The German Guidelines for the treatment of anxiety disorders: first revision.

Starting in 2019, the 2014 German Guidelines for Anxiety Disorders (Bandelow et al. Eur Arch Psychiatry Clin Neurosci 265:363-373, 2015) have been revised by a consensus group consisting of 35 experts representing the 29 leading German specialist societies and patient self-help organizations. While the first version of the guideline was based on 403 randomized controlled studies (RCTs), 92 additional RCTs have been included in this revision. According to the consensus committee, anxiety disorders should be treated with psychotherapy, pharmacological drugs, or their combination. Cognitive behavioral therapy (CBT) was regarded as the psychological treatment with the highest level of evidence. Psychodynamic therapy (PDT) was recommended when CBT was not effective or unavailable or when PDT was preferred by the patient informed about more effective alternatives. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs) are recommended as first-line drugs for anxiety disorders. Medications should be continued for 6-12 months after remission. When either medications or psychotherapy were not effective, treatment should be switched to the other approach or to their combination. For patients non-responsive to standard treatments, a number of alternative strategies have been suggested. An individual treatment plan should consider efficacy, side effects, costs and the preference of the patient. Changes in the revision include recommendations regarding virtual reality exposure therapy, Internet interventions and systemic therapy. The recommendations are not only applicable for Germany but may also be helpful for developing treatment plans in all other countries.

The German guidelines for the treatment of anxiety disorders.

A consensus group consisting of 36 experts representing 20 leading German specialist societies and patient self-help organizations developed evidence-based recommendations for the treatment of anxiety disorders in Germany. These were based on a systematic review of randomized controlled trials on anxiety disorders (n = 403) and on preexisting German and international guidelines. According to the consensus committee, anxiety disorders should be treated with psychotherapy or pharmacological drugs or a combination of both. Cognitive behavioral therapy (CBT) was regarded as the psychological treatment with the highest level of evidence. Psychodynamic therapy (PDT) was recommended for cases in which CBT was not effective or not available or in which PDT was the informed patient's preferred option. First-line drugs for anxiety disorders include selective serotonin reuptake inhibitors and serotonin-noradrenaline reuptake inhibitors. After remission, medications should be continued for 6-12 months. When either drug or psychotherapy was not effective, treatment should be switched to the other approach or to a combination of both. For patients non-responsive to standard treatments, alternative strategies are suggested. When developing a treatment plan, efficacy, side effects, costs and the preference of the patient should be considered. A large amount of data available from randomized controlled trials permit the formulation of robust evidence-based recommendations for the treatment of anxiety disorders. The recommendations were not only developed for the special situation in Germany, but may also be helpful for developing treatment plans in other countries.

The diagnosis of and treatment recommendations for anxiety disorders.

BACKGROUND: Anxiety disorders (panic disorder/agoraphobia, generalized anxiety disorder, social phobia, and specific phobias) are the most common mental illnesses. For example, the 12-month prevalence of panic disorder/agoraphobia is 6%. METHOD: This guideline is based on controlled trials of psychotherapy and pharmacotherapy, retrieved by a systematic search for original articles that were published up to 1 July 2013. Experts from 20 specialty societies and other organizations evaluated the evidence for each treatment option from all available randomized clinical trials and from a synthesis of the recommendations of already existing international and German guidelines. RESULTS: 403 randomized controlled trials were evaluated. It was concluded that anxiety disorders should be treated with psychotherapy, psychopharmacological drugs, or both. Response rates to initial treatment vary from 45% to 65%. Cognitive behavioral therapy is supported by higher-level evidence than any other psychotherapeutic technique. Psychodynamic therapy is recommended as a second-line treatment. Among anxiolytic drugs, the agents of first choice are selective serotonin reuptake inhibitors and serotoninnorepinephrine reuptake inhibitors. The patient's preference should be considered in the choice of treatment. Drug treatment should be continued for 6 to 12 months after remission. If psychotherapy or drug treatment is not adequately effective, then the treatment should be switched to the other form, or to a combination of both. CONCLUSION: The large amount of data now available from randomized controlled trials permits the formulation of robust evidence-based recommendations for the treatment of anxiety disorders. Future work should more closely address the necessary duration of psychotherapy and the efficacy of combined psychotherapy and drug treatment.

