemiologic LIFE Child study.

OBJECTIVES: The aim of this study was to investigate the associations between blood levels of stress-related hormones and early signs of periodontal disease in children and adolescents. MATERIALS AND METHODS: Within the LIFE (Leipzig research center for civilization diseases) Child study, 498 adolescents (10 to 18 years) were included. Early signs of periodontal inflammation were measured by probing depth (PD) at six index teeth (16, 11, 26, 36, 31, 46). Blood levels of stress-related hormones (cortisol, dehydroepiandosterone-sulfate [DHEA-S]) and, additionally interleukine-6 (IL-6) were measured. Socioeconomic status, oral hygiene, orthodontic appliances, and nutritional status, recorded by body-mass-index-standard-deviation-score (BMI-SDS), were considered as confounding factors. Additionally, in 98 participants, an oral chairside active matrix metalloproteinase-8 (aMMP-8) test was performed. Statistical tests are the Mann-Whitney U tests, chi-squared tests and multivariate logistic regression model. RESULTS: IL-6, BMI-SDS as well as positive aMMP-8 test result were significantly associated with maximum PD > 3 mm (p < 0.05). However, no statistically significant associations between stress-related hormones (cortisol and DHEA-S) and presence of maximum PD > 3 mm were found (p > 0.05). Higher DHEA-S and BMI were associated with positive aMMP-8 result, even after adjusting for age and gender (p = 0.027, padj = 0.026). CONCLUSION: The results reveal no associations between PD and stress-related hormones cortisol and DHEA-S. aMMP-8 test result might be associated with DHEA-S level. Nutritional status seems to influence periodontal disease in adolescents. CLINICAL RELEVANCE: DHEA-S and BMI-SDS show associations with early signs of periodontal disease in adolescents aged 10 to 18 years. This association should be confirmed by the investigation of high-risk groups.

Endocrinological and subjective stress responses in children with depressive, anxiety, or externalizing disorders.

In this study, we used a stress test to investigate endocrinological and subjective stress responses of 8- to 14-year-old children with internalizing or externalizing disorders and healthy controls. The sample (N = 170) consisted of clinical and community children. Parents were given a diagnostic interview to diagnose their children's psychiatric condition. We measured saliva cortisol and subjectively experienced arousal in children before and after the Trier Social Stress Test for Children. Children also rated their performance immediately after the stress test, and 1 hr later they rated their positive and negative thoughts about this stressful event. Children with internalizing or externalizing disorders exhibited a blunted cortisol response compared to healthy controls. Depressed children rated their test performance lower and reported more negative thoughts after the test in comparison to healthy controls, anxious children reported more arousal before and after the task, and children with externalizing disorders reported more positive thoughts. In regression analyses, cortisol and subjective stress responses were both predictive of psychiatric disorders. The study extends previous work on the relation between psychiatric disorders and children's stress responses to an experimentally induced stress task by including a broad range of psychiatric disorders and by integrating endocrinological and subjective stress responses.

Immunoassay or LC-MS/MS for the measurement of salivary cortisol in children?

BACKGROUND: Dysregulation of the adrenal cortex has been assessed with measurement of salivary cortisol. So far salivary cortisol is routinely measured with immunoassay (IA). However, liquid chromatography-tandem mass spectrometry (MS) is known to offer better specificity. We compared the concentrations of salivary cortisol measured by MS and IA at basal and stress induced conditions and evaluated reasons for the difference in method-dependent cortisol results. METHODS: Saliva samples (n=2703) were collected from 169 children (age range: 8-14 years; 81 healthy children; 55 with internalizing and 33 with externalizing disorders) under circadian conditions and during the Trier Social Stress Test for Children (TSST-C). Biochemical analyses were performed with MS for cortisol and cortisone, IA (IBL, RE62011) for cortisol, and enzyme kinetic assay for α-amylase. RESULTS: MS and IA showed mostly comparable results for circadian activity and TSST-C response with similar statistical power. However, IA measured cortisol concentrations about 2.39-fold higher than MS. We found that this difference in measured values between MS and IA was mainly due to different standardization of IA compared to MS. In addition, at cortisol IA concentration below 5 nmol/L, cross-reactivity with cortisone was found to contribute to the lower concordance between MS and IA. CONCLUSIONS: Immunoassay and LC-MS/MS were largely comparable in the interpretation of salivary cortisol dynamics in stress research. But the IA method revealed a restricted accuracy in the measuring range below 5 nmol/L.

