OBJECTIVES:Coronary artery disease (CAD) is a chronic inflammatory disorder characterized by immune dysregulation and a higher risk of viral infections. Among the immune cells involved, mucosal-associated invariant T (MAIT) cells participate in antimicrobial defense and tissue repair, yet their contribution to CAD has not been clearly defined. METHODS:Peripheral blood mononuclear cells and plasma were obtained from patients with CAD and from healthy controls. MAIT cell subsets, conventional T cells, and the SARS-CoV-2 receptors ACE2 and CD147 were analyzed by flow cytometry. Cytokines were quantified using ELISA. Additional in-vitro assays were performed to test whether recombinant SARS-CoV-2 spike proteins could influence cell apoptosis or proliferation. RESULTS:The number of circulating MAIT cells was markedly reduced in CAD, most notably within the CD8+ population. In contrast, CD4+ MAIT cells were relatively increased but expressed less CCR5 intensities, suggesting limited migratory ability. Plasma IL-7 concentrations were lower in CAD, while IL-18 and IFN-α2 were higher. These findings indicate a disturbed cytokine environment, especially for MAIT cell activation. CAD samples also showed more CD4+PD-1+ and fewer CD8+CD69+ T cells, pointing toward an exhausted phenotype. IL-18 levels correlated negatively with left-ventricular ejection fraction. Expression of ACE2 and CD147 was similar between groups, and spike-protein exposure did not trigger significant apoptosis or proliferation in vitro. CONCLUSION:CAD is associated with loss and functional alteration of MAIT cells, cytokine imbalance, and T-cell exhaustion. Together, these immune changes may weaken antiviral defense mechanisms in the context of viral infections, such as the SARS-CoV-2 infection.

Background: Schizophrenia (Sz), once considered solely a brain disorder, is now recognised as a systemic illness involving immune and metabolic dysregulation. Recently, attention has focused on the intestinal barrier as a potential factor that exerts influence via gut–brain–immune interactions. However, studies on gut permeability markers in early, antipsychotic-free stages remain scarce and often neglect confounders such as smoking and metabolic syndrome. Methods: We measured two complementary markers: lipopolysaccharide-binding protein (LBP), reflecting endotoxin exposure and systemic immune activation, and intestinal fatty acid-binding protein (I-FABP), indicating gut epithelial damage and permeability changes, in blood from 96 acutely ill, antipsychotic-free Sz patients (61 first-episode, 35 relapsed) and 96 matched controls. Associations with innate immune activation, metabolic parameters, smoking, and clinical features were assessed using nonparametric statistics and random forest regression. Group differences were tested with covariate adjustment and separately in non-smokers (Sz: n=42; controls: n=84). Results: Median LBP was higher in Sz (21.96 µg/mL) vs. controls (18.10 µg/mL; FDR-adjusted p=0.021, δ=0.209), but became non-significant after adjusting for smoking (FDR-adjusted p=0.199). In contrast, I-FABP was lower in Sz (218.2 pg/mL) than controls (315.0 pg/mL; FDR-adjusted p=0.021, δ=–0.195), and remained robust across smoking-adjusted analyses. No differences were found between first-episode and relapsed patients for either marker. LBP correlated strongly with CRP (r=0.557, p<0.001) and neutrophils (r=0.468, p<0.001), regardless of smoking, and was predicted moderately by immune models (pseudo-R² = 0.354 full sample; 0.273 Sz; 0.449 controls). Links to waist circumference and blood pressure were weaker (pseudo-R²: 0.048–0.104). I-FABP was less associated with immune markers and uncorrelated with LBP (r=–0.017, FDR-adjusted p=0.819), suggesting distinct underlying mechanisms. Conclusions: Our findings reveal multifaceted gut barrier disruptions in antipsychotic-free Sz. Elevated LBP, associated with CRP and neutrophils, suggests inflammation influenced by smoking and metabolic factors. In contrast, reduced I-FABP, independent of smoking, may indicate epithelial injury. Their lack of correlation highlights distinct pathophysiological dimensions of gut dysfunction. Longitudinal studies, ideally spanning prodromal phases and integrating microbiome, dietary, and permeability assessments, are needed to clarify temporal dynamics and guide stratified treatment approaches.

