Retinoid homeostasis in major depressive disorder.

The small, hormone-like molecule retinoic acid (RA) is a vital regulator in several neurobiological processes that are affected in depression. Next to its involvement in dopaminergic signal transduction, neuroinflammation, and neuroendocrine regulation, recent studies highlight the role of RA in homeostatic synaptic plasticity and its link to neuropsychiatric disorders. Furthermore, experimental studies and epidemiological evidence point to the dysregulation of retinoid homeostasis in depression. Based on this evidence, the present study investigated the putative link between retinoid homeostasis and depression in a cohort of 109 patients with major depressive disorder (MDD) and healthy controls. Retinoid homeostasis was defined by several parameters. Serum concentrations of the biologically most active Vitamin A metabolite, all-trans RA (at-RA), and its precursor retinol (ROL) were quantified and the individual in vitro at-RA synthesis and degradation activity was assessed in microsomes of peripheral blood-derived mononuclear cells (PBMC). Additionally, the mRNA expression of enzymes relevant to retinoid signaling, transport, and metabolism were assessed. Patients with MDD had significantly higher ROL serum levels and greater at-RA synthesis activity than healthy controls providing evidence of altered retinoid homeostasis in MDD. Furthermore, MDD-associated alterations in retinoid homeostasis differed between men and women. This study is the first to investigate peripheral retinoid homeostasis in a well-matched cohort of MDD patients and healthy controls, complementing a wealth of preclinical and epidemiological findings that point to a central role of the retinoid system in depression.

[Assessment of Patient-reported Outcomes in Routine Medical Care: Patient-reported Outcome Measures (PROMs) and Patient-reported Experience Measures (PREMs)]. / Empirische Erfassung patient*innenberichteter Merkmale: PROMs und PREMs.

Information from patients about their own quality of life, experiences in care, and individual assessments of treatment processes and outcomes are becoming increasingly important. Patient-reported characteristics can refer to subjective information about their own health (Patient-Reported Outcome Measures [PROMs]) or to objective information about their experience during the treatment process (Patient-Reported Experience Measures [PREMs]). This article provides an overview of the similarities and differences between PROMs and PREMs. Subsequently, ways to collect PROMs and PREMs are presented and in doing so, an insight into probabilistic testing theory (item response theory) and computer adaptive testing is given. Using national and international initiatives as examples, the implementation of PROMs and PREMs in health care systems is presented and future implementation strategies are discussed within an outlook.

M1/M2 polarization in major depressive disorder: Disentangling state from trait effects in an individualized cell-culture-based approach.

Accumulating evidence indicates the specific involvement of inflammatory processes in major depressive disorder (MDD), particularly affecting innate immunity. Most immune alterations have so far been determined based on plasma or cerebrospinal fluid cytokine levels. To precisely characterize putative innate immune-mediated mechanisms in MDD pathogenesis, we sought to disentangle "state" from "trait" effects in a patient-specific cell model by quantifying the impact of patient-derived autologous sera (AS) on patient-specific monocyte-derived macrophages (Mo-MФs) polarization in vitro. Mo-MФs were generated from 28 patients with moderate to severe MDD and 28 age-, sex-, smoking status- and BMI-matched healthy controls (HC). Cells were treated either with AS or fetal calf serum (FCS) and polarized into M1 (LPS), M2 (IL-10, IL-4, TGF-ß) or M0 (unstimulated) macrophages. Polarization capacity was quantified by means of specific M1 (CCR7, CD86, CXCL10, IL-12p70, TNF-α, IL-6, IL-1ß, IL-12p40, IL-23, IP-10) and M2 (CD206, IL-10, TARC, IL-1RA) markers. Compared to HC, significantly increased M1-polarization was observed for MDD patients in the presence of FCS, however, polarization in AS enriched media determined an increased M2-polarization in patients. Moreover, female MDD patients exhibited increased M1- and decreased M2-polarization in both conditions compared to male MDD patients. Our data suggests that Mo-MФs derived from patients with MDD exhibit facilitated M1-polarization under traditional cell culture conditions and an increased potential for M2-polarization when cultured in AS. Striking inter-individual variation and pronounced gender effects highlight the potential utility of our personalized cell model-based approach to aid diagnostic and therapeutic decisions.

Clozapine modulates retinoid homeostasis in human brain and normalizes serum retinoic acid deficit in patients with schizophrenia.

The atypical antipsychotic clozapine is one of the most potent drugs of its class, yet its precise mechanisms of action remain insufficiently understood. Recent evidence points toward the involvement of endogenous retinoic acid (RA) signaling in the pathophysiology of schizophrenia. Here we investigated whether clozapine may modulate RA-signaling. Effects of clozapine on the catabolism of all-trans RA (at-RA), the biologically most active metabolite of Vitamin A, were assessed in murine and human brain tissue and peripheral blood-derived mononuclear cells (PBMC). In patients with schizophrenia with and without clozapine treatment and matched healthy controls, at-RA serum levels and blood mRNA expression of retinoid-related genes in PBMCs were quantified. Clozapine and its metabolites potently inhibited RA catabolism at clinically relevant concentrations. In PBMC-derived microsomes, we found a large interindividual variability of the sensitivity toward the effects of clozapine. Furthermore, at-RA and retinol serum levels were significantly lower in patients with schizophrenia compared with matched healthy controls. Patients treated with clozapine exhibited significantly higher at-RA serum levels compared with patients treated with other antipsychotics, while retinol levels did not differ between treatment groups. Similarly, in patients without clozapine treatment, mRNA expression of RA-inducible targets CYP26A and STRA6, as well as at-RA/retinol ratio, were significantly reduced. In contrast, clozapine-treated patients did not differ from healthy controls in this regard. Our findings provide the first evidence for altered peripheral retinoid homeostasis in schizophrenia and suggest modulation of RA catabolism as a novel mechanism of action of clozapine, which may be useful in future antipsychotic drug development.

