Machiavellianism and psychopathy affect sleep quality in people with affective disorders and mentally healthy individuals.

Introduction: Deteriorated sleep quality is a predisposing factor and symptom of affective disorders (AD). It is important to investigate factors driving the relationship between sleep and AD, such as personality traits. Previous research has shown that personality traits such as the Dark Triad personality traits (DT) narcissism, Machiavellianism, and psychopathy are associated with sleep problems and AD. The current study examined the moderating influence of the DT in the relationship between AD [versus healthy controls (HC)] and sleep quality. Methods: Data of 657 individuals (267 HC, 390 AD; 483 female, 166 male, eight diverse; Mage = 34.87, SDage = 13.86) were collected in an online survey, which administered the Pittsburgh Sleep Quality Index and the Short Dark Triad questionnaire. Results: Moderation analyses controlling for age and gender revealed that Machiavellianism (b = -0.76, p < 0.05, R2 = 0.35) and psychopathy (b = -1.15, p < 0.05, R2 = 0.35), but not narcissism (b = -0.20, p = 0.620, R2 = 0.35), had a negative effect on sleep quality. Specifically, this effect is more pronounced in the HC group, but sleep quality is generally worse in AD. Conclusion: Our findings indicate that Machiavellianism and psychopathy should be considered in the prevention and treatment of AD-associated sleep problems. Particularly, monitoring these traits could help to implement timely measures for the prevention of sleep problems, such as psychoeducation and sleep hygiene. The results highlight the role of personality in the aetiopathogenesis of AD and require further differentiation to examine the underlying pathways between the DT, sleep, and AD.

The possible role of quinolinic acid as a predictive marker in patients with SARS-CoV-2.

BACKGROUND AND AIMS: Quinolinic acid (QA) is a metabolite of the kynurenine pathway, which is activated by inflammatory stimuli during viral infection. We investigated the role of QA in patients infected with SARS-CoV-2, particularly its prognostic value for survival. METHODS: Overall, 104 unvaccinated inpatients were included, divided into a survival (N = 80) and a deceased group (N = 24). Plasma levels of tryptophan, kynurenine, QA, C-reactive protein (CRP) and procalcitonin (PCT) were measured on admission and after seven days. The QA/TRP ratio and the relative differences between the measurements for QA (QA-Diff) and QA/TRP (Diff-QA/TRP) were calculated. RESULTS: Among the kynurenine pathway markers, QA-Diff showed the highest discriminatory power for the survival prognosis (Youden index 0.467, cut-off -1.3 %, AUC 0.733, p < 0.001, sensitivity 0.79, specificity 0.675). Among the inflammatory markers, CRP showed the highest discriminatory power (Youden index 0.533, cut-off 25.0 mg/L, AUC 0.794, p < 0.001, sensitivity 0.958, specificity 0.575). A significant correlation between QA and PCT was found on admission and after one week (Spearman's rho 0.455 and 0.539, all p-values < 0.001). CONCLUSIONS: QA may serve as prognostic marker for survival in patients with SARS-CoV-2. The repeated measurements during the first week of the disease may enhance the prognostic power.

Metabolic Syndrome in Affective Disorders: Associations with Dark Triad Personality Traits.

Previous research has focused on the relationship between affective disorders (AD) and metabolic syndrome (MetS). Aside from biological and lifestyle factors, personality traits were identified as influencing aspects. In particular, the Dark Triad personality traits (DT; Machiavellianism, narcissism, psychopathy) were connected to both AD and worse somatic health, thus possibly resulting in MetS. This observational study aimed to investigate the associations between DT and anthropometric parameters and differences in the DT traits concerning the presence of MetS in individuals with AD. A total of 112 individuals (females = 59, males = 51, diverse = 2, Mage = 47.5, SDage = 11.5) with AD filled out the Short Dark Triad questionnaire. Body Mass Index (BMI) and MetS criteria, including blood pressure, waist circumference, lipid, and glucose levels, were assessed. For Machiavellianism, a positive association with BMI (r = 0.29, p < 0.05) and a negative association with systolic blood pressure (r = -0.23, p < 0.05) were found. No relationship between the overall MetS and DT score (r = 0.08, p = 0.409) was observed. The results were limited by the lack of a control group and the cross-sectional study design, which does not allow for the determination of causality. Machiavellianism was associated with a higher BMI and lower systolic blood pressure, indicating a deteriorating health effect of this trait. Possibly, the higher prevalence of MetS in AD stems from aspects such as lifestyle or medication intake, which might also be influenced by DT. Further research is needed to disentangle underlying mechanisms.

