Acta Neuropsychiatrica

BackgroundAutoimmune autonomic ganglionopathy (AAG) is a rare disorder characterized by autonomic failure associated with the presence of anti-ganglionic acetylcholine receptor (gAChR) antibodies; however, several studies have reported that individuals with anti-gAChR antibodies present with central nervous system (CNS) symptoms such as impaired consciousness and seizures. In the present study, we investigated whether the presence of serum anti-gAChR antibodies correlated with autonomic symptoms in patients with functional neurological symptom disorder/conversion disorder (FNSD/CD). MethodsClinical data were collected for 59 patients presenting with neurologically unexplained motor and sensory symptoms at the Department of Neurology and Geriatrics between January 2013 and October 2017 and who were ultimately diagnosed with FNSD/CD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. Correlations between serum anti-gAChR antibodies and clinical symptoms and laboratory data were analyzed. Data analysis was conducted in 2021. ResultsOf the 59 patients with FNSD/CD, 52 (88.1%) exhibited autonomic disturbances and 16 (27.1%) were positive for serum anti-gAChR antibodies. Cardiovascular autonomic dysfunction, including orthostatic hypotension, was significantly more prevalent (75.0% vs 34.9%, p = 0.008), whereas involuntary movements were significantly less prevalent (31.3% vs 69.8%, p = 0.007), among anti-gAChR antibody-positive compared with - negative patients. Anti-gAChR antibody serostatus did not correlate significantly with the frequency of other autonomic, sensory, or motor symptoms analyzed. ConclusionsAn autoimmune mechanism mediated by anti-gAChR antibodies may be involved in the etiology of FNSD/CD in a subgroup of patients.

Depressive and anxiety symptoms occur more frequently in chronic encephalomyelitis. Inflammatory diseases are highly associated with psychiatric comorbidities, which has been well established in Multiple Sclerosis. However, no biomarkers have been found with the capacity to discern between MS and depression. Thirty-six individuals with a diagnosis of MS according to the revised McDonald criteria, were recruited from an outpatient Neurology and Psychiatry from the medical unit of high specialty in Mexico. We measured the association between BDNF, IL-1{beta}, and TNF in serum with the presence of depression and anxiety using the semi-structured psychiatric interview, the Beck Depression Inventory (IDB), and Hospital Anxiety and Depression Scale (HADS). This was a cross-sectional study. The Logistic Regression was used for the multivariate analysis adjusted by the Multiple Sclerosis Severity Score (MSSS). With a power of 0.75 in the final model, patients with multiple sclerosis, depression, and anxiety obtained the highest values of IL-1 {beta} in our study.

BackgroundCritical COVID-19 disease is accompanied by depletion of plasma tryptophan (TRY) and increases in indoleamine-dioxygenase (IDO)-stimulated production of neuroactive tryptophan catabolites (TRYCATs), including kynurenine (KYN) and quinolinic acid. The TRYCAT pathway has not been studied extensively in association with the physiosomatic and affective symptoms of Long COVID. MethodsIn the present study, we measured serum tryptophan (TRY), TRYCATs, insulin resistance (using the HOMA2-IR index), C-reactive protein (CRP), physiosomatic, depression and anxiety symptoms in 90 Long COVID patients, 3-10 months after remission of acute infection. ResultsWe were able to construct an endophenotypic class of severe Long COVID (22% of the patients) with very low TRY and oxygen saturation (SpO2, during acute infection), increased kynurenine, KYN/TRY ratio, CRP, and very high ratings on all symptom domains. One factor could be extracted from physiosomatic symptoms (including chronic fatigue-fibromyalgia), depression, and anxiety symptoms, indicating that all domains are manifestations of the common physio-affective phenome. Three Long COVID biomarkers (CRP, KYN/TRY, IR) explained around 40% of the variance in the physio-affective phenome. The latter and the KYN/TRY ratio were significantly predicted by peak body temperature (PBT) and lowered SpO2 during acute infection. One validated latent vector could be extracted from the three symptom domains and a composite based on CRP, KYN/TRY, IR (Long COVID), and PBT and SpO2 (acute COVID-19). ConclusionThe physio-affective phenome of Long COVID is a manifestation of inflammatory responses during acute and Long COVID and lowered plasma tryptophan and increased kynurenine may contribute to these effects.

