Association of hypertension, type 2 diabetes mellitus and dyslipidemia with the duration of inpatient treatments and recurrence of schizophrenia.

OBJECTIVE: People with schizophrenia have an increased cardiovascular risk with higher mortality than the general population. Only a few studies have investigated the impact of cardiovascular risk on the later course of schizophrenia. This study aims to explore the association of cardiovascular risk factors, as detected during an index inpatient treatment for schizophrenia, with the duration of psychiatric inpatient treatments and number of inpatient admissions in the subsequent 10 years, in patients with schizophrenia. METHODS: Cardiovascular risk factors of 736 patients with schizophrenia, identified through retrospective chart review, were assessed by hypertension, type 2 diabetes mellitus and dyslipidemia during an index inpatient stay. The duration of inpatient treatments, assessed by the total duration of psychiatric inpatient treatments in days, and the number of inpatient admissions, over the next 10 years were assessed and analyzed for an association with cardiovascular risk factors. RESULTS: Hypertension associated with longer duration of inpatient treatments and higher number of inpatient admissions. Type 2 diabetes mellitus and dyslipidemia associated with a higher number of psychiatric inpatient treatments. Hypertension remained significantly associated with the duration of inpatient treatments (ß = 0.174; p < 0.001) and the number of inpatient treatments (ß = 0.144; p < 0.001), when adjusting for age, sex and BMI. CONCLUSION: Out of the investigated cardiovascular risk factors documented during an index inpatient stay for schizophrenia, only hypertension associated with an increased duration of in-hospital stay and an increased number of re-hospitalizations during the subsequent ten years when adjusting for confounders. Screening for hypertension should be considered in all patients with schizophrenia.

Classical Risk Factors and Inflammatory Biomarkers: One of the Missing Biological Links between Cardiovascular Disease and Major Depressive Disorder.

BACKGROUND: Cardiovascular disorders (CVD) and major depressive disorder (MDD) are the most frequent diseases worldwide responsible for premature death and disability. Behavioral and immunological variables influence the pathophysiology of both disorders. We therefore determined frequency and severity of MDD in CVD and studied whether MDD without CVD or other somatic diseases influences classical and inflammatory biomarkers of cardiovascular risk. In addition, we investigated the influence of proinflammatory cytokines on antidepressant treatment outcome. METHODS: In a case-control design, 310 adults (MDD patients without CVD, CVD patients, and cardiologically and psychiatrically healthy matched controls) were investigated. MDD patients were recruited after admission in a psychiatric university hospital. Primary outcome criteria were clinical depression ratings (HAM-D scale), vital signs, classical cardiovascular risk factors and inflammatory biomarkers which were compared between MDD patients and healthy controls. RESULTS: We detected an enhanced cardiovascular risk in MDD. Untreated prehypertension and signs directing to a metabolic syndrome were detected in MDD. Significantly higher inflammatory biomarkers such as the high sensitivity C-reaktive protein (hsCRP) and proinflammatory acute phase cytokines interleukine-1ß (IL-1ß) and interleukine-6 (IL-6) underlined the higher cardiovascular risk in physically healthy MDD patients. Surprisingly, high inflammation markers before treatment were associated with better clinical outcome and faster remission. The rate of MDD in CVD patients was high. CONCLUSIONS: Patients suffering from MDD are at specific risk for CVD. Precise detection of cardiovascular risks in MDD beyond classical risk factors is warranted to allow effective prophylaxis and treatment of both conditions. Future studies of prophylactic interventions may help to provide a basis for prophylactic treatment of both MDD and CVD. In addition, the high risk for MDD in CVD patients was confirmed and underlines the requirement for clinical attention.

[Diagnosis of Metabolic Risk Factors in Psychiatric Inpatients]. / Diagnostik metabolischer Risikofaktoren bei stationär-psychiatrischen Patienten.

