Childhood maltreatment disrupts HPA-axis activity under basal and stress conditions in a dose–response relationship in children and adolescents

Abstract Background This study investigates the impact of childhood maltreatment (CM) on hypothalamic–pituitary–adrenal (HPA)-axis functioning and on anxiety perception. Moreover, the influence of CM severity and frequency was also explored. Methods In total, 187 participants aged 7–17 were assessed for CM history using validated questionnaires and ad hoc interviews to be classified according to the criteria of the Tool for Assessing the Severity of Situations in which Children are Vulnerable (TASSCV). Psychopathology was ascertained using the K-SADS-PL5. To assess HPA-axis functioning, salivary cortisol samples were collected throughout a normal day and during an acute psychosocial stressor, the Trier Social Stress Test for children (TSST-C). Subjective anxiety was evaluated using STAI/-C. Results Youth with a CM history had higher overall diurnal cortisol levels (p = 0.001), blunted cortisol response to acute psychosocial stress (p = 0.002) and greater perceived anxiety (p = 0.003), than those without CM. Specifically, participants exposed to moderate/severe or often/frequent CM showed the greater diurnal cortisol output (pseverity = 0.002; pfrequency = 0.003), and blunted cortisol response during the TSST-C (pseverity = 0.006; pfrequency = 0.008). Meanwhile, youth with low CM severity/frequency exhibited a similar cortisol response to those without CM. However, perceived anxiety was higher in those exposed to CM (p < 0.001), regardless of its severity/frequency. Conclusions Disturbances in HPA-axis functioning are already evident early after CM exposure, while psychological and physiological responses to an acute stressor are dissociated in youth exposed to CM. The dose–response relationship described in this paper highlights the need to comprehensively evaluate CM so that vulnerable children can be identified and assigned to proper interventions.

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Dose-Response Relationship of EAE Clinical Severity in a MOG35-55 Mouse Model: A Pilot Study

Annals of Behavioral Neuroscience ◽

10.18314/abne.v1i1.1263 ◽

2018 ◽

Vol 1 (1) ◽

pp. 123-132

Author(s):

Gerlinde AS Metz ◽

Bettenson D ◽

Babatunde S ◽

Gustafson C ◽

Chan R

Keyword(s):

Pilot Study ◽

Pertussis Toxin ◽

Dose Response ◽

Clinical Symptoms ◽

Clinical Severity ◽

Response Relationship ◽

Motor Impairments ◽

Dose Response Relationship ◽

Nociceptive Sensitivity ◽

The Impact

Experimental autoimmune encephalomyelitis (EAE) is a common animal model of multiple sclerosis (MS) which mimics the autoimmune, demyelinating, and inflammatory hallmarks of this human disorder. To better understand the severity of the symptoms in relation to the antigen in EAE, we explored the dose-symptom relationship between the quantity of MOG35-55 and clinical symptoms in a C57/BL6 mouse pilot study. To isolate the impact of MOG35-55 we developed an EAE model that does not require the additional application of pertussis toxin. Mice were treated with either 50µg, 100µg, or 150µg of MOG35-55 emulsified in complete Freund’s adjuvant. Following induction, the mice were assessed for clinical symptoms daily, and tested weekly for gross and fine motor impairments, mechanical allodynia, and anxiety-like behaviours. The time course of sensorimotor function loss was characterized by multiphasic disease progression. Findings also suggested an inverted U-shape dose-response relationship with a medium dosage of 100 µl MOG35-55 dosage aggravating symptom severity in induced animals. Outcomes measured by a clinical score correlated with performance on motor and nociceptive sensitivity tasks. As the disease progressed, fine and gross motor impairments and nociceptive sensitivity diminished and impairments persisted beyond 8 weeks. This study indicates that mild to moderate EAE can be induced in the absence of use of pertussis toxin. The progression suggests a spontaneously multiphasic disease course, which may have attractive implications for clinically relevant animal models.

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Setting-Specific and Symptom-Specific Association between Secondhand Smoke Exposure and Depressive Symptoms

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16071249 ◽

2019 ◽

Vol 16 (7) ◽

pp. 1249

Author(s):

Xiaohua Ye ◽

Jingya Huang ◽

Liang Xia ◽

Xiaojun Xu ◽

Xiao Gong ◽

...