BackgroundInflammation and autoimmune responses contribute to the pathophysiology of Long COVID, and its affective and chronic fatigue syndrome (CFS) symptoms, labeled "the physio-affective phenome." ObjectivesTo investigate whether Long COVID and its physio-affective phenome are linked to autoimmunity to the tight junction proteins, zonulin and occludin (ZOOC), and immune reactivity to lipopolysaccharides (LPS), and whether the latter are associated with signs of human herpes virus-6 reactivation (HHV-6), autoimmunity directed against oligodendrocyte and neuronal proteins, including myelin basic protein (MBP). MethodsIgA/IgM/IgG responses to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), HHV-6, ZOOC, and neuronal proteins, C-reactive protein (CRP) and advanced oxidation protein products (AOPP), were measured in 90 Long COVID patients and 90 healthy controls. The physio-affective phenome was conceptualized as a factor extracted from physical and affective symptom domains. ResultsNeural network identified IgA directed to LPS (IgA-LPS), IgG-ZOOC, IgG-LPS, and IgA-ZOOC as the most important variables associated with Long COVID diagnosis with an area under the ROC curve of 0.755. Partial Least Squares analysis showed that 40.9% of the variance in the physio-affective phenome was explained by CRP, IgA-MPB and IgG-MBP. A large part of the variances in both autoimmune responses to MBP (36.3-39.7%) was explained by autoimmunity (IgA and IgG) directed to ZOOC. The latter was strongly associated with indicants of HHV-6 reactivation, which in turn was associated with increased IgM-SARS-CoV-2. ConclusionsAutoimmunity against components of the tight junctions and increased bacterial translocation may be involved in the pathophysiology of Long COVIDs physio-affective phenome.

BackgroundPatients with transfusion-dependent thalassemia (TDT) are vulnerable to neurotoxicity due to frequent blood transfusions and the subsequent iron overload (IO) and inflammation. As a result, affective (depression and anxiety) and chronic fatigue syndrome (CFS) symptoms may develop. AimsTo investigate the potential association between TDT and neuronal injury, as assessed with serum concentrations of neuronal damage biomarkers, including neurofilament light (NFL), glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), and nestin. MethodsWe investigated the associations between those CNS injury biomarkers, neuro-immune markers (C-reactive protein (CRP), interleukin (IL)-6, and IL-10), calcium, magnesium, copper and zinc, and the Fibro-Fatigue (FF), the Childrens Depression Inventory (CDI), and the Spence Childrens Anxiety Scale (SCAS) scores in 126 children with TDT and 41 healthy children. ResultsTDT children show significant increases in IO, FF, CDI, and SCAS scores, serum NSE, GFAP, NF-L, CRP, copper, IL-6, and IL-10, and lowered magnesium, zinc, and calcium as compared with healthy children. There were significant correlations between the CDI score and NFL, NSE and GFAP; SCAS score and NFL, and FF score and NFL and GFAP. The neuronal damage biomarkers (except nestin) were significantly associated with inflammatory, erythron (hematocrit and hemoglobin) and IO (iron and ferritin) biomarkers. ConclusionsTDT is characterized by intertwined increases in neuronal injury biomarkers and neuropsychiatric symptoms suggesting that TDT-associated neurotoxicity plays a role in affective symptoms and CFS due to TDT. Inflammation and neurotoxicity are novel drug targets for the prevention of affective symptoms and CFS due to TDT.