The Use of Next-Generation Sequencing in Pharmacogenomics.

BACKGROUND: Next-generation sequencing (NGS) methods have become more commonly performed in clinical and research laboratories. METHODS: This review summarizes the current laboratory NGS-based diagnostic approaches in pharmacogenomics including targeted multi-gene panel sequencing, whole-exome sequencing (WES), and whole-genome sequencing (WGS). RESULTS: Clinical laboratories perform multiple non-uniform types of pharmacogenetic panels, which can reduce the overall number of single-gene tests to be more cost-efficient. Compared to the targeted multi-gene panels, which are not typically designed to detect novel variants, WES and WGS have a greater potential to identify secondary pharmacogenomic findings, which might be predictive for the pharmacotherapy outcome of different patient settings. WGS overcomes the limitations of WES enabling a more accurate exome-sequencing at appropriate coverage and the sequencing of non-coding regions. Different NGS-based study designs with different test strategies and study populations, varying sample sizes, and distinct analytical and interpretation procedures lead to different identification results of pharmacogenomic variants. CONCLUSIONS: The rapid progress in gene sequencing technologies will overcome the clinical and laboratory challenges of WES and WGS. Further high throughput NGS-based pharmacogenomics studies in different populations and patient settings are necessary to expand knowledge about rare functional variants and to enhance translation in clinical practice.

Myeloperoxidase as a Potential Biomarker of Acute-Myocardial-Infarction-Induced Depression and Suppression of the Innate Immune System.

While myeloperoxidase (MPO) serves as an indicator of both neutrophil and innate-immune-system function, the potential suppression of the innate immune system in patients with acute myocardial infarction (AMI)-induced depression might be evidenced by a decrease in MPO serum levels. The aim of this prospective study was to (1) determine whether serum concentrations of MPO vary immediately and 6 months after AMI and (2) to investigate whether MPO concentrations at the time of the AMI are significant predictors of AMI-induced depression and the depression-associated suppression of the innate immune system. A total of 109 AMI patients were assessed with the Hamilton Depression Scale (HAMD-17) immediately after admission to the hospital and 6 months later. The MPO status was assessed with serum samples, which were also collected immediately and 6 months after AMI. The depressive patients showed significantly lower MPO blood levels immediately and 6 months after the AMI compared to the patients without depression (ANCOVA: MPO (depression) F = 4.764, df = 1, p = 0.031). The baseline MPO was observed as a significant predictor (p = 0.027) of AMI-induced depression 6 months after AMI. MPO is a potential biomarker for AMI-induced depression, indicating a depression-associated suppression of the innate immune system.

Alteration of the kynurenine pathway is inversely associated with the humoral immune response in patients with SARS-CoV-2.

BACKGROUND: The scale and the course of antibody production in patients with SARS-CoV-2 is highly variable. Factors involved in the immune regulation during the infection may play a major role in the antibody response. We investigated the relationship between the inflammatory markers of the kynurenine pathway and the concentration of antibodies against SARS-CoV-2 in infected patients 8 - 11 days after admission. METHODS: The study included 72 SARS-CoV-2 - positive inpatients hospitalized between August 2020 and April 2021. The plasma concentrations of tryptophan, kynurenine, anti-SARS-CoV-2 antibodies and the leucocyte count were measured 8 - 11 days after admission. The kynurenine/tryptophan ratio (KYN/TRP ratio) was calculated. Tertiles based on the values for tryptophan, kynurenine, KYN/TRP ratio and the leucocytes were generated. RESULTS: Statistically significant correlations were observed between anti-SARS-CoV-2 antibodies and tryptophan, kynurenine, KYN/TRP ratio and the leucocytes (p-values < 0.001-0.007). The high kynurenine and KYN/TRP ratio tertiles showed significantly lower antibody titers compared to the low tertiles (p-values 0.017 and < 0.001). The low tryptophan and leucocytes tertiles showed significantly lower antibody titers compared to the high tertiles (p-values 0.001 and 0.008). CONCLUSION: Patients with higher activation levels of the kynurenine pathway tended to develop lower anti-SARS-CoV-2 antibody titers.

