Antidepressant use and salivary cortisol in depressive and anxiety disorders

AbstractAntidepressants are an effective treatment for depressive and anxiety disorders. Those disorders are frequently accompanied by heightened cortisol levels. Antidepressants may affect hypothalamic–pituitary–adrenal axis functioning, the alteration of which could be partially responsible for treatment efficacy. The association between antidepressants and cortisol was investigated in 1526 subjects of the Netherlands Study of Depression and Anxiety who were grouped into ‘serotonin reuptake inhibitor (SSRI) users’ (n=309), ‘tricyclic antidepressant (TCA) users’ (n=49), ‘other antidepressant users’ (n=100), and ‘non-users’ (n=1068). All subjects had a current or past diagnosis of anxiety and/or depression. Subjects provided 7 saliva samples from which 3 cortisol indicators were calculated: cortisol awakening response (CAR), evening cortisol, and cortisol suppression after ingestion of 0.5mg dexamethasone. As compared to non-users, TCA users had a flattened CAR (effect size: Cohen's d=0.34); SSRI users had higher evening cortisol levels (d=0.04); and SSRI users showed decreased cortisol suppression after dexamethasone ingestion (d=0.03). These findings suggest that antidepressant subtypes are associated with distinct alterations of the HPA axis. TCA users, who showed a flattened CAR, displayed the strongest alterations of salivary cortisol

Evening salivary alpha-amylase, major depressive disorder, and antidepressant use in the Netherlands Study of Depression and Anxiety (NESDA)

<p>Salivary alpha-amylase (sAA) may be a suitable index for sympathetic activity and dysregulation of the autonomic nervous system. The relationship between antidepressants and depression with sAA levels was studied, since antidepressants were previously shown to have a profound impact on heart rate variability as an ANS indicator. Data are from 1692 participants of the Netherlands Study of Depression and Anxiety (NESDA) who were recruited from the community, general practice, and specialized mental health care. Differences in evening sAA levels were examined between patient groups (i.e., 752 current major depressive disorder [MDD], 611 remitted MDD, and 329 healthy controls) and between 46 tricyclic antidepressant (TCA) users, 307 selective serotonin reuptake inhibitor (SSRI) users, 97 users of another antidepressant, and 1242 non-users. Each participant sampled twice at 22.00h and 23.00h. In multivariable analysis, there was a trend over the three groups with increasing sAA levels from controls to remitted MDD to current MDD that approached significance. Furthermore, in comparison to non-users of antidepressants, TCA rather than SSRI users showed higher sAA levels, that persisted after multivariable adjustment. The present study shows that higher evening sAA levels in depressed patients, indicative of an increased sympathetic activity, may be induced by TCAs. (C) 2013 Elsevier Ireland Ltd. All rights reserved.</p>

The relationships of working conditions, recent stressors and childhood trauma with salivary cortisol levels

SummaryBackgroundAn etiological model has been suggested where stress leads to high cortisol levels and hypothalamic–pituitary–adrenal (HPA) axis dysregulation, resulting in somatic diseases and psychopathology. To evaluate this model we examined the association of different stressors (working conditions, recent life events and childhood trauma) with various cortisol indicators in a large cohort study.MethodsData are from 1995 participants of the Netherlands Study of Depression and Anxiety (NESDA). Most of the selected participants had a current or remitted anxiety and/or depressive disorder. Working conditions were assessed with self-report questionnaires, life-events and childhood trauma were assessed with interview questionnaires. Cortisol levels were measured in seven saliva samples, determining the 1-h cortisol awakening response (CAR), evening cortisol levels and cortisol suppression after a 0.5mg dexamethasone suppression test (DST).ResultsRegression analyses – adjusted for covariates – showed two significant associations: low social support at work and high job strain were associated with more cortisol suppression after the DST. No other associations were found with any of the cortisol variables.ConclusionsWorking conditions, recent stressors and childhood trauma were not convincingly associated with cortisol levels

Salivary cortisol levels and the 2-year course of depressive and anxiety disorders

