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Introduction: Depressive disorders are a common illness worldwide. Major depression is known as a significant predictor of the metabolic syndrome. However, the effects of depression on adipose tissue compartments are controversial. This meta-analysis aimed to evaluate the state of research on the relationship between patients with depression and adipose tissue compartments as compared to nondepressed individuals., Methods: The PubMed database was searched for human studies that measured adipose tissue compartments such as visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and/or organ-specific adipose tissue measurements using dual-energy X-ray absorptiometry, magnetic resonance imaging or computed tomography scan and reported the means and a measure of variance separately for depressed individuals and healthy controls. Twelve articles were identified, including a total of 1,141 depressed and 2,545 nondepressed individuals., Results: Major depressive disorder and self-reported depressive symptoms were associated with elevated visceral adipose tissue and elevated subcutaneous adipose tissue. Subanalyses for gender, age, method of adipose tissue measurement, and method of depression assessment showed elevated visceral adipose in depressed individuals. The results could be replicated when focussing on studies controlling for body mass index (BMI). Regarding other adipose tissue compartments, meta-analysis could not be carried out due to lack of studies., Conclusions: Depression is associated with enlarged visceral and subcutaneous adipose tissue. Further, especially longitudinal, research is needed to identify the mechanism through which depressive disorders contribute to visceral adiposity., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

High lipoprotein(a) (Lp(a)) levels constitute a major risk factor for vascular mortality. Major depression also increases the risk of cardiovascular disease. We measured the concentrations of Lp(a) in depressed patients and controls and studied the effects of antidepressant treatment and treatment outcome. Lp(a) levels were analysed at baseline in 35 in-patients with DSM-IV major depression who were then treated in a randomized double-blind manner with amitriptyline (n = 14) or paroxetine (n = 21), as well as in 33 healthy controls. Lp(a) levels were re-assessed after 4 weeks of treatment. We found a significant decrease in Lp(a) in patients treated with paroxetine, but not in those treated with amitriptyline. Our results suggest that antidepressant treatment with paroxetine might contribute to a decrease in vascular mortality risk irrespective of treatment outcome.

Objective: Despite reports of lower plasma cholesterol in depressed patients, major depressive disorder has been shown to increase cardiovascular risk. Our objective was to study the composition of lipoproteins in depressed patients and controls and to examine the effects of pharmacologic treatment and treatment response on lipoprotein composition., Method: Lipoprotein composition was analyzed in 65 adult inpatients at a university psychiatric hospital in Germany with DSM-IV major depressive disorder and 33 healthy controls (recruited via newspaper and radio ads) matched for age and sex. After the cross-sectional study phase, the patients were randomized in an open-label prospective trial to treatment with either mirtazapine or venlafaxine. Lipoproteins were reanalyzed after 4 weeks of treatment. Main outcome measures were total cholesterol, the low-density lipoprotein (LDL) to high-density lipoprotein (HDL) cholesterol ratio, and the LDL triglycerides to apolipoprotein B ratio. Secondary outcome measures were total triglycerides, HDL and LDL cholesterol levels, and apolipoproteins A1 and B levels. Comparisons were made between the 2 drug groups and between remitters and nonremitters as measured by the 21-item Hamilton Depression Rating Scale. The study was conducted from April 2003 through December 2007., Results: Total cholesterol at baseline was lower in patients than in controls (mean ± SD = 4.99 ± 0.98 mmol/L vs 5.63 ± 1.01 mmol/L; P = .003), with significantly lower HDL cholesterol (P < .001) and LDL cholesterol (P = .03) in patients. However, the ratio of LDL triglycerides to apolipoprotein B, an index of size and atherogenic potential of LDL particles, was higher in depressed subjects (mean ± SD = 0.46 ± 0.14 mmol/g vs 0.38 ± 0.09 mmol/g; P = .002). Irrespective of treatment allocation, we found significant improvement of cardiovascular risk parameters in remitters but found deterioration in nonresponders. The LDL cholesterol mean change from baseline (remitters vs partial responders vs nonresponders) was -0.06 mmol/L versus +0.39 mmol/L versus +0.56 mmol/L (P = .014); the mean change in LDL/HDL cholesterol ratio was -0.50 versus +0.14 versus +0.80 (P = .002); and the mean change in the LDL triglycerides per apolipoprotein B ratio was -0.01 versus -0.01 versus +0.08 (P = .045). No drug-specific changes in lipid concentrations during treatment were observed except for total cholesterol (venlafaxine group mean = -0.02 mmol/L and mirtazapine group mean = +0.37 mmol/L; P = .033)., Conclusions: In depressed patients, lipoprotein structure is changed toward LDL particles with a higher atherogenic potential. Remission from depression is associated with an improvement of the LDL/HDL cholesterol ratio, shifting lipoproteins toward a less atherogenic composition. Our findings should be confirmed in a larger study, as they have relevance for both researchers and clinicians., Trial Registration: German Clinical Trial Registry Identifier: DRKS00000008., (© Copyright 2011 Physicians Postgraduate Press, Inc.)

