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
Jacobs, G.E.; Grond, J. van der; Teeuwisse, W.M.; Langeveld, T.J.C.; Pelt, J. van; Verhagen, J.C.M.; ... ; Gerven, J.M.A. van 2010
INTRODUCTION AND PURPOSE: Functional proton magnetic resonance spectroscopy (MRS) can be applied to measure pharmacodynamic effects of central nervous system (CNS)-active drugs. The serotonin... Show moreINTRODUCTION AND PURPOSE: Functional proton magnetic resonance spectroscopy (MRS) can be applied to measure pharmacodynamic effects of central nervous system (CNS)-active drugs. The serotonin precursor 5-hydroxytryptophan (5-HTP), administered together with carbidopa and granisetron to improve kinetics and reduce adverse effects, acutely enhances central serotonergic neurotransmission and induces hypothalamus-pituitary-adrenal-(HPA) axis activation. We studied the hypothalamic levels of glutamate/glutamine (Glx), choline (Chol), N-acetyl-aspartate (NAA) and creatine using 7-Tesla (7T) MRS, and adrenocorticotropic hormone (ACTH) and cortisol in peripheral blood, after the administration of the 5-HTP function test in healthy volunteers. METHODS: A randomized, double blind, placebo-controlled, two-way cross-over study was performed in 12 healthy males with a 7day wash-out period. After administration of the oral 5-HTP function test, ACTH and cortisol were measured over 4h and MRS scans at 7T were performed every 30min over 3h measuring Glx:Creatine, Chol:Creatine and NAA:Creatine ratios. RESULTS: In the hypothalamus, the administration of 5-HTP had no effect on the average Glx, Chol or NAA levels over 180min but induced a significant decrease of Glx at 60min on post-hoc analysis. 5-HTP-induced significant ACTH release reaching an E(max) of 60.2ng/L at 80min followed by cortisol with an E(max) of 246.4ng/mL at 110min. CONCLUSIONS: The reduction in hypothalamic Glx levels after serotonergic stimulation is compatible with activation of excitatory neurons in this region, which is expected to cause depletion of local glutamate stores. The hypothalamic MRS-response reached its maximum prior to subsequent increases of ACTH and cortisol, which support the functional relevance of hypothalamic Glx-depletion for activation of the HPA-axis. This exploratory study shows that MRS is capable of detecting neuronal activation following functional stimulation of a targeted brain area. 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
