PSYCHOPATHOLOGY, ILLNESS REPRESENTATION AND PATTERNS OF HEALTHCARE UTILIZATION IN FUNCTIONAL NEUROLOGIC DISORDERS: SIGNIFICANT FACTORS FOR CONSULTATIONLIAISON PSYCHIATRY AND PSYCHIATRIC REHABILITATION

Background: Functional neurological disorders (FNDs), also known as conversion disorder (CD), are a group of conditions that are characterized by neurological symptoms that are not caused by an underlying neurological disease or structural abnormality. These conditions are characterized by high symptom burden, low quality of life and high healthcare utilization. Methods: 48 patients with an established diagnosis of FND referred for psychiatric evaluation were recruited and assessed using the Brief Symptom Inventory-53 (BSI-53), Scale for Suicide Ideation (SSI), Toronto Alexithymia Scale (TAS), Adult Attachment Style (ASQ), Childhood Trauma Questionnaire (CTQ), Brief Illness Perception Questionnaire (BIPQ), Short Form-12 Health Survey (SF-12), Life Event Checklist and Fatigue Severity Scale (FSS). Patients also underwent the Structured Clinical Interview for the DSM-5 Alternative Model for Personality Disorders (SCID-5-AMPD) Module I. Data regarding emergency department (ED) accesses, specialist medical visits and instrumental examinations during the previous year and, for 26 patients, at 1 year follow up, were recorded using electronic databases. Results: high ED users at 1 follow up displayed worse functioning in personality domains and higher levels of suicidality. Specific illness beliefs at baseline were found to be associated with patterns of healthcare utilization at follow up. About a third (29.2%) of the patients was affected by active psychopathological symptoms and 12% were considered at risk of suicide. A significant number of patients (42.6%) had a history of severe childhood abuse. Conclusions: healthcare utilization in FND patients is influenced by illness beliefs and impairments in personality functioning. The data presented here confirm the importance of a comprehensive evaluation by the mental health professional who should not underrate the role of personological dimensions.Background: I disturbi neurologici funzionali (FND), noti anche come disturbo di conversione (CD), sono un gruppo di condizioni caratterizzate da sintomi neurologici che non sono causati da una malattia neurologica sottostante o da un'anomalia strutturale. Queste condizioni sono caratterizzate da un elevato carico di sintomi, una bassa qualità della vita e un elevato utilizzo dell'assistenza sanitaria. Metodi: 48 pazienti con diagnosi accertata di FND inviati per visita psichiatrica sono stati reclutati e valutati utilizzando il Brief Symptom Inventory-53 (BSI-53), Scale for Suicide Ideation (SSI), Toronto Alexithymia Scale (TAS), Adult Attachment Style ( ASQ), Childhood Trauma Questionnaire (CTQ), Brief Illness Perception Questionnaire (BIPQ), Short Form-12 Health Survey (SF-12), Life Event Checklist e Fatigue Severity Scale (FSS). I pazienti sono stati inoltre sottoposti al Colloquio Clinico Strutturato per il Modello Alternativo per i Disturbi di Personalità del DSM-5 (SCID-5-AMPD) Modulo I. I dati inerenti gli accessi in pronto soccorso (PS), le visite mediche specialistiche e gli esami strumentali durante l’anno precedente e, per 26 pazienti, al follow up di un anno, sono stati registrati utilizzando i database elettronici dei sistemi informatici locali. Risultati: gli alti utilizzatori di PS al follow-up di un anno hanno mostrato un peggiore funzionamento nei domini della personalità e livelli più elevati di suicidalità. Convinzioni specifiche di malattia al baseline sono risultate associate a modelli di utilizzo dell'assistenza sanitaria al follow-up. Circa un terzo (29,2%) dei pazienti era affetto da sintomi psicopatologici attivi e il 12% era considerato a rischio di suicidio. Un numero significativo di pazienti (42,6%) aveva una storia di gravi abusi infantili

Effect of obesity and metabolic syndrome on plasma oxysterols and fatty acids in human

BACKGROUND: Obesity and the related entity metabolic syndrome are characterized by altered lipid metabolism and associated with increased morbidity risk for cardiovascular disease and cancer. Oxysterols belong to a large family of cholesterol-derived molecules known to play crucial role in many signaling pathways underlying several diseases. Little is known on the potential effect of obesity and metabolic syndrome on oxysterols in human. OBJECTIVES: In this work, we questioned whether circulating oxysterols might be significantly altered in obese patients and in patients with metabolic syndrome. We also tested the potential correlation between circulating oxysterols and fatty acids. METHODS: 60 obese patients and 75 patients with metabolic syndrome were enrolled in the study along with 210 age- and sex-matched healthy subjects, used as control group. Plasma oxysterols were analyzed by isotope dilution GC/MS, and plasma fatty acids profiling was assessed by gas chromatography coupled with flame ionization detection. RESULTS: We found considerable differences in oxysterols profiling in the two disease groups that were gender-related. Compared to controls, males showed significant differences only in 4α- and 4β-hydroxycholesterol levels in obese and metabolic syndrome patients. In contrast, females showed consistent differences in 7-oxocholesterol, 4α-hydroxycholesterol, 25-hydroxycholesterol and triol. Concerning fatty acids, we found minor differences in the levels of these variables in males of the three groups. Significant changes were observed in plasma fatty acid profile of female patients with obesity or metabolic syndrome. We found significant correlations between various oxysterols and fatty acids. In particular, 4β-hydroxycholesterol, which is reduced in obesity and metabolic syndrome, correlated with a number of saturated and mono-unsaturated fatty acids that are end-products of de novo lipogenesis. CONCLUSIONS: Our data provide the first evidence that obesity and metabolic syndrome are associated with major, gender-specific, changes in circulating oxysterols and fatty acids. These findings suggest a metabolic link between oxysterols and fatty acids, and that oxysterols may contribute to the epidemic diseases associated with obesity and metabolic syndrome in female