Elevated IL-6 levels in patients with atypical depression but not in patients with typical depression.

Elevated levels of the proinflammatory cytokine Interleukin-6 (IL-6) are among the most consistent findings in patients with major depressive disorder (MDD). Additionally, some evidence suggests that elevated cytokine levels in patients with major depression are responsible for the development of metabolic syndrome in patients suffering from MDD. Therefore, the aim of the study was to examine the concentrations of IL-6 in specific subtypes of MDD and to investigate their relationship to metabolic factors. Twenty-four patients with typical (24) and atypical (eight) major depression according to DSM-IV criteria were studied and compared to 24 normal controls. Blood samples were collected during a stepwise glucose-clamp procedure, and IL-6 concentrations were measured by high sensitivity ELISA. IL-6 levels were elevated in patients suffering from atypical depression but not in patients with typical depression, compared to normal controls. IL-6 correlated significantly with HbA1c, insulin, waist girth, BMI, number of alcoholic drinks per week and C-reactive protein. Our data indicate that high concentrations of IL-6 during the glucose clamp may be limited to the atypical subgroup of patients with MDD.

Bone mineral density in a cohort of Estonian women with major depression.

SUMMARY: The study examines bone mineral density in 50 women (29 to 70 years) treated as outpatients for major depression and a healthy comparison group of 30 women. Women with major depression had lower T scores and Z scores at the lumbar spine but not at the femur. PURPOSE: The purpose of this study was to replicate the finding that women with depression have low bone mineral density (BMD) in an eastern European country. METHODS: A total of 50 women (29 to 70 years) treated as outpatients for major depression and a healthy comparison group of 30 women were included. Diagnosis was confirmed using the MINI interview. Bone density was assessed using dual-energy X-ray absorptiometry. RESULTS: Women with major depression had lower T scores and Z scores at the lumbar spine but not at the femur. Apart from age, there was no significant covariate that affected the difference between the groups. The concentration of ß-Crosslaps, a marker of bone metabolism, tended to be higher in women with depression. CONCLUSIONS: Women with depression have low BMD at the lumbar spine. The distinguishing characteristic of the study is that the finding could be replicated in an eastern European population of middle-aged to elderly patients who were not hospitalized and had relatively high levels of physical activity and low levels of alcohol use and smoking.

Intima-media thickness in women with borderline personality disorder.

OBJECTIVE: Patients with borderline personality disorder (BPD) may have a higher risk of developing cardiovascular disease caused by altered endocrine, metabolic, and inflammatory parameters. Increased intima-media thickness (IMT) is considered an early marker of atherosclerosis and is associated with most cardiovascular risk factors. METHODS: The mean IMT of the common carotid arteries was assessed by B-mode ultrasound in 47 women with BPD and 28 age-matched healthy women. Mean (standard deviation) age for BPD participants was 31.2 (10.4) years and 31.9 (11.0) years for the comparison group. In addition, Adult Treatment Panel III criteria for metabolic syndrome and markers of inflammation were measured. The patients were characterized by applying DSM-IV criteria and obtaining self-reports of adverse childhood experiences. RESULTS: Women with BPD had a significantly higher IMT than healthy women (mean [standard deviation] = 0.41 [0.11] versus 0.34 [0.11] mm, p = .02). In linear regression analysis, IMT was significantly associated with BPD even when adjusting for body mass index (ß = 0.27, p = .04) and physical activity (ß = 0.29, p = .02). CONCLUSIONS: The data suggest that women with BPD are at increased risk of developing subsequent cardiovascular disease.

Major depression, borderline personality disorder, and visceral fat content in women.