<p>Introduction: Depression and anxiety disorders have been associated with hyperactivity of the hypothalamic-pituitary adrenal (HPA) axis. However, lower cortisol levels have also been observed in depressed patients. Whether cortisol level predicts the course of these disorders has not been examined in detail. We examined whether salivary cortisol indicators predict the 2-year course of depression and anxiety disorders.</p><p>Methods: Longitudinal data are obtained from 837 participants of the Netherlands Study of Depression and Anxiety, with a DSM-IV based depressive and/or anxiety disorder at baseline. At baseline, seven saliva samples were obtained, including the 1-h cortisol awakening response, evening cortisol level and a 0.5 mg dexamethasone suppression test. At follow-up, DSM-IV based diagnostic interviews and Life Chart Interview integrating diagnostic and symptom trajectories over 2 years were administered to determine an unfavorable course.</p><p>Results: 41.5% of the respondents had a 2-year unfavorable course trajectory without remission longer than 3 months. Adjusted analyses showed that a tower awakening response was associated with an unfavorable course (RR = 0.83, p = 0.03). No associations were found between evening cortisol or cortisol suppression after dexamethasone ingestion and an unfavorable course trajectory.</p><p>Conclusions: Among patients with depressive or anxiety disorders, a lower cortisol awakening response - which may be indicative of underlying exhaustion of the HPA axis predicted an unfavorable course trajectory. (C) 2012 Elsevier Ltd. All rights reserved.</p>

Increased cortisol awakening response was associated with time to recurrence of major depressive disorder

Introduction: Although HPA-axis activity has been studied extensively in relation to depression, there is no consensus whether HPA-axis parameters predicts major depressive disorder (MDD) recurrence. We investigated whether HPA-axis parameters (cortisol awakening response (CAR), the dexamethasone suppression test (DST) and evening cortisol) predict time to recurrence in remitted subjects with a history of MDD and whether childhood trauma and life events interact with HPA-axis parameters in increasing the risk for recurrence. Method: Data were derived from 549 subjects with a lifetime diagnosis of MDD in remission for at least six months preceding the baseline assessment of the Netherlands Study of Depression and Anxiety (NESDA). Subjects were followed up with two interviews over the course of four years to assess recurrence. DSM-IV based diagnostic interviews were used to assess time to recurrence of MDD. Seven salivary cortisol samples collected at baseline with information on CAR, evening cortisol and the DST. Hazard ratios were calculated using Cox regression analysis, adjusted for covariates. Results: A higher CAR was associated with time to recurrence of MDD (HR = 1.03, 95%CI 1.003-1.060, p = 0.03) whereas evening cortisol and DST were not. No interactions between HPA-axis parameters and stress-related factors were found. Conclusions: Our data support previous studies reporting that subjects with a higher CAR are more vulnerable to recurrence of MDD. (C) 2014 Published by Elsevier Ltd

Associations between sociodemographic, sampling and health factors and various salivary cortisol indicators in a large sample without psychopathology

Background: Cortisol levels are increasingly often assessed in large-scale psychosomatic research. Although determinants of different salivary cortisol indicators have been described, they have not yet been systematically studied within the same study with a Large sample size. Sociodemographic, health and sampling-related determinants of salivary cortisol Levels were examined in a sample without potential disturbances because of psychopathology. Methods: Using 491 respondents (mean age = 43.0 years, 59.5% female) without lifetime psychiatric disorders from the Netherlands Study of Depression and Anxiety (NESDA), sociodemographic, sampling and health determinants of salivary cortisol levels were examined. Respondents collected seven salivary cortisol samples providing information about 1-h awakening cortisol, diurnal slope, evening cortisol and a dexamethasone (0.5 mg) suppression test (DST). Results: Higher overall morning cortisol values were found for smokers, physically active persons, persons without cardiovascular disease, sampling on a working day or in a month with less daylight. In addition, the cortisol awakening response was significantly flattened for mates, persons with cardiovascular disease, those with late awakening times and those with longer sleep duration. Diurnal slope was steeper in men, physically active persons, late awakeners, working persons, and season with less daylight. A higher evening cortisol level was associated with older age, smoking and season with more daylight. Cortisol suppression after dexamethasone ingestion was found to be less pronounced in smokers, less active persons and sampling on a weekday. Conclusion: Sociodemographic variables (sex, age), sampling factors (awakening time, working day, sampling month, steep duration) and health indicators (smoking, physical activity, cardiovascular disease) were shown to influence different features of salivary cortisol levels. Smoking had the most consistent effect on all cortisol variables. These factors should be considered in psychoneuroendocrinology research. (C) 2009 Elsevier Ltd. All rights reserved