Sex-specific differences in trimethylamine N-oxide (TMAO) concentrations before and after cardiac rehabilitation in acute myocardial infarction patients.

Trimethylamine N-oxide (TMAO) is a biomarker of cardiovascular risk and may enhance the progression of atherosclerosis. The aim of the study was to determine whether there are sex-specific differences in TMAO concentrations before and after cardiac rehabilitation in acute myocardial infarction (AMI) patients. A total of 56 participants [45/56 (80.4 %) males, 11/56 (19.6 %) females] were drawn from AMI inpatients hospitalized at the Division of Cardiology, Medical University of Graz, Austria. For the assessment of TMAO, serum samples were collected within the first day after hospital admission due to AMI and at the start and end of cardiac rehabilitation. Shortly after hospital admission due to AMI, females had significantly higher TMAO blood concentrations than males. These initially high TMAO levels remained almost unchanged in the female AMI patients until the start of cardiac rehabilitation and only reached the lower TMAO concentrations observed in the male patients after rehabilitation [female patients: TMAO (acute myocardial infarction) = 5.93 µmol/L (SE = 1.835); TMAO (start of rehabilitation) = 5.68 µmol/L (SE = 1.217); TMAO (end of rehabilitation) = 3.89 µmol/L (SE = 0.554); male patients: TMAO (acute myocardial infarction) = 3.02 µmol/L (SE = 0.255), TMAO (start of rehabilitation) = 3.91 µmol/L (SE = 0.346), TMAO (end of rehabilitation) = 4.04 µmol/L (SE = 0.363)]. After AMI, women might be at higher cardiovascular risk due to persistently higher levels of TMAO. High TMAO levels in women might decrease after cardiac rehabilitation due to cardiac rehabilitation-associated lifestyle modifications. These lifestyle modifications after AMI might also prevent increases in TMAO concentrations in men.

A biopsychosocial model of severe fear of COVID-19.

INTRODUCTION: COVID-19 is a respiratory infection that causes not only somatic health issues, but also frequently psychosocial burdens. The aims of this study were to investigate biopsychosocial factors that might further aggravate fear of COVID-19, and to establish a biopsychosocial model of severe fear of COVID-19. METHODS: 368 participants were included in this study. Biopsychosocial factors observed comprised biological factors (somatic risk), psychological factors (state/trait anxiety, physical symptoms of anxiety, severe health anxiety, specific phobias, depression), and psychosocial factors (social support, financial losses, social media consumption, social contacts with COVID-19 infected people). Psychometric questionnaires included State-Trait Anxiety Inventory, Beck's Anxiety Inventory, Whiteley-Index / Illness Attitude Scales, Specific Phobia Questionnaire, WHO-5 and Social Support Survey. RESULTS: 162/368 (44.0%) participants had almost no fear, 170/368 (46.2%) participants had moderate fear, and 45/368 (12.2%) participants had severe fear of COVID-19. Female participants showed higher levels of fear of COVID-19 than male participants (gender: χ2 = 18.47, p<0.001). However, the level of fear of COVID-19 increased in male participants when they had contact with people who were infected with COVID-19, while in contrast the level of fear of COVID-19 decreased in female participants when they had such contacts [ANCOVA: fear of COVID-19 (contact x gender): F(1,363) = 5.596, p = .019]. Moreover, participants without relationships showed higher levels of fear of COVID-19 (marital status: χ2 = 14.582, p = 0.024). Furthermore, financial losses due to the COVID-19 were associated with higher levels of fear of COVID-19 [ANCOVA: fear of COVID-19(financial loss x gender): F(1, 363) = 22.853, p< .001]. Multiple regression analysis revealed female gender, severe health anxiety (WI-IAS) and state /trait anxiety (STAI) as significant predictors of severe fear of COVID-19. CONCLUSION: In this study significant predictors of severe fear of COVID-19 were female gender, pre-existing state and trait anxiety, as well as severe health anxiety. The finding of significant predictors of fear of COVID-19 might contribute to detect people who might suffer most from severe, overwhelming fear of COVID-19 at an early stage.

