BACKGROUND Hypothalamic-pituitary-adrenal (HPA)-axis dysregulation has inconsistently been associated with posttraumatic stress disorder (PTSD). Yet, trauma exposure rather than PTSD may be... Show moreBACKGROUND Hypothalamic-pituitary-adrenal (HPA)-axis dysregulation has inconsistently been associated with posttraumatic stress disorder (PTSD). Yet, trauma exposure rather than PTSD may be responsible for HPA-axis dysregulation. In two meta-analyses, we assessed the association of adulthood trauma exposure and HPA-axis functioning in healthy subjects with and without PTSD. METHOD A literature search in Pubmed and PsychInfo, using keywords and MeSH terms such as cortisol, emotional trauma, and PTSD, was performed. Only studies that included mentally healthy trauma-exposed (TE) individuals as well as non-exposed (NE) healthy individuals and/or PTSD patients (PTSD) were selected. This resulted in 1511 studies of which ultimately, 37 studies (21 TE versus NE and 34 TE versus PTSD, N=2468) were included. Methodological quality of all studies was assessed according to specific quality criteria. Pooled effect sizes (Hedges's g) on cortisol levels were compared. For all analyses, random effect models were used. RESULTS Cortisol levels were neither significantly different between TE versus NE subjects (-0.029; 95%CI: -0.145; 0.088) nor between TE subjects versus PTSD patients (0.175; 95%CI: -0.012; -0.362). Subgroup analyses showed an increased cortisol suppression after the low dose dexamethasone suppression test (DST) in TE versus NE subjects (-0.509; 95%CI: -0.871; -0.148). This meta-analysis was limited by the fact that lifetime psychiatric illness and childhood trauma were not an exclusion criterion in all 37 studies. CONCLUSION Neither adulthood trauma exposure nor PTSD were associated with differences in HPA-axis functioning, although adulthood trauma may augment cortisol suppression after the DST. More evidence on other dynamic tests of HPA-axis functioning in PTSD and adulthood trauma exposure is needed. Show less
OBJECTIVE Personality and childhood trauma may affect cardiovascular disease (CVD) risk. However, evidence for an association with metabolic risk factors for CVD is limited and ambiguous. Moreover,... Show moreOBJECTIVE Personality and childhood trauma may affect cardiovascular disease (CVD) risk. However, evidence for an association with metabolic risk factors for CVD is limited and ambiguous. Moreover, despite their interrelatedness, personality and childhood trauma were not yet studied simultaneously. Therefore, we aimed to explore whether personality and childhood trauma are correlates of metabolic risk factors. METHODS Among 2755 participants of the Netherlands Study of Depression and Anxiety (NESDA), we investigated through linear regression models whether Big Five personality traits (i.e., extraversion, openness, agreeableness, neuroticism and conscientiousness) and childhood trauma type (i.e., emotional neglect, and psychological, physical and sexual abuse) were correlates of metabolic risk factors (i.e., lipids, waist circumference (WC), glucose and blood pressure). Basic covariates (i.e., age, sex and income level), lifestyle, severity of depressive symptoms and years of education were taken into account. RESULTS Openness was the most robust favorable correlate, and sexual abuse was the most robust unfavorable correlate of lipids and WC, and of overall metabolic risk (β=-.070; p<.001 and β=.035; p=.04, respectively). CONCLUSIONS People with a low openness trait and those who experienced childhood sexual abuse are at higher risk of dyslipidemia and abdominal obesity. Show less
BACKGROUND: Because of the heterogeneity of known predictive factors, course-predictions for depression and anxiety are often unspecific. Therefore, it was investigated whether symptom-dimensions... Show moreBACKGROUND: Because of the heterogeneity of known predictive factors, course-predictions for depression and anxiety are often unspecific. Therefore, it was investigated whether symptom-dimensions could be used as more specific course-predictors, on top of already known predictors, such as diagnosis and overall severity. METHODS: A sample of 992 subjects with depressive and/or anxiety disorders was followed in a 2-year prospective cohort study. Dimensions of the tripartite model (general distress, anhedonic depression and anxious arousal) were assessed at baseline. Diagnostic and course information were assessed at baseline and 2-year follow-up. RESULTS: Dimensional scores at baseline predicted diagnosis after two years and course-trajectories during follow-up. Increased general distress at baseline was associated with comorbid depression-anxiety at follow-up, increased anhedonic depression was associated with single depression and anxious arousal was associated with (comorbid) panic disorders at follow-up. Baseline general distress was associated with an unfavorable course in all patients. All associations were independent and added prognostic information on top of diagnosis and other predictive factors at baseline. LIMITATIONS: Only prevalent patients were included at baseline and only three dimensions were measured CONCLUSIONS: Symptom dimensions predict the future 2-year course of depression and anxiety. Importantly, the dimensions yield predictive information on top of diagnosis and other prognostic factors at baseline. Show less
