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Duan, Hongxia, Huihua Fang, Yuling Zhang, Xia Shi, and Liang Zhang. "Associations between cortisol awakening response and resting electroencephalograph asymmetry." PeerJ 7 (June 3, 2019): e7059. http://dx.doi.org/10.7717/peerj.7059.
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The cortisol awakening response (CAR), a rapid cortisol rise in the morning after awakening, has been proposed to provide energy to cope with daily demands and suggested to be associated with brain functions. Electroencephalogram (EEG) asymmetry studies have implicated asymmetric cortical activation, especially in frontal cortex, in approach-withdrawal motivation. In this study, we examined the relationship between the CAR and lateralized cortical activity under rest in 55 university male students. Saliva samples were collected at 0, 15, 30 and 60 min after awakening on the two consecutive workdays. The lateralized cortical activity at frontocentral sites was examined by alpha asymmetry score. The results showed that a higher CAR was positively associated with alpha asymmetry score, which indicated that the higher CAR is linked with more left-sided cortical activity at frontocentral sites under resting state. This association still existed even after controlling psychological and sleep quality variables. These results suggested that appropriately mobilizing energy resource storage after awakening revealed as CAR might be associated with goal-directed approach tendencies before any eventual stressful situation, characteristic of more left than right resting-state frontocentral cortical activity.
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Grosser, L., C. Yates, J. Dorrian, R. Matthews, and S. Banks. "O033 Is Sleeping and Waking Important for the Cortisol Awakening Response?" Sleep Advances 4, Supplement_1 (October 1, 2023): A11—A12. http://dx.doi.org/10.1093/sleepadvances/zpad035.033.
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Abstract Introduction The rapid rise in cortisol after waking is known as the cortisol awakening response (CAR). However, as part of its normal circadian rhythm cortisol also rises in the morning independent of awakening. If CAR is a direct response to awakening, it should be eliminated in conditions of sleep deprivation (SD). Given that an atypical CAR is associated with several psychiatric and medical disorders, understanding the factors that influence CAR is of clinical relevance. This study explored cortisol during the normal waking period prior, during, and post-SD. Methods N=21 (11F 22.80±4.40y) completed 62h of SD in the laboratory. Salivary cortisol was collected across 5-time-points (07:00h, 07:15h, 07:30h, and 07:45h) on 2-pre-at-home-study days, 4-in-lab-study days, and 2-post-at-home-study days. Mixed-effects ANOVAs tested for fixed effects of day, time, and their interactions on cortisol, and cortisol area under the curve (AUCi, AUCg). Results SD produced significant effects of time*day (p<0.001). Cortisol levels at +30 and +45min post-awakening were lower on SD days. Cortisol levels on awakening (0mins) did not differ between any study days. There were significant effects of day (p<0.001). AUCi and AUCg were greater on in-laboratory-baseline and recovery days compared to other study days. Discussion This study found CAR is not present during periods of SD when there is no ‘waking’ from sleep. It showed for the first time that CAR recovers to baseline levels following recovery sleep. While the role of the CAR remains unclear this study identified factors that future research should consider to advance understanding of its purpose.
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McGinnis, Ellen W., Nestor Lopez-Duran, Cecilia Martinez-Torteya, James L. Abelson, and Maria Muzik. "Cortisol awakening response and internalizing symptoms across childhood." International Journal of Behavioral Development 40, no. 4 (June 19, 2015): 289–95. http://dx.doi.org/10.1177/0165025415590185.
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Efforts to identify biological correlates of internalizing symptoms in childhood have involved examinations of HPA-axis functioning, namely Cortisol Awakening Response (CAR). However, research has not assessed the relationship between CAR and internalizing problems among children younger than 8 years. Findings with older samples have been somewhat equivocal, perhaps due to high rates of co-occurring externalizing symptoms during childhood and/or due to age-related differences. This cross-sectional study examined CAR in an at-risk sample of children aged 22 months to 8 years at various levels of risk for internalizing symptoms. Internalizing symptoms were associated with blunted CAR, but only after controlling for externalizing problems. The relationship between CAR and internalizing symptoms disappeared with age. Results demonstrate that a negative association between CAR and internalizing exists during early childhood and illustrate the importance of accounting for comorbid externalizing disorders and developmental stage when assessing the HPA-internalizing link.
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Dembinska, E., K. Rutkowski, J. Sobanski, K. Cyranka, M. Mielimaka, and A. Citkowska-Kisielewska. "The cortisol awakening response in anxiety disorders and personality disorders and changes in salivary cortisol level after psychotherapy." European Psychiatry 41, S1 (April 2017): S408. http://dx.doi.org/10.1016/j.eurpsy.2017.01.340.
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IntroductionThe hypothalamus—pituitary—adrenal axis (HPA axis) dysregulation plays an important role in the pathophysiology of anxiety disorders. Salivary cortisol level is a useful indicator of HPA axis dysfunction.ObjectivesMost data suggests elevated cortisol awakening response (CAR) in anxiety disorders, but there are studies indicating opposite pattern (flat CAR).AimGoal of this study was to determine whether patients with anxiety and personality disorders show a specific daily cortisol patterns and weather this pattern changes after 12 weeks of intensive predominantly psychodynamic combined group and individual psychotherapy.MethodThe studied population comprised 77 patients, mainly females (72.7%), with primary diagnosis of anxiety disorder 40.9% or personality disorder 59.1%. The Symptom Checklist “0” was used to assess the pre- and post-treatment levels of patients’ symptoms. Pre- and post-treatment cortisol levels were measured in three saliva samples collected during one day (at awakening, 30 min after awakening, at 22.00).ResultsThe obtained results were partly similar to previous research. We found four different daily CAR patterns: decreased (drop 30 min after awakening), flat (rise 0–49% 30 min after awakening), normal (rise 50–75% 30 min after awakening) and elevated (rise over 75% 30 min after awakening), two of them (flat and elevated) were considered as typical for anxiety disorders. Groups of CAR pattern differed significantly in the level of sleep symptoms, dysthymia symptoms and avoidance/dependency symptoms. The changes in the CAR pattern after psychotherapy were not significant.ConclusionsAnxiety disorders and personality disorders are characterized by more than two specific daily salivary cortisol patterns.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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Anderson, Travis, Laurie Wideman, Flavio A. Cadegiani, and Claudio E. Kater. "Effects of Overtraining Status on the Cortisol Awakening Response—Endocrine and Metabolic Responses on Overtraining Syndrome (EROS-CAR)." International Journal of Sports Physiology and Performance 16, no. 7 (July 1, 2021): 965–73. http://dx.doi.org/10.1123/ijspp.2020-0205.
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The cortisol awakening response (CAR) is a distinct component of the circadian cortisol profile and has promise as a biomarker for the monitoring of athlete readiness and training status. Although some studies have suggested the CAR may be affected by the development of overtraining syndrome (OTS), this has yet to be systematically investigated. Purpose: To compare the CAR and diurnal cortisol slope between athletes diagnosed with OTS, healthy athletes, and sedentary controls. Methods: This study was a secondary analysis of data from the Endocrine and Metabolic Responses on Overtraining study. Male participants were recruited to either OTS, healthy athlete, or sedentary control groups. The participants produced saliva samples immediately after waking (S1), 30 minutes after waking (S2), at 16:00 hours, and at 23:00 hours. Salivary cortisol concentration was determined by an electrochemiluminescence assay. Mixed-effects models were used to assess the conditional effect of group (sedentary controls, OTS, and healthy athletes) on the change in cortisol over time. Separate models were fit for the awakening samples (S1 and S2) and for the diurnal slope (linear change across S1, 16:00 h, and 23:00 h). Results: The models demonstrated significant time-by-group interaction for OTS for the 2 cortisol concentrations collected during the awakening period (β = −9.33, P < .001), but not for the diurnal cortisol slope (β = 0.02, P = .80). Conclusions: These results suggest the CAR may be associated with OTS and should be considered within a panel of biomarkers. Further research is necessary to determine whether alterations in the CAR may precede the diagnosis of OTS.
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Kontou, Thomas G., Gregory D. Roach, and Charli Sargent. "Mild to Moderate Sleep Restriction Does Not Affect the Cortisol Awakening Response in Healthy Adult Males." Clocks & Sleep 4, no. 4 (November 25, 2022): 722–34. http://dx.doi.org/10.3390/clockssleep4040054.
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The cortisol awakening response (CAR) is a distinct rise in cortisol that occurs upon awakening that is thought to contribute to arousal, energy boosting, and anticipation. There is some evidence to suggest that inadequate sleep may alter the CAR, but the relationship between sleep duration and CAR has not been systematically examined. Healthy males (n = 111; age: 23.0 ± 3.6 yrs) spent 10 consecutive days/nights in a sleep laboratory. After a baseline night (9 h time in bed), participants spent either 5 h (n = 19), 6 h (n = 23), 7 h (n = 16), 8 h (n = 27), or 9 h (n = 26) in bed for seven nights, followed by a 9 h recovery sleep. The saliva samples for cortisol assay were collected at 08:00 h, 08:30 h and 08:45 h at baseline, on experimental days 2 and 5 and on the recovery day. The primary dependent variables were the cortisol concentration at awakening (08:00 h) and the cortisol area under the curve (AUC). There was no effect of time in bed on either the cortisol concentration at awakening or cortisol AUC. In all the time in bed conditions, the cortisol AUC tended to be higher at baseline and lower on experimental day 5. Five consecutive nights of mild to moderate sleep restriction does not appear to affect the CAR in healthy male adults.
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Nagarajan, P., D. Nguyen, C. Dunbar, B. Lechat, T. Liebich, B. Zajamsek, K. Hansen, et al. "P013 The Effect of Noise Exposure during Sleep on the Cortisol Awakening Response." Sleep Advances 4, Supplement_1 (October 1, 2023): A38—A39. http://dx.doi.org/10.1093/sleepadvances/zpad035.098.