ObjectiveTo investigate the association between newly developed type 2 diabetes (T2D) and incident psychopharmacological treatment and psychiatric hospital contact. MethodsWe identified all individuals from the Central- and Northern Denmark Regions with newly developed T2D (defined by the first HbA1c measurement >6.5%) from 2000-2016 and up to five age and sex matched individuals without T2D (controls). Those having received psychopharmacological treatment or having had a psychiatric hospital contact in the five years prior to the onset of T2D were excluded. For this cohort, we first assessed the incidence of psychopharmacological treatment and psychiatric hospital contact among individuals with T2D and controls, respectively. Secondly, we compared the incidence of psychopharmacological/psychiatric hospital contact among individuals with T2D to propensity score matched controls. Finally, we assessed which baseline (T2D onset) characteristics that were associated with subsequent psychopharmacological treatment and psychiatric hospital contact. ResultsWe identified 56,640 individuals with newly developed T2D and 315,694 controls. A total of 8.3% of the individuals with T2D initiated psychopharmacological treatment within the 2 years following onset compared to 4.6% among the age and sex matched controls. Individuals with T2D were at increased risk of initiating psychopharmacological treatment compared to the propensity score matched controls (HR=1.51, 95% CI=1.43-1.59), whereas their risk of psychiatric hospital contact was not increased to the same extent (HR=1.14, 95% CI=0.98-1.32). Older age, somatic comorbidity, and being divorced/widowed was associated with both psychopharmacological treatment and psychiatric hospital contact following T2D. ConclusionIndividuals with T2D are at elevated risk of requiring psychopharmacological treatment. Significant outcomesO_LI8.3% of the individuals with T2D initiated psychopharmacological treatment within the 2 years following onset compared to 4.6% among the age and sex matched controls C_LIO_LIIndividuals with newly developed T2D were at increased risk of initiating psychopharmacological treatment and of having psychiatric hospital contact compared to propensity score matched controls. C_LIO_LIRisk factors for psychopharmacological treatment/psychiatric hospital contact following development of T2D include older age, somatic comorbidity and being divorced or widowed. C_LI LimitationsO_LIIdentification of T2D (a HbA1c level >6.5%) itself might lead to the identification of mental illness and thereby psychopharmacological treatment initiation/psychiatric hospital contact. C_LIO_LIA proportion of the individuals with T2D will likely have initiated treatment with an antidepressant due to neuropathic pain developed as a complication to T2D C_LI

The clinical diagnosis of major depressive disorder (MDD), a heterogeneous disorder, still depends on subjective information in terms of various symptoms regarding mood. Detecting extracellular vesicles (EVs) in blood may result in finding a diagnostic biomarker that reflects the depressive stage of patients with MDD. Here, we report the results on the glycosylation pattern of enriched plasma EVs from patients with MDD and age-matched healthy subjects. In this cohort, the levels of Triticum vulgaris (wheat germ) agglutinin (WGA), N-acetyl glucosamine (GlcNAc) and N-acetylneuraminic acid (Neu5Ac, sialic acid) - binding lectin, were significantly decreased in patients with MDD in depressive state compared to healthy subjects (area under the curve (AUC): 0.87 (95% confidence interval (CI) 0.76 - 0.97)) and in remission state (AUC: 0.88 (95% CI 0.72 - 1.00)). Furthermore, proteome analysis revealed that the von Willebrand factor (vWF) was a significant factor recognized by WGA. WGA-binding vWF antigen differentiated patients with MDD versus healthy subjects (AUC: 0.92 (95% CI 0.82 - 1.00)) and the same patients with MDD in depressive versus remission state (AUC: 0.98 (95% CI 0.93 - 1.00)). In this study, the change patterns in the glycoproteins contained in plasma EVs support the usability of testing to identify patients who are at increased risk of depression during antidepressant treatment.

The neuropsychiatric and somatic manifestations (physio-affective phenome) of Long COVID are substantially predicted by elevated peak body temperature (PBT) and diminished oxygen saturation (SpO2) during the acute infectious stage. The latter is linked to the immune pathophysiology of Long COVID involving activation of the immune-inflammatory response system (IRS) and the NLRP3 inflammasome. Nevertheless, there is a lack of data indicating whether NLRP3 and its components are implicated in the physio-affective phenome of Long COVID. We enrolled 161 Long COVID patients 6 to 9 months after the acute phase and divided them into two groups based on the baseline PBT and SpO2 levels, namely mild and severe acute COVID-19. We assessed serum NLRP3, caspase-1, C-reactive protein (CRP), interleukin (IL)-18, IL-1{beta}, IL-10, fibronectin, and Gasdermin D (GSDMD) during Long COVID. All of the aforementioned indicators (with the exception of IL-10) were substantially higher in Long COVID patients who had previously experienced severe COVID-19 than in those who had mild acute COVID-19. The physio-affective phenome of Long COVID and the severity of the acute COVID-19 were significantly correlated with these IRS biomarkers, with the exception of fibronectin. The variance in the overall severity of Long COVID is accounted for (49.5%) by the combined influence of fibronectin, IL-10, SpO2, and PBT. In conclusion, the severity of Long COVID is strongly associated with IRS and NRLP3 activation and the severity of the inflammatory response during the acute infectious phase. NLRP3 activation is a drug target to treat Long COVID.

