Caught in a web of trauma: Network analysis of childhood adversity and adult mental ill-health.

BACKGROUND: Current interventions for adverse childhood experiences have only limited effectiveness. OBJECTIVE: We sought to identify optimal targets for the development of new interventions against adverse childhood experiences (ACE), that is, ACEs that a) are so central in the network of childhood adversity that curbing them is likely to impact other types of adversity, too, and b) are so central to the link of childhood adversity and adult mental ill-health that curbing them is likely to prevent this negative long-term effect from developing. PARTICIPANTS AND SETTING: 384 adult psychiatric inpatients. METHODS: Using the R packages qgraph and IsingFit, we analyzed the ACE network and the common network of ACEs and adult mental disorders. RESULTS: We found two clusters of ACEs: direct interactions with the child and indirect traumatization via adverse circumstances. When controlling for interrelatedness, the associations of sexual abuse with posttraumatic stress disorder and borderline personality disorder were the only direct links between ACEs and adult mental disorders. CONCLUSIONS: As neglect and violence against the mother were the most influential ACEs, curbing them is likely to destabilize the whole network of adversity. Thus, neglect and violence against the mother lend themselves as candidate targets for the development of new interventions. As sexual abuse was the only link between childhood adversity and adult mental ill-health, interventions against it seem most likely to keep this negative long-term effect from developing. Further, ideally prospective, research is needed to corroborate these findings.

The Use of Antidepressive Agents and Bone Mineral Density in Women: A Meta-Analysis.

Antidepressive agents are one of the fastest-growing classes of prescribed drugs. However, the effects of antidepressive agents on bone density are controversial. The aim of this meta-analysis is to evaluate the state of research on the relationship between the use of tricyclic antidepressants (TCAs) or selective serotonin reuptake inhibitors (SSRIs) and bone mineral density (BMD) in women. The database searched was Pubmed. The meta-analysis included human studies in women fulfilling the following criteria: (i) an assessment of bone mineral density in the lumbar spine, the femoral neck or the total hip; (ii) a comparison of the BMD of depressed individuals using antidepressive agents (SSRIs or TCAs), and a control group that did not use antidepressive agents; (iii) measurement of BMD using dual-energy X-ray absorptiometry (DXA); and (iv) calculations of the mean BMD and standard deviation or standard error. Four studies were identified, which, in total, included 934 women using antidepressive agents and 5767 non-using individuals. The results showed that no significant negative composite weighted mean effect sizes were identified for the comparisons between SSRI users and non-users. Similarly, no significant negative composite weighted mean effect sizes were identified for the comparisons between TCA users and non-users, indicating similar BMD in SSRI or TCA users and non-users. The meta-analysis shows that the association between antidepressant medication and bone mineral density has not been extensively researched. Only four studies fulfilled the inclusion criteria. The global result of the literature review and meta-analysis was that the use of antidepressive agents was not associated with lower or higher BMD. This result applies to both SSRIs and TCAs and to all measurement locations (lumbar spine, femoral neck and total hip).

All Unhappy Childhoods Are Unhappy in Their Own Way-Differential Impact of Dimensions of Adverse Childhood Experiences on Adult Mental Health and Health Behavior.

Adverse childhood experiences have consistently been linked with poor mental and somatic health in adulthood. However, due to methodological restraints of the main lines of research using cumulative or selective models, little is known about the differential impact of different dimensions of adverse childhood experiences. Therefore, we gathered data from 396 psychiatric in-patients on the Adverse Childhood Experiences (ACE) questionnaire, extracted dimensions using factor analysis and compared this dimensional model of adverse childhood experiences to cumulative and selective models. Household Dysfunction (violence against the mother, parental divorce, substance abuse or incarceration of a household member) was associated with poor health behaviors (smoking, alcohol dependency and obesity as proxy marker for an imbalance between energy intake and physical activity) and with poorer socio-economic achievement (lower education and income) in adulthood. The previously reported associations of maltreatment and sexual abuse with these outcome criteria could not be corroborated. Both Maltreatment (emotional and physical neglect and abuse) and Sexual Abuse predicted BPD, PTSD and suicidal behavior. However, the two ACE dimensions showed sufficiently divergent validity to warrant separate consideration in future studies: Maltreatment was associated with affective and anxiety disorders such as social phobia, panic disorder and major depressive disorder, whereas Sexual Abuse was associated with dysregulation of bodily sensations such as pain intensity and hunger/satiation. Also, we found both quantitative and qualitative evidence for the superiority of the dimensional approach to exploring the consequences of adverse childhood experiences in comparison to the cumulative and selective approaches.

Bone density and depressive disorder: a meta-analysis.