Objectives: Steroid-synthesis inhibitors are reported to reduce psychopathology in treatment-resistant depressed patients., Methods: We studied the effect of a 3-week treatment with ketoconazole on the evening plasma concentrations of cortisol, corticosteroid-binding globulin (CBG), dehydroepiandrosterone-sulfate (DHEA-S) and adrenocorticotrope hormone (ACTH) as well as morning cerebrospinal fluid (CSF) concentrations of cortisol, corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP) in six elderly treatment-resistant depressed patients., Results: While we found plasma cortisol concentrations to be unchanged, a decline in plasma DHEA-S concentrations indicated effective steroid-synthesis inhibition. In morning CSF we found CRH concentrations that did not change., Conclusions: Our preliminary observations indicate that the treatment of depressed patients with the steroid-synthesis inhibitor ketoconazole does not lead to a major increase in CSF CRH secretion.

Lowering the concentrations of free cortisol in depressed patients may be an important prerequisite to prevent glucocorticoid-related sequelae of depression. We tested the hypothesis that the hypothalamus-pituitary-adrenal (HPA) system-dampening effects of venlafaxine and mirtazapine differ. We compared the course of morning (08.00h) and afternoon saliva cortisol (16.00h) in 42 mirtazapine- and 45 venlafaxine-treated depressed patients during a 1-week wash-out and a 4-week treatment period in a randomised open trial. Mirtazapine lowered afternoon cortisol from week 1 to 4. In contrast, during the course of the entire treatment period, venlafaxine did not attenuate saliva cortisol concentrations. Treatment effects of mirtazapine on cortisol concentrations did not differ in remitters and non-remitters to treatment. High baseline cortisol concentrations, on the other hand, were related to an unfavourable course during venlafaxine treatment and patients remitting during venlafaxine treatment had significantly lower afternoon cortisol concentrations in saliva, when compared to non-remitting patients. Thus, mirtazapine and venlafaxine show different effects on HPA system activity as measured by saliva cortisol. This may be of relevance with regard to physical sequelae of depression., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

Background: Chronic stress as well as major depressive disorders are associated with hypercortisolemia and impaired hypothalamic-pituitary-adrenocortical axis functioning. The aim of this study was to determine whether in major depression changes in the activity patterns of local modulators of glucocorticoid action might contribute to an increase in cortisol bioavailability and if they change during antidepressant treatment and clinical response., Methods: Concentrations of urinary total cortisol (UFF), urinary total cortisone (UFE), tetrahydrocortisone (THE), tetrahydrocortisol (THF) and allo-THF (5alpha-THF) were measured in 10-hour nocturnal urine samples of 19 depressed patients and 15 healthy controls. The activity of 11beta-hydroxysteroid dehydrogenases (11beta-HSD) as well as 5alpha- and 5beta-reductases was assessed by calculating the ratios of glucocorticoid metabolites. Patients were treated for 28 days with either mirtazapine or venlafaxine. Enzyme activity was observed during the course of treatment and compared to healthy controls. Responders to treatment were selected for this analysis., Results: Depressed patients showed reduced 5alpha-reductase activity manifested as a significantly lower amount of 5alpha-THF (102.8 +/- 167.2 vs. 194.6 +/- 165.8 microg, p = 0.019). The increase in the UFF/UFE ratio (0.73 +/- 0.32 vs. 0.29 +/- 0.13, p < 0.0001) indicates reduced activity of renal 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2). During pharmacological treatment, 5alpha-reductase activity in patients returned to the level of the control group, while the decrease in 11beta-HSD2 activity persisted until day 28., Conclusions: Our results show changes in activity of intracellular modulators of steroid action in major depressive disorders, particularly a reduced activity of the intracellular cortisol-deactivating enzymes 5alpha-reductase and 11beta-HSD2. These changes suggest an increase in cortisol bioavailability within tissues.