BackgroundVitamin B deficiency is common worldwide and may lead to psychiatric symptoms; however, vitamin B deficiency epidemiology in patients with intense psychiatric episode has rarely been examined. Moreover, vitamin deficiency testing is costly and time-consuming. It hampered to effectively rule out vitamin deficiency-induced intense psychiatric symptoms. In this study, we aimed to clarify the epidemiology of these deficiencies and efficiently predict them using machine-learning models from patient characteristics and routine blood test results that can be obtained within one hour. MethodsWe reviewed 497 consecutive patients deemed to be at imminent risk of seriously harming themselves or others over 2 years. Machine-learning models were trained to predict each deficiency from age, sex, and 29 routine blood test results. ResultsWe found that 112 (22.5%), 80 (16.1%), and 72 (14.5%) patients had vitamin B1, vitamin B12, and folate (vitamin B9) deficiency, respectively. Also, the machine-learning models well generalized to predict the deficiency in the future unseen data; areas under the receiver operating characteristic curves for the validation dataset (i.e. dataset not used for training the models) were 0.716, 0.599, and 0.796, respectively. The Gini importance of these vitamins provided further evidence of a relationship between these vitamins and the complete blood count, while also indicating a hitherto rarely considered, potential association between these vitamins and alkaline phosphatase (ALP) or thyroid stimulating hormone (TSH). DiscussionThis study demonstrates that machine-learning can efficiently predict some vitamin deficiencies in patients with active psychiatric symptoms, based on the largest cohort to date with intense psychiatric episode. The prediction method may expedite risk stratification and clinical decision-making regarding whether replacement therapy should be prescribed. Further research includes validating its external generalizability in other clinical situations and clarify whether interventions based on this method can improve patient care and cost-effectiveness.

BackgroundAnxiety disorders are the most frequent mental comorbidity in people with functional GI difficulties, and abdominal discomfort is one of the most known physical signs of sadness. Successful top-down treatments using antidepressants and psychosocial therapies in the treatment of irritable bowel syndrome (IBS) further define personality illnesses as more than merely CNS disorders, but disorders with highly extensive systemic interconnections. Therefore, we recently conducted a systematic review of the observational literature comparing the gut microbiota composition of persons with personality difficulties with healthy control. MethodsThis review was written according to the guidelines established by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Not a single rule was broken, yet a more thorough search strategy did provide more relevant results. Pubmed, Scopus, Embase, Web of Science, Ovid, Global Health, PsycINFO, etc. were searched thoroughly using the phrases "gut microbiota, psychological disorders, personality disorders, composition, major depressive disorder, bipolar disorders, schizophrenia, etc." ResultsResearchers did discover widespread differences in the gut microbiota of patients and controls under each category of personality disorder. They also found that there are distinct bacterial taxa that had differing abundances in patients with these three psychiatric illnesses compared to healthy controls. They found a great deal of variation in study designs and reporting, such as in the inclusion and exclusion of study populations, sampling feces for study of gut microbiota; taking into account or adjusting for important factors known to impact gut microbiota composition; storing feces; processing feces; analyzing feces. ConclusionOur systematic review did find that psychological disorders appeared to exhibit different overall compositional differences compared to controls. There was a general trend toward the finding of increased abundances of bacteria involved in glutamate and GABA metabolism, and lower abundances of butyrate-producing bacteria in psychological disorders

AimsThe aim of this study was prediction of blood sugar regulation based on ego boundary, healthy boundary and post trauma growth in patient with Diabetes. MethodsFor this purpose, 50 people with diabetes were selected by multistage cluster sampling. The questionnaires used in this study were the post trauma growth inventory (PGI), the ego strength (PIES), and Healthy Boundaries (HB) Questionnaire. ResultsStepwise regression analysis showed that there were a significant positive relationship between blood sugar level (HbA1c) and ego strength, health boundaries and post-trauma growth (PTG). ConclusionThe findings indicate a significant correlation between hyperglycemia and health boundaries, ego strength and post-traumatic growth. This means that controlling and recognizing the boundaries of mental health and post-traumatic emotions prevents high blood (HbA1c) sugar and Type 2 diabetes.