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Abstract Introduction Environmental noise could negatively impact the sleep and well-being of nearby residents. This study tested for overnight noise exposure effects on the cortisol awakening response (CAR), a potential marker of noise-related stress responses, and for differences in CAR and hair cortisol between different prior noise exposure groups. Methods A randomised controlled laboratory trial was conducted in 68 individuals from four groups; including WFN-exposed residents n=14 with and n=18 without WFN-related complaints, n=18 quiet rural control and n=18 urban traffic-noise exposed residents. Across six nights, after an initial adaptation night, participants were exposed in random order to different noise conditions, which included intermittent WFN and road traffic noise (RTN), WFN at average exposure levels throughout wake, sleep or both and a quiet control night. Salivary CAR responses were evaluated from 5 serial saliva samples collected following awakening. Hair cortisol levels were also collected. Mixed effects models were used to examine group and night effects on CAR and group effects on hair cortisol. Results There was a significant main effect of condition on CAR (p=0.038), but no significant pairwise differences between the control night and noise exposure nights, and no further differences between nights or groups on CAR or hair cortisol concentrations. Conclusions Acute in-laboratory noise-related sleep disturbance at the levels used in this study do not appear to alter acute cortisol awakening responses. A better understanding of chronic noise exposure effects and stress responses is important to help clarify and mitigate potential environmental noise exposure effects on nearby residents.
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Kwon, Oh Jeong, Munsoo Kim, Ho Sub Lee, Kang-keyng Sung, and Sangkwan Lee. "The Cortisol Awakening Response in Patients with Poststroke Depression Is Blunted and Negatively Correlated with Depressive Mood." BioMed Research International 2015 (2015): 1–6. http://dx.doi.org/10.1155/2015/709230.
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It is important to reduce poststroke depression (PSD) to improve the stroke outcomes and quality of life in stroke patients, but the underlying mechanisms of PSD are not completely understood. As many studies implicate dysregulation of hypothalamic-pituitary-adrenal axis in the etiology of major depression and stroke, we compared the cortisol awakening response (CAR) of 28 admitted PSD patients with that of 23 age-matched caregiver controls. Saliva samples for cortisol measurement were collected immediately, 15, 30, and 45 min after awakening for two consecutive days. Depressive mood status in PSD patients was determined with Beck Depression Inventory and Hamilton Depression Rating Scale. Salivary cortisol levels of PSD patients did not rise significantly at any sampling time, showing a somewhat flat curve. Caregiver controls showed significantly higher CAR at 15 and 30 min after awakening compared to PSD patients even though the two groups did not differ at awakening or 45 min after awakening. Area-under-the-curve analysis revealed a significant negative correlation between the CAR and the degree of depression in PSD patients. Thus, our findings suggest that poststroke depression is closely related with dysfunctional HPA axis indicated by blunted CAR.
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Sariñana-González, Patricia, Sara Vitoria-Estruch, Ángel Romero-Martínez, and Luis Moya-Albiol. "Aggression predicts Cortisol Awakening Response in healthy young adults." Anales de Psicología 31, no. 3 (September 16, 2015): 1044. http://dx.doi.org/10.6018/analesps.31.3.177641.
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Few studies have examined therelationship between the cortisol awakening response (CAR) and aggression inhealthy youth adults. This study analyzes this relationship in 83 women (38 inluteal phase and 45 in follicular phase of menstrual cycle) and 20 men.Salivary-free cortisol measures of the CAR were obtained immediately followingawakening and 30, 45, and 60 minutes afterwards. Additionally, participantscompleted a self-report of aggression. Men presented lower levels of CAR thanwomen in luteal phase. Men were also liable to present more physical aggressionthan women, independently of their menstrual phase. General aggression andspecifically verbal aggression are predictors of CAR in men. In women, verbalaggression predicts CAR during the follicular phase of the menstrual cycle;whereas anger and physical aggression do so during the luteal phase. CAR may beused as a valid marker of proneness to aggression – but must be considered differentlydepending on gender and menstrual cycle of women. This study offers relevantinformation on the hormonal bases of aggression and so contributes to theliterature on alleviating problems related to violence.
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Blanco, Ignacio Roura, Anastasi Kosmadopoulos, and Diane Boivin. "017 The Circadian Variation of the Cortisol Awakening Response." Sleep 44, Supplement_2 (May 1, 2021): A8—A9. http://dx.doi.org/10.1093/sleep/zsab072.016.
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Abstract Introduction The Cortisol Awakening Response (CAR) is a rapid increase in cortisol levels at awakening that lasts for about 1 hour. This secretory phenomenon has been proposed to be independent of circadian cortisol regulation. However, the contribution of the circadian system to the CAR remains unclear. The aim of this study is to assess the circadian variation of the CAR. Methods A total of eleven healthy participants (1 woman; 22.6 ± 3.4 years old) were enrolled. Following an 8-h baseline sleep period aligned to their habitual sleep times, participants underwent a 72-h ultradian sleep-wake cycle procedure (USW) consisting of 60-min wake periods in dim light (<10 lux) alternating with 60-min nap opportunities in total darkness. Participants remained in a semi-recumbent posture during the procedure. Salivary cortisol samples were collected at 0, 15, 30, and 50 minutes after waking up from each nap. Linear mixed-effects regression analyses were performed on log-transformed cortisol data from wake periods corresponding to the habitual bedtime (biological night) and habitual wake-time (biological morning). These served as proxies of circadian phases characterised by lowest and maximal cortisol secretory activity, respectively. Total cortisol secretion and CAR magnitude during these periods were computed, respectively, as the Area Under the Curve with respect to ground (AUCg) and to increase (AUCi) and compared with paired-samples t-tests. Results Significant main effects of wake period (p<.001) and sample time (p=.023) were found, with no interaction (p=.167). Cortisol levels were higher in the biological morning compared to the biological night and increased with elapsed time awake. The total amount of cortisol secreted (AUCg) after waking in the biological morning was significantly greater than during the biological night (p<.001). No significant differences between circadian phases were found in the AUCi (p=.223). Conclusion Our study suggests that some features of the CAR may at least partially be under circadian control. These findings are relevant for the understanding of the physiological mechanisms underlying circadian misalignment in shift workers and patients with severe sleep disorders. Support (if any) Project funded by the Canadian Institutes of Health Research. I.R.B received a Barrie Foundation Fellowship. A.K. received a Fonds de Recherche en Santé du Québec postdoctoral fellowship.
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Ruiz Roa, Silvia Liliana, Paula Conde Lamparelli Elias, Margaret Castro, and Ayrton Custodio Moreira. "The cortisol awakening response is blunted in patients with active Cushing's disease." European Journal of Endocrinology 168, no. 5 (May 2013): 657–64. http://dx.doi.org/10.1530/eje-12-0982.
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IntroductionCortisol awakening response (CAR) is a rapid increase of cortisol levels within 30–45 min after awakening.ObjectiveThis study evaluates CAR compared with cortisol circadian rhythm in active and in remission Cushing's disease (CD).Materials and methodsWe evaluated healthy controls (HC, n=19), obese (OB, n=10), in remission (n=08), and active CD patients (n=10). Salivary free cortisol (SF) was determined at 0800, 1100, 1700, 2000, and 2300 h on the first day. CAR was obtained the next morning immediately upon awakening and at 15, 30, 45, and 60-min post-wake up.ResultsWe observed differences in SF levels throughout the day in HC, OB, and in remission CD (ANOVA P=0.0001) but not in active CD (P=0.2). We demonstrated SF increment after awakening in HC, OB, and in remission CD (ANOVA P=0.007), with no effect of time on SF in active CD. The relative increment of SF obtained at the peak after awakening (CARi%) in the active CD (67±57%) was lower than in HC (154±107%), OB (240±188%), and in remission CD (186±184%) patients (P=0.009). There was a negative correlation between the SF at awakening and the CARi% in HC (r=−0.8), OB (r=−0.78), and in remission CD (r=−0.74) but not in active CD (r=−0.35; P=0.31).ConclusionThis study originally described a blunted CAR in active CD in contrast to its presence in HC, OB, and in remission CD. This subtle dysfunction of the hypothalamus–pituitary–adrenal axis may represent a distinct and additional physiopathological phenomenon superimposing the dysregulated cortisol circadian rhythm in this disease.
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De Riso, F., R. Giugliano, A. M. Monteleone, M. Nigro, F. Pellegrino, M. Calvanese, G. Patriciello, V. De Stefano, U. Volpe, and P. Monteleone. "Attachment style and salivary cortisol awakening response in eating disorders." European Psychiatry 33, S1 (March 2016): S162. http://dx.doi.org/10.1016/j.eurpsy.2016.01.318.
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IntroductionEarly life experiences can influence hypotalamus-pituitary-adrenal (HPA) axis regulation and adult attachment styles. Furthermore, several studies showed that in patients with eating disorders (EDs) there is a prevalence of insecure attachment. However, the relationship between adult attachment style, HPA axis functioning and onset of EDs is largely unknown.Objectives and aimsIn order to evaluate possible associations between attachment styles and HPA axis functioning in EDs, we investigated Cortisol Awakening Response (CAR) in ED patients with different attachment styles.MethodsTwenty adult patients with EDs were classified in three groups, according to the Experience in Close Relationship questionnaire (6 with secure attachment, 6 with anxious attachment and 8 with avoidant attachment). Saliva samples were collected at awakening and 15, 30 and 60 minutes after.ResultsThere was a significant difference among the groups in both awakening and post-awakening cortisol concentrations. In particular, compared to secure and avoidant groups, the anxious group exhibited lower cortisol concentrations at awakening and post-awakening with a preservation of the timing of the CAR.DiscussionPresent findings demonstrate that anxious attachment style is linked to flattened CAR in EDs. This pattern has been associated with other psychiatric disorders. Therefore, attachment style could influence the HPA functioning and it could play, although not specifically, a role in pathophysiology of EDs.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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Anderson, Travis, Amy R. Lane, and Anthony C. Hackney. "The Cortisol Awakening Response: Association With Training Load in Endurance Runners." International Journal of Sports Physiology and Performance 13, no. 9 (October 1, 2018): 1158–63. http://dx.doi.org/10.1123/ijspp.2017-0740.