Major Depressive Disorder and Hypothalamic-Pituitary-Adrenal Axis Activity Results From a Large Cohort Study

Context: There is a central belief that depression is associated with hyperactivity of the hypothalamic-pituitary-adrenal axis, resulting in higher cortisol levels. However, results are inconsistent. Objective: To examine whether there is an association between depression and various cortisol indicators in a large cohort study. Design, Setting, and Participants: Data are from 1588 participants of the Netherlands Study of Depression and Anxiety who were recruited from the community, general practice care, and specialized mental health care. Three groups were compared: 308 control subjects without psychiatric disorders, 579 persons with remitted (no current) major depressive disorder (MDD), and 701 persons with a current MDD diagnosis, as assessed using the DSM-IV Composite International Diagnostic Interview. Main Outcome Measures: Cortisol levels were measured in 7 saliva samples to determine the 1-hour cortisol awakening response, evening cortisol levels, and cortisol suppression after a 0.5-mg dexamethasone suppression test. Results: Both the remitted and current MDD groups showed a significantly higher cortisol awakening response compared with control subjects (effect size [Cohen d] range, 0.15-0.25). Evening cortisol levels were higher among the current MDD group at 10 PM but not at 11 PM. The postdexamethasone cortisol level did not differ between the MDD groups. Most depression characteristics (severity, chronicity, symptom profile, prior childhood trauma) were not associated with hypothalamic-pituitary-adrenal axis activity except for comorbid anxiety, which tended to be associated with a higher cortisol awakening response. The use of psychoactive medication was generally associated with lower cortisol levels and less cortisol suppression after dexamethasone ingestion. Conclusions: This large cohort study shows significant, although modest, associations between MDD and specific hypothalamic-pituitary-adrenal axis indicators. Because a higher cortisol awakening response was observed among both subjects with current MDD and subjects with remitted MDD, this may be indicative of an increased biological vulnerability for depression

The impact of stress systems and lifestyle on dyslipidemia and obesity in anxiety and depression

<p>Background: Dyslipidemia and obesity have been observed in persons with severe anxiety or depression, and in tricyclic antidepressant (TCA) users. This likely contributes to the higher risk of cardiovascular disease (CVD) in anxiety and depressive disorders. We aimed to elucidate whether biological stress systems or lifestyle factors underlie these associations. If so, they may be useful targets for CVD prevention and intervention.</p><p>Methods: Within 2850 Netherlands Study of Depression and Anxiety (NESDA) participants, we evaluated the explaining impact of biological stress systems (i.e., the hypothalamic-pituitary- adrenal [HPA] axis, autonomic nervous system [ANS] and inflammation) and lifestyle factors (i.e., tobacco and alcohol use, and physical activity) on adverse associations of anxiety and depression severity and TCA use with high and low-density lipoprotein cholesterol, triglycerides, body mass index and waist circumference. Through linear regression analyses, percentual change (%Delta) in beta was determined and considered significant when %Delta > 10.</p><p>Results: The inflammatory marker C-reactive protein had the most consistent impact (explaining 14-53% of the associations of anxiety and depression severity and TCA use with lipid and obesity levels), followed by tobacco use (explaining 34-43% of the associations with lipids). The ANS mediated all associations with TCA use (explaining 32-61%). The HPA axis measures did not explain any of the associations.</p><p>Conclusions: Increased dyslipidemia and (abdominal) obesity risk in patients with more severe anxiety disorders and depression may be partly explained by chronic low-grade inflammation and smoking. TCAs may increase metabolic risk through enhanced sympathetic and decreased parasympathetic ANS activity. That the HPA axis had no impact in our sample may reflect the possibility that the HPA axis only plays a role in acute stress situations rather than under basal conditions. (C) 2012 Elsevier Ltd. All rights reserved.</p>