Abstract TMP28: Serotonin Transporter Polymorphism Impact on Cortisol Level and Outcome After Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Einor Ben Assayag ◽  
Estelle Seyman ◽  
Jeremy Molad ◽  
Oren Tene ◽  
Amos Korczyn ◽  
...  

Background: The short (s) allele of a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) is related to reduced serotonin transporter efficiency and an increased vulnerability to stress and mental disorders. The 5-HTTLPR s allele was reported as associate with hypothalamic-pituitary-adrenal (HPA)-axis reactivity to stress, depression and negatively impact on memory. Acute stroke is associated with elevated cortisol levels as part of the body’s reaction to a stress provoking event. We investigated whether 5-HTT genotype interacts with physiological stress to impact on outcome after stroke. Methods: Data from 485 non-depressed cognitively intact first-ever mild to moderate stroke patients from the TABASCO study were available. Patients underwent 3T MRI scans, saliva cortisol measure and comprehensive neuropsychological assessments at admission, 6, and 12 and 24 months thereafter. Results: Carriers of the 5-HTT-s allele (23.2%) had significantly higher admission bedtime salivary cortisol (p=0.042) and more depressive symptoms 12 and 24 months after the index event (p=0.043, p=0.05, respectively) than non-carriers. Higher admission salivary cortisol levels negatively correlated with hippocampal and amigdalar volume at admission (r=-0.257, p=0.004; r=-0.177, p=0.048, respectively) as well as with lower cognitive and higher depression scores 24 months post-stroke (r=-0.2, p=0.032, r=0.245, p=0.007, respectively). The association between salivary cortisol levels, depressive and cognitive scores was stronger in 5-HTT-s carriers than non-carriers. Conclusions: We report that carriers of the 5-HTT-s allele may be at risk to develop depressive symptoms post-stroke. The interactive effects of the s allele and cortisol levels on hippocampal volume and post-stroke depressive symptoms, as well as cognitive performance, suggest that the negative effect of the serotonin polymorphism on the development of post-stroke depression and cognitive decline is mediated by the HPA axis. Since genetic factors may influence vulnerability to the adverse effects of stress, serotonin receptors may provide a novel target for therapeutics to prevent depression and cognitive deterioration in stroke patients.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eleonora Iob ◽  
Jessie R. Baldwin ◽  
Robert Plomin ◽  
Andrew Steptoe

AbstractDysregulated hypothalamic–pituitary–adrenal (HPA)-axis function might underlie the relationship between adverse childhood experiences (ACEs) and depression. However, limited research has examined the possible mediating role of the HPA-axis among young people using longitudinal data. Moreover, it remains unclear whether genetic influences could contribute to these associations. Participants were 290 children from the Twins Early Development Study. ACEs were assessed from age 3–11 years. We calculated a cumulative risk score and also derived different ACEs clusters using factor analysis and latent class analysis. HPA-axis activity was indexed by daytime salivary cortisol at age 11. Depressive symptoms were ascertained at age 21. Genetic liability to altered cortisol levels and elevated depressive symptoms was measured using a twin-based method. We performed causal mediation analysis with mixed-effects regression models. The results showed that ACEs cumulative exposure (b = −0.20, p = 0.03), bullying (b = −0.61, p = 0.01), and emotional abuse (b = −0.84, p = 0.02) were associated with lower cortisol levels at age 11. Among participants exposed to multiple ACEs, lower cortisol was related to higher depressive symptoms at age 21 (b = −0.56, p = 0.05). Lower cortisol levels mediated around 10–20% of the total associations of ACEs cumulative exposure, bullying, and dysfunctional parenting/emotional abuse with higher depressive symptoms. Genetic factors contributed to these associations, but the mediation effects of cortisol in the associations of ACEs cumulative exposure (b = 0.16 [0.02–0.34]) and bullying (b = 0.18 [0.01–0.43]) remained when genetic confounding was accounted for. In conclusion, ACEs were linked to elevated depressive symptoms in early adulthood partly through lower cortisol levels in early adolescence, and these relationships were independent of genetic confounding.