Schizophrenia (Sz), once seen solely as a brain disorder, is now recognised as a systemic illness involving immune and metabolic dysregulation. The intestinal barrier has emerged as a key player in gut–brain–immune interactions. However, studies in early, antipsychotic free stages remain scarce and often neglect confounding factors such as smoking and metabolic syndrome. We measured two complementary markers: lipopolysaccharide-binding protein (LBP), reflecting endotoxin exposure and systemic immune activation, and intestinal fatty acid-binding protein (I-FABP), indicating gut epithelial damage and permeability changes, in blood from 96 acutely ill, antipsychotic-free Sz patients (61 first-episode, 35 relapsed) and 96 matched controls. Associations with innate immunity, metabolic parameters, smoking, and clinical features were assessed using nonparametric statistics and random forest regression. Group differences were tested using covariate adjustment, as well as in a separate analysis of non-smokers (Sz: n = 42; controls: n = 84). Median LBP was higher in Sz (21.96 µg/mL) vs. controls (18.10 µg/mL; FDR-adjusted p = 0.021, δ = 0.209) but became non-significant after adjusting for smoking (FDR-adjusted p = 0.199). In contrast, I-FABP was lower in Sz (218.2 pg/mL) than controls (315.0 pg/mL; FDR-adjusted p = 0.021, δ = –0.195) and remained robust across smoking-adjusted analyses. No differences were found between first-episode and relapsed patients for either marker. LBP correlated strongly with CRP (r = 0.557, p < 0.001) and neutrophils (r = 0.468, p < 0.001) and was moderately predicted by immune models (pseudo-R2 = 0.354 overall; 0.273 Sz; 0.449 controls). Links to waist circumference and blood pressure were weaker (pseudo-R2: 0.048–0.104). I-FABP showed fewer immune associations and was not correlated with LBP (r = –0.017, FDR-adjusted p = 0.819), suggesting distinct mechanisms. Our findings suggest separable gut‑related processes in antipsychotic-free Sz. The apparent LBP elevation was not schizophrenia‑specific; its strong correlations with CRP and neutrophils point to smoking related inflammation rather than a schizophrenia specific effect. Accordingly, prior findings of LBP elevations in Sz likely reflect unaccounted smoking. In contrast, reduced I-FABP, independent of smoking, may indicate epithelial injury. The absent correlation between LBP and I-FABP highlights distinct pathophysiological dimensions of gut dysfunction. Longitudinal studies, ideally spanning prodromal phases and integrating microbiome, dietary, smoking, and permeability assessments, are needed to clarify temporal dynamics and guide stratified treatments.

Ethanol is metabolized by alcohol dehydrogenase to acetaldehyde and induces cytochrome P450 2E1 (CYP2E1), which generates reactive oxygen species that cause inflammatory liver damage. Clomethiazole, a drug approved for alcohol withdrawal treatment (AWT) in some European countries, inhibits CYP2E1. We hypothesized that clomethiazole would lead to a faster reduction in oxidative stress, inflammatory cytokines, and liver enzymes compared to diazepam treatment. We analysed respective biomarkers in 50 patients undergoing AWT and 25 healthy individuals but found no statistical difference between the two medication groups over 3–5 days. Hence, our hypothesis was not confirmed during this observation period.

The potential influence of astrocytes on neuronal circuitry and psychotic symptoms in schizophrenia have recently been highlighted. Human postmortem studies have observed reduced astrocyte numbers in schizophrenia, but whether this pathology is present at disease onset or accumulates progressively with further psychotic episodes remains unclear. Therefore, we analysed serum levels of the astrocyte-derived proteins glial fibrillary acidic protein (GFAP) and fatty acid-binding protein 7 (FABP7) in acutely ill first-episode (n = 60) and relapsed (n = 34) schizophrenia patients compared to 94 matched controls. Measurements were taken before and 6 weeks after antipsychotic treatment. We found significantly lower levels of GFAP (p < 0.001) and FABP7 (p < 0.001) in patients compared to controls, with no significant differences between first-episode and relapsed patients or changes after treatment. FABP7 negatively correlated with age in controls (r = -0.319, p = 0.002), but not in patients (r = -0.251, p = 0.015). In contrast, GFAP showed no correlation with age. Our findings suggest that lowered GFAP and FABP7 may serve as trait markers of astrocyte pathology in schizophrenia, even prior to antipsychotic treatment. The absent correlation between FABP7 and age in schizophrenia patients, in contrast to controls, may be related to premature brain aging in schizophrenia. Long-term studies are needed to explore the relationship between chronic disease and astrocyte pathology in schizophrenia.

