Biphasic Glucocorticoid Rhythm in One-Month-Old Infants: Reflection of a Developing HPA-Axis?

Abstract Context The hypothalamus-pituitary-adrenal (HPA) axis displays a diurnal rhythm. However, little is known about its development in early life. Objective To describe HPA-axis activity and study possible influencing factors in 1-month-old infants. Design Observational. Setting Amsterdam University Medical Center, location VU University Medical Center (VUMC), and Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam. Participants Fifty-five mother-infant pairs. Interventions Collection of breast milk and infants’ saliva 1 month postpartum for analysis of glucocorticoids (GCs; ie, cortisol and cortisone) using liquid chromatography– tandem mass spectrometry. Main Outcome Measure GC rhythm in infants’ saliva and associations with vulnerability for maternal psychological distress (increased Hospital Anxiety and Depression Scale [HADS] score) or consultation at the Psychiatric Obstetric Pediatric (POP clinic), season at sampling, sex, and breast milk GC rhythmicity analyzed with SigmaPlot 14.0 software (Systat Software, San Jose, CA, USA) and regression analyses. Results A significant biphasic GC rhythm was detected in infants, with mean peaks [standard error of the mean, SEM] at 6:53 am [1:01] and 18:36 pm [1:49] for cortisol, and at 8:50 am [1:11] and 19:57 pm [1:13] for cortisone. HADS score, POP consultation, season at sampling, and sex were not associated with the infants’ GC rhythm. Breast milk cortisol maximum was positively associated with infants’ cortisol area-under-the-curve (AUC) increase and maximum. Higher breast milk cortisone AUC increase, AUC ground, and maximum were associated with an earlier maximum in infants. Breast milk and infant GC concentrations were associated between 6:00 am and 9:00 am. Conclusions A biphasic GC rhythm, peaking in the morning and evening, was seen in 1-month-old infants at a group level. Breast milk GC parameters might be associated with the infants’ GC rhythm, possibly caused by a signaling effect of breast milk GCs, or as an associative effect of increased mother-infant synchrony. These results contribute to an increased understanding of early life HPA-axis development.

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Environmental enrichment effects on neurodevelopment, behavior and HPA axis activity in male and female Wistar rats with early life adverse experiences

IBRO Reports ◽

10.1016/j.ibror.2019.07.962 ◽

2019 ◽

Vol 6 ◽

pp. S311

Author(s):

Karen Corredor ◽

Laura Herrera-Isaza ◽

Juan Pablo Quintanilla ◽

Johanna Marcela Duran ◽

Gladys S. Martinez ◽

...

Keyword(s):

Hpa Axis ◽

Early Life ◽

Wistar Rats ◽

Environmental Enrichment ◽

Male And Female ◽

Adverse Experiences ◽

Female Wistar Rats ◽

Hpa Axis Activity

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The Association between Maternal Stress and Glucocorticoid Rhythmicity in Human Milk

Nutrients ◽

10.3390/nu13051608 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1608

Author(s):

Michelle Romijn ◽

Luca J. L. van Tilburg ◽

Jonneke J. Hollanders ◽

Bibian van der Voorn ◽

Paul de Goede ◽

...

Keyword(s):

Psychological Distress ◽

Breast Milk ◽

Human Milk ◽

Area Under The Curve ◽

Control Group ◽

Increased Risk ◽

Liquid Chromatography Tandem Mass ◽

Highly Correlated ◽

The Impact ◽

Diurnal Rhythmicity

Background: Chronic stress is often accompanied by alterations in the diurnal rhythm of hypothalamus–pituitary–adrenal activity. However, there are limited data on the diurnal rhythmicity of breast milk glucocorticoids (GCs) among women with psychological distress. We compared mothers who sought consultation at an expertise center for pregnant women with an increased risk of psychological distress with control mothers for GC diurnal rhythmicity in milk and saliva obtained at the same time. Methods: We included 19 mothers who sought consultation at the psychiatry–obstetric–pediatric (POP) outpatient clinic and 44 control mothers. One month postpartum, mothers collected on average eight paired milk and saliva samples during a 24 h period. GC levels were measured using liquid chromatography–tandem mass spectrometry. GC rhythmicity parameters were determined with specialized software. Results: For both milk and saliva, no group differences regarding GC rhythms were found. Milk cortisol area under the curve with respect to the ground was lower in the POP group than in the control group (p = 0.02). GC levels in human milk and saliva were highly correlated within each group (p < 0.001). Conclusion: Although there were no differences between groups in GC rhythmicity, the total amount of milk cortisol was lower in the POP group. Long-term follow-up is needed to address the impact of vertical transmission of breast milk GCs.

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Next-generation biomonitoring of the early-life chemical exposome in neonatal and infant development

10.26434/chemrxiv-2022-kwv4b ◽

2022 ◽

Author(s):

Thomas Jamnik ◽

Mira Flasch ◽

Dominik Braun ◽

Yasmin Fareed ◽

Daniel Wasinger ◽

...