Calcitonin as Biomarker for the Medullary Thyroid Carcinoma.

Calcitonin (CTN) is a polypeptide hormone consisting of 32 amino acids with a disulfide bridge between position 1 and 7 that is mainly produced by the C-cells of thyroid gland. The measurement of CTN concentrations in blood reflects C-cell activity and is performed in general by immunoassay methods. However, there are analytical, physiological, pharmacological, and pathological factors that can influence results of serum CTN values. Due to the influence of these factors, there is a high variability in assay-dependent cutoffs used to discriminate between MTC, C-cell hyperplasia (CCH), and the absence of the pathological impairment of C-cells. There is a lot of evidence that the measurement of serum CTN concentrations in patients with thyroid nodules can lead to an earlier diagnosis of MTC or CCH than the exclusive use of imaging procedures and/or fine-needle aspiration cytology. Basal CTN concentrations higher than 60-100 pg/mL are highly indicative for the diagnosis MTC. In the range between cutoff and 60 pg/mL CTN, both MTC and HCC may be a relevant diagnosis. PCT and CTN appear to have a comparable diagnostic capability to diagnose MTCs. However, "positive" PCT values of more than 50 pg/mL may be reached also in subclinical infections and will lead, therefore, to an overdiagnosis of the tumor. Pentagastrin- or calcium-stimulated serum CTN concentrations higher than cutoff values might improve diagnostics of MTC, but the non-availability of the first and the lacking of relevant cutoff values for the second tool favors the use of only basal values currently.

Subacute Oral Toxicity Evaluation of Expanded-Polystyrene-Fed Tenebrio molitor Larvae (Yellow Mealworm) Powder in Sprague-Dawley Rats.

Tenebrio molitor larvae, as known as edible insects, has advantages of being rich in protein, and has been recognized as a suitable alternate protein source for broiler and pig feed. Moreover, given their ability to biodegrade polystyrene, a major pollutant, Tenebrio molitor larvae has been proposed as an innovative solution to environmental problems. In the present study, we investigated the toxicity of Tenebrio molitor larvae powder (TMlp) ingested with expanded-polystyrene (W/ eps) through in vitro and in vivo experiments. The objective of this study was to determine whether TMlp W/ eps can be applied as livestock alternative protein source. For in vitro experiments, cytotoxicity test was performed to investigate the effects of TMlp-extract on the viability of estrogen-dependent MCF-7 cells. The possibility of estrogen response was investigated in two groups: Expanded-polystyrene-fed (W/ eps) TMlp group and without expanded-polystyrene-fed (W/o eps) TMlp group. For in vivo experiments, The male Sprague-Dawley rats were divided based on the dosage of TMlp administered and oral administration was performed to every day for 5 weeks. A toxicological assessments were performed, which included clinical signs, food consumption, body and organ weights, hematology, serum chemistry, and hematoxylin and eosin staining of liver and kidney. There were no specific adverse effect of TMlp W/ eps-related findings under the experimental conditions of this study, but further studies on both sexes and animal species differences should be investigated. In conclusion, TMlp W/ eps was considered non-toxic and observed to be applicable as an alternative protein source for livestock feed.

Prospective evaluation of aldosterone LC-MS/MS-specific cutoffs for the saline infusion test.