OBJECTIVE: Individuals suffering from mental illness have one to two decades reduced life expectancy. The increased morbidity and mortality is mainly due to cardiometabolic disorders. Despite these numbers, international studies give evidence that diagnoses and treatment of metabolic risk factors in psychiatric patients is insufficient. We assume that in Germany metabolic risk factors are also underdiagnosed and insufficiently treated. METHODS: We tested for the frequency of diagnoses of the metabolic risk factors obesity, nicotine dependence and abuse, disorders of lipid metabolism, hypertension and diabetes in 139 307 cases of residential treatment and semi-residential care in 47 psychiatric hospitals in Germany in the year 2012. Data were derived from the VIPP(indicators of treatment quality in psychiatry and psychosomatic medicine)-project, a project that comprises the routine data of psychiatric hospitals, that are sent to the InEK (institute for the lump sum payment system for hospitals). Frequencies were compared with prevalence of metabolic risk factors in the German population and prevalences of metabolic risk factors found in psychiatric patients in international studies. RESULTS: In particular obesity (2.8 %), disorders of lipid metabolism (2.8 %) and nicotin dependence (4.2 %) were underdiagnosed. We assume that also diabetes (6.8 %) and hypertension (17.7 %) were underdiagnosed. CONCLUSION: The results give evidence that metabolic risk factors are underdiagnosed and possibly insufficiently treated in German psychiatric hospitals. We cannot exclude that the results might also be due to poor documentation. It remains to be seen if the introduction of the PEPP (the new lump sum payment system in German psychiatry) will heighten the level of attention for metabolic risk factors and their treatment.

[Incidence and Costs of 1:1 Care in Psychiatric Hospitals in Germany - A Descriptive Analysis Based on the VIPP Project Data Set]. / Häufigkeit und Kosten der 1:1-Betreuung in der Erwachsenenpsychiatrie in Deutschland - Eine deskriptive Analyse anhand des VIPP-Datensatzes.

OBJECTIVE: 1:1 care is applied for patients requiring close psychiatric monitoring and care like patients with acute suicidality. The article describes the frequency of 1:1 care across different diagnoses and age groups in German psychiatric hospitals. METHODS: The analysis was based on the VIPP Project from the years 2011 and 2012. A total of 47 hospitals with more than 120,000 cases were included. Object of the analysis was the OPS code 9-640.0 1:1 care. The evaluation was performed on case level. RESULTS: Data of 47 hospitals were included. Of the 121,454 cases evaluated in 2011 3.8 % documented a 1:1 care within the meaning of OPS 9-640.0 additional code. Of the 66 245 male cases a 1:1 care was documented in 3.5 % and the 55 207 female cases was 4.1 %. Compared to 2011, the proportion of 1:1 care in 2012 rose to 4.8 %. CONCLUSION: The results show that 1:1 care is frequently applied in German psychiatric hospitals. The Data of the VIPP project have proven to be a useful tool to gain information on the frequency of cost-intensive interventions in German psychiatric hospitals. Further analyses should create the possibility of evaluation at the level of the individual codes.

Aging without depression: a cross-sectional study.

OBJECTIVES: The aim of the study was to analyze the association between secure attachment style, loneliness, and social network as risk factors for late-life depression. METHODS: This cross-sectional study examined 969 subjects of the KORA-Age study. We applied the Relationship-Specific Attachment Scales for Adults (Beziehungsspezifische Bindungsskalen für Erwachsene, BBE), the UCLA Loneliness Scale, and the Social Network Index (SNI). Depression was operationalized through the Geriatric Depression Scale (GDS-15) and/or use of antidepressants. Logistic-regression models were calculated, sex-stratified, and controlled for age and living status. RESULTS: For men, lower depression scores were associated with higher attachment security scores (OR = 0.26, 95% CI = 0.15-0.44) and not reporting feelings of loneliness (OR = 0.27, 95% CI = 0.14-0.53). For women, independent determinants of not having late life depression consist of not feeling lonely (OR = 0.22, 95% CI = 0.13-0.38). DISCUSSION: Loneliness is a risk factor for late life depression in women and men, attachment style is a risk factor more for men, while social network size is not a risk factor.

Posttraumatic stress disorder and not depression is associated with shorter leukocyte telomere length: findings from 3,000 participants in the population-based KORA F4 study.