Author(s):  
Davide Ponzi ◽  
Harold Dadomo ◽  
Laura Filonzi ◽  
Paola Palanza ◽  
Annalisa Pelosi ◽  
...  

Abstract Objectives There is evidence suggesting that in martial arts competitions athletes characterized by higher anxiety and harm avoidance may be more likely to lose a fight. This psychological profile has been hypothesized to explain in part the observation that cortisol is higher in losers before and in response to a competition. An important research target that needs further exploration is the identification of phenotypic traits that can be helpful in predicting athletes’ performance. Here we present a brief description of the theoretical bases that drives our research in the evolutionary psychobiology of sports and illustrate preliminary data on the relationship between the 5HTTLPR genotype, salivary cortisol, temperament and competition. Methods Sixty-five healthy male non-professional athletes provided saliva samples 10 min before and after a kumite session and filled out the Tridimensional Personality Questionnaire. Results Salivary cortisol levels 10 min before the competition were higher in losers and in athletes with the S allele. Temperament was associated with competition outcome and cortisol: losers were characterized by higher scores of harm avoidance and harm avoidance was positively correlated with cortisol levels. Conclusions The results confirm previous findings linking temperamental traits, pre-and post- competition physiological stress response with competition outcome in kumite fight. Moreover, they indicate an association between the 5HTTLPR polymorphism and pre-competition salivary cortisol, thus providing a preliminary but non-conclusive evidence on the role played by the 5HTTLPR genotype as a vulnerability factor in sport competition.


PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259806
Author(s):  
Brent Strong ◽  
Michele C. Fritz ◽  
Liming Dong ◽  
Lynda D. Lisabeth ◽  
Mathew J. Reeves

Introduction Post-stroke depression is a disabling condition that occurs in approximately one-third of stroke survivors. There is limited information on changes in depressive symptoms shortly after stroke survivors return home. To identify factors associated with changes in post-stroke depressive symptoms during the early recovery period, we conducted a secondary analysis of patients enrolled in a clinical trial conducted during the transition period shortly after patients returned home (MISTT). Methods The Michigan Stroke Transitions Trial (MISTT) tested the efficacy of social worker case management and access to online information to improve patient-reported outcomes following an acute stroke. Patient Health Questionnaire-9 (PHQ-9) scores were collected via telephone interviews conducted at 7 and 90 days post-discharge; higher scores indicate more depressive symptoms. Generalized estimating equations were used to identify independent predictors of baseline PHQ-9 score at 7 days and of changes over time to 90 days. Results Of 265 patients, 193 and 185 completed the PHQ-9 survey at 7 and 90 days, respectively. The mean PHQ-9 score was 5.9 at 7 days and 5.1 at 90 days. Older age, being unmarried, and having moderate stroke severity (versus mild) were significantly associated with lower 7-day PHQ-9 scores (indicating fewer depressive symptoms). However, at 90 days, both unmarried patients and those with moderate or high stroke severity had significant increases in depressive symptoms over time. Conclusions In stroke patients who recently returned home, both marital status and stroke severity were associated with depressive symptom scores; however, the relationships were complex. Being unmarried and having higher stroke severity was associated with fewer depressive symptoms at baseline, but both factors were associated with worsening depressive symptoms over time. Identifying risk factors for changes in depressive symptoms may help guide effective management strategies during the early recovery period.


2021 ◽  
Vol 10 (18) ◽  
pp. 4230
Author(s):  
Rita Polito ◽  
Giovanni Messina ◽  
Anna Valenzano ◽  
Alessia Scarinci ◽  
Ines Villano ◽  
...  