Keyword(s):

Depressive Symptoms ◽

Dose Response ◽

Secondhand Smoke ◽

Negative Binomial ◽

Negative Binomial Regression ◽

Response Relationship ◽

Dose Response Relationship ◽

Cross Sectional ◽

Shs Exposure ◽

The Impact

Few studies have focused on the potential relationship between secondhand smoke (SHS) exposure and depressive symptoms. This study aimed to explore the potential association between SHS exposure and depressive symptoms and differentiate this association in setting-specific exposure and symptom-specific outcomes. A cross-sectional study was conducted in Guangdong province of China from September to December 2010 using a multistage sampling method to randomly sample adults aged 18 years and older. SHS exposure was defined as inhalation by non-smokers of the smoke exhaled from smokers for at least 1 day a week in the past 30 days. Depressive symptoms were measured using the nine-item Patient Health Questionnaire. The zero-inflate negative binomial regression models were used to explore the associations between SHS exposure and depressive symptoms. A total of 2771 non-smokers were included in this study, with mean age of 49.6 ± 14.0 years and 70.3% of females. The prevalence of depressive symptoms was significantly higher in participants with SHS exposure than in those without exposure (incidence rate ratio (IRR) = 1.32, 95% confidence interval (CI) 1.16–1.51), and there were similar positive associations for SHS exposure in medical facilities (IRR = 1.37, 95% CI 1.17–1.61) and in schools (IRR = 1.46, 95% CI 1.20–1.77). Notably, there was a monotonically increasing dose-response relationship between frequency of SHS exposure and depressive symptoms. When differentiating this relationship by the dimensions of depressive symptoms, there were similar dose-response relationships for cognitive-affective and somatic symptoms. When differentiating this relationship by sex, only females showed a significant dose-response relationship. Our findings suggest dose-response relationships between SHS exposure and depressive symptoms in sex-specific and symptom-specific manners. Future longitudinal studies are needed to establish the biological mechanisms of the impact of SHS exposure.

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Childhood Trauma and Cortisol Response to the Trier Social Stress Test in Symptomatic Patients with Eating Disorders

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.286 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S91-S91

Author(s):

F. Marciello ◽

V.-M. Buonomenna ◽

V. Caivano ◽

G. Cascino ◽

G. D’Agostino ◽

...

Keyword(s):

Childhood Trauma ◽

Hpa Axis ◽

Childhood Maltreatment ◽

Social Stress ◽

Stress Test ◽

Trauma Exposure ◽

Trier Social Stress Test ◽

Cortisol Response ◽

History Of Childhood ◽

History Of

IntroductionChildhood trauma exposure is associated with the risk of eating disorders (EDs) in adulthood. The biological basis of this link may involve a persistent dysregulation of the endogenous stress response system, in particular the hypothalamic-pituitary-adrenal (HPA) axis, as a consequence of early life maltreatment.ObjectiveAdult patients with EDs and history of childhood trauma may have a dysregulation of the HPA axis that could be different from EDs patients without childhood trauma exposure.AimsIn order to assess the effects of childhood trauma experiences on HPA-axis activity in EDs, we compared the salivary cortisol response to the Trier Social Stress Test (TSST) of adult patients with EDs according to their history of childhood trauma.MethodTwenty-seven EDs patients and 13 healthy women participated in the study. Salivary cortisol responses during exposure to the TSST was measured. Participants also completed the childhood trauma questionnaire (CTQ) and eating-related psychopathological rating scales.ResultsAccording to CTQ, 15 individuals with EDs reported childhood maltreatment whereas 12 EDs patients and all the healthy women did not experience childhood maltreatment. Compared with the control group, non-maltreated EDs patient group exhibited a slightly enhanced cortisol response to TSST, whereas the group of non-maltreated EDs patients showed a normal cortisol response. Moreover, EDs patients with childhood maltreatment exhibited statistically significant blunting of cortisol compared to non-maltreated ones.ConclusionsThe present findings support the evidence that, in patients with EDs, there is a dysregulation of HPA-axis activity and that childhood trauma exposure may contribute to this dysregulation.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Association between fish consumption and risk of dementia: a new study from China and a systematic literature review and meta-analysis

Public Health Nutrition ◽

10.1017/s136898001800037x ◽

2018 ◽

Vol 21 (10) ◽

pp. 1921-1932 ◽

Cited By ~ 11

Author(s):

Aishat T Bakre ◽

Ruoling Chen ◽

Ranjit Khutan ◽

Li Wei ◽

Tina Smith ◽

...

