ObjectiveRecently, salivary alpha-amylase (sAA) has been proposed as a suitable index for sympathetic activity and dysregulation of the autonomic nervous system (ANS). Although determinants of sAA... Show moreObjectiveRecently, salivary alpha-amylase (sAA) has been proposed as a suitable index for sympathetic activity and dysregulation of the autonomic nervous system (ANS). Although determinants of sAA have been described, they have not been studied within the same study with a large sample size without potential disturbances of psychopathology. In this paper, we report about correlates of evening sAA in saliva. MethodsIn 487 participants (mean age=42.9years, 59.8% female) without lifetime psychiatric disorders from the Netherlands Study of Depression and Anxiety (NESDA), sociodemographic, health and sampling determinants of sAA levels were examined using multivariable linear regression analysis. sAA was measured in two saliva samples that participants collected in the late evening, at 22:00h and 23:00h, after which these were averaged. ResultsIn multivariate analysis, age (β=0.20, p<0.001) and daily alcohol intake (β=−0.13, p=0.01) were independent determinants of evening sAA levels. Gender, allergy or lung disease, and the use of oral contraceptives were univariate correlates, but no longer associated with sAA in the multivariate model. ConclusionsAge and alcohol use were identified as potential confounding factors that should be taken into account in epidemiologic studies that examine the ANS function using sAA. Show less
OBJECTIVE: Recently, salivary alpha-amylase (sAA) has been proposed as a suitable index for sympathetic activity and dysregulation of the autonomic nervous system (ANS). Although determinants of... Show moreOBJECTIVE: Recently, salivary alpha-amylase (sAA) has been proposed as a suitable index for sympathetic activity and dysregulation of the autonomic nervous system (ANS). Although determinants of sAA have been described, they have not been studied within the same study with a large sample size without potential disturbances of psychopathology. In this paper, we report about correlates of evening sAA in saliva. METHODS: In 487 participants (mean age=42.9years, 59.8% female) without lifetime psychiatric disorders from the Netherlands Study of Depression and Anxiety (NESDA), sociodemographic, health and sampling determinants of sAA levels were examined using multivariable linear regression analysis. sAA was measured in two saliva samples that participants collected in the late evening, at 22:00h and 23:00h, after which these were averaged. RESULTS: In multivariate analysis, age (β=0.20, p<0.001) and daily alcohol intake (β=-0.13, p=0.01) were independent determinants of evening sAA levels. Gender, allergy or lung disease, and the use of oral contraceptives were univariate correlates, but no longer associated with sAA in the multivariate model. CONCLUSIONS: Age and alcohol use were identified as potential confounding factors that should be taken into account in epidemiologic studies that examine the ANS function using sAA. Show less
Background It is unclear whether altered hypothalamic-pituitary-adrenal (HPA) axis regulation, which frequently accompanies depression and anxiety disorders, represents a trait rather than a state... Show moreBackground It is unclear whether altered hypothalamic-pituitary-adrenal (HPA) axis regulation, which frequently accompanies depression and anxiety disorders, represents a trait rather than a state factor. Aims To examine whether HPA axis dysregulation represents a biological vulnerability for these disorders, we compared cortisol levels in unaffected people with and without a parental history of depressive or anxiety disorders. We additionally examined whether possible HPA axis dysregulations resemble those observed in participants with depression or anxiety disorders. Method Data were from the Netherlands Study of Depression and Anxiety. Within the participants without a lifetime diagnoses of depression or anxiety disorders, three groups were distinguished: 180 people without parental history, 114 with self-reported parental history and 74 with CIDI-diagnosed parental history. These groups were additionally compared with people with major depressive disorder or panic disorder with agoraphobia (n = 1262). Salivary cortisol samples were obtained upon awakening, and 30, 45 and 60 min later. Results As compared with unaffected participants without parental history, unaffected individuals with diagnosed parental history of depression or anxiety showed a significantly higher cortisol awakening curve (effect size (d) = 0.50), which was similar to that observed in the participants with depression or anxiety disorders. Unaffected people with self-reported parental history did not differ in awakening cortisol levels from unaffected people without parental history. Conclusions Unaffected individuals with parental history of depression or anxiety showed a higher cortisol awakening curve, similar to that of the participants with depression or anxiety disorders. This suggests that a higher cortisol awakening curve reflects a trait marker, indicating an underlying biological vulnerability for the development of depressive and anxiety disorders. Show less