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The cortisol awakening response (CAR) is commonly used as a marker of psychological stress; however, it is unknown whether CAR is affected by regular physical-exercise-induced stress. Purpose: To assess the relationship between training load and CAR. Methods: Recreational endurance athletes were recruited from local running clubs. Subjects (n = 15) completed training logs for 2 wk, with various training loads, including psychometric analysis (Recovery-Stress Questionnaire for Athletes). Subjects provided saliva samples each day immediately after waking and 30 min postwaking. Samples were analyzed for cortisol concentration via enzyme-linked immunosorbent assay and subsequently were analyzed for CAR and CAR%. Daily training load was calculated and analyzed as training impulse. Simple linear regression was used to assess the relationship between CAR and training impulse. Results: CAR (r2 = .352, P = .025) and CAR% (r2 = .373, P = .012) both showed a significant negative relationship with training load. Conclusions: These results suggest that CAR is affected by regular exercise training loads in recreational athletes. It is recommended that future CAR research control for fitness level and exercise training load in physically active populations.
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Yu, Rongqin, Susan Branje, Wim Meeus, Philip Cowen, and Seena Fazel. "Depression, violence and cortisol awakening response: a 3-year longitudinal study in adolescents." Psychological Medicine 49, no. 6 (July 17, 2018): 997–1004. http://dx.doi.org/10.1017/s0033291718001654.
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AbstractBackgroundDespite evidence of links between depression and violent outcomes, potential moderators of this association remain unknown. The current study tested whether a biological marker, cortisol, moderated this association in a longitudinal sample of adolescents.MethodsParticipants were 358 Dutch adolescents (205 boys) with a mean age of 15 years at the first measurement. Depressive symptoms, the cortisol awakening response (CAR) and violent outcomes were measured annually across 3 years. The CAR was assessed by two measures: waking cortisol activity (CAR area under the curve ground) and waking cortisol reactivity (CAR area under the curve increase). Within-individual regression models were adopted to test the interaction effects between depressive symptoms and CAR on violent outcomes, which accounted for all time-invariant factors such as genetic factors and early environments. We additionally adjusted for time-varying factors including alcohol drinking, substance use and stressful life events.ResultsIn this community sample, 24% of adolescents perpetrated violent behaviours over 3 years. We found that CAR moderated the effects of depressive symptoms on adolescent violent outcomes (βs ranged from −0.12 to −0.28). In particular, when the CAR was low, depressive symptoms were positively associated with violent outcomes in within-individual models, whereas the associations were reversed when the CAR was high.ConclusionsOur findings suggest that the CAR should be investigated further as a potential biological marker for violence in adolescents with high levels of depressive symptoms.
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Fries, Eva, Lucia Dettenborn, and Clemens Kirschbaum. "The cortisol awakening response (CAR): Facts and future directions." International Journal of Psychophysiology 72, no. 1 (April 2009): 67–73. http://dx.doi.org/10.1016/j.ijpsycho.2008.03.014.
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Ahn, Ryun S., Jee H. Choi, Bum C. Choi, Jung H. Kim, Sung H. Lee, and Simon S. Sung. "Cortisol, estradiol-17β, and progesterone secretion within the first hour after awakening in women with regular menstrual cycles." Journal of Endocrinology 211, no. 3 (September 29, 2011): 285–95. http://dx.doi.org/10.1530/joe-11-0247.
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Cortisol concentration in both serum and saliva sharply increases and reaches a peak within the first hour after waking in the morning. This phenomenon is known as the cortisol awakening response (CAR) and is used as an index of hypothalamus–pituitary–adrenal (HPA) axis function. We examined whether ovarian steroid concentrations increased after awakening as with the CAR in the HPA axis. To do this, cortisol, estradiol-17β (E2), and progesterone (P4) concentrations were determined in saliva samples collected immediately upon awakening and 30 and 60 min after awakening in women with regular menstrual cycles and postmenopausal women. We found that both E2and P4concentrations increased during the post-awakening period in women with regular menstrual cycles, but these phenomena were not seen in any postmenopausal women. The area under the E2and P4curve from the time interval immediately after awakening to 60 min after awakening (i.e. E2auc and P4auc) in women with regular menstrual cycles were greater than those in the postmenopausal women. E2and P4secretory activity during the post-awakening period was influenced by the phase of the menstrual cycle. E2auc in the peri-ovulatory phase and P4auc in the early to mid-luteal phase were greater than in the menstrual phase. Meanwhile, cortisol secretory activity during the post-awakening period was not influenced by menstrual status or the phase of menstrual cycle. These findings indicate that, as with the CAR in the HPA axis function, ovarian steroidogenic activity increased after awakening and is closely associated with menstrual status and phase of menstrual cycle.
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Nigro, M., A. M. Monteleone, F. Pellegrino, M. Cimino, V. Di Maso, U. Volpe, and P. Monteleone. "Cortisol awakening response in binge-purging and restrictive anorexia nervosa." European Psychiatry 41, S1 (April 2017): S558. http://dx.doi.org/10.1016/j.eurpsy.2017.01.803.
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IntroductionAnorexia nervosa (AN) is a complex psychiatric disorder characterized by severe restriction of food intake and aberrant behaviours. The endogenous stress response system, including the hypothalamus-pituitary-adrenal (HPA) axis, may have a role in the pathophysiology of AN.ObjectivesIt has been shown that specific clinical traits of AN, such as binge-purging behaviours, may be associated with higher psychopathology and poorer outcomes. Therefore, the HPA axis functioning could differ between patients with restrictive AN (ANR) and those with binge-purging AN (ANBP).AimsIn order to evaluate whether HPA axis functioning differs between the two subtypes of AN, we assessed the cortisol awakening response (CAR) of symptomatic ANR and ANBP patients.MethodsOur sample included 17 ANBP and 18 ANR patients, and 42 healthy women. All of them filled in the Eating Disorder Inventory-2 (EDI-2). For CAR assessment, participants collected saliva samples at home. Saliva cortisol concentrations were measured by an enzyme immunoassay method.ResultsANR and ANBP patients exhibited a CAR significantly higher than healthy women. Furthermore, the CAR of ANBP women was higher than that of ANR women and positively correlated with the bulimia subitem score of the EDI-2.ConclusionsPresent findings show, for the first time, differences in the CAR between ANBP and ANR subtypes supporting the idea that binge-purging behaviours may have a specific connection with HPA axis.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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Hinkelmann, K., C. Muhtz, L. Dettenborn, A. Agorastos, S. Moritz, K. Wingenfeld, C. Spitzer, S. M. Gold, K. Wiedemann, and C. Otte. "Association between cortisol awakening response and memory function in major depression." Psychological Medicine 43, no. 11 (February 27, 2013): 2255–63. http://dx.doi.org/10.1017/s0033291713000287.
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BackgroundWhile impaired memory and altered cortisol secretion are characteristic features of major depression, much less is known regarding the impact of antidepressant medication. We examined whether the cortisol awakening response (CAR) is increased in depressed patients with and without medication compared with healthy controls (HC) and whether CAR is associated with memory function in each group.MethodWe examined 21 patients with major depression without medication, 20 depressed patients on antidepressant treatment, and 41 age-, sex- and education-matched healthy subjects. We tested verbal (Auditory Verbal Learning Task) and visuospatial (Rey figure) memory and measured CAR on two consecutive days.ResultsPatient groups did not differ in severity of depression. We found a significant effect of group (p = 0.03) for CAR. Unmedicated patients exhibited a greater CAR compared with medicated patients (p = 0.04) with no differences between patient groups and HC. We found a significant effect of group for verbal (p = 0.03) and non-verbal memory (p = 0.04). Unmedicated patients performed worse compared with medicated patients and HC in both memory domains. Medicated patients and HC did not differ. Regression analyses revealed a negative association between CAR and memory function in depressed patients, but not in HC.ConclusionsWhile in unmedicated depressed patients the magnitude of CAR is associated with impaired memory, medicated patients showed a smaller CAR and unimpaired cognitive function compared with HC. Our findings are compatible with the idea that antidepressants reduce CAR and partially restore memory function even if depressive psychopathology is still present.
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Battipaglia, M., N. Attianese, S. Donato, R. Ceres, R. Cerra, A. M. Monteleone, P. Monteleone, and G. Cascino. "Cortisol awakening response in bipolar patients with comorbid type 2 diabetes mellitus." European Psychiatry 67, S1 (April 2024): S325—S326. http://dx.doi.org/10.1192/j.eurpsy.2024.674.