BACKGROUND: The aim of this study was to evaluate the evidence of low bone mineral density (BMD) in depression. Low BMD is a major risk factor for osteoporotic fractures and frailty. METHODS: The searched database was Pubmed, Meta-analysis included human studies in men and women fulfilling the following criteria: (1) assessment of BMD in the lumbar spine, the femur or the total hip; (2) comparison of BMD between depressed individuals and the healthy control group; (3) measurement of BMD using dual-energy X-ray absorptiometry (DEXA); and (4) data on the mean, standard deviation, or standard error of BMD. RESULTS: Twenty-one studies were identified, encompassing 1842 depressed and 17,401 nondepressed individuals. Significant negative composite weighted mean effect sizes were identified for the lumbar spine (d = -0.15, 95%CL -0.22 to -0.08), femur (d = -0.34, 95%CL -0.64 to -0.05), and total hip (d = -0.14, 95%CL -0.23 to -0.05) indicating low BMD in depression. Examining men and women shows low bone density in the lumbar spine and femur in women and low bone density in the hip in men. The differences between men and women with MDD and the comparison group tended to be higher when examined by expert interviewers. Low bone density was found in all age groups. CONCLUSIONS: Bone mineral density is reduced in patients with depressive disorders. The studies provide little evidence for potential relevant mediating factors.

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.

Prevalence of the metabolic syndrome in patients with borderline personality disorder: results from a cross-sectional study.

Metabolic syndrome (MetS) is an important risk factor for the development of type-2 diabetes and coronary artery disease. We aimed to compare the MetS prevalence in patients with borderline personality disorder (BPD) with comparison subjects followed in primary care from a similar region. One hundred and thirty-five BPD patients according to DSM-IV diagnostic criteria were compared to 1009 subjects from primary care. We used the American Heart Association/National Heart, Lung and Blood Institute criteria to determine the rate of MetS. The age-standardized prevalence of MetS was more than double in patients with BPD compared to comparison subjects (23.3 vs. 10.6 %, p < 0.05). Regarding individual MetS criteria, hyperglycemia was significantly more prevalent in both genders (p < 0.05). Abdominal obesity (p < 0.05) and hypertriglyceridemia (p < 0.05) were significantly higher only in women with BPD. Within BPD patients, an increased rate of MetS was associated with higher BMI (p = 0.004), age (p = 0.03), treatment with second-generation antipsychotics (quetiapine, olanzapine and clozapine; p = 0.032), dysthymia (p = 0.031), panic disorder (p = 0.032), benzodiazepine dependency (p = 0.015) and binge eating disorder p = 0.02). Our results demonstrate an increased MetS rate, dysregulated glucose and lipid metabolism in patients with BPD. Cardiometabolic monitoring and careful screening for physical health conditions among people with BPD is warranted.

Prevalence of the metabolic syndrome in unipolar major depression.

Previous studies on the association between affective disorders and the metabolic syndrome yielded inconclusive results. Therefore, we examined the prevalence of the metabolic syndrome in 230 men and women with unipolar major depressive disorder during inpatient treatment and compared it to 1,673 subjects from primary care from a similar region in northern Germany. We used the AHA/NHBLI criteria to determine the rate of metabolic syndrome (MetS) and each single criterion of MetS in both groups. The age-standardized prevalence of MetS was 2.4× as high in patients with major depressive disorder (MDD) compared with data from comparison subjects (41.0% vs. 17.0%). With respect to the single criteria, elevations were found in MDD patients for fasting glucose and triglycerides in both genders, and waist circumference in women. Men in the patient and the comparison groups were found to have higher rates of increased fasting glucose and triglycerides than women in the respective groups. Factors associated with the MetS in MDD patients comprise body mass index and the severity of depression. Our results demonstrate an increased prevalence of the MetS in men and women with MDD. Interventions for the frequently untreated metabolic abnormalities and careful screening for physical health conditions among people with MDD are warranted.

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.

Prevalence of the metabolic syndrome in men and women with alcohol dependence: results from a cross-sectional study during behavioural treatment in a controlled environment.

AIMS: Prevalence of metabolic syndrome (MetS) in men and women who use alcohol has been inconsistent in the literature. The aim of this study is to compare the prevalence of MetS in patients with a diagnosis of alcohol dependence who are currently abstinent in a controlled environment, and in control subjects followed in primary care from a similar region in Northern Germany. DESIGN: Cross-sectional study. SETTING: In-patient cognitive behavioural therapy. PARTICIPANTS: One hundred and ninety-seven men and women with alcohol dependence during behavioural treatment in a controlled environment were compared to 1158 subjects from primary care from a similar region in northern Germany. MEASUREMENTS: We used the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHBLI) criteria to determine the rate of MetS and each single criterion of MetS in both groups. FINDINGS: The prevalence of MetS was almost twice as high in men and women with alcohol dependence compared to control subjects (30.6% versus 17.0%). With respect to the single criteria, elevations were found for fasting glucose and blood pressure in both genders and for triglycerides in women only. High density lipoprotein (HDL)-cholesterol was higher in men and women with alcohol dependence. CONCLUSIONS: Our results demonstrate an increased rate of MetS, increased blood pressure and dysregulation of glucose and lipid metabolism in alcohol-dependent patients. Whether high HDL-cholesterol has cardioprotective effects in this context remain doubtful.

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.

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.