Adipose tissue is considered an endocrine organ, and its excess compromises the immune response and metabolism of hormones and nutrients. Furthermore, the accumulation of visceral fat helps to increase the synthesis of cortisol. The hypothalamus-pituitary-adrenal (HPA) axis is a neuroendocrine system involved in maintaining homeostasis in humans under physiological conditions and stress, and cortisol is the main hormone of the HPA axis. It is known that a stress-induced diet and cortisol reactivity to acute stress factors may be related to dietary behavior. In obesity, to reduce visceral adipose tissue, caloric restriction is a valid strategy. In light of this fact, the aim of this study was to assess the effects of a commercial dietary ketosis program for weight loss on the sympathetic nervous system and HPA axis, through evaluation of salivary cortisol and GSR levels. Thirty obese subjects were recruited and assessed before and after 8 weeks of Very Low Calorie Ketogenic Diet (VLCKD) intervention to evaluate body composition and biochemical parameters. Salivary cortisol levels and GSR significantly decreased after dietary treatment; in addition, body composition and biochemical features were ameliorated. The VLCKD had a short-term positive effect on the SNS and HPA axes regulating salivary cortisol levels. Finally, the effects of the VLCKD on the SNS and HPA axis may lead to more individualized treatment strategies that integrate obesity and stress and support the usefulness of such therapeutic interventions in promoting the reduction of the individual disease burden.


PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250459
Author(s):  
Richelle Vlenterie ◽  
Pauline M. Geuijen ◽  
Marleen M. H. J. van Gelder ◽  
Nel Roeleveld

The hypothalamic-pituitary-adrenal axis, with cortisol as its final metabolite, has been proposed as a potential underlying biological mechanism for associations between depression and stress symptoms during pregnancy and adverse perinatal outcomes. In this study, we explored associations between salivary cortisol as a potential biomarker for stress and depressive symptoms and several self-completed psychological measurement scales among pregnant women. In total, 652 pregnant women participating in the PRegnancy and Infant DEvelopment (PRIDE) Study completed the Edinburgh Depression Scale (EDS), Patient Health Questionnaire-2 (PHQ-2), Pregnancy-Related Anxiety Questionnaire-Revised (PRAQ-R), and Tilburg Pregnancy Distress Scale (TPDS) and collected a single awakening salivary cortisol sample around gestational week 17. Odds ratios, Spearman’s correlation coefficients (ρs) and Cohen’s Kappa coefficients (κ) were calculated to examine the associations between the EDS, PHQ-2, PRAQ-R, TPDS, and maternal cortisol levels. The overall correlation coefficient between the score on the EDS and the salivary cortisol level was 0.01 (p = 0.89) with κ = -0.01 (95% confidence interval [CI] -0.08–0.06). We did not observe agreement between the PHQ-2 and cortisol levels either (κ = 0.06 (95% CI -0.02–0.14)). The results for the PRAQ-R and TPDS were similar with overall correlations with maternal cortisol levels of ρs = 0.01 (p = 0.81) and ρs = 0.06 (p = 0.35) and agreements of κ = 0.02 (95% CI -0.06–0.09) and κ = -0.02 (95% CI -0.11–0.07), respectively. Maternal awakening salivary cortisol levels and measures of maternal psychological distress, anxiety, depressive symptoms, and pregnancy-related anxiety, assessed by self-completed questionnaires, did not seem to be related in mid-pregnancy.


2009 ◽  
Vol 31 (3) ◽  
pp. 202-207 ◽  
Author(s):  
Luisa de Marillac Niro Terroni ◽  
Renério Fráguas ◽  
Mara de Lucia ◽  
Gisela Tinone ◽  
Patricia Mattos ◽  
...  