BACKGROUND: A link between severe mental stress and shorter telomere length (TL) has been suggested. We analysed the impact of Posttraumatic Stress Disorder (PTSD) on TL in the general population and postulated a dose-dependent TL association in subjects suffering from partial PTSD compared to full PTSD. METHODS: Data are derived from the population-based KORA F4 study (2006-2008), located in southern Germany including 3,000 individuals (1,449 men and 1,551 women) with valid and complete TL data. Leukocyte TL was measured using a quantitative PCR-based technique. PTSD was assessed in a structured interview and by applying the Posttraumatic Diagnostic Scale (PDS) and the Impact of Event Scale (IES). A total of 262 (8.7%) subjects qualified for having partial PTSD and 51 (1.7%) for full PTSD. To assess the association of PTSD with the average TL, linear regression analyses with adjustments for potential confounding factors were performed. RESULTS: The multiple model revealed a significant association between partial PTSD and TL (beta = -0.051, p = 0.009) as well as between full PTSD and shorter TL (beta = -0.103, p = 0.014) indicating shorter TL on average for partial and full PTSD. An additional adjustment for depression and depressed mood/exhaustion gave comparable beta estimations. CONCLUSIONS: Participants with partial and full PTSD had significantly shorter leukocyte TL than participants without PTSD. The dose-dependent variation in TL of subjects with partial and full PTSD exceeded the chronological age effect, and was equivalent to an estimated 5 years in partial and 10 years in full PTSD of premature aging.

Metabolomic profiles in individuals with negative affectivity and social inhibition: a population-based study of Type D personality.

BACKGROUND: Individuals with negative affectivity who are inhibited in social situations are characterized as distressed, or Type D, and have an increased risk of cardiovascular disease (CVD). The underlying biomechanisms that link this psychological affect to a pathological state are not well understood. This study applied a metabolomic approach to explore biochemical pathways that may contribute to the Type D personality. METHODS: Type D personality was determined by the Type D Scale-14. Small molecule biochemicals were measured using two complementary mass-spectrometry based metabolomics platforms. Metabolic profiles of Type D and non-Type D participants within a population-based study in Southern Germany were compared in cross-sectional regression analyses. The PHQ-9 and GAD-7 instruments were also used to assess symptoms of depression and anxiety, respectively, within this metabolomic study. RESULTS: 668 metabolites were identified in the serum of 1502 participants (age 32-77); 386 of these individuals were classified as Type D. While demographic and biomedical characteristics were equally distributed between the groups, a higher level of depression and anxiety was observed in Type D individuals. Significantly lower levels of the tryptophan metabolite kynurenine were associated with Type D (p-value corrected for multiple testing=0.042), while no significant associations could be found for depression and anxiety. A Gaussian graphical model analysis enabled the identification of four potentially interesting metabolite networks that are enriched in metabolites (androsterone sulfate, tyrosine, indoxyl sulfate or caffeine) that associate nominally with Type D personality. CONCLUSIONS: This study identified novel biochemical pathways associated with Type D personality and demonstrates that the application of metabolomic approaches in population studies can reveal mechanisms that may contribute to psychological health and disease.

Major depressive disorder is associated with cardiovascular risk factors and low Omega-3 Index.

OBJECTIVE: Cardiovascular disease (CVD) and major depressive disorder (MDD) are frequent worldwide and have a high comorbidity rate. Omega-3 fatty acids have been suggested as disease modulators for both CVD and MDD. Therefore, we studied whether polyunsaturated fatty acids and the Omega-3 Index may represent markers for assessment of the cardiovascular risk in somatically healthy patients suffering from MDD. METHOD: We conducted a case-control study from July 2004 to December 2007 in 166 adults (86 inpatients with MDD but without CVD from the Department of Psychiatry and Psychotherapy and 80 age- and sex-matched healthy controls from an outpatient clinic of the Division of Preventive Cardiology, Ludwig Maximilian University of Munich, Germany). Information gathered at baseline included MDD diagnosis according to DSM-IV criteria, depression ratings, conventional cardiovascular risk factors, and fatty acid and interleukin-6 determinations. Fatty acid composition was analyzed according to the HS-Omega-3 Index methodology. During the study, patients received no supplementation with omega-3 fatty acids. The main inclusion criteria were the diagnosis of MDD according to DSM-IV and a 17-item Hamilton Depression Rating Scale (HDRS-17) score of at least 17. Treatment response and remission were defined using the HDRS-17. RESULTS: Several conventional risk factors such as high triglyceride (mean, 152 mg/dL vs 100 mg/dL; P < .001) and fasting glucose (mean, 96 mg/dL vs 87 mg/dL; P = .005) values as well as greater waist circumference (mean, 97 cm vs 87 cm; P = .019) and higher body mass index (calculated as kg/m(2); mean, 26 vs 24; P = .011) were more prevalent in MDD patients in comparison with controls. The Omega-3 Index (mean, 3.9% vs 5.1%; P < .001) and individual omega-3 fatty acids were significantly lower in MDD patients. An Omega-3 Index < 4% was associated with high concentrations of the proinflammatory cytokine interleukin-6 (χ(2) = 7.8, P = .02). CONCLUSIONS: Conventional cardiovascular risk factors, the Omega-3 Index, and interleukin-6 levels indicated an elevated cardiovascular risk profile in MDD patients currently free of CVD. Our results support the employment of strategies to reduce the cardiovascular risk in still cardiovascularly healthy MDD patients by targeting conventional risk factors and the Omega-3 Index.