BackgroundThe adverse effects of COVID-19 pandemic on the mental health of high-risk group patients for morbidity and mortality and its impact on public health in the long term have not been clearly determined. ObjectiveTo determine the level of COVID-19 related transmission fear and anxiety in healthcare workers and patients with primary immunodeficiency disorder (PID), severe asthma, and the ones with other comorbidities. MethodsThe healthcare workers and patients with PID, severe asthma (all patients receiving biological agent treatment), malignancy, cardiovascular disease, hypertension (90% of patients receiving ACEI or ARB therapy), diabetes mellitus (42 % of patients receiving DPP-4 inhibitor therapy) were included in the study. A total of 560 participants, 80 individuals in each group, were provided. The hospital anxiety and depression scale (HADS) and Fear of illness and virus evaluation (FIVE) scales were applied to the groups with face to face interview methods. ResultsThe mean age was 49.30 {+/-} 13.74 years and 306 (55 %) were female. The FIVE Scale and HADS-A scale scores of health care workers were significantly higher than other groups scores (p = 0.001 and 0.006). The second-highest scores belonged to patients with PID. There was no significant difference between the groups for the HADS-D score (p=0.07). The lowest score in all scales was observed in patients with hypertension. ConclusionsThis study demonstrated that in the pandemic process, patients with primary immunodeficiency, asthma patients, and other comorbid patients, especially healthcare workers, should be referred to the centers for the detection and treatment of mental health conditions.

BackgroundDifficulty in the diagnosis of high stress and depression has been recognized conventionally depending on the observation of patient symptoms and psychiatrist diagnosis. These approaches are time-consuming and cannot respond to the excessive demands for large-scale tests with the increasing populations worldwide. This study thus developed an alternative approach to perform fast stress screening, which is based on fingerprinting of highly volatile compounds in axillary sweat. MethodsSweat samples were collected from 227 firefighters, comprising 65 with high stress, 14 with depression, and 148 healthy volunteers. High stress and depression were determined using the standardized Thai versions of the Perceived Stress Scale (PSS-10) and the Beck Depression Inventory II (BDI-II), in conjunction with psychiatric interviews. The samples were collected by placing cotton rods under the axillaries, then analyzed using gas chromatography- ion mobility spectrometry (GC-IMS). The potential marker peaks were selected based on accuracy data. Principal component analysis (PCA) and logistic regression with machine learning were also performed to select significant composite markers. MVOC 3.0, Amibase and Metaboanalyst 6.0 databases were applied to predict the possible metabolomic pathways. ResultsAnalysis against genuine standard compound injections identified acetonitrile, ammonia, diethyl ether, formaldehyde, and octane as potential biomarkers for both high stress and depression, with butane, dimethylamine and pentane additionally observed for high stress. Receiver operating characteristic (ROC) curves demonstrated accuracies of 81.3% for stress screening and 82.8% for depression screening. ConclusionThe biomarkers delineated here indicate the participation of particular metabolic pathways and commensal skin bacteria in the stress response.

BackgroundAssociation between inflammation and depression has been known for a long time. Activation of pro-inflammatory molecular complexes such as inflammasomes in depression was suggested as the most relevant hypothesis among many others. Psychological stress is considered to cause sterile inflammation through inflammasomes, and the NLRP3 inflammasome was proposed as a crucial molecule for the pro-inflammatory response in depression. ObjectiveIn the current study, we aimed to explore the relationship of NLRP3 inflammasome and its regulatory protein NEK7 with major depressive disorder in a drug naive study sample. MethodsIn total 58 patients with major depressive disorder and 58 age and gender-matched healthy persons were included. The mRNA expressions of NLRP3, ASC, caspase-1 and NEK7 coding proteins were evaluated with quantitative PCR, plasma IL-1{beta} levels were detected by ELISA. ResultsPatients with major depressive disorder had higher gene expressions of NLRP3 (p= 0.03) and ASC (p= 0.002) compared to healthy persons. Higher gene expressions of NLRP3 (OR= 1.17, 95% CI= 1.01, 1.37, p= 0.04), ASC (OR= 1.45, 95% CI= 1.15, 1.82, p= 0.002) and NEK7 (OR= 1.33, 95% CI= 1.08, 1.63, p= 0.007) were related to the increased likelihood of having major depressive disorder. ConclusionThe results of this study support the role of NLRP3 inflammasome in the increased risk for major depressive disorder.