OBJECTIVE: Post-stroke major depressive episode is very frequent, but underdiagnosed. Researchers have investigated major depressive episode symptomatology, which may increase its detection. This study was developed to identify the depressive symptoms that better differentiate post-stroke patients with major depressive episode from those without major depressive episode. METHOD: We screened 260 consecutive ischemic stroke patients admitted to the neurology clinic of a university hospital. Seventy-three patients were eligible and prospectively evaluated. We assessed the diagnosis of major depressive episode using the Structured Clinical Interview for DSM-IV and the profile of depressive symptoms using the 31-item version of the Hamilton Depression Rating Scale. For data analysis we used cluster analyses and logistic regression equations. RESULTS: Twenty-one (28.8%) patients had a major depressive episode. The odds ratio of being diagnosed with major depressive episode was 3.86; (95% CI, 1.23-12.04) for an increase of one unit in the cluster composed by the domains of fatigue/interest and retardation, and 2.39 (95% CI, 1.21-4.71) for an increase of one unit in the cluster composed by the domains of cognitive, accessory and anxiety symptoms. The domains of eating/weight and insomnia did not contribute for the major depressive episode diagnosis. CONCLUSION: The domains of retardation and interest/fatigue are the most relevant for the diagnosis of major depressive episode after stroke.


2017 ◽  
Vol 25 (7) ◽  
pp. 993-1003 ◽  
Author(s):  
Chelsea Siwik ◽  
Allison Hicks ◽  
Kala Phillips ◽  
Whitney N Rebholz ◽  
Lauren A Zimmaro ◽  
...  

We explored associations between problem-focused, emotional processing, and emotional expression coping strategies and markers of stress including perceived stress, depressive symptoms, and diurnal cortisol profiles among women with gynecologic cancer. Problem-focused coping was associated with less perceived stress, fewer depressive symptoms, and more rhythmic diurnal salivary cortisol profiles. Emotional processing was associated with lower perceived stress and fewer depressive symptoms. Emotional expression was associated with fewer depressive symptoms and elevated diurnal mean and evening cortisol levels. Results point to key differences in coping strategies. In this sample, only problem-focused coping was linked with adaptive differences in both psychological and physiological stress measures.


Author(s):  
Renerio Fraguas ◽  
Luisa Terroni ◽  
Edson Amaro Jr ◽  
Dan Iosifescu ◽  
Patricia Mattos ◽  
...  

2016 ◽  
Vol 117 (1) ◽  
pp. 18-33 ◽  
Author(s):  
Michaela Dušková ◽  
Kateřina Šimůnková ◽  
Jana Vítků ◽  
Lucie Sosvorová ◽  
Hana Jandíková ◽  
...  

Numerous diagnostic tests are used to evaluate the hypothalamic-pituitary-adrenal axis (HPA axis). The gold standard is still considered the insulin tolerance test (ITT), but this test has many limitations. Current guidelines therefore recommend the Synacthen test first when an HPA axis insufficiency is suspected. However, the dose of Synacthen that is diagnostically most accurate and sensitive is still a matter of debate. We investigated 15 healthy men with mean/median age 27.4/26 (SD ±4.8) years, and mean/median BMI (body mass index) 25.38/24.82 (SD ±3.2) kg/m2. All subjects underwent 4 dynamic tests of the HPA axis, specifically 1 μg, 10 μg, and 250 μg Synacthen (ACTH) tests and an ITT. Salivary cortisol, cortisone, pregnenolone, and DHEA (dehydroepiandrosterone) were analysed using liquid chromatography-tandem mass spectrometry. During the ITT maximum salivary cortisol levels over 12.5 nmol/l were found at 60 minutes. Maximum cortisol levels in all of the Synacthen tests were higher than this; however, demonstrating that sufficient stimulation of the adrenal glands was achieved. Cortisone reacted similarly as cortisol, i.e. we did not find any change in the ratio of cortisol to cortisone. Pregnenolone and DHEA were higher during the ITT, and their peaks preceded the cortisol peak. There was no increase of pregnenolone or DHEA in any of the Synacthen tests. We demonstrate that the 10 μg Synacthen dose is sufficient stimulus for testing the HPA axis and is also a safe and cost-effective alternative. This dose also largely eliminates both false negative and false positive results.


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