Keyword(s):

Breast Milk ◽

Early Life ◽

Large Scale ◽

Infant Development ◽

Association Studies ◽

Post Partum ◽

Tropane Alkaloids ◽

Human Biomonitoring ◽

Chemical Exposure ◽

Liquid Chromatography Tandem Mass

Exposure to man-made and natural chemicals is a major, yet not sufficiently considered, environmental risk factor in the etiology of chronic diseases. Current human biomonitoring approaches typically measure a limited number of exposures rather than investigating complex mixtures. The latter would be fundamental and necessary for a holistic assessment of chemical exposure in exposome-wide association studies. In this work, an highly-sensitive liquid chromatography-tandem mass spectrometry approach was developed and thoroughly-validated. The assay enables the simultaneous and targeted assessment of more than 80 highly-diverse xenobiotics in the investigated body fluids of urine, serum/plasma, and breast milk; the detection limit for most toxicants are in the pg-ng/mL range. In the plasma of extremely-premature infants (gestational age <28 weeks, birth weight <1 kg) a total of 27 different xenobiotics are identified; including severe contamination with synthetic plasticizers, perfluorinated alkylated substances and parabens. In an independent sample set of breast milk that was longitudinally collected over the first 211 days post-partum, a total of 29 analytes is detected, including the first-ever identification of pyrrolizidine- and tropane alkaloids in this matrix. Based on the generated data, a preliminary estimation of daily toxicant intake via breast milk is conducted. In conclusion, our proof-of-principle experiments show significant early-life co-exposure to multiple toxicants, and demonstrate the method’s applicability in future large-scale exposomics-type cohort studies in vulnerable populations.

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Associations between early life experience, chronic HPA axis activity, and adult social rank in rhesus monkeys

Social Neuroscience ◽

10.1080/17470919.2016.1176952 ◽

2016 ◽

Vol 12 (1) ◽

pp. 92-101 ◽

Cited By ~ 13

Author(s):

Amanda M. Dettmer ◽

Lauren J. Wooddell ◽

Kendra L. Rosenberg ◽

Stefano S. K. Kaburu ◽

Melinda A. Novak ◽

...

Keyword(s):

Hpa Axis ◽

Early Life ◽

Rhesus Monkeys ◽

Life Experience ◽

Social Rank ◽

Early Life Experience ◽

Hpa Axis Activity

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Hypothalamic–pituitary–adrenal axis activity in adults who were prenatally exposed to the Dutch famine

Acta Endocrinologica ◽

10.1530/eje.1.02193 ◽

2006 ◽

Vol 155 (1) ◽

pp. 153-160 ◽

Cited By ~ 44

Author(s):

Susanne R de Rooij ◽

Rebecca C Painter ◽

David I W Phillips ◽

Clive Osmond ◽

Robert P J Michels ◽

...

Keyword(s):

Hpa Axis ◽

Area Under The Curve ◽

Later Life ◽

Hypothalamic Pituitary Adrenal ◽

Adult Age ◽

Suppression Test ◽

Design And Methods ◽

Prenatal Famine ◽

Hpa Axis Activity ◽

Dexamethasone Suppression

Objective: The hypothalamic–pituitary–adrenal (HPA) axis has been proposed to be susceptible to fetal programming, the process by which an adverse fetal environment elicits permanent physiological and metabolic alterations predisposing to disease in later life. It is hypothesized that fetal exposure to poor circumstances alters the set point of the HPA axis, leading to increased HPA axis activity and subsequent increased cortisol concentrations. In this study, we tested the hypothesis that prenatal exposure to famine during different periods of gestation is associated with increased activity of the HPA axis. Design and methods: We assessed plasma cortisol concentrations after a dexamethasone suppression and an ACTH1–24-stimulation test in a group of 98 men and women randomly sampled from the Dutch famine birth cohort. Cohort members were born as term singletons around the 1944–1945 Dutch famine. Results: Cortisol profiles after dexamethasone suppression and ACTH1–24 stimulation were similar for participants exposed to famine during late, mid- or early gestation (P=0.78). Cortisol concentrations after dexamethasone suppression test did not differ between those exposed and those unexposed to famine in utero (mean difference −2% (95% confidence interval (CI) −27 to 23)). Neither peak cortisol concentration (20 nmol/l (95% CI −27 to 66)), cortisol increment (−5 nmol/l (95% CI −56 to 47)) or cortisol area under the curve post-ACTH1–24 injection (4% (95% CI −4 to 12)) differed between exposed and unexposed participants. Conclusions: Prenatal famine exposure does not seem to affect HPA axis activity at adult age, at least not at the adrenal level. This does not exclude altered HPA axis activity at the levels of the hippocampus and hypothalamus.