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IntroductionBipolar Disorder (BD) is a severely debilitating psychiatric disorder with high rates of morbidity and mortality, and patients with BD have a 10-year reduction in their life expectancy. Bipolar disorder (BD) is frequently associated with type 2 diabetes mellitus (T2DM). BD patients with comorbid T2DM have been shown to have three times higher odds of a chronic course and rapid cycling and are more likely to present worse outcomes to treatment with lithium and/or other mood stabilisers when compared to BD patients without IGM (impaired glucose metabolism).ObjectivesThe functioning of the hypothalamic-pituitary-adrenal (HPA) axis has been never investigated in BD with respect to the glucose metabolic status. Therefore, we assessed the cortisol awakening response (CAR) in bipolar patients with or without comorbid T2DM.MethodsTwenty euglycemic bipolar patients [12 males and eight females; mean age (±SD): 47.4 ± 14.4 years; mean (±SD) duration of illness: 18.3 ± 12.1 years], 16 BD patients with T2DM [11 males and five females; mean age (±SD): 63.6 ± 12.8 years; mean (±SD) duration of bipolar illness: 17.1 ± 10.8 years; mean (±SD) duration of T2DM: 5.2 ± 5.3 years], 18 healthy subjects [seven males and 11 females; mean age (±SD): 45.0 ± 12.1 years] and 12 non-psychiatric subjects with T2DM [eight males and four females; mean age (±SD): 56.7 ± 11.2 years; mean (±SD) duration of T2DM: 5.2 ± 3.5 years] were recruited. Saliva cortisol was measured at awakening and after 15, 30, and 60 min.ResultsWith respect to both healthy controls and controls with T2DM, euglycemic and diabetic BD patients exhibited a CAR occurring at significantly lower levels. No significant difference emerged in the CAR between the two groups of bipolar patients. Controls with T2DM had an overall post-awakening cortisol production significantly higher than healthy controls.ConclusionsOur results show that the CAR of patients with BD is reduced in terms of overall cortisol production but normal in terms of cortisolo reactivity independently from the occurrence of comorbid T2DM. The dampened CAR points to a tuning down of the functioning of the HPA axis in both euglycemic and diabetic BD patients, which may be a factor of vulnerability, since a preserved HPA axis functioning is essential to deal with stressors, which may precipitate affective episodesDisclosure of InterestNone Declared
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Starr, Lisa R., Kimberly Dienes, Catherine B. Stroud, Zoey A. Shaw, Y. Irina Li, Fanny Mlawer, and Meghan Huang. "Childhood adversity moderates the influence of proximal episodic stress on the cortisol awakening response and depressive symptoms in adolescents." Development and Psychopathology 29, no. 5 (November 22, 2017): 1877–93. http://dx.doi.org/10.1017/s0954579417001468.
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AbstractChildhood adversity (CA) is known to predict sensitization to proximal stressors. Researchers have suggested that disruptions in hypothalamus–pituitary–adrenal axis functioning may be a biological mechanism. If so, CA may predict altered associations between proximal life stress and markers of cortisol secretion. We examined whether CA moderates associations between recent episodic stress and (a) the cortisol awakening response (CAR), and (b) depressive symptoms, in 241 adolescents aged 14–17 years (cortisoln= 196). Salivary cortisol was sampled at 0, 30, and 60 min postawakening for 2 days. The CAR was calculated as the area under the curve with respect to increase and waking cortisol. CA and episodic stress were assessed using contextual-threat-method-coded objective interviews. CA significantly interacted with episodic stress to predict both the CAR and depression. Among those with low CA, episodic stress predicted increased CAR but did not predict depression. For adolescents with high CA, episodic stress predicted lower CAR and higher depression. These interactions were found only for independent (uncontrollable, fateful) events, and not for dependent (self-generated) stress. Increased allostatic load resulting from CA exposure may interfere with adolescents' ability to optimally regulate their CAR in relation to recent stress, contributing to increased depression risk.
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Grąźlewski, Tomasz, Jolanta Kucharska-Mazur, Błażej Misiak, and Jerzy Samochowiec. "Disturbances of cortisol awakening response in psychotic disorders and at-risk states – a literature review." Archives of Psychiatry and Psychotherapy 25, no. 2 (June 22, 2023): 7–14. http://dx.doi.org/10.12740/app/159085.
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Background and objective: According to the diathesis-stress model, disturbances of the hypothalamic-pituitary-adrenal (HPA) axis are thought to play a role in the development, onset, and progression of psychosis. The aim of this paper is to present the available body of evidence on the abnormalities of the cortisol awakening response (CAR) in psychotic disorders and at-risk states. Methods: Review of literature from the years 2011-2022 available across three databases (Scopus, PubMed and Google Scholar) was performed. With an aim to: i) ensure that the review covers a wide range of research related to psychotic presentations as manifested in a broad range of clinical populations (from CHR/UHR to full-blown psychosis), and ii) identify the neurobiological background thereof, the following combination of search terms was applied: "chr" OR "uhr" OR "arms" OR "first-episode schizophrenia" OR "psychosis" AND "cortisol" OR "HPA axis" OR "CAR" OR "cortisol awakening response". Results and conclusion: Research suggests that abnormalities of the HPA axis (in this case, disturbances of the CAR) appear to be an important factor in the pathogenesis of psychotic disorders. The cortisol awakening response was blunted in patients with first-episode psychosis or schizophrenia. On the other hand, in subjects with at-risk states, the results were inconclusive. These findings, however, are based on a small number of studies; therefore, more research in this area is required
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Taylor, Zoe E., Carly D. Evich, Kristine Marceau, Nayantara Nair, and Blake L. Jones. "Associations Between Effortful Control, Cortisol Awakening Response, and Depressive Problems in Latino Preadolescents." Journal of Early Adolescence 39, no. 7 (September 7, 2018): 1050–77. http://dx.doi.org/10.1177/0272431618798509.
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The present study examined associations between effortful control, a trait marker of self-regulation, adaptive hypothalamic-pituitary-adrenal (HPA) system functioning (as reflected by the cortisol awakening response [CAR]), and concurrent and longitudinal depressive problems, in a sample of preadolescent Latino youth ( N = 119, mean age = 11.53 years, 59% girls). We hypothesized that trait readiness for self-regulation (specifically effortful control) could be related to physiological state readiness for self-regulation (as measured using the Cortisol Awakening Response or CAR), and that both may counter depressive problems. We found that youth’s CAR was positively associated with effortful control, and negatively with youth depressive problems. Effortful control and youth depressive problems were also negatively associated. Longitudinal relations of CAR and effortful control on depressive problems at T2 were not significant in the structural equation model after controlling for T1 depressive problems, although these variables were significant in the bivariate correlations. Results suggest that both trait regulation and physiological regulation may counter depressive problems in Latino youth.
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Figueiro, Mariana G., and Mark S. Rea. "Short-Wavelength Light Enhances Cortisol Awakening Response in Sleep-Restricted Adolescents." International Journal of Endocrinology 2012 (2012): 1–7. http://dx.doi.org/10.1155/2012/301935.
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Levels of cortisol, a hormone produced by the adrenal gland, follow a daily, 24-hour rhythm with concentrations reaching a minimum in the evening and a peak near rising time. In addition, cortisol levels exhibit a sharp peak in concentration within the first hour after waking; this is known as the cortisol awakening response (CAR). The present study is a secondary analysis of a larger study investigating the impact of short-wavelength(λmax≈470 nm)light on CAR in adolescents who were sleep restricted. The study ran over the course of three overnight sessions, at least one week apart. The experimental sessions differed in terms of the light exposure scenarios experienced during the evening prior to sleeping in the laboratory and during the morning after waking from a 4.5-hour sleep opportunity. Eighteen adolescents aged 12–17 years were exposed to dim light or to 40 lux (0.401 W/m2) of 470-nm peaking light for 80 minutes after awakening. Saliva samples were collected every 20 minutes to assess CAR. Exposure to short-wavelength light in the morning significantly enhanced CAR compared to dim light. Morning exposure to short-wavelength light may be a simple, yet practical way to better prepare adolescents for an active day.
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Okun, Michele, Suzanne Segerstrom, Kharah Ross, Chris Dunkel Schetter, and Mary Coussons-Read. "0732 Poor Perinatal Sleep Quality Is Associated with an Elevated Cortisol Awakening Response." SLEEP 47, Supplement_1 (April 20, 2024): A313. http://dx.doi.org/10.1093/sleep/zsae067.0732.
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Abstract Introduction The perinatal period is a time of disrupted sleep. Sleep quality progressively worsens across gestation and into the postpartum. A mechanism linking poor sleep with certain adverse pregnancy outcomes is dysregulation of the HPA axis resulting in atypically elevated cortisol production. Although total cortisol output normally increases across pregnancy, the cortisol awakening response (CAR) attenuates as pregnancy progresses, with normalization in the first couple of weeks after delivery. The objective of this study was to evaluate longitudinal associations between maternal sleep quality and indices of cortisol across the perinatal period. Methods Data were collected as part of the HB3 study. PSQI and saliva were collected at four time-points (8-16 weeks, 30-36 weeks, 6 months postpartum, and 1-year postpartum). Participants (N = 230) who had sleep and cortisol data from at least 1 of 4 time-points were included in analyses. Multi-level models were run to predict cortisol parameters based on deviations in average maternal sleep quality at each wave. Values below the detectable limit were imputed and samples taken < 20 minutes or > 60 minutes were excluded. Results Multilevel (time, wave, and person) modeling indicated an average positive CAR slope (g=0.29, p=.02) that was affected by whether sleep quality was better or worse at that wave (p=.04). When PSQI scores were higher than the woman's own average, the CAR slope was steeper (+1 point in PSQI, g=0.32), and when scores were lower than average, the CAR slope was flatter (-1 point, g=0.25). CAR slope was not affected by average sleep quality across waves (p=.21). Diurnal slope was not affected by sleep quality being better or worse at that wave (p = .82) or by average sleep quality across waves (p=.61). Conclusion Women with poorer sleep quality than their average had a larger CAR than women with better sleep quality than their average. There was no association between sleep quality and the diurnal slope. These data suggest that greater variability in sleep quality significantly increases the amount of cortisol secreted upon awakening. Further examination is needed to determine if sleep quality is associated with adverse pregnancy/delivery outcomes via HPA axis dysregulation. Support (if any) NICHD R01HD073491-01
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Buonomenna, V. M., F. Marciello, V. Caivano, G. Cascino, G. D’Agostino, D. Nunziata, and P. Monteleone. "Cortisol Awakening Response and Depression in Acute Coronary Syndrome Patients." European Psychiatry 41, S1 (April 2017): S142. http://dx.doi.org/10.1016/j.eurpsy.2017.01.1979.