BACKGROUND Burnout is a stress state characterized by symptoms of mental exhaustion and physical fatigue, detachment from work, and feelings of diminished competence. Several biomarkers have been... Show moreBACKGROUND Burnout is a stress state characterized by symptoms of mental exhaustion and physical fatigue, detachment from work, and feelings of diminished competence. Several biomarkers have been tested for association with burnout, but the results are conflicting. AIM The objective of this review was to identify potential biomarkers for burnout. METHODS We carried out a systematic review of studies comparing biomarkers in individuals with burnout and healthy controls, or individuals with low scores and those with high scores on burnout questionnaires. Literature searches in MEDLINE and EMBASE were performed. We describe biomarkers on which at least three studies were available. Where appropriate, a meta-analysis was carried out. RESULTS We identified 31 studies on 38 biomarkers involved in the hypothalamus-pituitary-adrenal axis, autonomic nervous system, immune system, metabolic processes, antioxidant defense, hormones, and sleep. At least 3 studies were available for cortisol in saliva and blood, blood pressure, heart rate, cholesterol, dehydroepiandrosterone sulfate, (numbers or activity of) natural killer cells, C-reactive protein, and prolactin. The comparability of studies was limited, due to differences in the methods used to characterize patients and controls, to assess biomarkers, and to control for confounders. Furthermore, burnout was operationalized in different ways. Meta-analyses showed no differences for cortisol awakening response and cortisol awakening response after administration of dexamethasone, cortisol in blood, and blood pressure. CONCLUSIONS No potential biomarkers for burnout were found, largely due to the incomparability of studies. We emphasize the need for a dimensional and longitudinal approach in future research to account for the heterogeneity of burnout. Show less
AIM Results on determinants of benzodiazepine (BZD) use in general and inappropriate use were inconsistent and mostly univariate. The relative importance of sociodemographic, psychological and... Show moreAIM Results on determinants of benzodiazepine (BZD) use in general and inappropriate use were inconsistent and mostly univariate. The relative importance of sociodemographic, psychological and physical determinants has never been investigated in a comprehensive, multivariate model. METHODS We included 429 BZD users and 2423 non-users from the Netherlands Study of Depression and Anxiety (NESDA) in order to investigate sociodemographic, psychological and physical determinants of BZD use and inappropriate use by logistic and linear regression analyses. RESULTS BZDs were used by a considerable proportion of the 2852 NESDA participants (15.0%). BZD use was independently associated with older age, singleness, unemployment, treatment in secondary care, higher medical consumption (more severe) anxiety, depression (OR [95% CI] = 1.95 [1.29, 2.93]), comorbidity, insomnia, SSRI (OR [95% CI] = 2.05 [1.55, 2.70]), TCA and other antidepressant (OR [95% CI] = 2.44 [1.64, 3.62]) use. Overall, BZD use was rarely in accordance with all guidelines, mainly because most users (82.5%) exceeded the recommended duration of safe use. Inappropriate use was independently associated with older age (beta = 0.130) and chronic illnesses (beta = 0.120). Higher scores on agreeableness were associated with less inappropriate use. CONCLUSIONS Mentally or physically vulnerable subjects were most likely to use BZDs. The most vulnerable (i.e. the old and physically ill) BZD users were at highest risk of inappropriate BZD use. Without further evidence of the effectiveness of BZDs in long-term use, caution in initiating BZD prescriptions is recommended, particularly when patients are chronically ill and old, as those are most likely to display inappropriate use. Show less