Introduction: The present study was designed to test the hypothesis that total and free insulin-like growth factor-I (IGF-I) serum concentrations in depressed patients are related to hypothalamus-pituitary-adrenal (HPA) system activity and show a longitudinal decline in patients responding to treatment as well as to declining HPA system activity., Methods: We measured total and free IGF-I as well as IGF-binding protein-3 in 77 depressed patients after wash-out of pre-medication and again after 28 or 35 days of treatment with paroxetine or amitriptyline., Results: Total but not free IGF-I serum concentrations are related to saliva cortisol concentrations in drug-free depressed patients. In responders to both amitriptyline and paroxetine, total IGF-I serum concentrations declined during treatment., Discussion: Our findings show IGF-I to be related to HPA system activity and to decline in responders to treatment while serum concentrations of the biologically active free IGF-I are neither related to HPA system activity nor do they change during the course of treatment. Our data do not support the hypothesis that free IGF-I may play a major role in physical disturbances in depressed patients.

Major depression is associated with an increased risk for myocardial infarction. Adipokines have been shown to link obesity with metabolic disturbances. Based on this finding the present study was designed to investigate the effect of antidepressive treatment with either amitriptyline or paroxetine on circulating concentrations of resistin and adiponectin in depressed patients, and to establish, whether these adipokines are associated with the activation of the hypothalamic-pituitary-adrenal (HPA)-system. Thirty-seven depressed in-patients were treated in a double-blind, randomized protocol with either amitriptyline or paroxetine over a period of five weeks. After six drug free days blood was drawn on day 1 and again 36 days after antidepressive treatment for the measurement of resistin and adiponectin, fasting glucose and insulin concentrations. For quantification of free cortisol levels saliva was obtained daily at 0800 hours during weeks 1 and 5. While resistin concentrations decreased in patients remitting under amitriptyline and paroxetine (p<0.03), no changes were observed in non-remitters. At baseline, though not during treatment, circulating resistin concentrations correlated positively with free cortisol levels and with BMI (p<0.01). Adiponectin levels, however, did not change during treatment and were not associated with free cortisol concentrations but were instead positively related to QUICKI (p<0.03). In conclusion, the present data revealed resistin but not adiponectin to be related to free cortisol concentrations and to decline in remitters to antidepressive treatment.

Objective: There is substantial evidence that depression constitutes a risk factor for type 2 diabetes mellitus. A recent study has shown that high salivary cortisol levels are associated with decreased insulin sensitivity in unmedicated, depressed patients. Further, antidepressive treatment might have differential effects on hypothalamus-pituitary-adrenal (HPA) system activity. Therefore, the aim of the present study was to examine whether insulin sensitivity improves during anti-depressive treatment in depressed patients with declining HPA system activity., Method: Eighty inpatients with an episode of major depressive disorder (DSM-IV criteria) were treated in a double-blind, randomized protocol with either amitriptyline or paroxetine over a period of 5 weeks. After 6 drug-free days, an oral glucose tolerance test was performed on day 1 and again 35 days after antidepressive treatment. For quantification of free cortisol levels, saliva was obtained daily at 8:00 a.m. during weeks -1 (washout) and 5. The study was conducted from May 2005 to December 2005., Results: The insulin sensitivity index(Matsuda) increased in only those patients who remitted from major depressive disorder as a result of treatment with either antidepressant (F = 7.0, df = 1,74; p < .01), while correcting for body mass index. Further, cortisol concentrations declined in remitters and responders to amitriptyline (F = 2.1, df = 1,70; p < .05), but not in any other subgroup., Conclusion: Successful antidepressive treatment with either a selective serotonin reuptake inhibitor or a tricyclic substance increases the sensitivity to insulin in nondiabetic depressed patients. The herein presented longitudinal data do not exclude the HPA system as a major contributor to insulin resistance in depressed patients, but underscore the assumption of additional factors.