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The Validity and Reliability of the Sinhala Translation of the Patient Health Questionnaire (PHQ-9) and PHQ-2 Screener

Depression Research and Treatment ◽

10.1155/2014/768978 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 9

Author(s):

Raveen Hanwella ◽

Shakya Ekanayake ◽

Varuni A. de Silva

Keyword(s):

Depression Scale ◽

Area Under The Curve ◽

Epidemiological Studies ◽

Patient Health Questionnaire ◽

Health Questionnaire ◽

Validity And Reliability ◽

Significant Difference ◽

Patient Health ◽

Dsm Iv ◽

The Mean

The Patient Health Questionnaire (PHQ-9) was adapted and translated into Sinhala. Sample consisted of 75 participants diagnosed with MDD according to DSM-IV criteria and 75 gender matched controls. Concurrent validity was assessed by correlating total score of PHQ-9 with that of Centre for Epidemiological Studies Depression Scale (CESD). The Structured Clinical Interview for DSM-IV (SCID-II) conducted by a psychiatrist was the gold standard. Mean age of the sample was 33.0 years. There were 91 females (60.7%). There was significant difference in the mean PHQ-9 scores between cases (14.71) and controls (2.55) (P<0.001). The specificity of the categorical algorithm was 0.97; the sensitivity was 0.58. Receiver operating characteristic (ROC) analysis found that cut-off score of ≥10 had sensitivity of 0.75 and specificity of 0.97. The area under the curve (AOC) was 0.93. The sensitivity of the two-item screener (PHQ-2) was 0.80 and the specificity was 0.97. Cronbach’s alpha was 0.90. The PHQ-9 is a valid and reliable instrument for diagnosing MDD in a non-Western population. The threshold algorithm is recommended for screening rather than the categorical algorithm. The PHQ-2 screener has good sensitivity and specificity and is recommended as a quick screening instrument.

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Gonadotropin-releasing hormone agonist in premenopausal women does not alter hypothalamic-pituitary-adrenal axis response to corticotropin-releasing hormone

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00221.2017 ◽

2018 ◽

Vol 315 (2) ◽

pp. E316-E325 ◽

Cited By ~ 2

Author(s):

Kathleen M. Gavin ◽

Karen L. Shea ◽

Ellie Gibbons ◽

Pamela Wolfe ◽

Robert S. Schwartz ◽

...

Keyword(s):

Hpa Axis ◽

Area Under The Curve ◽

Premenopausal Women ◽

Gonadotropin Releasing Hormone ◽

Corticotropin Releasing Hormone ◽

Hypothalamic Pituitary Adrenal ◽

Releasing Hormone ◽

Gonadotropin Releasing Hormone Agonist ◽

Total Cortisol ◽

Hpa Axis Activity

Sex hormones appear to play a role in the regulation of hypothalamic-pituitary-adrenal (HPA) axis activity. The objective was to isolate the effects of estradiol (E2) on central activation of the HPA axis. We hypothesized that the HPA axis response to corticotropin-releasing hormone (CRH) under dexamethasone (Dex) suppression would be exaggerated in response to chronic ovarian hormone suppression and that physiologic E2 add-back would mitigate this response. Thirty premenopausal women underwent 20 wk of gonadotropin-releasing hormone agonist therapy (GnRHAG) and transdermal E2 (0.075 mg per day, GnRHAG + E2, n = 15) or placebo (PL) patch (GnRHAG + PL, n = 15). Women in the GnRHAG + PL and GnRHAG + E2 groups were of similar age (38 (SD 5) yr vs. 36 (SD 7) yr) and body mass index (27 (SD 6) kg/m2 vs. 27 (SD 6) kg/m2). Serum E2 changed differently between the groups ( P = 0.01); it decreased in response to GnRHAG + PL (77.9 ± 17.4 to 23.2 ± 2.6 pg/ml; P = 0.008) and did not change in response to GnRHAG + E2 (70.6 ± 12.4 to 105 ± 30.4 pg/ml; P = 0.36). The incremental area under the curve (AUCINC) responses to CRH were different between the groups for total cortisol ( P = 0.03) and cortisone ( P = 0.04) but not serum adrenocorticotropic hormone (ACTH) ( P = 0.28). When examining within-group changes, GnRHAG + PL did not alter the HPA axis response to Dex/CRH, but GnRHAG + E2 decreased the AUCINC for ACTH (AUCINC, 1,623 ± 257 to 1,211 ± 236 pg/ml·min, P = 0.004), cortisone (1,795 ± 367 to 1,090 ± 281 ng/ml·min, P = 0.009), and total cortisol (7,008 ± 1,387 to 3,893 ± 1,090 ng/ml·min, P = 0.02). Suppression of ovarian hormones by GnRHAG therapy for 20 wk did not exaggerate the HPA axis response to CRH, but physiologic E2 add-back reduced HPA axis activity compared with preintervention levels.

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