Rationale, aims and objectives The Global Assessment of Functioning Scale (GAF) is widely used to assess psychological, social and occupational functioning. The validity and reliability of the GAF... Show moreRationale, aims and objectives The Global Assessment of Functioning Scale (GAF) is widely used to assess psychological, social and occupational functioning. The validity and reliability of the GAF in clinical practice have only scarcely been studied in naturalistic samples. Methods A total of 432 outpatients with a current major depressive disorder (MDD) were evaluated with routine outcome monitoring (ROM). At baseline the GAF score was assessed by the treating clinician and at ROM baseline and follow-up sessions also by a trained test nurse. Sociodemographic data, the Mini International Neuropsychiatric Interview Plus and scores on the Montgomery-Äsberg Depression Rating Scale, Beck Depression Inventory-revised, Brief Symptom Inventory and Short Form-36 were assessed. Results At baseline, the mean GAF score by the clinician was 54.8 (range 35-85), and this was systematically lower than the mean GAF score by the test nurse of 57.5 (range 31-88). GAF scores by the clinician and test nurse correlated weakly (r = 0.26). The GAF scores of the clinicians correlated strongly with disease severity, and social and physical functioning. Conclusion The GAF showed rather poor inter-rater reliability as well as poor discriminant validity with disease severity and physical limitations in a large naturalistic sample of outpatients with MDD. 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 (MOD) 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 (MOD) 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 MOD 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 MOD 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. (C) 2009 Elsevier B.V. All rights reserved. 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 MOD 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. (C) 2010 Elsevier B.V. All rights reserved. Show less
Wardenaar, K.J.; Veen, T. van; Giltay, E.J.; Beurs, E. de; Penninx, B.W.J.H.; Zitman, F.G. 2010
The original Mood and Anxiety Symptoms Questionnaire (MASQ) is a 90-item self-report, designed to measure the dimensions of Clark and Watson's tripartite model. We developed and validated a 30-item... Show moreThe original Mood and Anxiety Symptoms Questionnaire (MASQ) is a 90-item self-report, designed to measure the dimensions of Clark and Watson's tripartite model. We developed and validated a 30-item short adaptation of the MASQ: the MASQ-D30, which is more suitable for large-scale psychopathology research and has a clearer factor structure. The MASQ-D30 was developed through a process of item reduction and grouping of the appropriate subscales in a sample of 489 psychiatric outpatients, using a validated Dutch translation, based on the original English MASQ as a starting point. Validation was done in two other large samples of 1461 and 2471 subjects, respectively, with an anxiety, somatoform and/or depression diagnosis or no psychiatric diagnosis. Psychometric properties were investigated and compared between the MASQ-D30 and the full (adapted) MASQ. A three-dimensional model (negative affect, positive affect and somatic arousal) was found to represent the data well, indicating good construct validity. The scales of the MASQ-D30 showed good internal consistency (all alphas >0.87) in patient samples. Correlations of the subscales with other instruments indicated acceptable convergent validity. Psychometric properties were similar for the MASQ-D30 and the full questionnaire. In conclusion, the MASQ-D30 is a valid instrument to assess dimensional aspects of depression and anxiety and can easily be implemented in psychopathology studies. (C) 2009 Elsevier Ireland Ltd. All rights reserved. Show less
Objective: The metabolic syndrome (MetSyn) predisposes to cardiovascular disease and diabetes mellitus. There might also be an association between the MetSyn and anxiety and depression, but its... Show moreObjective: The metabolic syndrome (MetSyn) predisposes to cardiovascular disease and diabetes mellitus. There might also be an association between the MetSyn and anxiety and depression, but its nature is unclear. We aimed to investigate whether diagnosis, symptom severity and antidepressant use are associated with the MetSyn. Method: We addressed the odds for the MetSyn and its components among 1217 depressed and/or anxious subjects and 629 controls, and their associations with symptom severity and antidepressant use. Results: Symptom severity was positively associated with prevalence of the MetSyn, [adjusted odds ratio (OR) 2.21 for very severe depression: 95% confidence interval (CI): 1.06-4.64, P = 0.04], which could be attributed to abdominal obesity and dyslipidemia. Tricyclic antidepressant (TCA) use also increased odds for the MetSyn (OR 2.30, 95% CI: 1.21-4.36, P = 0.01), independent of depression severity. Conclusion: The most severely depressed people and TCA users more often have the MetSyn, which is driven by abdominal adiposity and dyslipidemia. Show less