OBJECTIVE: Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) has become state of the art for the quantitative analysis of steroid hormones. Although method comparisons show that aldosterone measurement using LC-MS/MS yields considerably lower levels than immunoassays (IAs), method-specific cutoff values for primary aldosteronism (PA) are largely missing. Objective of this study was to analyze the diagnostic accuracy of proposed LC-MS/MS-specific cutoff values for the saline infusion test (SIT). DESIGN AND METHODS: From 2016 to 2019, 104 consecutive patients suspected of PA underwent the SIT and captopril challenge test in the tertiary medical center at the University Hospital of Leipzig, Germany. Patients with positive case confirmation underwent adrenal imaging and adrenal venous sampling for subtype classification. RESULTS: Overall, proposed assay-specific PACLC-MS/MS cutoff values for the SIT achieved higher diagnostic accuracy than established PACIA values with a sensitivity and specificity of 87.5% (95% CI: 71.0-96.5) and 97% (95% CI: 89.6-99.6) for a cutoff of 120 pmol/L and 93.8% (95% CI: 79.2-99.2) and 92.5% (95% CI: 83.4-97.5) for a cutoff of 94 pmol/L. The most accurate post-SIT PACLC-MS/MS cutoff value in this study was 83 pmol/L, yielding a sensitivity and specificity of 96.9% (95% CI: 83.8-99.9) and 92.5% (95% CI: 83.4-97.5), respectively. CONCLUSIONS: The present data confirm the need for the implication of lower method-specific aldosterone cutoff values for the diagnosis of PA with LC-MS/MS based aldosterone measurement.

Unraveling the steroid hormone response in male marathon runners: Correlation of running time with aldosterone and progesterone.

Marathon running is a physical and psychological stressor. We aimed to characterize the response of nine steroid hormones, which include estradiol, progesterone, testosterone, cortisol, aldosterone, 17-hydroxyprogesterone, cortisone, androstenedione, and dehydroepiandrosterone sulfate, to marathon running and their association with performance. Blood samples of sixty men (age: 49.3 ± 5.9 years) who participated in the Berlin marathon were collected within 3 days before, within 30 min and within 58 h after the end of the marathon. The nine steroid hormones in serum were quantified using liquid chromatography-tandem mass spectrometry. The responses of nine steroid hormones to marathon running were characterized. Aldosterone (fold change: 8.5), progesterone (fold change: 6.6), and cortisol (fold change: 3.7) showed significant increases within 30 min after the marathon (all p < 0.0001). Estradiol but not testosterone increased in the male runners. Marathon running time was significantly related to aldosterone increase (beta=-0.238, p = 0.008) and progesterone increase (beta=-0.192, p = 0.036) in addition to body mass index, self-reported training distance, and age. Serum progesterone correlated with aldosterone and cortisol (r = 0.81 and r = 0.92, respectively, p < 0.001). Progesterone, as a precursor hormone, is increased after the completion of marathon running in association with the increase of aldosterone and cortisol. These findings reveal a contribution of progesterone during the response to the psycho-physical stress of marathon running in males.

Differentiation of atrial fibrillation progression phenotypes using Troponin T.

BACKGROUND: Electro-anatomical remodeling in atrial fibrillation (AF) is associated with disease initiation and progression. Troponin T (TropT) - a specific biomarker for myocardial damage - is associated with AF incidence. However, its association with AF progression is understudied. The aim of the current analysis was to investigate the association between TropT and AF progression phenotypes: persistent AF and left atrial low voltage areas (LVAs). METHODS: Patients undergoing first AF ablation were included into analyses. LVAs were determined using high-density maps and defined as <0.5 mV. Blood samples from femoral vein were collected before catheter ablation. The analysis of TropT serum concentrations was performed using a high-sensitive assay from Roche Diagnostics. Biomarkers, clinical, anthropometric and echocardiographic data were compared with healthy individuals from the epidemiological cohort. RESULTS: The study included 824 healthy individuals without overt cardiovascular disease (54 ±â€¯10 years, 40% males) from epidemiological cohort and 241 AF patients (64 ±â€¯11 years, 59% males, 59% persistent AF, 27% LVAs). Patients with AF had higher TropT levels and larger left atrium (LA), while healthy individuals had better renal function and ejection fraction (all p < 0.001). In clinical cohort, there were significant differences between TropT levels according to AF progression groups: paroxysmal AF without/with LVAs (n = 86/12), persistent AF without/with LVAs (n = 90/53): means 7.3, 12.9, 8.4, 11.3 pg/ml, p < 0.001, respectively. Similar findings were observed for LA and renal function (all p < 0.001). On ROC analysis, TropT significantly predicted LVAs (AUC 0.675, 95%CI 0.598-0.752, p < 0.001) in AF patients. CONCLUSIONS: TropT may be useful to differentiate AF progression phenotypes.