Keyword(s):

Rural Communities ◽

Literature Review ◽

Systematic Literature Review ◽

Dose Response ◽

Fish Consumption ◽

Meta Analysis ◽

Response Relationship ◽

Dose Response Relationship ◽

Cross Sectional ◽

The Impact

AbstractObjectiveTo assess the association of fish consumption with risk of dementia and its dose–response relationship, and investigate variations in the association among low-, middle- and high-income countries.DesignA new community-based cross-sectional study and a systematic literature review.SettingsUrban and rural communities in China; population-based studies systematically searched from worldwide literature.SubjectsChinese adults aged ≥60 years in six provinces (n 6981) took part in a household health survey of dementia prevalence and risk factors. In addition, 33 964 participants from eleven published and eligible studies were included in the systematic review and meta-analysis.ResultsIn the new study in China, 326 participants were diagnosed with dementia (4·7 %); those who consumed any amount of fish in the past two years v. those who consumed no fish had reduced risk of dementia (adjusted OR=0·73, 95 % CI 0·64, 0·99), but the dose–response relationship was not statistically significant. The meta-analysis of available data from the literature and the new study showed relative risk (RR) of dementia of 0·80 (95 % CI 0·74, 0·87) for people with fish consumption; the impact was similar among countries with different levels of income. Pooled dose–response data revealed RR (95 % CI) of 0·84 (0·72, 0·98), 0·78 (0·68, 0·90) and 0·77 (0·61, 0·98) in people with low, middle and high consumption of fish, respectively. Corresponding figures for Alzheimer’s disease were 0·88 (0·74, 1·04), 0·79 (0·65, 0·96) and 0·67 (0·58, 0·78), respectively.ConclusionsGreater consumption of fish is associated with a lower risk of dementia. Increasing fish consumption may help prevent dementia worldwide regardless of income level.

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Key components of the delirium syndrome and mortality: greater impact of acute change and disorganised thinking in a prospective cohort study

10.1101/251272 ◽

2018 ◽

Author(s):

RA Diwell ◽

D Davis ◽

V Vickerstaff ◽

EL Sampson

Keyword(s):

Dose Response ◽

Prospective Cohort ◽

Acute Onset ◽

Mortality Data ◽

Intermediate Risk ◽

Response Relationship ◽

Dose Response Relationship ◽

Subsyndromal Delirium ◽

Diagnostic Symptoms ◽

The Impact

ABSTRACTBackgroundDelirium increases the risk of mortality during an acute hospital admission. Full syndromal delirium (FSD) is associated with greatest risk and subsyndromal delirium (SSD) is associated with intermediate risk, compared to patients with no delirium - suggesting a dose-response relationship. It is not clear how individual diagnostic symptoms of delirium influence the association with mortality. Our objectives were to measure the prevalence of FSD and SSD, and assess the effect that FSD, SSD and individual symptoms of delirium (from the Confusion Assessment Method-short version (s-CAM)) have on mortality rates.MethodsExploratory analysis of a prospective cohort (aged ≥ 70 years) with acute (unplanned) medical admission (4/6/2007-4/11/2007). The outcome was mortality (data censored 6/10/2011). The principal exposures were FSD and SSD compared to no delirium (as measured by the CAM), along with individual delirium symptoms on the CAM. Cox regression was used to estimate the impact FSD and SSD and individual CAM items had on mortality.ResultsThe cohort (n=610) mean age was 83 (SD 7); 59% were female. On admission, 11% had FSD and 33% had SSD. Of the key diagnostic symptoms for delirium, 17% acute onset, 19% inattention, 17% disorganised thinking and 17% altered level of consciousness. Unadjusted analysis found FSD had an increased hazard ratio (HR) of 2.31 (95%CI 1.71, 3.12), for SSD the HR was 1.26 (1.00, 1.59). Adjusted analysis remained significant for FSD (1.55 95%CI 1.10, 2.18) but nonsignificant for SSD (HR=0.92 95% CI 0.70, 1.19). Two CAM items were significantly associated with mortality following adjustment: acute onset and disorganised thinking.ConclusionWe observed a dose-response relationship between mortality and delirium, FSD had the greatest risk and SSD having intermediate risk. The CAM items “acute onset” and “disorganised thinking” drove the associations observed. Clinically, this highlights the necessity of identifying individual symptoms of delirium.

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DHEA Moderates the Impact of Childhood Trauma on the HPA Axis in Adolescence

Neuropsychobiology ◽

10.1159/000511629 ◽

2021 ◽

pp. 1-14

Author(s):

Sarah J. Taylor-Cavelier ◽

Valerie J. Micol ◽

Andrea G. Roberts ◽

Elisa G. Geiss ◽

Nestor Lopez-Duran

Keyword(s):