Major depressive disorder (MDD) is associated with increased volumes of visceral fat and a high prevalence of the metabolic syndrome. In turn, affective disorders are frequently found in patients with borderline personality disorder (BPD). It is therefore unclear whether BPD per se may influence body composition. In order to clarify a potential relationship between BPD and body composition, we measured visceral fat content (VFC) in young depressed women with and without comorbid BPD and related this parameter to various features of the metabolic syndrome. Visceral fat content was measured by magnetic resonance imaging in 22 premenopausal women with MDD only, in 44 women with comorbid MDD and BPD, in 12 female BPD patients without MDD, and in 34 healthy women (CG). Data showed that depressed women without comorbid BPD had a 335% higher VFC and women with comorbid BPD had a 250% higher VFC than the CG women. When controlling for age, data showed significant effects of MDD on VFC (F = 8.4; P = 0.005). However, BPD, with or without MDD, was not related to VFC. Young depressed women with and without comorbid BPD display increased visceral fat content when compared to control subjects and may therefore constitute a risk group for the development of the metabolic syndrome. BPD per se is not an additive risk factor in this context.

Pain complaints in a sample of psychiatric inpatients.

OBJECTIVE: We examined the prevalence of pain and pain severity in a sample of psychiatric inpatients. Currently, scant information exists about which patient groups are most affected by pain. METHODS: Pain was assessed in 416 psychiatric inpatients using the brief pain inventory. Patients were characterized by applying DSM-IV criteria and obtaining self-reports of adverse childhood experiences. RESULTS: Of psychiatric inpatients, 31.0% reported having substantial pain. Women with posttraumatic stress disorder (PTSD) had the highest prevalence of substantial pain among all psychiatric inpatients and a significantly higher rate compared to women without PTSD (49% vs. 28%, P=.02). Pain was significantly associated with adverse childhood experiences in both men and women. CONCLUSION: Within a group of psychiatric inpatients, pain is associated with PTSD in women and with adverse childhood experiences in both men and women. Attention should therefore be paid towards such high-risk groups and the consequences that the pain might entail for physical and mental health.

Short Hypoxia Does not Affect Plasma Leptin in Healthy Men under Euglycemic Clamp Conditions.

Leptin is involved in the endocrine control of energy expenditure and body weight regulation. Previous studies emphasize a relationship between hypoxic states and leptin concentrations. The aim of this study was to investigate the effects of acute hypoxia on leptin concentrations in healthy subjects. We examined 14 healthy men. Hypoxic conditions were induced by decreasing oxygen saturation to 75% for 30 minutes. Plasma leptin concentrations were determined at baseline, after 3 hours of euglycemic clamping, during hypoxia, and repeatedly the following 2.5 hours thereafter. Our results show an increase of plasma leptin concentrations in the course of 6 hours of hyperinsulinemic-euglycemic clamping which may reflect diurnal rhythmicity. Notwithstanding, there was no difference between levels of leptin in the hypoxic and the normoxic condition (P = .2). Since we did not find any significant changes in leptin responses upon hypoxia, plasma leptin levels do not seem to be affected by short hypoxic episodes of moderate degree.

Impact of glycemic variations on the regulation of androgen metabolism in obese women with polycystic ovary syndrome.

OBJECTIVE: To assess the influence of alterations in glucose concentrations on androgen levels in patients with polycystic ovary syndrome (PCOS) and in healthy controls. DESIGN: Prospective, controlled study. SETTING: Tertiary care center. PATIENT(S): Seven patients with PCOS and 20 healthy controls. INTERVENTION(S): Hyperinsulinemic glucose clamp study with stepwise reduction of the plasma glucose level from hyperglycemia to hypoglycemia. MAIN OUTCOME MEASURE(S): Concentrations of insulin, C-peptide, cortisol, T, androstenedione, 17-hydroxyprogesterone, DHEA, and DHEAS during hyperglycemia, euglycemia, and hypoglycemia. RESULT(S): Total T levels and the free androgen index were significantly higher in the PCOS group at baseline and throughout the clamp. The levels of T, androstenedione, DHEAS, and 17-hydroxyprogesterone were not influenced by short-term changes of plasma glucose concentrations in both groups. However, hypoglycemia led to a significant increase in DHEA levels in PCOS patients as well as in controls. Cortisol levels were not increased during hypoglycemia in either group. CONCLUSION(S): In contrast to men, androgen levels are not influenced by short-term changes of plasma glucose levels in PCOS patients and in healthy women. However, DHEA concentrations increase with decreasing glucose levels independently from an activation of the hypothalamic-pituitary-adrenal axis. This supports a gender difference regarding the counterregulatory hormone response to hypoglycemia.