Objective: The amygdaloid complex is a subcortical limbic group of distinct nuclei. In a previous patient-control study, differential amygdala nuclei alterations were found in acute anorexia nervosa (AN); rostral-medial nuclei involved in fear and reward processing were substantially reduced in volume and associated with hypoleptinemia, a key neuroendocrine characteristic of AN. Here, longitudinal amygdala nuclei alterations in AN were investigated in relation to weight status and their associations with leptin levels. Method: T1-weighted structural magnetic resonance imaging scans were longitudinally processed with FreeSurfer. Amygdala nuclei volumes in young female patients with acute AN before and after short-term weight restoration (n = 110, >14% body mass index increase over 3 months) and female participants with a history of AN (n = 79, long-term [mean 5 years] weight recovered) were compared with female healthy control participants (n = 271) using linear mixed effects models. Results: Rostral-medially clustered amygdala nuclei volumes, accessory basal, cortical, medial nuclei, and corticoamygdaloid transition, increased during short-term weight restoration (Cohen's d range 0.18-0.30). However, volumetric normalization across nuclei was heterogeneous. Right cortical, medial nuclei, bilateral corticoamygdaloid transitions, and anterior amygdaloid areas were only partially normalized following short-term weight restoration. Right anterior amygdaloid area remained reduced after long-term weight recovery compared with control participants (d = 0.36). Leptin increase, accompanying short-term weight restoration, mediated the effect of weight gain on volumetric increase in left corticoamygdaloid transition and bilateral medial nuclei. Conclusion: Rostral-medially clustered amygdala nuclei show pronounced volumetric increase but incomplete normalization in AN during and after short-term weight restoration. Leptin increase may be relevant for the recovery of specific amygdala nuclei in addition to nutritional rehabilitation, indicating links between amygdala substructure and leptin dynamics of potential pathophysiological and clinical relevance in AN. Plain language summary: The amygdala plays a critical role in processing fearful and rewarding stimuli, and alterations in the amygdala are associated with anorexia nervosa. In this study, the authors measured amygdala nuclei volumes in female patients with acute anorexia nervosa undergoing weightrestoration treatment (n = 110), long-term weight-recovered individuals with anorexia (n = 79), and healthy control participants (n = 271). Structural magnetic resonance imaging revealed that volumes of specific nuclei, clustered in the rostral-medial amygdala, were substantially reduced in acute anorexia nervosa and only partially normalized following weight restoration treatment. Residual reductions in volume persisted even after long-term weight-recovery, compared to healthy control participants. Short-term weight restoration was associated with increases in the neurohormone leptin, and increasing leptin levels were found to mediate the positive impact of weight gain on increased amygdala volume over the treatment course. Diversity & Inclusion Statement: We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our participated in the data collection, design, analysis, and/or interpretation of the work.

Anorexia nervosa (AN) is a severe eating disorder that predominantly affects females and typically manifests during adolescence. There is increasing evidence that serum cytokine levels are altered in individuals with AN. Previous research has largely focused on adult patients, assuming a low-grade pro-inflammatory state. The serum levels of the cytokine tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6 and IL-15, which are pro-inflammatory, were examined in 63 female adolescents with AN and 41 age-matched healthy controls (HC). We included three time points (admission, discharge, and 1-year follow-up) and investigated the clinical data to assess whether the gut microbiota was associated with cytokine alterations. Relative to the HC group, serum levels of IL-1β and IL-6 were significantly lower during the acute phase (admission) of AN. IL-1β expression was normalised to control levels after weight recovery. TNF-α levels were not significantly different between the AN and HC groups. IL-15 levels were significantly elevated in patients with AN at all time points. We found associations between cytokines and bodyweight, illness duration, depressive symptoms, and the microbiome. In contrast to most findings for adults, we observed lower levels of the pro-inflammatory cytokines IL-1β and IL-6 in adolescent patients, whereas the level of IL-15 was consistently increased. Thus, the presence of inflammatory dysregulation suggests a varied rather than uniform pro-inflammatory state.