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IntroductionAlthough the available evidence strongly supports an association between depression and coronary heart disease (CHD), the possible biological link between these two conditions still remains to be clarified. The hypothalamus-pituitary-adrenal (HPA) axis is the main endogenous system mediating the stress response and changes in cortisol secretion have been associated with depressed mood in patients with CHD. Therefore, the study of the correlation between cortisol levels and depressed mood in acute coronary syndrome (ACS) patients could help to clarify the nature of the relationship between ACS and the risk to develop a depressive syndrome.ObjectiveWe aimed to explore the relationships between HPA axis activity and depressed mood in ACS patients.AimsThe purpose of this study was to determine whether the cortisol awakening response (CAR) is associated and/or predict depressive symptoms in patients with an ACS.MethodPatients admitted to an ACS ward were asked to fill in the Beck Depression Inventory (BDI) and to collect saliva samples in the morning to measure their CAR. All the procedures were carried out within 1 week after an ACS. Patients were asked again to fill in the BDI six months after their ACS.ResultsA lower CAR was associated with higher BDI scores after 6 months from an ACS.ConclusionsOur preliminary results suggest that hypoactivity of the HPA axis in the first week of an ACS may predict more severe depressive symptoms after 6 months from the ACS.
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Ostinelli, Giada, Melissa Pelletier, Sylvain Iceta, Andreanne Michaud, Catherine Begin, and Andre Tchernof. "The Absence of Cortisol Awakening Response Is Associated With Personality Traits in Bariatric Women." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A28. http://dx.doi.org/10.1210/jendso/bvab048.054.
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Abstract Background: There is a large body of evidence linking obesity to the HPA axis and cortisol secretion or metabolism. Early work hypothesized that obesity onset may be associated with over-activation of the HPA axis, causing an extenuation of the system. The cortisol awakening response (CAR) has been suggested to be a reliable marker of HPA axis activity and has already been examined in samples of individuals with obesity. Our objective was to compare individuals showing a morning cortisol peak (CAR responders) from those who did not (non-responders) and identify possible metabolic or psychological differences among these two groups. Our hypothesis was that the two groups differed in the level of anxiety and aspects of their personality rather than in their metabolic profile. Methods: CAR response was determined using a baseline to peak cut-off of 2.5 nM. Nine CAR non-responder women awaiting bariatric surgery (BMI: 50.8 ± 4.6 kg/m2) were compared to 9 sex- and age-matched CAR responders (BMI: 48.1 ± 5.9 kg/m2). Participants collected salivary cortisol upon awakening as well as 15, 30 minutes after and responded to psychological questionnaires that measured anxiety (State and trait anxiety inventory questionnaire) and personality traits (Temperament and character inventory). Results: Non-responders were all non-diabetic women aged 37 ± 8 years. There was no significant difference between CAR responders and non-responders in terms of BMI or waist circumference. No difference was found in metabolic variables such as glycaemia or the lipid profile. As expected, non-responders had a significantly lower CAR AUCi when compared to responders (p<0.001). However there was no difference in awakening cortisol concentration. Despite our hypothesis, no significant difference was found in general level of anxiety between the two groups. Finally, we analyzed aspects of human personality. We found that CAR responders scored significantly higher in character traits such as self-directedness (p=0.02), cooperativeness (p=0.03) and self-transcendence (p<0.01). Conclusion: The CAR differences in women with severe obesity are not associated with adiposity. Our data show that non-responders exhibit traits related to reduced self-determination and responsibility but also lower level of self-consciousness and helpfulness, which could be associated with a reduction in patient compliance and possibly less weight loss after surgery.
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Wolfram, Maren, Silja Bellingrath, and Brigitte M. Kudielka. "The cortisol awakening response (CAR) across the female menstrual cycle." Psychoneuroendocrinology 36, no. 6 (July 2011): 905–12. http://dx.doi.org/10.1016/j.psyneuen.2010.12.006.
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Markopoulou⁎, K., A. Papadopoulos, L. Poon, and A. Cleare. "The cortisol awakening response (CAR) in treatment resistant unipolar depression." Journal of Affective Disorders 122 (April 2010): S72. http://dx.doi.org/10.1016/j.jad.2010.02.104.
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Cascino, G., A. M. Monteleone, F. Marciello, V. Ruzzi, F. Pellegrino, and P. Monteleone. "Alexithymia and cortisol awakening response in people with eating disorders." European Psychiatry 64, S1 (April 2021): S114. http://dx.doi.org/10.1192/j.eurpsy.2021.326.
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IntroductionAlexithymia, that is the inability to recognize and describe one’s own emotions, is a transdiagnostic feature across eating disorders (EDs) and it has been associated to a prolonged stress exposure.ObjectivesTherefore, we evaluated whether alexithymia affects the hypothalamus-pituitary-adrenal (HPA) axis functioning in patients with anorexia nervosa (AN) or bulimia nervosa (BN).MethodsTwenty-six women with AN and 26 with BN participated in the study. Alexithymia was evaluated by the Toronto Alexithymia Scale–20 and eating-related psychopathology was measured by the Eating Disorder Inventory-2. The activity of the HPA axis was assessed by the salivary cortisol awakening response (CAR). Group differences in saliva CAR were tested by repeated measures 3-way ANOVA with diagnosis and alexithymia as between-subject factors.ResultsThe prevalence of alexithymia did not differ significantly between the two diagnostic groups (c2=1.24, p=0.26). Alexithymia was associated with more severe eating-related psychopathology in AN women but not in BN women. A significant reduction in the magnitude of CAR occurred in alexithymic patients with BN compared to non-alexithymic patients with BN (t = 3.39, p = 0.008), but not in alexithymic women with AN (t = 0.67, p = 0.54).ConclusionsThese results confirm the presence of a more severe eating-related psychopathology in alexithymic individuals with AN and show, for the first time, an association between alexithymia and a dampened basal activity of the HPA axis in BN.DisclosureNo significant relationships.
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Babilon, Sebastian, Paul Myland, Julian Klabes, Joel Simon, and Tran Quoc Khanh. "Study protocol for measuring the impact of (quasi-)monochromatic light on post-awakening cortisol secretion under controlled laboratory conditions." PLOS ONE 17, no. 5 (May 18, 2022): e0267659. http://dx.doi.org/10.1371/journal.pone.0267659.
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Cortisol secretion has a fundamental role in human circadian regulation. The cortisol awakening response (CAR) can be observed as a daily recurring sharp increase in cortisol concentration within the first hour after awakening and is influenced by environmental light conditions. The current work provides the study protocol for an ongoing research project that is intended to explore the spectral dependencies and to discuss measures of emotional state and cognitive functioning potentially related to the CAR. Based on a controlled within-subjects sleep laboratory study, the impact of a two-hour, (quasi-)monochromatic, post-awakening light exposure of different peak wavelength (applied from 6:00 to 8:00 am) on resulting CAR levels should be investigated in a systematic manner to eventually derive a corresponding spectral sensitivity model. As a secondary outcome, it should be explored whether a potentially light-enhanced cortisol secretion might also impact different measures of sleepiness, mood, and vigilance for certain wavelengths. The study protocol described in the present work discusses the various protocol steps using pilot data collected for two different wavelength settings (i.e., short-wavelength blue-light at λmax = 476 nm and long-wavelength red-light at λmax = 649 nm) experienced by a group of four healthy male adults at an average ± SD age of 25.25 ± 3.59 years.
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Coco, Marinella, Andrea Buscemi, Emanuele Pennisi, Paolo Cavallari, Giacomo Papotto, Giulio Maria Federico Papotto, Vincenzo Perciavalle, Donatella Di Corrado, and Valentina Perciavalle. "Postural Control and Stress Exposure in Young Men: Changes in Cortisol Awakening Response and Blood Lactate." International Journal of Environmental Research and Public Health 17, no. 19 (October 2, 2020): 7222. http://dx.doi.org/10.3390/ijerph17197222.
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Background: It has recently been noticed that the quantity of stress affects postural stability in young women. The study was conducted with the goal of investigating whether increased stress may damagingly effect posture control in 90 young men (71 right-handed and 19 left-handed) while maintaining an upright bipedal posture, while keeping their eyes open or closed. Perceived Stress Scale (PSS) was administered and changes in free cortisol levels were monitored (Cortisol Awakening Response, CAR) in order to evaluate the amount of stress present during awakening, while the Profile of Mood States (POMS) was used to estimate distress on the whole. Posture control was evaluated with the use of a force platform, which, while computing a confidence ellipse area of 95%, was engaged by the Center of Pressure through five stability stations and was sustained for a minimum of 52 s, with and without visual input. Another goal of the experiment was to find out whether or not cortisol increases in CAR were linked with rises of blood lactate levels. Results: CAR, PSS and POMS were found to be extensively related. Furthermore, it has been observed that increases in salivary cortisol in CAR are associated with small but significant increases in blood lactate levels. As expected, stress levels did affect postural stability. Conclusions: The results of the present study confirm that the level of stress can influence postural stability, and that this influence is principally obvious when visual information is not used in postural control.
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Hughes, MacKenzie, Christopher Hertzog, Shevaun Neupert, and Scott Moffat. "STRESSOR REACTIVITY DEPENDS ON THE CORTISOL AWAKENING RESPONSE AND REACTIVITY TO WORK OVERLOAD." Innovation in Aging 6, Supplement_1 (November 1, 2022): 681. http://dx.doi.org/10.1093/geroni/igac059.2502.