Adaptation and Validation of the Korean Version of the Urticaria Control Test and Its Correlation With Salivary Cortisone.

PURPOSE: Frequent changes in chronic urticaria (CU) activity over time can cause psychological stress, which also serves as a trigger of CU. To measure the control status of CU, the Urticaria Control Test (UCT) was developed in Germany. This study aimed to investigate the validity, reliability and responsiveness to changes in CU for the Korean version of the UCT (K-UCT) and its relation with salivary cortisol and cortisone levels. METHODS: Linguistic adaptation of the UCT into Korean was conducted. A total of 96 CU patients were enrolled, and 80 of them completed the study. The K-UCT and other outcome scores for CU were measured and repeated after 4 weeks of treatment. Control status was classified by physicians into well-controlled, partly-controlled, and uncontrolled CU. Salivary cortisol and cortisone were measured by liquid chromatography-tandem mass spectrometry. RESULTS: Excellent internal consistency and intra-class reliability were obtained. Strong correlations between the K-UCT and disease severity, reflected in the Urticaria Activity Score (UAS)/global assessment of urticaria control by physicians/patient assessment of symptom severity/CU-specific quality of life were noted. K-UCT scores ≥12 were found to be optimal for determining well-controlled CU (sensitivity, 75.0%; specificity, 758%; area under the curve, 0.824). Perceived stress scale scores were significantly correlated with the UAS and the K-UCT. Salivary cortisone levels were significantly correlated with K-UCT (r = 0.308, P = 0.009) and differed significantly according to control status determined by a K-UCT ≥12. CONCLUSIONS: This study demonstrated that the K-UCT can be a valid instrument with which to gauge CU control status in Korean patients. Further studies are needed to validate salivary cortisone as a biomarker for CU control.

Salivary cortisone, as a biomarker for psychosocial stress, is associated with state anxiety and heart rate.

BACKGROUND: Stress activates the central nervous, the autonomic nervous, and the endocrine system. This study aimed to (1) test the usability of salivary cortisone in a standardized psychosocial stressor, (2) create a comprehensive profile of hormonal responses to determine laboratory parameters with high discriminatory power, and (3) analyze their association with psychometric and autonomic stress measures. METHODS: Healthy young men (18-35 years) completed either the Trier Social Stress Test (TSST) (n = 33) or a Placebo-TSST (n = 34). Blood and saliva were collected at 14 time points along with state-anxiety (STAI) and heart rate. Serum steroids (cortisol*, cortisone*, dehydroepiandrosterone-sulfate, androstenedione*, progesterone*, 17-hydroxyprogesterone*, testosterone, estradiol*, aldosterone*), salivary cortisol* and cortisone*, copeptin*, adrenocorticoptropic hormone*, corticosteroid-binding globulin, and salivary alpha-amylase* were analyzed. We used mixed-design ANOVAs to test group differences, receiver operator characteristic (ROC) curve analyses to assess the discriminatory power of each measure, and Spearman correlation analyses to probe the association between measures. RESULTS: The largest area under the ROC curve was observed in salivary cortisone at 20 min after the end of the TSST (AUC = 0.909 ± 0.044, p < 0.0001). Significant time-by-group interactions were found in the parameters marked with * above, indicating stress-induced increases. The peak response of salivary cortisone was significantly associated with those of STAI (rho = 0.477, p = 0.016) and heart rate (rho = 0.699, p < 0.0001) in the TSST group. CONCLUSION: Our study found salivary cortisone to be a stress biomarker with high discriminatory power and significant correlations with subjective and autonomic stress measures. Our results can inform future stress studies of sampling time for different laboratory parameters.