The neurotrophic growth factor brain-derived neurotrophic factor (BDNF) plays a crucial role in various neurodegenerative and psychiatric diseases, such as Alzheimer's disease, schizophrenia and depression. BDNF has been proposed as a potential biomarker for diagnosis, prognosis and monitoring therapy. Understanding the factors influencing BDNF levels and whether they follow a circadian rhythm is essential for interpreting fluctuations in BDNF measurements. We aimed to investigate the circadian rhythm of BDNF by collecting multiple peripheral venous blood samples from young, healthy male participants at 12 different time points over 24 h. In addition, vital parameters, cortisol and insulin like growth factor 1 (IGF1) were measured to explore potential regulatory mechanisms, interfering variables and their correlations with BDNF concentration. The findings revealed that plasma BDNF did not exhibit any significant fluctuations over 24 h, suggesting the absence of a circadian rhythm. However, serum BDNF levels decreased during sleep. Furthermore, serum BDNF showed a positive correlation with heart rate but a negative correlation with IGF1. No significant correlation was observed between cortisol and BDNF or IGF1. Although plasma BDNF suggests steady-state conditions, the decline of serum BDNF during the nocturnal period could be attributed to physical inactivity and associated with reduced haemodynamic blood flow (heart rate reduction during sleep). The type of sample collection (peripheral venous cannula vs. blood sampling using a butterfly system) does not significantly affect the measured BDNF levels. The sample collection during the day did not significantly affect BDNF analysis, emphasizing the importance of considering activity levels rather than timing when designing standardized protocols for BDNF assessments.

One of the key challenges for successful cancer therapy is the capacity of tumors to evade immune surveillance. Tumor immune evasion can be accomplished through the induction of T cell exhaustion via the activation of various immune checkpoint molecules. The most prominent examples of immune checkpoints are PD-1 and CTLA-4. Meanwhile, several other immune checkpoint molecules have since been identified. One of these is the T cell immunoglobulin and ITIM domain (TIGIT), which was first described in 2009. Interestingly, many studies have established a synergistic reciprocity between TIGIT and PD-1. TIGIT has also been described to interfere with the energy metabolism of T cells and thereby affect adaptive anti-tumor immunity. In this context, recent studies have reported a link between TIGIT and the hypoxia-inducible factor 1-α (HIF1-α), a master transcription factor sensing hypoxia in several tissues including tumors that among others regulates the expression of metabolically relevant genes. Furthermore, distinct cancer types were shown to inhibit glucose uptake and effector function by inducing TIGIT expression in CD8+ T cells, resulting in an impaired anti-tumor immunity. In addition, TIGIT was associated with adenosine receptor signaling in T cells and the kynurenine pathway in tumor cells, both altering the tumor microenvironment and T cell-mediated immunity against tumors. Here, we review the most recent literature on the reciprocal interaction of TIGIT and T cell metabolism and specifically how TIGIT affects anti-tumor immunity. We believe understanding this interaction may pave the way for improved immunotherapy to treat cancer.

Abstract Objectives Severe asthma is heterogeneous, with childhood-onset asthma believed more likely to be allergic, whereas adult-onset asthma is considered typically non-allergic. However, the allergic diagnosis is typically by exclusion: if patients do not react to an allergen panel, which is not standardized and often limited to few allergens, they are considered non-allergic. The overall aim of the ATLAS study was to characterize the sensitization to allergens in severe asthma (independent of phenotype). Methods Single-visit, cross-sectional, non-interventional study in adults with severe asthma. Analyses were conducted for total and specific immunoglobulin E against 53 allergens, overall and in subgroups, including age at asthma onset (<20 [childhood-onset] and >40 years of age). Results Among 1010 recruited patients, 28.4% reported childhood-onset asthma and 33.6% onset >40 years of age. After excluding patients receiving omalizumab/anti-IL5 therapy, 27.6% were not sensitized to any tested allergens, whereas 19.1% were sensitized to >10 allergens. All allergens triggered sensitization in some patients. Baseline characteristics in the two onset subgroups were similar; 23.2% with childhood-onset asthma were not sensitized to any allergen, compared to 32.0% with onset >40 years of age. Conclusion When a broad panel of allergens is used for sensitization testing, as many as three quarters of patients with severe asthma display sensitivity to at least one allergen, with substantial overlaps in all characteristics between the two age-at-onset subgroups. All of the tested allergens triggered a response in at least some patients, emphasizing the importance of including a broad range of allergens in any testing panel.