Assessment of tryptophan and kynurenine as prognostic markers in patients with SARS-CoV-2.

BACKGROUND: Immune dysregulation and inflammation in patients with SARS-CoV-2 is associated with a poor clinical outcome. We investigated the value of the inflammatory markers tryptophan and kynurenine in predicting the survival outcome of patients with SARS-CoV-2. METHODS: The study included 252 inpatients with a SARS-CoV-2 infection hospitalized between August 2020 and April 2021. Two groups were generated based on disease survival (survival group: n = 199; deceased group: n = 53). Plasma concentrations of tryptophan, kynurenine and interleukin-6 (IL-6) were measured on admission. In a subset of patients (n = 105; 81 survivors and 24 deceased) concentrations of tryptophan and kynurenine were checked 7 days after admission. The kynurenine/tryptophan ratio (TRP/KYN ratio) was calculated. RESULTS: On admission, the deceased group showed significantly higher concentrations of kynurenine and a significantly higher KYN/TRP ratio compared to the survival group (p-values < 0.001). Kynurenine and the KYN/TRP ratio significantly correlated with IL-6 (ρ = 0.441 and 0.448, p-values < 0.001). In the survival group, kynurenine and the KYN/TRPratio were significantly lower after seven days (p-values < 0.001). In the deceased group, no significant differences were found between the measurements. CONCLUSION: Kynurenine and the KYN/TRP ratio are potentially useful parameters in predicting the survival outcome in SARS-CoV-2 positive patients.

Assessment of trimethylamine N-oxide (TMAO) as a potential biomarker of severe stress in patients vulnerable to posttraumatic stress disorder (PTSD) after acute myocardial infarction.

Background: Posttraumatic stress disorder (PTSD) is a frequently observed stress-related disorder after acute myocardial infarction (AMI) and it is characterized by numerous symptoms, such as flashbacks, intrusions and anxiety, as well as uncontrollable thoughts and feelings related to the trauma. Biological correlates of severe stress might contribute to identifying PTSD-vulnerable patients at an early stage. Objective: Aims of the study were (1) to determine whether blood levels of trimethylamine N-oxide (TMAO) vary immediately after AMI in patients with/without AMI-induced PTSD symptomatology, (2) to investigate whether TMAO is a potential biomarker that might be useful in the prediction of PTSD and the PTSD symptom subclusters re-experiencing, avoidance and hyperarousal, and (3) to investigate whether TMAO varies immediately after AMI in patients with/without depression 6 months after AMI. Method: A total of 114 AMI patients were assessed with the Hamilton-Depression Scale after admission to the hospital and 6 months later. The Clinician Administered PTSD Scale for DSM-5 was used to explore PTSD-symptoms at the time of AMI and 6 months after AMI. To assess patients' TMAO status, serum samples were collected at hospitalization and 6 months after AMI. Results: Participants with PTSD-symptomatology had significantly higher TMAO levels immediately after AMI than patients without PTSD-symptoms (ANCOVA: TMAO(PTSD x time), F = 4.544, df = 1, p = 0.035). With the inclusion of additional clinical predictors in a hierarchical logistic regression model, TMAO became a significant predictor of PTSD-symptomatology. No significant differences in TMAO levels immediately after AMI were detected between individuals with/without depression 6 months after AMI. Conclusions: An elevated TMAO level immediately after AMI might reflect severe stress in PTSD-vulnerable patients, which might also lead to a short-term increase in gut permeability to trimethylamine, the precursor of TMAO. Thus, an elevated TMAO level might be a biological correlate for severe stress that is associated with vulnerability to PTSD.