BackgroundAutoimmune responses contribute to the pathophysiology of Long COVID, affective symptoms and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ObjectivesTo examine whether Long COVID, and its accompanying affective symptoms and CFS are associated with immunoglobulin (Ig)A/IgM/IgG directed at neuronal proteins including myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), synapsin, +{beta}-tubulin, neurofilament protein (NFP), cerebellar protein-2 (CP2), and the blood-brain-barrier-brain-damage (BBD) proteins claudin-5 and S100B. MethodsIgA/IgM/IgG to the above neuronal proteins, human herpes virus-6 (HHV-6) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were measured in 90 Long COVID patients and 90 healthy controls, while C-reactive protein (CRP), and advanced oxidation protein products (AOPP) in association with affective and CFS ratings were additionally assessed in a subgroup thereof. ResultsLong COVID is associated with significant increases in IgG directed at tubulin (IgG-tubulin), MBP, MOG and synapsin; IgM-MBP, MOG, CP2, synapsin and BBD; and IgA-CP2 and synapsin. IgM-SARS-CoV-2 and IgM-HHV-6 antibody titers were significantly correlated with IgA/IgG/IgM-tubulin and -CP2, IgG/IgM-BBD, IgM-MOG, IgA/IgM-NFP, and IgG/IgM-synapsin. Binary logistic regression analysis shows that IgM-MBP and IgG-MBP are the best predictors of Long COVID. Multiple regression analysis shows that IgG-MOG, CRP and AOPP explain together 41.7% of the variance in the severity of CFS. Neural network analysis shows that IgM-synapsin, IgA-MBP, IgG-MOG, IgA-synapsin, IgA-CP2, IgG-MBP and CRP are the most important predictors of affective symptoms due to Long COVID with a predictive accuracy of r=0.801. ConclusionBrain-targeted autoimmunity contributes significantly to the pathogenesis of Long COVID and the severity of its physio-affective phenome.

Acute malignant catatonia with autonomic instability developed in a previously healthy man with PCR-verified SARS-CoV-2. CT and MRI were normal, EEG showed slowing and cerebrospinal fluid showed a subtle indication of inflammation. There were no signs of pathology in other organs. 18F-FDG-PET conveyed high bilateral uptake in the striatum. While commercial tests were negative, immunohistochemical staining of mouse brain revealed anti-neuronal IgG antibodies against neuronal targets in the hippocampus, thalamus, striatum and cortex. Early treatment with plasmapheresis and corticosteroid reversed disease progression and may have prevented large-scale neurological damage. We are not aware of other types of encephalitis with such distinct pyramidal tract symptoms and raise the possibility that this may be a novel form of autoimmune encephalitis induced by infection with SARS-CoV-2.

BackgroundMetabolic syndrome (MetS) is highly prevalent among adults and is frequently accompanied by depressive symptoms. While high-sensitivity C-reactive protein (hsCRP) has been proposed as a potential indicator of depression, existing evidence remains inconclusive. ObjectiveThis study aimed to determine whether increased serum hsCRP or other immune-metabolic biomarkers are associated with depressive symptoms in drug-naive individuals with obesity and MetS. MethodsA total of 88 drug-naive patients with obesity and MetS but without coronary-artery disease were enrolled and serum levels of neuro-immune and metabolic biomarkers were assessed. ResultsIn MetS, the severity of depression, as assessed using the von Zerssen Depression Rating (VZDR) scale was significantly associated with interleukin (IL)-6, leukocyte numbers, triglyceride x glucose (Tyg) index, low-density lipoprotein cholesterol, Apolipoprotein B (all positively) and mean platelet volume (MPV), visfatin and adiponectin (all negatively). There were no significant associations between hsCRP and severity of depression. In MetS patients, hsCRP is strongly associated with increased leukocyte numbers, alkaline phosphatase, {gamma}-glutamyl transferase, uric acid, platelet numbers and MPV, thereby shaping a distinct subtype of MetS, which is not related to depression. ConclusionsOur findings indicate that depressive symptoms in MetS patients are associated with immune-metabolic biomarkers indicating immune activation, atherogenicity and insulin resistance, but not with hsCRP. The reason is that hsCRP in MetS is a biomarker of a specific MetS subtype that is characterized by megakaryopoiesis, hepatocyte activation, and uric acid production, which were not associated with depression.