Genetic Association Study of Eight Steroid Hormones and Implications for Sexual Dimorphism of Coronary Artery Disease.

CONTEXT: Steroid hormones are important regulators of physiological processes in humans and are under genetic control. A link to coronary artery disease (CAD) is supposed. OBJECTIVE: Our main objective was to identify genetic loci influencing steroid hormone levels. As a secondary aim, we searched for causal effects of steroid hormones on CAD. DESIGN: We conducted genome-wide meta-association studies for eight steroid hormones: cortisol, dehydroepiandrosterone sulfate (DHEAS), estradiol, and testosterone in two independent cohorts (LIFE-Adult, LIFE-Heart, maximum n = 7667), and progesterone, 17-hydroxyprogesterone, androstenedione, and aldosterone in LIFE-Heart only (maximum n = 2070). All genome-wide significant loci were tested for sex interactions. Furthermore, we tested whether previously reported CAD single-nucleotide polymorphisms were associated with our steroid hormone panel and investigated causal links between hormone levels and CAD status using Mendelian randomization (MR) approaches. RESULTS: We discovered 15 novel associated loci for 17-hydroxyprogesterone, progesterone, DHEAS, cortisol, androstenedione, and estradiol. Five of these loci relate to genes directly involved in steroid metabolism, that is, CYP21A1, CYP11B1, CYP17A1, STS, and HSD17B12, almost completing the set of steroidogenic enzymes with genetic associations. Sexual dimorphisms were found for seven of the novel loci. Other loci correspond, for example, to the WNT4/ß-catenin pathway. MR revealed that cortisol, androstenedione, 17-hydroxyprogesterone, and DHEA-S had causal effects on CAD. We also observed enrichment of cortisol and testosterone associations among known CAD hits. CONCLUSION: Our study greatly improves insight into genetic regulation of steroid hormones and their dependency on sex. These results could serve as a basis for analyzing sexual dimorphism in other complex diseases.

Reference intervals of nine steroid hormones over the life-span analyzed by LC-MS/MS: Effect of age, gender, puberty, and oral contraceptives.

New reference intervals need to be established for a new analytical method with improved sensitivity and specificity. We aimed to establish the new reference intervals from infancy to senescence of nine steroid hormones (cortisol, cortisone, progesterone, 17-hydroxyprogesterone (17-OHP), androstenedione, testosterone, estradiol, DHEAS, and aldosterone) for LC-MS/MS method. Serum samples from 4678 reference individuals (age range: 0.3-79 years) were measured with LC-MS/MS. Samples were collected between 7 a.m. and 10 a.m. Exclusion criteria were concomitant endocrine diseases and body mass index ≥ 33. Generalized additive model for location, scale and shape, the nonparametric or robust method was applied. We established the reference intervals of the nine steroid hormones by sex, age, and pubertal stage. Below the age of one, we observed the surge of androgen and estrogen which implied mini-puberty. At the same period of life, aldosterone and cortisone levels were very high reflecting physiological hyperaldosteronism. An increase of steroid hormones during the pubertal development and slow decrease towards senescence after the peak at early adulthood were observed. Due to the increase of CBG synthesis, cortisol levels were increased under oral contraceptives (OC) significantly (p < 0.0001), while OC suppressed progesterone, 17-OHP, androstenedione, and estradiol (p < 0.0001). Our results will facilitate the interpretation of patient data in routine diagnostics with the use of LC-MS/MS method. Since LC-MS/MS methods have shown good comparability among the different laboratories, our reference intervals can be further adopted in other laboratories equipped with LC-MS/MS, once the validation with a small number of reference samples is performed.

Associations Between Anxiety, Body Mass Index, and Sex Hormones in Women.