Antecedentes: El trastorno de estrés postraumático (TEPT) es un trastorno relacionado con el estrés que se observa con frecuencia después de un infarto agudo de miocardio (IAM) y se caracteriza por numerosos síntomas, como flashbacks, intrusiones y ansiedad, así como pensamientos y sentimientos incontrolables relacionados con el trauma. Los correlatos biológicos del estrés severo podrían contribuir a identificar a los pacientes vulnerables al TEPT en una etapa temprana.Objetivo: Los objetivos del estudio fueron (1) determinar si los niveles sanguíneos de N-óxido de trimetilamina (TMAO, por sus siglas en ingles) varían inmediatamente después del IAM en pacientes con o sin sintomatología de TEPT inducida por IAM, (2) investigar si el TMAO es un biomarcador potencial que podría ser útil en la predicción de TEPT y los subgrupos de síntomas de TEPT que experimentan, evitación e hiperactivación, y (3) para investigar si el TMAO varía inmediatamente después del IAM en pacientes con o sin depresión 6 meses después del IAM.Método: Un total de 114 pacientes con IAM fueron evaluados con la Escala de Depresión de Hamilton tras su ingreso al hospital y 6 meses después. La Escala de TEPT para el DSM-5 administrada por el médico se utilizó para explorar los síntomas de TEPT en el momento del IAM y 6 meses después del IAM. Para evaluar el estado de TMAO de los pacientes, se recolectaron muestras de suero en la hospitalización y 6 meses después del IAM.Resultados: Los participantes con sintomatología de TEPT tenían niveles de TMAO significativamente más altos inmediatamente después del IAM que los pacientes sin síntomas de TEPT (ANCOVA: TMAO (TEPT x tiempo), F = 4.544, df = 1, p = 0.035). Con la inclusión de predictores clínicos adicionales en un modelo de regresión logística jerárquica, TMAO se convirtió en un predictor significativo de la sintomatología del TEPT. No se detectaron diferencias significativas en los niveles de TMAO inmediatamente después del IAM entre individuos con o sin depresión 6 meses después del IAM.Conclusiones: Un nivel elevado de TMAO inmediatamente después del IAM podría reflejar un estrés severo en pacientes vulnerables al TEPT, lo que también podría conducir a un aumento a corto plazo de la permeabilidad intestinal a la trimetilamina, el precursor de TMAO. Por lo tanto, un nivel elevado de TMAO podría ser un correlato biológico del estrés severo asociado con la vulnerabilidad al TEPT.

Interleukin-6 is associated with tryptophan metabolism and signs of depression in individuals with carbohydrate malabsorption.

The aim of the present study was to investigate possible associations between interleukin-6 (IL-6), interferon-gamma (INF-γ), tumor necrosis factor-alpha (TNF-α), lactoferrin and lipopolysaccharide binding protein (LBP) with TRP metabolism and signs of depression in a large cohort of outpatients referred for carbohydrate malabsorption testing. Serum concentrations of IL-6, INF-γ, TNF-α, lactoferrin, LBP, tryptophan (TRP), kynurenine (KYN) and kynuric acid were determined in 250 adults referred for lactose and fructose malabsorption testing. All participants filled out the Beck Depression Inventory (BDI). Serum IL-6 levels were positively correlated with the BDI score (p = 0.001, ρ = 0.205) and indicators of TRP metabolism (KYN/TRP ratio, KYN) (P-values < 0.05, ρ = 0.176 and 0.136). Ninety-five individuals with a BDI score > 13 showed significantly higher IL-6 serum levels (1.7 [1.0 - 2.8] vs. 1.1 [0.8 - 1.7] pg/mL, p < 0.001) compared to 115 individuals with a BDI score ≤ 13. LBP showed a positive correlation with the KYN/TRP ratio (p = 0.005, ρ = 0.177). IL-6 and LBP were associated with indicators of TRP metabolism. IL-6 was found to be linked to signs of depression. Individuals with the presence of depressive symptoms showed higher serum IL-6 levels compared to individuals without depressive symptoms.

Assessment of trimethylamine-N-oxide at the blood-cerebrospinal fluid barrier: Results from 290 lumbar punctures.