Context: Stress is suggested to lead to metabolic dysregulations as clustered in the metabolic syndrome, but the underlying biological mechanisms are not yet well understood. Objective: We examined... Show moreContext: Stress is suggested to lead to metabolic dysregulations as clustered in the metabolic syndrome, but the underlying biological mechanisms are not yet well understood. Objective: We examined the relationship between two main str systems, the autonomic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis, with the metabolic syndrome and its components. Design: Thedesignwasbaseline data (yr 2004-2007) of a prospective cohort: the Netherlands Study of Depression and Anxiety (NESDA). Setting: The study comprised general community, primary care, andspecialized mental health care. Participants: This study included 1883 participants aged 18-65 yr. Main Outcome Measures: Autonomic nervous system measures included heart rate, respiratory sinus arrhythmia (RSA; high RSA reflecting high parasympathetic activity), and preejection period (PEP; high PEP reflecting low sympathetic activity). HPA axis measures included the cortisol awakening response, evening cortisol, and a 0.5 mg dexamethasone suppression test as measured in saliva. Metabolic syndrome was based on the updated Adult Treatment Panel III criteria and included high waist circumference, serum triglycerides, blood pressure, serum glucose, and low high-density lipoprotein cholesterol. Results: RSA and PEP were both independently negatively associated with the presence of the metabolic syndrome, the number of metabolic dysregulations as well as all individual components except high-density lipoprotein cholesterol (all P < 0.02). Heart rate was positively related to the metabolic syndrome, the number of metabolic dysregulations, and all individual components (all P < 0.001). HPA axis measures were not related to metabolic syndrome or its components. Conclusion: Our findings suggest that increased sympathetic and decreased parasympathetic nervous system activity is associated with metabolic syndrome, whereas HPA axis activity is not. (J Clin Endocrinol Metab 95: 2458-2466, 2010) Show less
Vreeburg, S.A.; Zitman, F.G.; Pelt, J. van; DeRijk, R.H.; Verhagen, J.C.M.; Dyck, R. van; ... ; Penninx, B.W.J.H. 2010
Objective: To examine the association between several subtypes of anxiety disorders and various cortisol indicators in a large cohort study. Anxiety disorders have been suggested to be linked to... Show moreObjective: To examine the association between several subtypes of anxiety disorders and various cortisol indicators in a large cohort study. Anxiety disorders have been suggested to be linked to hypothalamic-pituitary-adrenal (HPA) axis activity, although results are scarce and inconsistent. No earlier studies have examined consistency of HPA axis findings across several anxiety subtypes and whether associations are state or trait dependent. Methods: Data are derived from 1427 participants of the Netherlands Study of Depression and Anxiety. Three groups were compared: 342 control participants without psychiatric disorders; 311 persons with a remitted (no current) anxiety disorder (social phobia, generalized anxiety disorder, panic disorder); and 774 persons with a current anxiety disorder, as diagnosed using the Composite International Diagnostic Interview psychiatric interview. Cortisol levels were measured in seven saliva samples, determining the 1-hour cortisol awakening response, evening cortisol, and cortisol response after 0.5 mg of dexamethasone ingestion. Results: Current anxiety disorder was associated with higher awakening cortisol levels (p = .002). These findings were mainly present for patients with panic disorder with agoraphobia and anxious patients with comorbid depressive disorder. Remitted anxiety only showed a trend toward higher morning cortisol (p = .08). No associations were observed for anxiety status and evening cortisol level or cortisol suppression after dexamethasone. Conclusions: This study showed a modest but significantly higher 1-hour cortisol awakening response among anxiety patients, which was driven by those with panic disorder with agoraphobia and those with comorbid depression. Show less
BACKGROUND As benzodiazepines (BZDs) have anxiolytic effects, it is expected that they influence the stress system. During short-term treatment, BZD use was found to suppress cortisol levels.... Show moreBACKGROUND As benzodiazepines (BZDs) have anxiolytic effects, it is expected that they influence the stress system. During short-term treatment, BZD use was found to suppress cortisol levels. However, little research has been done on the effects of long-term BZD administration on the hypothalamic-pituitary-adrenal (HPA) axis. METHODS The association between long-term BZD use and cortisol levels was investigated in subjects of the Netherlands Study of Depression and Anxiety with a lifetime diagnosis of anxiety or depression (n = 1531). The subjects were categorized as "daily