Background: Several studies have shown a positive association between anxiety and obesity, particularly in women. We aimed to study whether sex hormone alterations related to obesity might play a role in this association. Patients and methods: Data for this study were obtained from a population-based cohort study (the LIFE-Adult-Study). A total of 3,124 adult women (970 premenopausal and 2,154 postmenopausal) were included into the analyses. The anxiety symptomatology was assessed using the GAD-7 questionnaire (cut-off ≥ 10 points). Sex hormones were measured from fasting serum samples. Results: We did not find significant differences in anxiety prevalence in premenopausal obese women compared with normal-weight controls (4.8% vs. 5.5%). Both obesity and anxiety symptomatology were separately associated with the same sex hormone alteration in premenopausal women: higher total testosterone level (0.97 ± 0.50 in obese vs. 0.86 ± 0.49 nmol/L in normal-weight women, p = 0.026 and 1.04 ± 0.59 in women with vs. 0.88 ± 0.49 nmol/L in women without anxiety symptomatology, p = 0.023). However, women with anxiety symptomatology had non-significantly higher estradiol levels than women without anxiety symptomatology (548.0 ± 507.6 vs. 426.2 ± 474.0 pmol/L), whereas obesity was associated with lower estradiol levels compared with those in normal-weight group (332.7 ± 386.5 vs. 470.8 ± 616.0 pmol/L). Women with anxiety symptomatology had also significantly higher testosterone and estradiol composition (p = 0.006). No associations of sex hormone levels and BMI with anxiety symptomatology in postmenopausal women were found. Conclusions: Although both obesity and anxiety symptomatology were separately associated with higher testosterone level, there was an opposite impact of anxiety and obesity on estradiol levels in premenopausal women. We did not find an evidence that the sex hormone alterations related to obesity are playing a significant role in anxiety symptomatology in premenopausal women. This could be the explanation why we did not find an association between obesity and anxiety. In postmenopausal women, other mechanisms seem to work than in the premenopausal group.

Testosterone imbalance may link depression and increased body weight in premenopausal women.

Accumulating evidence supports a link between depression and being overweight in women. Given previously reported sex differences in fat accumulation and depression prevalence, as well as the likely role of sex hormones in both overweight and mood disorders, we hypothesised that the depression-overweight association may be mediated by sex hormones. To this end, we investigated the association of being overweight with depression, and then considered the role of sex hormones in relation to being overweight and depression in a large population-based cohort. We included a total of 3124 women, 970 premenopausal and 2154 postmenopausal from the LIFE-Adult cohort study in our analyses. We evaluated associations between being overweight (BMI >25 kg/m2), sex hormone levels, and depressive symptomatology according to Centre for Epidemiologic Studies Depression (CES-D) scores, and explored mediation of depression in a mediation model. Being overweight was significantly associated with depressive symptoms in premenopausal but not postmenopausal women. Both premenopausal and postmenopausal overweight women had higher free testosterone levels compared with normal weight women. Premenopausal women with depressive symptomatology had higher free testosterone levels compared to women without. We found a significant mediation effect of depressive symptomatology in overweight premenopausal women through free testosterone level. These findings highlight the association between being overweight and depressed, and suggest that high free testosterone levels may play a significant role in depression of overweight premenopausal women. Based on this, pharmacological approaches targeting androgen levels in overweight depressed females, in particular when standard anti-depressive treatments fail, could be of specific clinical relevance.

Adipokines in human breast milk.

The review describes the molecular characteristics of so far detected breast milk adipokines and ranks their breast milk level compared to the respective levels in maternal and infant blood. Moreover, analytical knowledge for measurements of breast milk adipokines will be delineated. Next, we summarized data about two main potential influencing factors on adipokine concentration in breast milk, maternal weight and pasteurization of milk. Finally, associations between adipokines in breast milk and weight gain in infants as well as the putative mechanisms for effects of breast milk adipokines on food intake and weight gain in later life will debated. Our findings suggest that a source of adipokines in human breast milk cannot be uniformly defined. In dependence on the ratio between serum and breast milk levels the major quantity of these proteins may be derived from peripheral tissues, from the breast tissue itself or from both. Thus, leptin and in part adiponectin levels in breast milk are dependent on a plenty of influencing factors with an important relevance of maternal anthropometric characteristics There is some evidence that leptin, adiponectin and ghrelin levels in breast milk may be associated with growth gain of infants and even with increased risk for being overweight during infancy or childhood. We hypothesize that a dysregulation in adipokine homeostasis in early life could promote obesity and metabolic disturbance in later life.