Angiogenic factors in patients with current major depressive disorder comorbid with borderline personality disorder.

BACKGROUND: Major depression has been associated with endocrine and immune alterations, in particular a dysregulation of the hypothalamus-pituitary-adrenal system with subsequent hypercortisolism and an imbalance of pro- and anti-inflammatory cytokines. Recent studies suggest that vascular endothelial growth factor (VEGF), a cytokine involved in angiogenesis and neurogenesis, may also be dysregulated during stress and depression. These observations prompted us to examine VEGF and other angiogenic factors in patients with major depressive disorder. METHODS: Twelve medication-free female patients with a major depressive episode in the context of borderline personality disorder (MDD/BPD) and twelve healthy women were included. Concentrations of VEGF, VEGF receptors 1 and 2, basic fibroblast growth factor-2 (FGF-2), hepatocyte growth factor (HGF), angiopoetin-2, interleukin-8 (IL-8) and transforming growth factor-beta1 (TGF-beta1) were determined from serum profiles. RESULTS: Increased concentrations of VEGF and FGF-2 were found in MDD/BPD patients compared to the healthy comparator group. No group differences were found concerning the other angiogenic factors examined. CONCLUSION: Depressive episodes in the context of borderline personality disorder may be accompanied by increased serum concentrations of VEGF and FGF-2. Similar findings have been observed in patients with major depression without a borderline personality disorder. A dysregulation of angiogenic factors may be another facet of the endocrine and immunologic disturbances frequently seen in patients with depressive episodes.

Disturbed glucose disposal in patients with major depression; application of the glucose clamp technique.

OBJECTIVE: To assess the whole-body glucose disposal in patients with both typical and atypical depression and to characterize the neuroendocrine responses during a hyper-, eu-, hypoglycemic stepwise clamp experiment in patients with both subtypes of major depression. Depressive disorders and alterations in glucose metabolism are closely associated. The glucose clamp technique is considered to be the "gold standard" for the assessment of whole-body glucose disposal. METHODS: We studied 19 patients with typical major depressive disorder (MDD), 7 patients with atypical major depression, and 30 men and women of a healthy comparator group using a stepwise glucose clamp procedure. Glucose disposal rates were assessed and concentrations of hormones involved in glucose allocation were measured. RESULTS: Glucose disposal rates were lower by 19% in patients with typical MDD and 30% in patients with atypical MDD than in the group of healthy controls (3.2 +/- 0.8 and 2.8 +/- 0.7 versus 4.0 +/- 1.0 mmol h(-1) kg(-1)). C-peptide concentrations were 26% higher in patients with atypical MDD and similar in patients with typical MDD and healthy controls. Vascular endothelial growth factor concentrations were 30% higher in typical MDD and similar in atypical MDD and the control group. CONCLUSIONS: Whole-body glucose disposal is reduced in patients with typical and atypical depression. The observed neuroendocrine responses suggest a hyperactive allocation system in typical depression and a hypoactive allocation system in atypical depression.

[Effectiveness of dialectical behavior therapy for patients with borderline personality disorder in the long-term course--a 30-month-follow-up after inpatient treatment]. / Effektivität der dialektischen Verhaltenstherapie bei Patienten mit Borderline-Persönlichkeitsstörung im Langzeitverlauf--Eine 30-Monats-Katamnese nach stationärer Behandlung.