The accumulation of visceral fat is promoted by a specific endocrine syndrome, which is similarly found in major depression. The aim of this study was to investigate whether visceral fat depots increase in depressed patients during a follow-up period explaining the increased risk for cardiovascular disorders. Intraabdominal fat was measured in 29 depressed patients and 17 controls by computer tomography at the level of lumbar vertebra 4. In patients fat measurements were done initially during a major depressive episode and again after a follow-up period of 14 months; in controls the mean time interval between measurements was 28 months. In both groups, saliva was taken at 800 h over a period of seven days prior to each CT for the estimation of free cortisol. In patients only, an oral glucose tolerance test was also carried out. Compared to controls hyper- and normocortisolemic depressed patients showed a larger accumulation of visceral fat mass over time (hypercort.:132.0 +/- 45 vs. 144.7 +/- 47 cm(2), p = 0.07; normocort.: 115.5 +/- 53 vs. 135.0 +/- 51 cm(2), p = 0.002; controls: 130.1 +/- 66 vs. 137.3 +/- 76 cm(2), p = 0.4), despite similar weight gain (hypercort.: 2.1 +/- 5 kg, normocort.: 1.7 +/- 5 kg and controls: 2.3 +/- 4 kg). Further, normocortisolemic patients showed a trend for an higher percentile increase in visceral fat accumulation than controls (23.9 +/- 27 vs. 5.8 +/- 28%, p = 0.07). At follow-up, free cortisol concentrations were still above normal in patients who had been hypercortisolemic at first assessment (35.0 +/- 8 vs. 28.8 +/- 18 nmol/l, p = 0.1). Fasting and 2 h glucose concentrations were higher in hypercortisolemic compared to normocortisolemic patients at the index examination (6.2 +/- 1.1 vs. 5.0 +/- 0.05 mmol/l, p = 0.02; 11.5 +/- 2.7 vs. 7.8 +/- 1.9 mmol/l, p = 0.01). The larger proportion of visceral fat accumulation in patients may constitute a link for explaining the increased cardiovascular mortality in patients suffering from major depression.

Major depression increases cardiovascular risk despite lower cholesterol levels. Little is known about effects of antidepressants on metabolic risk factors. We studied lipoprotein composition, insulin sensitivity (quantitative insulin sensitivity check index), and saliva cortisol in 78 depressed patients before and after 35 days of amitriptyline or paroxetin treatment. Data were analyzed by principal component factor analyses and analysis of variance (ANOVA). At baseline, quantitative insulin sensitivity check index was inversely correlated with cortisol (r = -0.46; P = 0.005) in normal weight patients, with body mass index in overweight patients (r = -0.50; P < 0.001). In overweight patients, hypercortisolemia correlated inversely with total and low density lipoprotein cholesterol (eg, cortisol at 4:00 PM and low density lipoprotein cholesterol: r = -0.49, P = 0.002). After treatment, quantitative insulin sensitivity check index was unchanged. Triglycerides increased in responders to amitriptyline only (P < 0.05). Parameters of cholesterol metabolism improved slightly without differences between treatment groups (eg, high density lipoprotein: pre 43.5 +/- 12.0; post 47.6 +/- 13.0 mg/dL; P = 0.01; low density lipoprotein triglycerides, a measure of low density lipoprotein atherogenicity: pre 458 +/- 120; post 415 +/- 130 mg/g; P < 0,01). The inverse correlation of cortisol and cholesterol, at least in the obese subgroup, proposes a mechanism for the known association of depression with low cholesterol. As determinants of plasma lipids in major depression, we identified body mass index, insulin sensitivity, and cortisol. Although uncontrolled, our data suggest that treatment of depression exerts a mainly beneficial effect on lipid regulation.

Introduction: The temporal course of recovery of depressed patients' cognitive impairment is not fully understood., Methods: We used the California Verbal Learning Test (CVLT) to test declarative memory in 24 depressed patients before and after 35 days of antidepressive treatment as well as after long-term follow-up (> 12 months) in order to relate improvement of depression to recovery of cognitive impairment., Results: Patients with complete remission after 35 days had generally been less impaired at baseline. The disturbance of declarative memory in treatment responders as well as in non-responders did not change from baseline to end of treatment (day 35). However, our results revealed normal values in the CVLT sum score as well as in measures of short- and long-delay free-recall measures in both groups after long-term full remission., Discussion: We conclude that clinical response to antidepressive treatment precedes improvement of declarative memory. A low degree of impairment of declarative memory is associated with early complete remission of depression.