Childhood Trauma ◽

Hpa Axis ◽

Childhood Maltreatment ◽

Social Stress ◽

Stress Test ◽

Trier Social Stress Test ◽

Neuroprotective Effects ◽

Response To Stress ◽

The Impact

Background: Trauma can lead to long-term downregulation of the hypothalamic pituitary adrenal (HPA) axis. However, dehydroepiandrosterone (DHEA) has neuroprotective effects that may reduce the need for downregulation of the axis in response to stress. Furthermore, high DHEA/cortisol ratios are often conceptualized as better markers of DHEA’s availability than DHEA alone, as ratios account for the coupling of DHEA and cortisol in response to stress. Objectives: In this study, we explored if DHEA and DHEA/cortisol ratios moderated the association between childhood maltreatment and the HPA axis stress response. Methods: The sample consisted of 101 adolescents (ages 12–16) who completed the Child Trauma Questionnaire (CTQ) and the Trier Social Stress Test (TSST). Cortisol was modeled using saliva samples at 8 time points throughout the TSST. Cortisol and DHEA ratios were examined at baseline and 35 min after stress initiation. Results: Childhood maltreatment was associated with less steep cortisol activation slope and peak cortisol levels, but DHEA and DHEA/cortisol ratios moderated this effect. At high levels of DHEA, the impact of childhood maltreatment on cortisol peak levels was no longer significant. In contrast, high DHEA/cortisol ratios were associated with an intensification of the impact of childhood maltreatment on peak levels. Conclusions: Results suggest that DHEA can limit the blunting of the HPA axis in response to childhood maltreatment. However, this protective effect was not reflected in high DHEA/cortisol ratios as predicted. Therefore, high DHEA and high DHEA/cortisol ratios may reflect different, and potentially opposite, processes.

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Association of Vitamin D Status and COVID-19-Related Hospitalization and Mortality

Journal of General Internal Medicine ◽

10.1007/s11606-021-07170-0 ◽

2022 ◽

Author(s):

Karen H. Seal ◽

Daniel Bertenthal ◽

Evan Carey ◽

Carl Grunfeld ◽

Daniel D. Bikle ◽

...

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Dose Response ◽

Health Care Facilities ◽

Primary Study ◽

Vitamin D Status ◽

Response Relationship ◽

Dose Response Relationship ◽

Race Ethnicity ◽

The Impact

Abstract Background The relationship between vitamin D status and COVID-19-related clinical outcomes is controversial. Prior studies have been conducted in smaller, single-site, or homogeneous populations limiting adjustments for social determinants of health (race/ethnicity and poverty) common to both vitamin D deficiency and COVID-19 outcomes. Objective To evaluate the dose-response relationship between continuous 25(OH)D and risk for COVID-19-related hospitalization and mortality after adjusting for covariates associated with both vitamin D deficiency and COVID-19 outcomes. Design Retrospective cohort study. Patients Veteran patients receiving care in US Department of Veteran Affairs (VA) health care facilities with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test and a blood 25(OH)D test between February 20, 2020, and November 8, 2020, followed for up to 60 days. Main Measures Exposure was blood 25(OH)D concentration ascertained closest to and within 15 to 90 days preceding an index positive SARS-CoV-2 test. Co-primary study outcomes were COVID-19-related inpatient hospitalization requiring airborne, droplet, contact, or other isolation and mortality ascertained within 60 days of an index positive SARS-CoV-2 test. Key Results Of 4,599 veterans with a positive SARS-CoV-2 test, vitamin D deficiency (< 20 ng/mL) was identified in 665 (14.5%); 964 (21.0%) were hospitalized; and 340 (7.4%) died. After adjusting for all covariates, including race/ethnicity and poverty, there was a significant independent inverse dose-response relationship between increasing continuous 25(OH)D concentrations (from 15 to 60 ng/mL) and decreasing probability of COVID-19-related hospitalization (from 24.1 to 18.7%, p=0.009) and mortality (from 10.4 to 5.7%, p=0.001). In modeling 25(OH)D as a log-transformed continuous variable, the greatest risk for hospitalization and death was observed at lower 25(OH)D concentrations. Conclusions Continuous blood 25(OH)D concentrations are independently associated with COVID-19-related hospitalization and mortality in an inverse dose-response relationship in this large racially and ethnically diverse cohort of VA patients. Randomized controlled trials are needed to evaluate the impact of vitamin D supplementation on COVID-19-related outcomes.

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A SUBCUTANEOUS INJECTION ASSAY FOR ANTI-ANDROGENS IN THE CHICK

Acta Endocrinologica ◽

10.1530/acta.0.0410268 ◽

1962 ◽

Vol 41 (2) ◽

pp. 268-273 ◽

Cited By ~ 9

Author(s):

Ralph I. Dorfman

Keyword(s):

Dose Response ◽

Subcutaneous Injection ◽

Response Relationship ◽

Dose Response Relationship

ABSTRACT The stimulating action of testosterone on the chick's comb can be inhibited by the subcutaneous injection of 0.1 mg of norethisterone or Ro 2-7239 (2-acetyl-7-oxo-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene), 0.5 mg of cortisol or progesterone, and by 4.5 mg of Mer-25 (1-(p-2-diethylaminoethoxyphenyl)-1-phenyl-2-p-methoxyphenyl ethanol). No dose response relationship could be established. Norethisterone was the most active anti-androgen by this test.

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