BACKGROUND: The beneficial effects of Dialectical Behavior Therapy (DBT) for patients with borderline personality disorder (BPD) are well established. However, it is not well known whether this type of treatment relieves symptoms and signs of BPD in the long-term course thereafter and whether the results of DBT are transferable for patients with high comorbidity. METHODS: We conducted a follow-up examination of 50 consecutive inpatients with BPD as defined by DSM-IV. The patients were examined at admission, at discharge and 15 and 30 months after discharge. For the clinical diagnosis and to survey psychopathology we used the Structured Clinical Interview for DSM-IV (SCID), the Global Assessment of Functioning (GAF) and several self-rating-instruments. RESULTS: Compared to admission 30 months after discharge we observed the following results: A significant number of patients did not meet the DSM-IV criteria for BPD anymore, comorbidity (particularly mood disorders, drug or alcohol abuse/dependence and eating disorders) was reduced, psychosocial functioning was improved and general and BPD-typical symptoms were relieved. CONCLUSION: Our findings support the efficacy of DBT in an inpatient setting and show that the achieved success of therapy is stable for a prolonged period of time. Patients with high comorbidity seem to profit from DBT as well.

Bone mineral density, bone turnover, and osteoprotegerin in depressed women with and without borderline personality disorder.

OBJECTIVE: Low bone mineral density has repeatedly been reported in patients with major depressive disorder (MDD), and MDD has been discussed as a risk factor for the development of osteoporosis. MDD in young adults often occurs in the context of borderline personality disorder (BPD), and both MDD and BPD have been associated with a dysregulation of the hypothalamic-pituitary-adrenal system and subsequent hypercortisolemia. To date, it is unclear whether comorbid BPD in depressed patients modulates the extent of bone mass reduction. Therefore, we examined bone density, markers of bone turnover, and proinflammatory cytokines in depressed patients with and without BPD. Patients with BPD alone and healthy women served as comparison groups. METHOD: Twenty-four patients with MDD and 23 patients with comorbid MDD and BPD were included. Sixteen patients with BPD and 20 healthy women of similar body mass index served as the comparison group. BMD was assessed by means of dual-energy x-ray absorptiometry. Markers of bone turnover, endocrine and immune parameters were determined. For data analysis, the group of depressed patients without comorbid BPD was divided according to age into two groups (younger depressed patients with a mean age of 30 years and older patients with a mean age of 42.9 years). RESULTS: BMD at the lumbar spine was significantly reduced in a) depressed women with comorbid BPD (mean age, 28.6 years) and in b) older depressed patients without BPD (mean age, 42.9 years). Osteocalcin, a marker of osteoblastic activity, and crosslaps, a marker of bone loss, were significantly different between the study groups. Tumor necrosis factor-alpha was increased in depressed patients when compared with healthy women. Furthermore, TNF-alpha was positively correlated with serum crosslaps, a marker for osteoclastic activity. CONCLUSION: Depression is associated with reduced bone mass, in particular in patients with comorbid BPD. Possible factors contributing to BMD reduction include endocrine and immune alterations associated with either MDD or BPD. We conclude from our data that a history of MDD with and without comorbid BPD should be considered as a risk factor in clinical assessment instruments for the identification of persons prone to osteoporosis.

Persistent suppression of resting energy expenditure after acute hypoxia.

Resting energy expenditure (REE) is known to be influenced by various ambient conditions such as oxygen supply. Investigations in healthy subjects during acute hypoxia revealed a drop in REE, but persistent effects after hypoxia had ended have not been examined so far. Although indirect calorimetry is a well-established method to measure REE, it may lead to false conclusions when hyperventilation, rise in lactate or catecholamines, and decrease of food intake accompany hypoxia. Therefore, we determined REE in healthy men after hypoxia had ended and under conditions of controlled energy supply during a glucose clamp. In a double-blind crossover study design, we induced hypoxia for 30 minutes by decreasing oxygen saturation to 75% (vs 96% in a control session) in 13 healthy men. Indirect calorimetry was performed at baseline and 150 minutes after hypoxia had ended. Plasma glucose was held stable between 4.5 and 5.5 mmol/L, and lactate as well as catecholamine concentrations were monitored. In parallel, we measured alterations in hormones of the hypothalamic-pituitary-thyroid axis, which is one known factor mediating changes in REE. Resting energy expenditure was decreased after hypoxia (from 1656+/-80 to 1564+/-97 kcal/d) as compared with the normoxic control condition (1700+/-82 to 1749+/-79 kcal/d, P=.037), whereas the respiratory quotient remained stable (P=.79). Plasma lactate, catecholamine levels, and the pituitary thyroid secretory activity were unchanged after hypoxia (P>.2). Our data demonstrate that the REE decrease persists 150 minutes after acute hypoxia, indicating an adaptation of energy metabolism. This should be valued as an additive pathogenic factor in diseases with disturbed energy metabolism.