OBJECTIVE:The amygdaloid complex plays a pivotal role in emotion processing and has been associated with rumination transdiagnostically. In anorexia nervosa (AN), we previously observed differential reductions of amygdala nuclei volumes (rostral-medial cluster substantially affected) and, in another study, elevated food-/weight-related rumination. Both amygdala volumes and rumination frequency correlated with characteristically suppressed leptin levels in AN. Thus, we hypothesized that amygdala nuclei alterations might be associated with AN-related rumination and potentially mediate the leptin-rumination relationship in AN. METHODS:Rumination (food-/weight-related) was assessed using ecological momentary assessment for a 14-day period. We employed frequentist and Bayesian linear mixed effects models in females with AN (n = 51, 12-29 years, majority admitted to inpatient treatment) and age-matched healthy females (n = 51) to investigate associations between rostral-medial amygdala nuclei volume alterations (accessory basal, cortical, medial nuclei, corticoamygdaloid transitions) and rumination. We analyzed mediation effects using multi-level structural equation models. RESULTS:Reduced right accessory basal and cortical nuclei volumes predicted more frequent weight-related rumination in AN; both nuclei fully mediated the effect of leptin on weight-related rumination. In contrast, we found robust evidence for the absence of amygdala nuclei volume effects on rumination in healthy females. CONCLUSION:This study provides first evidence for the relevance of specific amygdala substructure reductions regarding cognitive symptom severity in AN and points toward novel mechanistic insight into the relationship between hypoleptinemia and rumination, which might involve the amygdaloid complex. Our findings in AN may have important clinical value with respect to understanding the beneficial neuropsychiatric effects of leptin (treatment) in AN and potentially other psychiatric conditions such as depression.

Anorexia nervosa (AN) is a complex psychiatric disorder accompanied by a variety of endocrine effects. Altered levels of the sex steroid hormones progesterone and dehydroepiandrosterone (DHEA) have been shown to occur in patients with AN using short-term hormonal measurement methods based on blood, saliva, and urine samples. However, since sex steroid hormone levels fluctuate during the menstrual cycle, these measurement methods require a great deal of effort due to the need to collect multiple samples in order to correctly determine the basal level of sex hormones. In contrast, hair-based assessments provide a marker of accumulated longer-term hormone exposure using a single, non-invasive sample. The aim of this study was to investigate sex steroid hormone levels via hair-based assessments in acutely underweight AN in comparison with healthy, age-matched, female control participants. Additionally, we compared progesterone and DHEA hair levels longitudinally during inpatient treatment in AN. Collected hair samples were analyzed using liquid chromatography-mass spectrometry (LC-MS/MS) to determine a monthly hormone level of progesterone and DHEA. Our results indicate that DHEA hair hormone levels were similar across groups but progesterone was suppressed in underweight AN compared with healthy controls. In the longitudinal design, no significant change in hair hormone levels during partial weight restoration in patients with AN was observed. Our findings suggest that hair analysis can be used to detect suppressed progesterone levels in severe AN, and that progesterone does not increase during short-term weight restoration.

Background: Disruptions of neuronal macro- and microcircuits in schizophrenia (SCZ) have been attributed to pathologies of neuronal connectivity. We hypothesized that during acute psychosis structural damage to axons and synapses occurs in a subset of patients, rendering them more susceptible to poor treatment outcomes or relapse. Methods: Neurofilament light-chain protein (NfL), a marker of axonal and synaptic damage, was quantified in sera of acutely ill unmedicated schizophrenia patients (SCZ, n=98) at hospital admission (T0) and after 6 weeks of inpatient treatment (T6), compared to healthy controls (HC, n=132). Additionally, we analyzed blood cell counts, the levels of 171 serum biomarkers, clinical symptomatology and functioning relapse occurrences requiring hospitalisation during the 5-year follow-up. Univariate analysis and support vector machine learning were employed to identify SCZ with increased NfL, interrogate the relationship between biological factors and NfL and examine whether NfL and associated biological factors can predict treatment outcome or likelihood of relapse. Results: NfL was increased in SCZ versus HC (p=0.014), correlated positively with positive and negative syndrome scale-positive scores (rho=0.265, P=0.019) and inversely with global assessment of functioning-scores (rho=-0.365, P<0.001) at T0. Decreased NfL at T6 (P<0.001) did not correlate with administered cumulative antipsychotic dosage. NfL levels were predicted using a serum biomarker set with a balanced accuracy of 67.2 % (P5000=0.0008). Higher levels of insulin-like growth factor binding protein 2 (IGFBP-2), granulocytes, leukocytes, thrombocytes, Creactive protein (CRP) and mean corpuscular volume (MCV) predicted elevated NfL, whereas erythrocytes, hematocrit, HbA1c and hemoglobin predicted normal NfL levels. NfL and these associated factors also predicted psychotic relapse during 5-year follow-up with a balanced accuracy of 66.3% (P5000=0.0382). Conclusions: NfL is embedded in a circuitry of neurobiological factors related to synaptic plasticity (IGFBP-2), innate immune response (granulocytes, leukocytes, CRP), glucose metabolism (IGFBP-2, glucose, HbA1c), and haemodynamics (MCV, hematocrit, thrombocytes, haemoglobin). Approximately 25% of the SCZ patients showed increased NfL levels. The identified associated network of biological factors was predictive for long-term treatment outcome in schizophrenia in terms of the likelihood of future relapses thus pointing towards innate immunity–based acutely destabilized neuronal circuits as an endophenotype for future therapy and disease monitoring in schizophrenia.