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Abstract Ecological momentary assessment (EMA) was used to understand the influence of individual differences in stress reactivity measured by the Perceived Stress Reactivity Scale (PSRS) and the cortisol awakening response (CAR) on emotional reactivity to stressors, operationalized as the within-person change in negative affect (NA) associated with stressor exposure. Five times per day for 10 days, 178 working adults ages 20-80 years old (M = 49.22, SD = 19.07) reported in EMAs their current NA and whether they had experienced a stressor since the previous survey. During the same period, participants provided seven salivary cortisol samples per day. Samples collected at awakening and 30-minutes post-awakening were used to calculate the CAR. Steeper CARs are hypothesized to have a role in preparing individuals to cope with upcoming daily demands. Before the EMA period, participants completed the PSRS, including its Work Overload Reactivity subscale. Multilevel models revealed a significant 3-way interaction between Stressor Exposure x CAR x Work Overload Reactivity predicting daily NA. Individuals with high Work Overload generally reported greater NA, regardless of stressor exposure or the magnitude of their CAR. Individuals with low Work Overload reported lower levels of NA on days they experienced more stressors than usual and had steeper CARs. Effects remained significant after controlling for neuroticism and the Perceived Stress Scale. Findings suggest the CAR’s potential role of preparing individuals for upcoming demands is moderated by work-related stress reactivity. Steeper CARs on days with more stressor exposure may provide enhanced emotional benefits for individuals low in workload reactivity.
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Monteleone, A. M., P. Monteleone, U. Volpe, F. De Riso, G. Fico, R. Giugliano, M. Nigro, and M. Maj. "Impaired cortisol awakening response in eating disorder women with childhood trauma exposure: evidence for a dose-dependent effect of the traumatic load." Psychological Medicine 48, no. 6 (August 29, 2017): 952–60. http://dx.doi.org/10.1017/s0033291717002409.
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BackgroundChildhood trauma is a non specific risk factor for adult eating disorders (ED), and the hypothalamic-pituitary-adrenal (HPA) axis seems to mediate such a risk. Here we explored the impact of different types of childhood trauma and of traumatic load on the cortisol awakening response (CAR) of women with anorexia nervosa (AN) or bulimia nervosa (BN).MethodsSaliva samples were collected at awakening and after 15, 30, 60 min to measure cortisol levels by 121 women (44 AN patients, 36 BN patients and 41 healthy women). Participants filled in the Childhood Trauma Questionnaire.ResultsAN and BN patients with childhood maltreatment exhibited an attenuated CAR compared with non-maltreated ones. In the whole ED patient group, the CAR showed a progressive impairment with the increasing number of reported trauma types. Although significant negative correlations emerged between the type or the number of traumas and the CAR, only the number of traumas remained significantly associated with the CAR in a stepwise multiple regression analysis.ConclusionsPresent findings confirm that childhood trauma is associated with an impaired CAR in adult AN and BN patients and demonstrate for the first time a negative dose-dependent effect of the traumatic load on HPA axis activity.
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Garre-Morata, Laura, Tomás de Haro, Raquel González Villén, María Luisa Fernández-López, Germaine Escames, Antonio Molina-Carballo, and Darío Acuña-Castroviejo. "Changes in Cortisol and in Oxidative/Nitrosative Stress Indicators after ADHD Treatment." Antioxidants 13, no. 1 (January 12, 2024): 92. http://dx.doi.org/10.3390/antiox13010092.
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Although ADHD is one of the most prevalent diseases during childhood, we still do not know its precise origin; oxidative/nitrosative stress and the hypothalamic–pituitary–adrenal axis are suggested contributors. Methylphenidate, among others, is the main drug used in ADHD patients, but its effects on relevant markers and structures remain unclear. This study, involving 59 patients diagnosed with ADHD according to DSM-5 criteria, aimed to assess changes in cortisol levels (using cortisol awakening response, CAR) and oxidative/nitrosative status with the treatment. Blood samples before and 3 months after treatment with methylphenidate were used to measure oxidative and inflammatory markers, as well as the endogenous antioxidant activity, while saliva samples tracked cortisol awakening response (CAR). The results showed a treatment-related improvement in the redox profile, with the reduction in advanced oxidation protein products (AOPP), lipid peroxidation (LPO), and nitrite plus nitrate (NOx) levels, and the increase in the enzymatic activities of glutathione reductase (GRd) and catalase (CAT). Moreover, the area under the curve (AUC) of CAR increased significantly, indicating increased reactivity of the HPA axis. These results support, for the first time, the involvement of the endogenous antioxidant system in the pathophysiology of ADHD.
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Rausch, Juliane, Elisa Flach, Angelika Panizza, Romuald Brunner, Sabine C. Herpertz, Michael Kaess, and Katja Bertsch. "Associations between age and cortisol awakening response in patients with borderline personality disorder." Journal of Neural Transmission 128, no. 9 (August 14, 2021): 1425–32. http://dx.doi.org/10.1007/s00702-021-02402-3.
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AbstractPatients with borderline personality disorder (BPD) often display increased stress vulnerability, which may be linked to altered hypothalamus–pituitary–adrenal (HPA) axis functioning. Corresponding deviations of the cortisol awakening response (CAR) are presumed to mirror maladaptive neuroendocrine processes, which may explain why CARs are increased compared to healthy controls (HC). Prior research speculated that these alterations may be caused by early life stress and/or chronic stress related to the ongoing burden of the disorder. Yet, it remains to be investigated how BPD influences CAR in the course of development. Therefore, the current study examined CAR in female adolescents and adults with BPD compared to HC with a particular focus on associations with age. These potential associations were especially focused, as it was hypothesized that the CAR would be even more elevated (i.e., higher) in older individuals with BPD. CAR was assessed in 54 female individuals with BPD (aged 15–40 years) and 54 sex-, age-, and intelligence-matched HC (aged 15–48 years). Group differences were investigated and analyses of covariance using age as continuous predictor were performed to analyze potential developmental associations with CAR alongside BPD-specific effects. Pearson’s correlations were calculated to examine associations between CAR and age. Analyses were repeated with potential confounders as control factors. Results not only demonstrated increased CARs in female individuals with BPD compared to HC but demonstrated elevated CARs with increasing age in BPD individuals exclusively. Effects remained stable after controlling for potential confounders. Thereby, findings suggest that endocrine alterations in BPD may reinforce with increasing age and BPD chronicity.
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Yuksel, Dilara, Boshra Khajehpiri, Mohamad Forouzanfar, Orsolya Kiss, Devin Prouty, Nicole Arra, Laila Volpe, Fiona C. Baker, and Massimiliano de Zambotti. "0157 Physiological responses to acute psychosocial stress in adolescents with insomnia." SLEEP 46, Supplement_1 (May 1, 2023): A70. http://dx.doi.org/10.1093/sleep/zsad077.0157.
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Abstract Introduction Insomnia often develops during adolescence, with girls being at greater risk than boys. Alterations in response to psychosocial stress have been linked to the etiology of the disorder, but it remains unclear whether the reactivity of the major stress systems (hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS)) in response to stress is altered in adolescents with insomnia. Methods Forty-seven post-pubertal adolescents (age range: 16-20 years, 28 female) with (N=16; insomnia group) and without (N=31; control group) insomnia symptomatology underwent two randomized nights of polysomnographic (PSG) laboratory recordings. Participants underwent an experimental pre-bedtime stress anticipation protocol (stress night) and a control night during which they engaged in neutral activities before bedtime. The morning after the stress night, participants underwent the Trier Social Stress Test (TSST), a standardized protocol that requires participants to complete verbal and arithmetic tasks in front of observers. On both nights, heart rate (HR) was measured across the night and cortisol was collected upon awakening and 30 minutes later to calculate cortisol awakening responses (CAR). Stress perception, salivary cortisol (HPA activity), and HR were measured during the TSST. Results There were no differences in nocturnal HR recovery or in the CAR on the stress night compared with the control night in either group. Morning pre-TSST stress levels did not differ between groups. Both groups exhibited significant increases in HR in response to the TSST (p< 0.05). HR was higher in girls compared to boys in the control group at baseline (p< 0.05). Potential group differences in HPA responses to the TSST were inconclusive due to the apparent confounding effect of the CAR on cortisol responses to stress: many participants did not show a cortisol response to the task and larger CARs were associated with an attenuated cortisol response. Conclusion There were no significant differences in HR responses to anticipation of experimental stress during the night or in response to the morning TSST between adolescents with and without insomnia. Further work is needed to examine whether altered responses to stress may emerge if insomnia becomes chronic. Support (if any) This study was supported by the National Heart, Lung and Blood Institute (NHLBI) grant R01HL139652(MdZ).
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Romney, Chelsea E., Amber Carmen Arroyo, Theodore F. Robles, and Matthew J. Zawadzki. "Hugs and Cortisol Awakening Response the Next Day: An Ecological Momentary Assessment Study." International Journal of Environmental Research and Public Health 20, no. 7 (March 30, 2023): 5340. http://dx.doi.org/10.3390/ijerph20075340.
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Previous research suggests that affectionate touch such as hugs might downregulate stress systems such as the hypothalamic pituitary adrenal (HPA) axis. However, the current literature lacks in generalizability beyond the laboratory setting and outside the context of romantic relationships. The cortisol awakening response (CAR) is a measure of the HPA axis and is responsive to daily fluctuations in stress and social information. However, associations between affectionate touch and the CAR have never been assessed. This study used ecological momentary assessment (EMA) to measure daily hugging behaviors in 104 first-year college students and salivary cortisol to assess the CAR. Participants who reported more daily hugs in their social interactions had significantly smaller CARs the next morning compared to days they reported fewer hugs. This study contributes to the literature on social interactions and stress responsive systems and emphasizes the importance of assessing affectionate touch behaviors such as hugs that can be exchanged outside the context of romantic relationships.