Cortisol, the cortisol-dehydroepiandrosterone ratio, and pro-inflammatory cytokines in patients with current major depressive disorder comorbid with borderline personality disorder.

BACKGROUND: Major depression in young women is often comorbid with borderline personality disorder (BPD); however, adrenal steroids and pro-inflammatory cytokines in patients with comorbid current major depressive disorder and BPD (MDD/BPD) have not been systematically examined. Therefore, our study aimed at examining serum profiles of cortisol, cytokines, and the cortisol/dehydroepiandrosterone (cortisol/DHEA) ratio in MDD/BPD patients and a healthy comparison group. METHODS: Twelve medication-free female patients with MDD/BPD and 12 healthy women were included. Serum profiles of cortisol, DHEA, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1beta were sampled, and the molar cortisol/DHEA ratio was determined. RESULTS: Concentrations of serum cortisol, TNF-alpha, and IL-6, as well as the cortisol/DHEA ratios were significantly increased in MDD/BPD patients as compared with the healthy comparison group. CONCLUSIONS: Depressed patients with comorbid BPD display endocrine and immune alterations similar to those observed in cases of melancholic MDD without BPD. Elevated concentrations of serum cortisol, cortisol/DHEA ratios, and pro-inflammatory cytokines might indicate a state marker in these patients and might contribute to long-term metabolic alterations that have also been associated with MDD.

Acute hypoxia decreases plasma VEGF concentration in healthy humans.

Vascular endothelial growth factor (VEGF) is known to be upregulated by hypoxia in vitro. However, in vivo data about VEGF regulation in chronic hypoxic diseases are conflicting. We investigated the effects of hypoxia on plasma VEGF concentration in healthy subjects. To control known confounders, such as insulin, glucose concentrations, or exercise, hypoxic effects on VEGF were studied during experimentally clamping glucose concentrations at rest. In a double-blind crossover study design, we induced hypoxia for 30 min by decreasing oxygen saturation to 75% (vs. normoxic control) in 14 healthy men. Plasma VEGF concentration was determined at baseline, immediately after hypoxia had ended, and after a further 150 min. Levels of its soluble (s)Flt-1 receptor were assessed at baseline and at the end of the clamp. In parallel, catecholamine and cortisol levels were monitored. To investigate potential effects of glucose administration on the release of VEGF, we performed a third session, reducing glucose infusion for 30 min while serum insulin was held stable thereby inducing hypoglycemia. Hypoxia decreased VEGF levels compared with the normoxic control (P<0.05). VEGF concentrations increased during hypoglycemia (P<0.02) but were comparable to the normoglycemic control at the end of the clamp (P>0.80). sFlt-1 receptor concentration remained unchanged during hypoxia and hypoglycemia compared with control (both P>0.4). Epinephrine concentration (P<0.01) increased upon hypoxia, whereas norepinephrine and cortisol did not change. Contrary to in vitro studies, in healthy humans hypoxia decreases plasma VEGF concentration, suggesting that systemic VEGF concentration may be differently regulated than the expression on cellular basis.

Effectiveness of dialectical behaviour therapy for borderline personality disorder in an inpatient setting.

This study evaluates the effectiveness of dialectical behaviour therapy (DBT) for borderline personality disorder (BPD) in an unselected, comorbid population seeking 3-month inpatient treatment. We studied 50 consecutively admitted individuals (44 women, six men) with BPD as defined by DSM-IV at three time points (at admission, at discharge, and at the 15-month follow-up). For the clinical diagnoses, we used the Structured Clinical Interview for DSM-IV (SCID) and compared the frequencies of comorbid axis I and axis II disorders at admission and at the 15-month follow-up. Overall, participants showed a high degree of comorbidity. Psychopathology was significantly reduced at post-treatment and at follow-up. Effect sizes for outcome measures were within the range of those of previous studies. Our findings support the notion that the results of the DBT efficacy research can be generalized to an inpatient setting and to patients with BPD disorder with high comorbidity.

