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
Klaassens, E.R.; Veen, T. van; Giltay, E.J.; Rinne, T.; Pelt, J. van; Zitman, F.G. 2010
Hypothalamic-pituitary-adrenal (HPA) axis alterations have been found in veterans with posttraumatic stress disorder (PT D). It is unclear whether trauma exposure during adulthood in the absence of... Show moreHypothalamic-pituitary-adrenal (HPA) axis alterations have been found in veterans with posttraumatic stress disorder (PT D). It is unclear whether trauma exposure during adulthood in the absence of psychopathology is also associated with HPA-axis dysregulation. Thirty-six trauma-exposed peacekeepers, 23 nonexposed peacekeepers, and 25 nonexposed civilians, all without lifetime psychopathology were studied. Basal HPA-axis functioning was assessed with salivary cortisol samples obtained over 2 days. HPA-axis reactivity was assessed with the dexamethasonel/corticotropin-releasing hormone test. Lower afternoon salivary cortisol levels were found in both veteran groups versus controls alder adjustment for confounders. The authors concluded that this study does not support the idea that HPA-axis functioning is durably altered by trauma exposure during adulthood in men. Show less
Klaassens, E.R.; Veen, T. van; Giltay, E.J.; Rinne, T.; Pelt, J. van; Zitman, F.G. 2010
Hypothalamic-pituitary-adrenal (HPA) axis alterations have been found in veterans with posttraumatic stress disorder (PTSD). It is unclear whether trauma exposure during adulthood in the absence of... Show moreHypothalamic-pituitary-adrenal (HPA) axis alterations have been found in veterans with posttraumatic stress disorder (PTSD). It is unclear whether trauma exposure during adulthood in the absence of psychopathology is also associated with HPA-axis dysregulation. Thirty-six trauma-exposed peacekeepers, 23 nonexposed peacekeepers, and 25 nonexposed civilians, all without lifetime psychopathology were studied. Basal HPA-axis functioning was assessed with salivary cortisol samples obtained over 2 days. HPA-axis reactivity was assessed with the dexamethasone/corticotropin-releasing hormone test. Lower afternoon salivary cortisol levels were found in both veteran groups versus controls after adjustment for confounders. The authors concluded that this study does not support the idea that HPA-axis functioning is durably altered by trauma exposure during adulthood in men. Show less
Wardenaar, K.J.; Veen, T. van; Giltay, E.J.; Hollander-Gijsman, M. den; Penninx, B.W.J.H.; Zitman, F.G. 2010
BACKGROUND: The Inventory of Depressive Symptomatology Self Report (IDS-SR) is a widely used but heterogeneous measure of depression severity. Insight in its factor structure and dimensionality... Show moreBACKGROUND: The Inventory of Depressive Symptomatology Self Report (IDS-SR) is a widely used but heterogeneous measure of depression severity. Insight in its factor structure and dimensionality could help to develop more homogeneous IDS-SR subscales. However previous factoranalytical studies have found mixed results. Therefore, the present study tested which factor structure underlies the IDS-SR and, in addition, if the factors can be used as unidimensional subscales. METHODS: Confirmatory factor analysis (CFA) was done to identify the best-fitting factor structure. The study sample consisted of 2600 individuals (mean age 40.5+/-12.1). We assessed model fit in 4 groups: 957 Major Depressive Disorder (MDD) patients, 450 remitted MDD patients, 570 patients with an anxiety disorder and 623 healthy controls to test the consistency of model fit. Rasch analyses in the full sample were used to evaluate and optimize the unidimensionality and psychometric quality of the factors. RESULTS: CFA indicated that a 3-factor model fits the IDS-SR data best and is consistent across groups, with a 'mood/cognition' factor, an 'anxiety/arousal' factor and a 'sleep' factor. In addition, Rasch analyses indicated that the 'mood/cognition' and 'anxiety/arousal' factors could be optimized to be used as unidimensional subscales. LIMITATIONS: The fit of only 4 models was tested, ranging from a 1- to 4-factor model. CONCLUSIONS: The IDS-SR is a heterogeneous instrument with a multifactorial underlying structure. It is possible to measure more homogeneous symptomatology with IDS-SR subscales, which could be useful in clinical practice and scientific research. Show less
Noorden, M.S. van; Giltay, E.J.; Hollander-Gijsman, M.E. den; Wee, N.J.A. van der; Veen, T. van; Zitman, F.G. 2010
BACKGROUND: No previous large scale studies have assessed gender differences in naturalistic samples of major depressive disorder (MDD) outpatients. We therefore determined gender differences in... Show moreBACKGROUND: No previous large scale studies have assessed gender differences in naturalistic samples of major depressive disorder (MDD) outpatients. We therefore determined gender differences in comorbidity, symptom patterns and subjective health status in these outpatients in a mental healthcare setting. METHODS: Of 3798 consecutive adult patients (age range: 18-65), 1131 (65.1% women) fulfilled DSM-IV criteria of current MDD on the Mini-International Neuropsychiatric Interview (MINI-Plus). Patients were routinely assessed with Routine Outcome Monitoring (ROM), including the Montgomery-Asberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI-II), Brief Symptom Inventory (BSI) and Short Form-36 (SF-36). RESULTS: No gender differences were found in disease severity using the clinician-rated MADRS. However, women showed a significant higher depression severity measured with the self-report BDI-II. Also, psychopathological symptoms self-reported with the BSI were higher, and reported health status on the SF-36 was lower in women. In men with MDD, social phobia, attention deficit hyperactivity disorder, and alcohol and drug misconduct were more common comorbid disorders, while in women with MDD posttraumatic stress disorder and bulimia nervosa were more common, as well as atypical features of depression. LIMITATIONS: The use of retrospective reports of lifetime psychopathology might have led to recall bias. 20% of subjects were excluded from ROM due to language problems or logistical reasons. CONCLUSIONS: Although women self-reported higher depression severity, more severe general psychopathological symptoms and lower health status, no differences in disease severity were found on interviewer ratings. These findings could have implications for clinical decision making and treatment. Show less