Recently, the microbiome-derived trimethylamine-N-oxide (TMAO) was shown to be present in human cerebrospinal fluid (CSF). However, data on the potential of TMAO crossing the blood-CSF barrier are still lacking. This retrospective study aimed at investigating possible associations between the CSF/serum albumin (QALB) and TMAO (QTMAO) quotient and evaluating QTMAO values in individuals with and without blood-CSF barrier dysfunction. A total of 290 patients, who underwent diagnostic lumbar puncture with QALB and QTMAO determination, were evaluated. Serum and CSF TMAO measurements were performed on a tandem mass spectrometry SCIEX QTRAP 4500 (Applied Biosystems, Framingham, MA, USA) coupled with an Agilent 1260 Infinity HPLC system (Agilent Technologies Santa Clara, CA, USA). Serum and CSF albumin were measured on the Atellica® NEPH 630 system (Siemens Healthineers, Erlangen, Germany). CSF TMAO levels were positively correlated with serum TMAO levels (ρ = 0.709, p < 0.001). The QALB was significantly associated with the QTMAO (ß-coefficient = 0.312; p < 0.001). A total of 117 patients with blood-CSF barrier dysfunction had significantly higher median (Q1 - Q3) QTMAO values (4.7 (2.8 - 7.5) vs. 3.8 (2.5 - 5.7) x 10-1, p = 0.002) compared to 173 individuals with normal blood-CSF barrier function. CSF and serum TMAO concentrations were significantly associated in 290 CSF/serum pairs from lumbar punctures of clinical routine. QALB showed a relevant influence on QTMAO. Present results indicate that TMAO may cross the blood-CSF barrier.

Determination of Trimethylamine-N-oxide by a Simple Isocratic High-Throughput Liquid-Chromatography Tandem Mass-Spectrometry Method.

BACKGROUND: As trimethylamine-N-oxide (TMAO) is considered to be associated with various diseases, rapid determination of serum TMAO concentration is of clinical interest. This study is aimed at evaluating the analytical performance of a simple isocratic liquid chromatography-tandem mass-spectrometry (LC-MS/MS) method for TMAO quantification. METHODS: TMAO measurements were performed on a tandem mass spectrometer, SCIEX QTRAP 4500 (Applied Biosystems, Framingham, MA, USA), coupled with an Agilent 1260 Infinity HPLC system (Agilent Technologies, Santa Clara, CA, USA). The separation was performed on a Hypercarb Porus Grahitic Carbon (PGC) column (ThermoFisher Scientific, Waltham, MA, USA) by isocratic elution mode. Linearity, precision, recovery, and pre-analytical requirements of the TMAO LC-MS/MS method were evaluated. The imprecision acceptance criteria were defined 15%. We investigated sample stability at room temperature (RT) and assessed the serum TMAO concentrations of 188 healthy adults. RESULTS: The TMAO LC-MS/MS method was linear over the concentration range of 0.5 - 80 µmol/L. Intra- and inter-day precision ranged between 2.24 - 3.37% and 6.95 - 9.97%, recovery between 106 - 114%, respectively. At RT, serum samples were stable for 8 days. The median serum TMAO concentration of 188 healthy adults was 2.27 µmol/L (2.5th and 97.5th percentile: 0.75 - 10.46 µmol/L), respectively. CONCLUSIONS: The isocratic TMAO LC-MS/MS shows a broad analytical range and meets the imprecision acceptance criteria of 15%. This method is a robust and reliable diagnostic tool for the assessment of the human TMAO status. Serum samples are stable at RT for at least 8 days.

Sex-Specific Associations of Trimethylamine-N-Oxide and Zonulin with Signs of Depression in Carbohydrate Malabsorbers and Nonmalabsorbers.

BACKGROUND: The microbiome-derived trimethylamine-N-oxide (TMAO) and the intestinal permeability marker zonulin are considered to be linked with depression. Moreover, carbohydrate malabsorption (CMA) was shown to be associated with signs of depression. This study is aimed at investigating possible sex-specific associations between TMAO and zonulin and the presence of depressive signs in individuals with and without CMA. METHODS: Serum concentrations of TMAO and zonulin were determined in 115 and 136 individuals with the presence or absence of CMA. All 251 study participants underwent lactase gene C/T-13910 polymorphism genotyping and fructose H2/CH4 breath testing. Additionally, they filled in the Beck Depression Inventory (BDI-II) questionnaire. RESULTS: The median TMAO and zonulin serum concentrations were 2.66 (1.93-4.14) µmol/L and 40.83 (34.73-47.48) ng/mL. Serum TMAO levels were positively correlated with depressive symptoms (P = 0.011, ρ = 0.160). The strongest correlations were observed in 87 females (P = 0.010, ρ = 0.274) and 49 males (P = 0.027, ρ = 0.315) without CMA, whereas 115 patients with CMA showed no significant correlations. Zonulin tended to be negatively correlated with the BDI-II score in 49 males without CMA (P = 0.062, ρ = -0.269). CONCLUSION: This study demonstrates a positive correlationship between the serum TMAO concentrations and the severity of depressive symptoms in females and males without CMA. Serum zonulin levels were negatively correlated with signs of depression in males without CMA. These findings suggest a gender-specific relationship between the serum TMAO and zonulin concentrations, depression, and CMA.