BackgroundLong coronavirus disease 2019 (LC) is a chronic sequel of acute COVID-19. The exact pathophysiology of the affective, chronic fatigue and physiosomatic symptoms (labeled as "physio-affective phenome") of LC has remained elusive. ObjectiveThe current study aims to delineate the effects of oxygen saturation (SpO2) and body temperature during the acute phase on the physio-affective phenome of LC. MethodWe recruited 120 LC patients and 36 controls. For all participants, we assessed the lowest SpO2 and peak body temperature during acute COVID-19, and the Hamilton Depression and Anxiety Rating Scale (HAMD/HAMA) and Fibro Fatigue (FF) scales 3 to 4 months later. ResultsLowered SpO2 and increased body temperature during the acute phase and female sex predict 60.7% of the variance in the physio-affective phenome of LC. Using unsupervised learning techniques we were able to delineate a new endophenotype class, which comprises around 26.7% of the LC patients and is characterized by very low SpO2 and very high body temperature, and depression, anxiety, chronic fatigue, and autonomic and gastro-intestinal symptoms scores. Single latent vectors could be extracted from both biomarkers, depression, anxiety and FF symptoms or from both biomarkers, insomnia, chronic fatigue, gastro-intestinal and autonomic symptoms. ConclusionThe newly constructed endophenotype class and pathway phenotypes indicate that the physio-affective phenome of LC is at least in part the consequence of the pathophysiology of acute COVID-19, namely the combined effects of lowered SpO2, increased body temperature and the associated immune-inflammatory processes and lung lesions.

IntroductionOrthostatic intolerance is highly prevalent in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and is caused by an abnormal reduction in cerebral blood flow (CBF). In healthy controls (HC) regulation of CBF is complex and involves multiple mechanisms including cardiac output (CO), cerebral perfusion pressure, PO2 and PCO2, flow-metabolism coupling, and innervation of cerebral vessels. In ME/CFS multiple other mechanisms have also been identified. Aim of the studyWe previously found that both CBF and CO were reduced in ME/CFS patients during tilt testing, and we hypothesized that the relation between CBF and CO is abnormal and different from HC. In this retrospective study we analyzed this relation in a large group of patients. To compare the patient data with those of HC, we focused on patients with a normal heart rate (HR) and blood pressure (BP) response to upright tilt. Also, the influence of clinical data was analyzed. MethodsA total of 534 ME/CFS patients and 49 HC underwent tilt testing with measurements of HR, BP, CBF, and CO. In 46 (9%) patients CO and CBF changes were in the normal range of HC, and in 488 (91%) an abnormal CO and CBF reduction was found. Resultspatients with a CO and CBF reduction in the range of HC had less severe disease and were more likely to be male. In patients with an abnormal CO and CBF reduction the slope of the regression line of CO versus CBF reduction was almost 1. A multiple regression analysis of the latter group, including patients with PetCO2 measurements (440/488: 90%) showed that the CO reduction for the major part predicted the CBF reduction, with a limited role for the PetCO2 reduction and the tilt duration. Other data did not add to the model. ConclusionsTwo different patient groups with a normal HR and BP response during the tilt were identified: those with a CO and CBF in the normal range of HC and those with an abnormal CO and CBF reduction during the tilt (91% of patients). The former group had milder disease and included more men. In the largest group of patients there was an almost 1:1 relation between the CO and CBF reduction, suggesting absence of compensatory vasodilation in the cerebral vasculature. This may be an appropriate target for clinical and therapeutic interventions.

Life-long infection with Toxoplasma, which affects 30% of the human population, has specific behavioral effects. The stress-coping hypothesis explains why the toxoplasmosis-associated behavioral changes go in opposite directions in men and women. It suggests that toxoplasmosis impairs the health of humans, which results in chronic stress. Men and women are known to cope with stress in opposite ways. The first presumption of the hypothesis, impaired health, was confirmed in many studies. The second, higher level of stress, was tested only rarely. Levels of stress and anxiety, measured with the Perceived Stress Scale, and the State-Trait Anxiety Inventory X-2, respectively, were compared in a population of 614 Toxoplasma-free and 162 Toxoplasma-infected subjects. Higher stress was detected in the infected men, but not women. We also found that physical health had a positive rather than negative effect on stress when mental health is controlled, which seems to contradict the prediction of the stress-coping hypothesis. No differences were found in the anxiety of infected and noninfected subjects. Subjects who have objective reasons for stress (those with worse physical health) are less stressed than those without such reasons.