Trait emotion regulation strategies and diurnal cortisol profiles in healthy adults.

OBJECTIVE: Experimental studies have shown that 2 emotion regulation strategies-suppression and reappraisal-are associated with differential profiles of physiological activation in response to a stress test. The present study aims to add to those findings by investigating whether individual differences in trait emotion regulation strategies are associated with diurnal cortisol patterns in a naturalistic context. METHOD: A sample of 46 men and women from the Midlife in the United States II (MIDUS II) study completed the Emotion Regulation Questionnaire (ERQ) and provided 4 salivary cortisol samples per day over 4 consecutive days. Trait reappraisal and suppression were tested as predictors of 3 cortisol parameters averaged across days: cortisol awakening response (CAR), diurnal cortisol slope (DCS), and area under the curve with respect to ground (AUCg). RESULTS: Higher scores on the suppression scale were associated with more physiological activation, as indicated by steeper CAR and flatter DCS. Suppression was not associated with AUCg, and reappraisal was not predictive of any cortisol parameter. CONCLUSIONS: Individual differences in suppression, but not reappraisal, were linked to greater cortisol activation in this naturalistic study. These preliminary results add to a growing body of findings that link suppression to adverse psychological and physiological profiles. (PsycINFO Database Record

High-fat taste challenge reveals altered striatal response in women recovered from bulimia nervosa: A pilot study.

OBJECTIVES: Individuals with anorexia nervosa (AN) and bulimia nervosa (BN) tend to have disordered thinking and eating behaviours in regards to fat containing foods. This is the first study to investigate neuronal pathways that may contribute to altered fat consumption in eating disordered patients. METHODS: We used functional magnetic resonance imaging (fMRI) to compare responses to a high-fat cream stimulus, water, and a non-caloric viscous stimulus (CMC) to control for response to viscosity in individuals recovered from AN (N = 15), BN (N = 14) and a healthy control sample (CW, N = 18). RESULTS: An interaction analysis (ANOVAR) comparing the three groups (AN, BN, CW) and the three conditions (cream, CMC, water) revealed significant differences in the left anterior ventral striatum (AVS). A post hoc analysis displayed a higher magnitude of response for the contrast cream/water in BN compared to AN or CW and for the contrast CMC/water in BN compared to AN. CONCLUSIONS: BN showed an exaggerated AVS response for the cream/water contrast in comparison to AN or CW. Moreover, BN showed an exaggerated AVS response for the CMC/water contrast in comparison to AN. These findings support the possibility that BN have an altered hedonic and/or motivational drive to consume fats.

Travel-related chronic hemorrhagic leg ulcer infection by Shewanella algae.

Shewanella algae is an emerging seawater-associated bacterium. In immunocompromised patients, infections may result in bacteremia, osteomyelitis, and necrotizing fasciitis. Our patient, suffering from autoimmune vasculitis and myasthenia gravis, developed typical hemorrhagic bullae and leg ulcers because of S algae. She was treated efficiently with a combination of ciprofloxacin and piperacillin.

Development of a multiplex real-time PCR for detection and differentiation of malignant catarrhal fever viruses in clinical samples.

A multiplex real-time PCR was developed using a single pair of primers and fluorescent probes specific for five malignant catarrhal fever viruses and an internal positive control. The assay was able to simultaneously detect and differentiate the viruses in clinical samples with high sensitivity (97.2%) and specificity (100%).

Bioactive poly(L-lactic acid) conduits seeded with Schwann cells for peripheral nerve regeneration.

This study attempted to enhance the efficacy of peripheral nerve regeneration using our previously tested poly(L-lactic acid) (PLLA) conduits by incorporating them with allogeneic Schwann cells (SCs). The SCs were harvested, cultured to obtain confluent monolayers and two concentrations (1 x 10(4) and 1 x 10(6) SC/ml) were combined with a collagen matrix (Vitrogen) and injected into the PLLA conduits. The conduits were then implanted into a 12 mm right sciatic nerve defect in rats. Three control groups were used: isografts, PLLA conduits filled with collagen alone and empty silicone tubes. The sciatic functional index (SFI) was calculated monthly through four months. At the end of second and fourth months, the gastrocnemius muscle was harvested and weighed for comparison and the graft conduit and distal nerve were harvested for histomorphologic analysis. The mean SFI demonstrated no group differences from isograft control. By four months, there was no significant difference in gastrocnemius muscle weight between the experimental groups compared to isograft controls. At four months, the distal nerve demonstrated a statistically lower number of axons mm2 for the high and low SC density groups and collagen control. The nerve fiber density was significantly lower in all of the groups compared to isograft controls by four months. The development of a "bioactive" nerve conduit using tissue engineering to replace autogenous nerve grafts offers a potential approach to improved patient care. Although equivalent nerve regeneration to autografts was not achieved, this study provides promising results for further investigation.