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Pruessner, M., L. Bechard-Evans, S. Pira, R. Joober, D. L. Collins, J. C. Pruessner, and A. K. Malla. "Interplay of hippocampal volume and hypothalamus-pituitary-adrenal axis function as markers of stress vulnerability in men at ultra-high risk for psychosis." Psychological Medicine 47, no. 3 (October 24, 2016): 471–83. http://dx.doi.org/10.1017/s0033291716002658.
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BackgroundAltered hypothalamus-pituitary-adrenal (HPA) axis function and reduced hippocampal volume (HV) are established correlates of stress vulnerability. We have previously shown an attenuated cortisol awakening response (CAR) and associations with HV specifically in male first-episode psychosis patients. Findings in individuals at ultra-high risk (UHR) for psychosis regarding these neurobiological markers are inconsistent, and assessment of their interplay, accounting for sex differences, could explain incongruent results.MethodStudy participants were 42 antipsychotic-naive UHR subjects (24 men) and 46 healthy community controls (23 men). Saliva samples for the assessment of CAR were collected at 0, 30 and 60 min after awakening. HV was determined from high-resolution structural magnetic resonance imaging scans using a semi-automatic segmentation protocol.ResultsCortisol measures and HV were not significantly different between UHR subjects and controls in total, but repeated-measures multivariate regression analyses revealed reduced cortisol levels 60 min after awakening and smaller left HV in male UHR individuals. In UHR participants only, smaller left and right HV was significantly correlated with a smaller total CAR (ρ = 0.42, p = 0.036 and ρ = 0.44, p = 0.029, respectively), corresponding to 18% and 19% of shared variance (medium effect size).ConclusionsOur findings suggest that HV reduction in individuals at UHR for psychosis is specific to men and linked to reduced post-awakening cortisol concentrations. Abnormalities in the neuroendocrine circuitry modulating stress vulnerability specifically in male UHR subjects might explain increased psychosis risk and disadvantageous illness outcomes in men compared to women.
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Petrovsky, Darina, Fanghong Dong, Liming Huang, Subhash Aryal, G. Adriana Perez, and Nancy Hodgson. "Salivary Cortisol Patterns in People Living With Dementia." Innovation in Aging 5, Supplement_1 (December 1, 2021): 435. http://dx.doi.org/10.1093/geroni/igab046.1692.
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Abstract Salivary cortisol has a well-documented circadian pattern in older adults. Yet, the pattern of salivary cortisol in persons living with dementia (PLWD) due to circadian rhythm disturbances is unknown. This study examined diurnal salivary cortisol patterns in 176 PLWD (mean age 73.6±8.8, 33.3% male, clinical dementia rating >=0.5) by collecting saliva at waking (AM1), 30 minutes after waking (AM2) and bedtime (PM) over two consecutive days. Cortisol awakening response (CAR) was calculated as the change between AM2 and AM1 cortisol levels. The mean baseline salivary cortisol levels (ug/dl) were 0.35 (SD:0.3) at AM1, 0.40 (SD:0.39) at AM2, and 0.19 (SD:0.4) at PM. On average, cortisol levels decreased from morning to evening, with 58% exhibiting a positive CAR (mean 0.05; SD:0.34). There were no significant associations between cortisol levels with age, sex, obesity, and comorbidities. The findings demonstrated that diurnal cortisol rhythms are maintained in PLWD with a flattened CAR.
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Attianese, N., M. Battipaglia, S. Donato, R. Ceres, R. Cerra, G. Cascino, P. Monteleone, and A. M. Monteleone. "Perceived parental bonding and cortisol awakening response in people with eating disorders." European Psychiatry 67, S1 (April 2024): S65. http://dx.doi.org/10.1192/j.eurpsy.2024.181.
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IntroductionEarly life experiences may have an impact on hypothalamic–pituitary–adrenal (HPA) axis functioning in eating disorders (EDs). Parental bonding is defined as the parental contribution of care and control to parent–child relationships. We evaluated whether perceived care and protection of parental bonding in childhood and adolescence were associated with HPA axis functioning in adult patients with EDs. The activity of the HPA axis was assessed by measuring the salivary cortisol awakening response (CAR).ObjectivesWe evaluated whether parental care and control in childhood and adolescence were associated with HPA axis functioning in adults with EDs. On the basis of literature data on healthy participants, we hypothesized that people with high levels of parental care would show a reduced CAR compared to people with low levels of parental care.MethodsWe admitted patients according to the following inclusion criteria: (a) female sex, (b) age > 18 years, (c) current diagnosis of AN or BN according to DSM-5 criteria, (d) absence of severe physical disorders, (e) no history of endocrine disorders, psychoactive substance use, schizophrenia or other psychoses, bipolar disorders or head trauma. Participants completed the Italian version of the Parental Bonding Instrument (PBI). To measure the CAR, participants were instructed to collect saliva samples at awakening and 15, 30, and 60 min after awakening.Results64 women with EDs participated in the study: 37 with AN and 27 with BN. 28 participants reported low levels of both maternal and paternal care while 12 participants reported high levels of care from both parents; 31 participants reported high levels of both maternal and paternal control, while 12 participants reported low levels of control from both parents. When maternal care was entered as between factor in the analysis, the repeated measures 3-way ANOVA showed a significant time effect (F3, 180 = 2.81, p < 0.05) and a significant maternal care X time interaction (F3, 180 = 2.99, p < 0.05), while, when paternal care was entered as between factor, the repeated measures 3-way ANOVA did not show significant effects for time and no significant paternal care X time interaction.ConclusionsOur results show an association of perceived maternal care with the time pattern of CAR in female patients with ED, while perceived parental control was not associated with any CAR feature in EDs. Maternal control, paternal care and paternal control were not associated with any difference in the CAR.Disclosure of InterestNone Declared
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Vrshek-Schallhorn, S., L. D. Doane, S. Mineka, R. E. Zinbarg, M. G. Craske, and E. K. Adam. "The cortisol awakening response predicts major depression: predictive stability over a 4-year follow-up and effect of depression history." Psychological Medicine 43, no. 3 (June 1, 2012): 483–93. http://dx.doi.org/10.1017/s0033291712001213.
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BackgroundThe cortisol awakening response (CAR) has been shown to predict major depressive episodes (MDEs) over a 1-year period. It is unknown whether this effect: (a) is stable over longer periods of time; (b) is independent of prospective stressful life events; and (c) differentially predicts first onsets or recurrences of MDEs.MethodA total of 270 older adolescents (mean age 17.06 years at cortisol measurement) from the larger prospective Northwestern-UCLA Youth Emotion Project completed baseline diagnostic and life stress interviews, questionnaires, and a 3-day cortisol sampling protocol measuring the CAR and diurnal rhythm, as well as up to four annual follow-up interviews of diagnoses and life stress.ResultsNon-proportional person-month survival analyses revealed that higher levels of the baseline CAR significantly predict MDEs for 2.5 years following cortisol measurement. However, the strength of prediction of depressive episodes significantly decays over time, with the CAR no longer significantly predicting MDEs after 2.5 years. Elevations in the CAR did not significantly increase vulnerability to prospective major stressful life events. They did, however, predict MDE recurrences more strongly than first onsets.ConclusionsThese results suggest that a high CAR represents a time-limited risk factor for onsets of MDEs, which increases risk for depression independently of future major stressful life events. Possible explanations for the stronger effect of the CAR for predicting MDE recurrences than first onsets are discussed.
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Moya-Albiol, Luis, Miguel Ángel Serrano, and Alicia Salvador. "Job Satisfaction and Cortisol Awakening Response in Teachers Scoring high and low on Burnout." Spanish journal of psychology 13, no. 2 (November 2010): 629–36. http://dx.doi.org/10.1017/s1138741600002304.
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The burnout syndrome is an important psychosocial risk in the job context, especially in professions with a strong social interaction, as in the case of teaching. High levels of burnout have been related to negative psychological indicators and hormonal alterations. This study compares job satisfaction and the cortisol awakening response (CAR) in teachers scoring high (HB) and low (LB) on burnout. HB teachers showed lower job satisfaction and no significant differences in the CAR when compared with the LB group. The results of the study suggest a general dissatisfaction with work along with a different functioning of the hypothalamo-pituitary-adrenocortical axis in HB teachers. Although non significantly, they showed a lower magnitude of the CAR than LB teachers. When considering the whole sample, emotional exhaustion and depersonalization correlated negatively and personal accomplishment positively with each subscale of the job satisfaction questionnaire whereas cortisol levels or CAR did not correlate significantly with both burnout subscales and job satisfaction. These results should be taken into account when working to prevent burnout in teachers, as the modified parameters could be considered indicators of the onset or development of the syndrome.
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Pellegrino, F., A. M. Monteleone, M. Nigro, V. Ruzzi, M. Cimino, U. Volpe, and P. Monteleone. "Investigation of Salivary Cortisol Response to Awakening in Underweight and Weight-Restored Patients with Anorexia Nervosa." European Psychiatry 41, S1 (April 2017): S283. http://dx.doi.org/10.1016/j.eurpsy.2017.02.133.