The combined dexamethasone/CRH Test (DEX/CRH test) and prediction of acute treatment response in major depression.

BACKGROUND: In this study the predictive value of the combined dexamethasone/CRH test (DEX/CRH test) for acute antidepressant response was investigated. METHODOLOGY/PRINCIPAL FINDINGS: In 114 depressed inpatients suffering from unipolar or bipolar depression (sample 1) the DEX/CRH test was performed at admission and shortly before discharge. During their stay in the hospital patients received different antidepressant treatment regimens. At admission, the rate of nonsuppression (basal cortisol levels >75.3 nmol/l) was 24.6% and was not related to the later therapeutic response. Moreover, 45 out of 114 (39.5%) patients showed an enhancement of HPA axis function at discharge in spite of clinical improvement. In a second sample, 40 depressed patients were treated either with reboxetine or mirtazapine for 5 weeks. The DEX/CRH test was performed before, after 1 week, and after 5 weeks of pharmacotherapy. Attenuation of HPA axis activity after 1 week was associated with a more pronounced alleviation of depressive symptoms after 5-week mirtazapine treatment, whereas downregulation of HPA system activity after 5 weeks was related to clinical response to reboxetine. However, early improvement of HPA axis dysregulation was not necessarily followed by a beneficial treatment outcome. CONCLUSIONS/SIGNIFICANCE: Taken together, performance of a single DEX/CRH test does not predict the therapeutic response. The best predictor for response seems to be an early attenuation of HPA axis activity within 1 or 2 weeks. However, early improvement of HPA system dysfunction is not a sufficient condition for a favourable response. Since a substantial part of depressive patients display a persistence of HPA axis hyperactivity at discharge, downregulation of HPA system function is not a necessary condition for acute clinical improvement either. Our data underline the importance of HPA axis dysregulation for treatment outcome in major depression, although restoration of HPA system dysfunction seems to be neither a necessary nor a sufficient determinant for acute treatment response.

Mirtazapine monotherapy versus combination therapy with mirtazapine and aripiprazole in depressed patients without psychotic features: a 4-week open-label parallel-group study.

BACKGROUND: There is preliminary evidence that the atypical antipsychotic aripiprazole, which is a partial agonist at D(2) and 5-HT(1A) receptors and a potent antagonist at 5-HT(2A) receptors, may be useful as an augmentation strategy in treatment-resistant depression. METHOD: In this 4-week open-label non-randomized parallel-group study, the safety and efficacy of aripiprazole as add-on treatment strategy in patients suffering from non-delusional depression was investigated. Forty drug-free depressed inpatients without psychotic symptoms (13 men, 27 women), suffering from a major depressive episode or bipolar disorder, depressive state (DSM-IV criteria), were included in the study. The patients were treated either with mirtazapine monotherapy (45 mg/day) or combination therapy (mirtazapine 45 mg/day plus aripiprazole 15 mg/day) for 4 weeks. Safety and efficacy were assessed weekly using the Hamilton Depression Rating Scale, the Simpson-Angus Scale and the Barnes Akathisia Scale. RESULTS: Mirtazapine monotherapy and combined treatment with mirtazapine and aripiprazole showed comparable antidepressant effects as assessed at the endpoint of the study period. However, additional administration of aripiprazole accelerated the onset of antidepressant action in patients suffering from treatment-resistant depression. Additive use of aripiprazole reduced the mirtazapine-induced increase in the body mass index. Moreover, mirtazapine had favourable effects on aripiprazole-induced akathisia. No other extrapyramidal side effects were seen in the combination therapy group. CONCLUSION: Combined therapy with mirtazapine and aripiprazole is a safe and well-tolerated treatment option which may be useful especially in treatment-resistant depression. Double-blind controlled studies are needed to further explore the efficacy and safety of aripiprazole in depressed patients.