Multivessel coronary artery disease (CAD) is characterized by underlying chronic vascular inflammation and occlusion in the coronary arteries, where these patients undergo coronary artery bypass grafting (CABG). Since post-cardiotomy inflammation is a well known phenomenon after CABG, attenuation of this inflammation is required to reduce perioperative morbidity and mortality. In this study, we aimed to phenotype circulating frequencies and intensities of monocyte subsets and monocyte migration markers, respectively, and to investigate the plasma level of inflammatory cytokines and chemokines between preoperative and postoperative CAD patients and later, to intervene the inflammation with sodium selenite. We found a higher amplitude of inflammation, postoperatively, in terms of CCR1high monocytes and significantly increased pro-inflammatory cytokines, IL-6, IL-8, and IL-1RA. Further, in vitro intervention with selenium displayed mitigating effects on the IL-6/STAT-3 axis of mononuclear cells derived from postoperative CAD patients. In addition, in vitro selenium intervention significantly reduced IL-1β production as well as decreased cleaved caspase-1 (p20) activity by preoperative (when stimulated) as well as postoperative CAD mononuclear cells. Though TNF-α exhibited a positive correlation with blood troponin levels in postoperative CAD patients, there was no obvious effect of selenium on the TNF-α/NF-κB axis. In conclusion, anti-inflammatory selenium might be utilized to impede systemic inflammatory cytokine axes to circumvent aggravating atherosclerosis and further damage to the autologous bypass grafts during the post-surgical period.

Objective: Although anorexia nervosa (AN) in males has recently gained attention, knowledge of its psychological and physiological outcomes is still scarce. We explore sex-specific characteristics of long-term remitted AN with respect to residual eating disorder (ED) psychopathology, body image, and endocrinology.Method: We recruited 33 patients with AN in remission for at least 18 months (24 women, 9 men) and 36 matched healthy controls (HCs). Eating disorder psychopathology and body image ideals were assessed via clinical interviews, questionnaires, and an interactive 3D body morphing tool. Plasma levels of leptin, free triiodothyronine, cortisol, and sex hormones were quantified. Univariate models controlled for age and weight were used to test for the effects of diagnosis and sex.Results: Both patient groups showed residual ED psychopathology but normal weight and hormone levels relative to HCs. Male remitted patients demonstrated significantly stronger muscularity-focused body image ideals, evident in interviews, self-reports, and behavioural data, than both female patients and HCs.Conclusions: Sex-specific body image characteristics in patients with remitted AN point towards the need to adjust test instruments and diagnostic criteria to male-specific psychopathology. In the future, sufficiently powered studies should evaluate the risk of men with AN developing muscle dysmorphia in the long term.