BZD users" (n = 96), "infrequent BZD users" (n = 172), and "nonusers" (n = 1263). Possible associations between characteristics of BZD use (dose, duration, and dependence) and salivary cortisol levels were analyzed. MAIN OUTCOME MEASURE Subjects provided 7 saliva samples, from which 4 cortisol indicators were calculated: the cortisol awakening response, diurnal slope, evening cortisol, and cortisol suppression after ingestion of 0.5 mg of dexamethasone. RESULTS Daily users used BZDs for a median duration of 26.5 months and had a median daily dosage of 6.0 mg as measured in diazepam equivalents. Evening cortisol levels were significantly lower in daily users (P = 0.004; effect size: d = 0.24) and infrequent users (P = 0.04; effect size: d = 0.12) compared to nonusers. We did not find significant differences in the cortisol awakening response, diurnal slope, or in the dexamethasone suppression test. CONCLUSIONS Despite the finding of slightly lower evening cortisol levels in daily and infrequent BZD users compared to nonusers, results indicate that long-term BZD use is not convincingly associated with HPA axis alterations. Show less
Background: As benzodiazepines (BZDs) have anxiolytic effects, it is expected that they influence the stress system. During short-term treatment, BZD use was found to suppress cortisol levels.... Show moreBackground: As benzodiazepines (BZDs) have anxiolytic effects, it is expected that they influence the stress system. During short-term treatment, BZD use was found to suppress cortisol levels. However, little research has been done on the effects of long-term BZD administration on the hypothalamic-pituitary-adrenal (HPA) axis. Methods: The association between long-term BZD use and cortisol levels was investigated in subjects of the Netherlands Study of Depression and Anxiety with a lifetime diagnosis of anxiety or depression (n = 1531). The subjects were categorized as "daily BZD users[(n = 96), "infrequent BZD users[(n = 172), and "nonusers[(n = 1263). Possible associations between characteristics of BZD use (dose, duration, and dependence) and salivary cortisol levels were analyzed. Main Outcome Measure: Subjects provided 7 saliva samples, from which 4 cortisol indicators were calculated: the cortisol awakening response, diurnal slope, evening cortisol, and cortisol suppression after ingestion of 0.5 mg of dexamethasone. Results: Daily users used BZDs for a median duration of 26.5 months and had a median daily dosage of 6.0 mg as measured in diazepam equivalents. Evening cortisol levels were significantly lower in daily users (P = 0.004; effect size: d = 0.24) and infrequent users (P = 0.04; effect size: d = 0.12) compared to nonusers. We did not. find significant differences in the cortisol awakening response, diurnal slope, or in the dexamethasone suppression test. Conclusions: Despite the. finding of slightly lower evening cortisol levels in daily and infrequent BZD users compared to nonusers, results indicate that long-term BZD use is not convincingly associated with HPA axis alterations. Show less
Vreeburg, S.A.; Zitman, F.G.; Pelt, J. van; DeRijk, R.H.; Verhagen, J.C.M.; Dyck, R. van; ... ; Penninx, B.W.J.H. 2010
Objective: To examine the association between several subtypes of anxiety disorders and various cortisol indicators in a large cohort study. Anxiety disorders have been suggested to be linked to... Show moreObjective: To examine the association between several subtypes of anxiety disorders and various cortisol indicators in a large cohort study. Anxiety disorders have been suggested to be linked to hypothalamic-pituitary-adrenal (HPA) axis activity, although results are scarce and inconsistent. No earlier studies have examined consistency of HPA axis findings across several anxiety subtypes and whether associations are state or trait dependent. Methods: Data are derived from 1427 participants of the Netherlands Study of Depression and Anxiety. Three groups were compared: 342 control participants without psychiatric disorders; 311 persons with a remitted (no current) anxiety disorder (social phobia, generalized anxiety disorder, panic disorder); and 774 persons with a current anxiety disorder, as diagnosed using the Composite International Diagnostic Interview psychiatric interview. Cortisol levels were measured in seven saliva samples, determining the 1-hour cortisol awakening response, evening cortisol, and cortisol response after 0.5 mg of dexamethasone ingestion. Results: Current anxiety disorder was associated with higher awakening cortisol levels (p = .002). These findings were mainly present for patients with panic disorder with agoraphobia and anxious patients with comorbid depressive disorder. Remitted anxiety only showed a trend toward higher morning cortisol (p = .08). No associations were observed for anxiety status and evening cortisol level or cortisol suppression after dexamethasone. Conclusions: This study showed a modest but significantly higher 1-hour cortisol awakening response among anxiety patients, which was driven by those with panic disorder with agoraphobia and those with comorbid depression. Show less