Background: Dysregulation of the hypothalamic pituitary adrenal (HPA)-axis is hypothesized to underlie stress-related psychiatric disorders such as post-traumatic stress disorder (PTSD). We aimed... Show moreBackground: Dysregulation of the hypothalamic pituitary adrenal (HPA)-axis is hypothesized to underlie stress-related psychiatric disorders such as post-traumatic stress disorder (PTSD). We aimed to explore whether trauma exposure is associated with alterations in HPA-axis functioning in the absence of lifetime psychiatric morbidity. Method: We included 39 trauma-exposed healthy male subjects (mean age = 47 years; SD = 9.2) and 24 non-exposed healthy male controls (mean age = 47.4 years; SD = 14.5). All subjects were free of lifetime psychopathology. Basal salivary cortisol levels (on two consecutive days) as well as the cortisol and adrenocorticotropic hormone (ACTH) response to the combined dexamethasone/corticotropin releasing hormone (Dex/CRH) challenge test were analyzed using general linear models (GLM) adjusted for body mass index, age and smoking status. Results: A blunted salivary cortisol awakening response was found in the exposed group compared to the non-exposed group (F(1,57) = 5.46, p = .02). Consistent with these findings, salivary diurnal cortisol was lower in the trauma-exposed versus non-exposed group (F(1,57) = 4.04, p =.05). No differences, however, were found between both groups for plasma cortisol or ACTH responses to the Dex/CRH test. Conclusion: Low basal cortisol levels were found in trauma-exposed men, suggesting that HPA-axis alterations in men are associated with trauma exposure during adulthood, also in the absence of psychopathology. (C) 2009 Elsevier Ltd. All rights reserved. Show less
Dortland, A.K.B.V.; Giltay, E.J.; Veen, T. van; Pelt, J. van; Zitman, F.G.; Penninx, B.W.J.H. 2010
Background: Several studies have suggested an association between lipids or lipoproteins and depression, but findings are contradictory. However, previous studies did not always take into... Show moreBackground: Several studies have suggested an association between lipids or lipoproteins and depression, but findings are contradictory. However, previous studies did not always take into consideration potentially mediating factors or heterogeneity of symptoms, which may clarify contradicting findings. Method: We compared levels of serum total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol and triglyceride between 761 subjects with current major depressive disorder (MDD) (Composite International Diagnostic Interview, based on the DSM-IV), 1,071 subjects with remitted MDD, and 629 controls, aged 18 to 65 years. Subjects participated in the baseline assessment of the Netherlands Study of Depression and Anxiety, which lasted from September 2004 to February 2007. We studied the impact of adjustment for sociodemographics, lifestyle-related covariates, and antidepressant use and examined the association between specific psychopathological characteristics and lipid/lipoprotein levels. Results: HDL cholesterol level was lower (P=.007) and triglyceride level was higher (P=.001) in current MDD versus remitted MDD and controls. After adjustment for level of education, body mass index (BMI), smoking status, and alcohol use, dissimilarities lost statistical significance. Depression severity, comorbid dysthymia, and melancholic and atypical features were all associated with lipids/lipoproteins, but most associations attenuated after adjustment for covariates, especially BMI. The association between melancholic features and lower HDL cholesterol (P=.038) and between atypical depression and higher total and LDL cholesterol (P=.004 and P=.002, respectively) persisted after full adjustment. Conclusions: Adverse lipoprotein patterns were found in patients with MDD. The fact that these associations diminished after adjustment for lifestyle-related factors, especially BMI, suggests that the unfavorable lipid/lipoprotein pattern among depressed subjects is mainly secondary to lifestyle-related factors. However, melancholic features were independently associated with lower HDL cholesterol, and atypical depression was independently associated with higher total and LDL cholesterol. J Clin Psychiatry 2010;71(6):729-736 (C) Copyright 2009 Physicians Postgraduate Press, Inc. Show less