Background: To assess the effects of ambulatory blood pressure measurement (ABPM) upon sleep in mentally depressed patients with near absence of deep (stage 3 and 4) sleep., Methods: Twelve depressed patients aged 50.5+/-13.5 (21-item Hamilton Depression Rating Scale: 23.8+/-5.1) were studied on three consecutive nights in the sleep laboratory. In a random order, blood pressure was measured with a portable device over 24 h on either day 2 or 3. Polysomnographic data were analysed according to the criteria of Rechtschaffen and Kales., Results: Compared to the control night, there was a significant increase of awakenings during the ABPM night. However, total sleeping time as well as sleep efficiency remained unchanged. Percentage of nocturnal decrease in both systolic and diastolic blood pressure was unrelated to the number of arousals., Conclusion: In depressed patients with severe disturbances of sleep architecture, ABPM did not lead to a prolongation of time awake or decrease in sleep efficiency.

With regard to the course of basal human hypothalamus-pituitary-adrenal (HPA) system activity, there is a lack of data for comparing different classes of antidepressants. Ninety-four patients were included in a study comparing standardized treatment with paroxetine (PAROX) and amitriptyline (AMI) after a drug-free period of at least 6 days. Saliva for measurement of cortisol concentrations was obtained daily at 0800, 1600, and 2200 during the 6 days of drug-free washout and 35 days of active treatment. The course of HPA system activity and psychopathology, as assessed by the Hamilton Depression Scale, was compared by means of repeated-measurement analyses of variance (ANOVA-rm). Only AMI responders-not PAROX responders or nonresponders to either antidepressant-had a significant decline in saliva cortisol concentrations. In hypercortisolemically depressed patients, treatment with AMI may be preferable to PAROX in order to lower HPA system activity.

Objective: Similar to patients with a metabolic syndrome, patients with major depression are at increased risk of developing cardiovascular disorders. Interestingly, both disorders share a specific endocrine syndrome that promotes the accumulation of visceral fat, which again is considered a marker of increased cardiovascular morbidity and mortality., Methods: Intra-abdominal fat was measured in 22 postmenopausal depressed women and 23 age-matched healthy women by computer tomography at the level of lumbar vertebrae 1 (L1) and 4 (L4). Saliva was taken in patients and control subjects at 08:00 hours over a period of 7 drug-free days for the measurement of free cortisol. In patients only we performed an oral glucose tolerance test., Results: Compared with control subjects, depressed patients with elevated free cortisol concentrations showed similar visceral fat depots at L1 (113.0 +/- 41.6 vs. 94.3 +/- 53.2 cm(2)). Hypercortisolemic depressed patients also showed greater fat depots in this area (74.5 +/- 55.5 cm(2), p =.04) than the normocortisolemic patients. However, a comparison of all patients with control subjects revealed no difference in fat accumulation at either L1 or L4. Finally, glucose concentrations during the glucose tolerance test were higher in hypercortisolemic than in normocortisolemic patients, whereas their insulin levels showed only a tendency toward being increased., Conclusions: Hypercortisolemic depressed patients suffer from resistance to insulin and increased visceral fat. The fact that hypercortisolemia reverses depression-related fat loss, particularly in the visceral area, might partially explain why major depression can be considered a risk factor for cardiovascular disorders.

There is compelling evidence that depression constitutes an independent risk factor for cardiovascular morbidity and mortality. As exaggerated platelet reactivity is associated with an increased risk of intra-arterial thrombus formation, we studied platelet aggregability in patients with major depression both before and after 5 weeks of anti-depressant therapy as well as in healthy control subjects. Twenty-two depressed patients and 24 healthy control subjects participated in the study. Washed and rediluted platelets were stimulated with the agonists collagen and thrombin in three concentration steps. Depression was associated with a higher aggregability after stimulation with thrombin in the intermediate concentration and with collagen at the low concentration, with ceiling effects for the other concentrations. After 5 weeks of anti-depressant therapy, aggregability was somewhat less exaggerated, although this effect did not reach statistical significance. We thus conclude that major depression is associated with increased platelet aggregability, which seems to persist even under a marked improvement in depressive symptomatology. This effect may contribute to the increased cardiovascular morbidity in depressed patients.