Branched-chain amino acids are linked with iron metabolism.

BACKGROUND: The branched-chain amino acids (BCAAs) valine, leucine and isoleucine are reported to influence erythropoiesis and the human iron status. Large study cohorts encompassing biomarkers of iron metabolism and BCAAs are still lacking. METHODS: We investigated potential interactions between blood concentrations of all three BCAAs valine, leucine and isoleucine and biomarkers of iron metabolism [i.e., hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), iron, transferrin, ferritin, transferrin saturation, soluble transferrin receptor (sTfR)] in 430 outpatients referred for a medical health check-up. Linear regression models were performed to assess possible associations between variables. RESULTS: All three BCAAs were positively correlated with Hb, ferritin and the sTfR (r-values: 0.145-0.382; P values: <0.001-0.003). The strongest correlation was observed between valine and Hb (r=0.382; P value <0.001). Linear regression models showed a statistically significant influence of all three BCAAs on Hb and ferritin (ß-coefficients: 0.173-0.351; all P values: <0.001). Seventeen patients with anemia (4%) were found with significantly lower serum BCAA concentrations compared to 413 non-anemic individuals (P<0.05). CONCLUSIONS: These data indicate a pathophysiological link between the three BCAAs valine, leucine and isoleucine and the human iron indicators Hb and ferritin. Further studies are needed to clarify the exact causal mechanisms of these findings.

[Strangulation as scenic behavior. A case report of a pseudosuicide in the course of a NREM-parasomnia]. / Strangulation als szenische Handlung. Ein Fallbericht über einen Pseudosuizidversuch im Verlauf einer NREM-Parasomnie.

It is generally accepted, that sleepwalkers show complex behaviors leading to non-intended consequences. It is not unusual that these persons are thereby injured. However, sporadically a bizarre endangering of themselves or others is reported also, which ranges from homicide of the life partner to accidental (pseudo-)suicide.In this article, we report on a 28year-old man who unexpectedly attempted to hang himself by a whip at night. We discuss the reasons, why this bizarre act should actually be taken as a scenic behavior in the course of a NREM-parasomnia, and the difficulty to proof this claim.

Metabolomics approach in the investigation of depression biomarkers in pharmacologically induced immune-related depression.

BACKGROUND: The aim of this study was to identify previously unrecognised biological pathways and biomarkers that might expand the inflammatory hypothesis of depression. METHODS: Broad metabolomics analyses in plasma samples from 31 chronic hepatitis C-infected patients with and without immune-related depression were carried out using the Absolute IDQ p180 kit-a targeted metabolomics approach of combined direct flow injection and liquid chromatography that measures acylcarnitines, amino acids, biogenic amines, glycerophospholipids, sphingolipids, and sugars. RESULTS: The measurements showed that the average concentration of the branched-chain amino acid isoleucine was significantly lower in depressive HCV patients in comparison to non-depressive HCV patients [depression group: Median 51.35 (43.4-60.2 µmol/L) vs. Median 62.10 (38.4-81.7 µmol/L); U = -2.958; p = 0.002]. All other amino acids, acylcarnitines, biogenic amines, glycerophospholipids, sphingolipids, sugars, liver enzymes and thyroid levels showed no statistically significant differences. CONCLUSIONS: The results of the present study suggest that the branched-chain amino acid isoleucine might play a role in the pathophysiology of immune-related major depression, which expands existing knowledge about inflammatory hypothesis of depression.