Vitamin D and calcium in the human breast milk.

Vitamin D and calcium in the human milk is essential for the growth and the prevention of rickets in infants. In this review, we will discuss the physiology and the functions of vitamin D and calcium and the mechanisms of vitamin D and calcium transfer into the human breast milk. This review describes the recommended intake of vitamin D and calcium for infants and lactating mothers and the factors influencing the content of vitamin D and calcium in human milk. Furthermore, the measurement of vitamin D compounds and calcium in human breast milk is described in this review.

Increased estrogen level can be associated with depression in males.

BACKGROUND: Several studies have shown a positive association between depression and obesity; however the underlying mechanisms are not fully understood. It is not known if this association is driven by altered sex hormone levels in men due to increased BMI. PATIENTS AND METHODS: Data were obtained from the LIFE-Adult-Study, a population-based cohort study. A total of 3925 men (2244<60years and 1681>60years) were included into analyses. Associations between BMI, sex hormones and depressive symptomatology according to CES-D score were evaluated. RESULTS: Obese men had compared to normal weight controls lower total testosterone (12.6±4.7 vs 19.4±5.5 nmol/L, p<0.001 in <60years, and 13.8±6.9 vs 18.3±5.9 nmol/L, p<0.001 in >60years group) and free testosterone (249.0±73.9 vs 337.2±82.0pmol/L, p<0.001, and 217.8±71.2 vs 263.4±72.2pmol/L, p<0.001), and increased estradiol in older group only (97.3±43.0 vs 82.3±34.2pmol/L, p<0.001 in obese). Men <60years old with depressive symptomatology had higher estradiol levels compared to those without depressive symptomatology (96.3±40.7 vs 84.4±36.6pmol/L, p<0.001), however no association with BMI was observed. CONCLUSIONS: Selected sex hormone parameters were significantly different in overweight and obese compared to normal weight males and certain differences could be seen between younger and older males. Depressive symptomatology was associated with increased estradiol levels in younger men, regardless of BMI.

Liquid chromatography quadrupole linear ion trap mass spectrometry for quantitative steroid hormone analysis in plasma, urine, saliva and hair.

Steroid analysis is being conquered by liquid chromatography tandem mass spectrometry (LC-MS/MS) benefiting from higher standardization, selectivity and diversity. Regarding high throughput in routine diagnostics rapid chromatography is mandatory. Introducing MS(3) (MS/MS/MS), specificity of mass spectrometric detection can be enhanced without sacrificing analysis time. 100mL of human plasma/serum, saliva, urine and 10-20mg of hair are used for the simultaneous quantification of 17α-hydroxyprogesterone, aldosterone, androstenedione, cortisol, cortisone, dehydroepiandrosterone sulfate (DHEAS), estradiol, progesterone, and testosterone using online solid phase extraction (SPE) LC-MS/MS or LC-MS(3). Steroids can be analyzed in 4min after a single manual dilution and protein precipitation step. In complex sample matrices like hair MS(3) detection was found to be appropriate for quantitation. Lower limits of quantitation ranged from 37pmol/L (estradiol) up to 3.1nmol/L (DHEAS). General accuracy was 89-107% with between-run imprecision ≤10%. Comparison to immunoassays revealed significant differences in quantitation for urinary cortisol (-71% mean), aldosterone (-40% mean) and plasma aldosterone (-45% mean). The comparison of MS(2) and MS(3) quantitation of hair cortisol also revealed significant differences. In general, quantitation via MS(3) was not applicable for a long time. But with the current generation of mass spectrometers quantitation via MS(3) can be superior to MS(2) regarding specificity and accuracy when dealing with matrix issues. However, drawbacks regarding flexibility and precision have to be taken into account. Concludingly, simple protein precipitation combined with rapid online SPE LC-MS/MS/MS allows us to quantify over broad, essential concentration ranges in human serum, saliva, urine and hair.