IntroductionAnorexia nervosa (AN) is an often chronic and debilitating psychiatric disease whose etiology is not completely understood. Recently, a potential role of inflammation has emerged in other psychiatric diseases, such as depression, PTSD and schizophrenia. The first results in adults with AN seemed to confirm a low-grade proinflammatory state until recent studies presented more differential findings. Studying adolescents with a shorter illness duration and fewer confounding factors might help elucidate the role of inflammation in the underlying pathophysiology of AN; however, the few available studies in adolescents remain ambiguous, and no longitudinal data are available in this age range.MethodsWe examined the proinflammatory cytokines Tumor Necrosis Factor-alpha (TNF-α), Interleukin (IL)-1β, IL-6, IL-15, and the cytokine-receptor IL-6 Receptor alpha (IL-6 Rα) in the serum of twenty-two hospitalized female adolescent patients with AN longitudinally at admission and discharge and compared their results to nineteen healthy controls (HC). We also collected clinical data and stool samples that were analyzed with 16S rRNA amplicon sequencing to explore potential influencing factors of cytokine changes.ResultsTNF-α serum levels were significantly elevated in patients with AN at admission, while IL-1β and IL-6 levels were lower at admission and discharge than in HC. After treatment, we also found significantly elevated levels of IL-6 Rα compared to HC, while IL-15 did not show significant changes. Exploratory analyses revealed positive associations of cytokine and genus-level changes between admission and discharge for IL-1β (Bacteroides) and IL-15 (Romboutsia), and negative associations for IL-15 (Anaerostipes) and TNF-α (uncultured Lachnospiraceae).ConclusionWe confirmed a previous finding of elevated levels of TNF-α also in adolescents with AN; however, the reduced IL-1β and IL-6 levels differed from the mostly increased levels found in adults. A mixed pro- and anti-inflammatory state appears to be present in adolescents, potentially due to their shorter illness duration. The gut microbiota, with its regulatory function on cytokine production, might play a role in mediating these inflammatory processes in AN and could offer targets for new therapeutic approaches.

Tafazzin-an acyltransferase-is involved in cardiolipin (CL) remodeling. CL is associated with mitochondrial function, structure and more recently with cell proliferation. Various tafazzin isoforms exist in humans. The role of these isoforms in cardiolipin remodeling is unknown. Aim of this study was to investigate if specific isoforms like Δ5 can restore the wild type phenotype with respect to CL composition, cellular proliferation and gene expression profile. In addition, we aimed to determine the molecular mechanism by which tafazzin can modulate gene expression by applying promoter analysis and (Ingenuity Pathway Analyis) IPA to genes regulated by TAZ-deficiency. Expression of Δ5 and rat full length TAZ in C6-TAZ- cells could fully restore CL composition and-as proven for Δ5-this is naturally associated with restoration of mitochondrial respiration. A similar restoration of CL-composition could not be observed after re-expression of an enzymatically dead full-length rat TAZ (H69L; TAZMut). Re-expression of only rat full length TAZ could restore proliferation rate. Surprisingly, the Δ5 variant failed to restore wild-type proliferation. Further, as expected, re-expression of the TAZMut variant completely failed to reverse the gene expression changes, whereas re-expression of the TAZ-FL variant largely did so and the Δ5 variant to somewhat less extent. Very likely TAZ-deficiency provokes substantial long-lasting changes in cellular lipid metabolism which contribute to changes in proliferation and gene expression, and are not or only very slowly reversible.

Abstract Background We recently reported increased levels of neutrophils, monocytes and C-reactive protein (CRP) correlated with symptom severity in acute schizophrenia. Here, we investigated if a similar pattern of innate immune system activation occurs in major depression (MD). Methods We assessed differential blood counts, CRP, depression symptoms (HAMD-21) and psychosocial functioning (GAF) in controls (n = 129) and patients with first (FEMD: n = 82) or recurrent (RMD: n = 47) disease episodes of MD at baseline (T0; hospital admission) and after 6-weeks treatment (T6). Results Considering smoking, BMI and gender as covariates, neutrophils (FEMD: p = 0.034, RMD: p = 0.034) and CRP (FEMD: p < 0.001, RMD: p = 0.021) were higher, and eosinophils (FEMD: p = 0.005, RMD: p = 0.004) lower in patients versus controls at T0. Baseline lymphocyte counts were elevated in RMD (p = 0.003) but not FEMD. Results were confirmed by analyses of nonsmokers. At follow-up, eosinophils rose significantly in FEMD (p = 0.011) but no significant changes were observed in RMD. Improvement in HAMD-21 correlated with T0–T6 changes of neutrophil counts in FEMD (r = 0.364, p = 0.024). Compared with our previous schizophrenia study, raised baseline neutrophil and reduced eosinophil counts in MD had smaller effect sizes and treatment had a weaker association with T0-T6 changes in neutrophils. In addition, lymphocytes were elevated at T0 in recurrent MD but not in schizophrenia patients. Conclusions These findings suggest that innate immunity may be involved in early stages of MD, and adaptive immunity may be involved in chronic disease. Thus, further studies may lead to new disease stage-dependent MD treatment strategies targeting different aspects of immune system activation.