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IntroductionAnorexia nervosa (AN) is characterized by dysregulated eating that leads to chronic malnutrition, which may be responsible for several physical complications, including endocrine alterations, such as hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis.ObjectivesSeveral studies have shown a dysregulation of the cortisol awakening response (CAR) in symptomatic AN patients. However, it has not been established if the deranged CAR of underweight AN patients is a primary phenomenon or an alteration secondary to malnutrition.AimsThe aim of this study was to explore the salivary CAR in both underweight and weight-restored patients with AN.MethodsWe recruited 59 women: 18 undernourished AN patients, 15 weight-restored AN women and 26 normal-weight healthy controls. Saliva samples were collected in the morning, immediately after awakening and after 15, 30 and 60 minutes, in order to measure saliva levels of cortisol. Participants filled in the state-trait anxiety inventory (STAI) to test their anxiety levels in the morning of the test.ResultsCompared to healthy controls, underweight AN patients showed an enhanced CAR whereas the weight recovered patients had a normal CAR. These results were not correlated with levels of anxiety.ConclusionsFor the first time, our results demonstrate that the deranged CAR found in acute AN patients is not present in weight-restored ones, suggesting that altered activity of the HPA axis of symptomatic AN patients is a state-dependent phenomenon.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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Bogudzińska, Bogna, Julian Maciaszek, Bartłomiej Stańczykiewicz, Tomasz Bielawski, Agnieszka Dybek, Julia Alejnikowa, Tomasz Pawłowski, and Błażej Misiak. "Blunted Cortisol Awakening Response Is Associated with External Attribution Bias Among Individuals with Personality Disorders." Brain Sciences 14, no. 10 (October 20, 2024): 1040. http://dx.doi.org/10.3390/brainsci14101040.
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Background/Objectives: The dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis has been associated with various mental disorders. One of the most commonly described parameters of HPA axis functioning is the cortisol awakening response (CAR). To date, few studies have been conducted on the relationship between personality disorders and CAR. The present study aimed to compare the CAR between individuals with personality disorders and healthy controls. Moreover, the study aimed to assess the association of CAR with cognitive biases and psychopathological symptoms in people with personality disorders. Methods: A total of 43 individuals with personality disorders and 45 healthy controls were enrolled. Participants completed questionnaires measuring the severity of depressive symptoms, anxiety, cognitive biases, and psychotic-like experiences. Cortisol levels were measured in four morning saliva samples: immediately after awakening, and after 15, 30, and 45 min. Results: A significantly lower CAR was found among individuals with personality disorders, even after adjustment for age, sex, and the level of education. However, the receiver operating characteristic (ROC) curve analysis showed a relatively low area under the curve (AUC = 0.362). Furthermore, a significant negative correlation was observed between the CAR and the level of external attribution bias among individuals with personality disorders. No significant associations of the CAR with psychopathological symptoms and other cognitive biases were observed. Conclusions: Findings from this study indicate that the HPA axis activity might be altered in personality disorders. However, the clinical utility of this observation needs further studies in larger samples. External attribution might be related to the HPA axis alterations in this population.
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Monaco, F., A. M. Monteleone, F. Pellegrino, F. De Riso, G. Patriciello, M. Cimino, M. Calvanese, U. Volpe, and P. Monteleone. "Childhood trauma and cortisol awakening response in eating disorders: A dose-dependent trauma effect." European Psychiatry 33, S1 (March 2016): S165. http://dx.doi.org/10.1016/j.eurpsy.2016.01.329.
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IntroductionA role for the hypothalamus-pituitary-adrenal (HPA) axis has been suggested in the pathophysiology of anorexia nervosa (AN) and bulimia nervosa (BN), and childhood trauma experiences have been detected frequently in patients with AN and BN. Since trauma exposure in the childhood may persistently affect HPA axis functioning, we explored HPA axis activity in AN and BN patients with and without childhood trauma history.Objectives and aimsWe aimed to examine possible associations between childhood traumatic experiences and HPA axis functioning, as assessed by the cortisol awakening response (CAR), in adult patients with AN or BN as compared to adult healthy controls.MethodsSaliva samples were collected by 41 patients with symptomatic AN, 32 with symptomatic BN and 45 healthy controls at wakening and after 15, 30 and 60 min. They filled in the Childhood Trauma Questionnaire (CTQ), which assesses five specific types of childhood trauma.ResultsAs compared to the control group, the no-maltreated AN patient group exhibited an enhanced CAR whereas the no-maltreated BN patient group showed a similar CAR. On the contrary, both AN and BN patients with a positive history of childhood maltreatment exhibited statistically significant blunted CAR as compared to no-maltreated patients. Moreover, in maltreated ED patients the CAR tended to decrease when the number of trauma types increased.DiscussionPresent findings confirm a dysregulation of the HPA axis activity in symptomatic patients with AN and BN and suggest a dose-dependent effect of childhood adverse experiences on the CAR of adult ED patients.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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Nederhof, E., F. V. A. van Oort, E. M. C. Bouma, O. M. Laceulle, A. J. Oldehinkel, and J. Ormel. "Predicting mental disorders from hypothalamic-pituitary-adrenal axis functioning: a 3-year follow-up in the TRAILS study." Psychological Medicine 45, no. 11 (March 19, 2015): 2403–12. http://dx.doi.org/10.1017/s0033291715000392.
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BackgroundHypothalamic-pituitary-adrenal axis functioning, with cortisol as its major output hormone, has been presumed to play a key role in the development of psychopathology. Predicting affective disorders from diurnal cortisol levels has been inconclusive, whereas the predictive value of stress-induced cortisol concentrations has not been studied before. The aim of this study was to predict mental disorders over a 3-year follow-up from awakening and stress-induced cortisol concentrations.MethodData were used from 561 TRAILS (TRacking Adolescents’ Individual Lives Survey) participants, a prospective cohort study of Dutch adolescents. Saliva samples were collected at awakening and half an hour later and during a social stress test at age 16. Mental disorders were assessed 3 years later with the Composite International Diagnostic Interview (CIDI).ResultsA lower cortisol awakening response (CAR) marginally significantly predicted new disorders [odds ratio (OR) 0.77, p = 0.06]. A flat recovery slope predicted disorders with a first onset after the experimental session (OR 1.27, p = 0.04). Recovery revealed smaller, non-significant ORs when predicting new onset affective or anxiety disorders, major depressive disorder, or dependence disorders in three separate models, corrected for all other new onsets.ConclusionsOur results suggest that delayed recovery and possibly reduced CAR are indicators of a more general risk status and may be part of a common pathway to psychopathology. Delayed recovery suggests that individuals at risk for mental disorders perceived the social stress test as less controllable and less predictable.
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Conradi, Juliane, Jonas E. Svensson, Søren V. Larsen, and Vibe G. Frokjaer. "Is serotonin transporter brain binding associated with the cortisol awakening response? An independent non-replication." PLOS ONE 18, no. 8 (August 31, 2023): e0290663. http://dx.doi.org/10.1371/journal.pone.0290663.
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Background Serotonergic brain signaling is considered critical for an appropriate and dynamic adaptation to stress, seemingly through modulating limbic system functions, such as the hypothalamic-pituitary-adrenal (HPA)-axis. This interplay is of great interest since it holds promise as a target for preventing stress-related brain disorders, e.g., major depression. Our group has previously observed that prefrontal serotonin transporter (5-HTT) binding, imaged with positron emission tomography (PET), is positively associated with the cortisol awakening response (CAR), an index of HPA axis stress hormone dynamics. The aim of this cross-sectional study was to replicate the previous finding in a larger independent group of healthy individuals. Methods Molecular imaging and cortisol data were available for 90 healthy individuals. Prefrontal 5-HTT binding was imaged with [11C]DASB brain PET. Non-displaceable 5-HTT binding potential (BPND) was quantified using the Multilinear Reference Tissue Model 2 (MRTM2) with cerebellum as the reference region. CAR was based on five serial salivary cortisol samples within the first hour upon awakening. The association between CAR and prefrontal 5-HTT BPND was evaluated using a multiple linear regression model adjusted for age and sex. Further, we tested for sex differences in the association. Finally, an exploratory analysis of the association, was performed in 8 additional brain regions. Results We observed no statistically significant association between 5-HTT binding and CAR corrected for age and sex in the prefrontal cortex (β = -0.28, p = 0.26). We saw no interaction with sex on the association (p = 0.99). Conclusion We could not confirm a positive association between CAR and prefrontal 5-HTT BPND in this independent dataset. Also, sex differences in the association were not apparent. Our data do not exclude that the serotonin transporter system is involved in the regulation of stress responses in at-risk or manifest depressed states.
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Corbett, Blythe A., and Clayton W. Schupp. "The cortisol awakening response (CAR) in male children with autism spectrum disorder." Hormones and Behavior 65, no. 4 (April 2014): 345–50. http://dx.doi.org/10.1016/j.yhbeh.2014.01.012.
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Zinke, Katharina, Eva Fries, Matthias Kliegel, Clemens Kirschbaum, and Lucia Dettenborn. "Children with high-functioning autism show a normal cortisol awakening response (CAR)." Psychoneuroendocrinology 35, no. 10 (November 2010): 1578–82. http://dx.doi.org/10.1016/j.psyneuen.2010.03.009.
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Quevedo, Karina, Anna E. Johnson, Michelle L. Loman, Theresa L. LaFavor, and Megan Gunnar. "The confluence of adverse early experience and puberty on the cortisol awakening response." International Journal of Behavioral Development 36, no. 1 (June 17, 2011): 19–28. http://dx.doi.org/10.1177/0165025411406860.
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Associations between early deprivation/neglect in the form of institutional care with the cortisol awakening response (CAR) were examined as a function of pubertal status among 12- and 13-year-old postinstitutionalized youth. CARs indexed hypothalamic-pituitary-adrenocortical reactivity. Postinstitutionalized youth were compared to youth adopted internationally from foster care (adoption control) and to nonadopted youth reared in families comparable in parental education and income to the adoptive families. Postinstitutionalized youth exhibited a blunted CAR if they were at earlier, but not if they were at later, stages of puberty. Similarly, for both groups of internationally adopted youth combined, earlier but not later stages of puberty were associated with more blunted CARs at higher but not lower levels of parent-reported preadoption physical and social neglect.