Visceral fat deposition and insulin sensitivity in depressed women with and without comorbid borderline personality disorder.

OBJECTIVE: Major depressive disorder (MDD) is associated with increased intra-abdominal fat, an important antecedent of noninsulin-dependent diabetes mellitus (NIDDM) and cardiovascular disorders. Furthermore, MDD is commonly accompanied by endocrine and immune dysregulation that has also been discussed in connection with the pathogenesis of NIDDM and ischemic heart disease. In borderline personality disorder (BPD), a dysregulation of the hypothalamic-pituitary-adrenal system has also been described. Therefore, our study aimed at examining visceral fat, insulin resistance, and alterations of cortisol and cytokines in young depressed women with and without comorbid BPD. METHODS: Visceral fat was measured in 18 premenopausal women with MDD and in 18 women comorbid with MDD and BPD by means of magnetic resonance tomography at the level of the first lumbar vertebral body. Twelve BPD patients without MDD and 20 healthy women served as the comparison groups. Concentrations of fasting cortisol, tumor necrosis factor-alpha, and interleukin-6 were measured, and indicators of insulin resistance and beta-cell sensitivity were calculated according to the homeostasis assessment model. RESULTS: We found increased visceral fat in women comorbid with MDD and BPD, and to a lesser extent, in women with MDD but without BPD. Insulin sensitivity was reduced in comorbid patients. Serum interleukin-6 (IL-6) and tumor necrosis factor-alpha concentrations were significantly increased in both groups of depressed patients. Reduced insulin sensitivity correlated with the amount of visceral fat and with serum concentrations of IL-6. CONCLUSION: Young depressed women with and without comorbid BPD display increased visceral fat and may constitute a risk group for the development of NIDDM and the metabolic syndrome. Our data support the hypothesis that the immune and endocrine alterations associated with MDD and BPD may contribute to the pathophysiologic processes associated with NIDDM.

Bone mineral density, markers of bone turnover, and cytokines in young women with borderline personality disorder with and without comorbid major depressive disorder.

OBJECTIVE: The pathogenesis of bone loss in major depressive disorder is a matter of debate. Studies of bone loss in nonpsychiatric medical disorders have found an association between the activation of osteoclastic cells and an imbalance of pro- and antiinflammatory cytokines. Since major depressive disorder is also associated with alterations in serum cytokine concentrations, the authors hypothesized that bone loss in patients with major depressive disorder and comorbid borderline personality disorder may be associated with cytokines capable of activating osteoclastic cells. METHOD: Twenty-two patients with borderline personality disorder and comorbid current or lifetime major depressive disorder were compared with 16 patients with borderline personality disorder who did not have major depressive disorder and 20 healthy volunteers. Bone mineral density was assessed by means of dual-energy x-ray absorptiometry. Markers of bone turnover as well as endocrine and immune measures were determined. RESULTS: The bone mineral density of 10 patients with borderline disorder plus current major depressive episode was significantly lower than that of the healthy subjects and the patients with borderline personality disorder without depression. Values of crosslaps, osteocalcin, serum cortisol, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 were significantly higher in the patients with borderline disorder plus current major depressive episode than in the healthy subjects. Crosslaps correlated positively with TNF-alpha but negatively with bone mineral density at the lumbar spine. Patients with borderline personality disorder who did not have current or lifetime depression displayed no alterations of either bone mineral density or the immunological and hormonal measures examined. CONCLUSIONS: Young women with comorbid borderline personality disorder and major depressive disorder have an elevated risk for osteoporosis. Borderline personality disorder per se is not associated with low bone mineral density. These data suggest that the immune and endocrine disturbances associated with depressive disorders in the context of borderline personality disorder may play a role in the pathophysiological process underlying bone loss in the patients studied.