Endothelial cells, endoplasmic reticulum stress and oxysterols

Oxysterols are bioactive lipids that act as regulators of lipid metabolism, inflammation, cell viability and are involved in several diseases, including atherosclerosis. Mounting evidence linked the atherosclerosis to endothelium dysfunction; in fact, the endothelium regulates the vascular system with roles in processes such as hemostasis, cell cholesterol, hormone trafficking, signal transduction and inflammation. Several papers shed light the ability of oxysterols to induce apoptosis in different cell lines including endothelial cells. Apoptotic endothelial cell and endothelial denudation may constitute a critical step in the transition to plaque erosion and vessel thrombosis, so preventing the endothelial damaged has garnered considerable attention as a novel means of treating atherosclerosis. Endoplasmic reticulum (ER) is the site where the proteins are synthetized and folded and is necessary for most cellular activity; perturbations of ER homeostasis leads to a condition known as endoplasmic reticulum stress. This condition evokes the unfolded protein response (UPR) an adaptive pathway that aims to restore ER homeostasis. Mounting evidence suggests that chronic activation of UPR leads to cell dysfunction and death and recently has been implicated in pathogenesis of endothelial dysfunction. Autophagy is an essential catabolic mechanism that delivers misfolded proteins and damaged organelles to the lysosome for degradation, maintaining basal levels of autophagic activity it is critical for cell survival. Several evidence suggests that persistent ER stress often results in stimulation of autophagic activities, likely as a compensatory mechanism to relieve ER stress and consequently cell death. In this review, we summarize evidence for the effect of oxysterols on endothelial cells, especially focusing on oxysterols-mediated induction of endoplasmic reticulum stress

Screening Performance of Edmonton Symptom Assessment System in Kidney Transplant Recipients

An average prevalence of 35% for psychiatric comorbidity has been reported in kidney transplant recipients (KTRs) and an even higher prevalence of other psychosocial syndromes, as defined by the Diagnostic Criteria for Psychosomatic Research (DCPR), has also been found in this population. Consequently, an easy, simple, rapid psychiatric tool is needed to measure physical and psychological symptoms of distress in KTRs. Recently, the Edmonton Symptom Assessment System (ESAS), a pragmatic patient-centred symptom assessment tool, was validated in a single cohort of KTRs. The aims of this study were: to test the screening performances of ESAS for the International Classification of Diseases-10th Revision (ICD-10) psychiatric diagnoses in KTRs; to investigate the optimal cut-off points for ESAS physical, psychological and global subscales in detecting ICD-10 psychiatric diagnoses; and to compare ESAS scores among KTR with ICD-10 diagnosis and DCPR diagnosis. 134 KTRs were evaluated and administered the MINI International Neuropsychiatric Interview 6.0 and the DCPR Interview. The ESAS and Canadian Problem Checklist (CPC) were given as self-report instruments to be filled in and were used to examine the severity of physical and psychological symptoms and daily-life problems. The physical distress sub-score (ESAS-PHYS), psychological distress sub-score (ESAS-PSY) and global distress score (ESAS-TOT) were obtained by summing up scores of six physical symptoms, four psychological symptoms and all single ESAS symptoms, respectively. Routine biochemistry, immunosuppressive agents, socio-demographic and clinical data were collected. Receiving Operating Characteristic (ROC) analysis was used to examine the ability of the ESAS emotional distress (DT) item, ESAS-TOT, ESAS-PSY and ESAS-PHYS, to detect psychiatric cases defined by using MINI6.0. The area under the ROC curve for ESAS-TOT, ESAS-PHYS, ESAS-PSY and DT item were 0.85, 0.73, 0.89, and 0.77, respectively. The DT item, ESAS-TOT and ESAS-PSY optimal cut-off points were 654 (sensitivity 0.74, specificity 0.73), 6520 (sensitivity 0.85, specificity 0.74) and 6512 (sensitivity 0.85, specificity 0.80), respectively. No valid ESAS-PHYS cut-off was found (sensitivity <0.7, specificity <0.7). Thirty-nine (84.8%) KTRs with ICD-10 diagnosis did exceed both ESAS-TOT and ESAS-PSY cut-offs. Higher scores on the ESAS symptoms (except shortness of breath and lack of appetite) and on the CPC problems were found for ICD-10 cases and DCRP cases than for ICD-10 no-cases and DCPR no-cases. This study shows that ESAS had an optimal screening performance (84.8%) to identify ICD-10 psychiatric diagnosis, evaluated with MINI; furthermore, ESAS-TOT and ESAS-PSY cut-off points could provide a guide for clinical symptom management in KTRs

Regulatory T cells in the pathogenesis of graves' disease

Maintaining a delicate balance between the prompt immune response to pathogens and tolerance towards self-antigens and commensals is crucial for health. T regulatory (Treg) cells are pivotal in preserving self-tolerance, serving as negative regulators of inflammation through the secretion of anti-inflammatory cytokines, interleukin-2 neutralization, and direct suppression of effector T cells. Graves' disease (GD) is a thyroid-specific autoimmune disorder primarily attributed to the breakdown of tolerance to the thyroid-stimulating hormone receptor. Given the limitations of currently available GD treatments, identifying potential pathogenetic factors for pharmacological targeting is of paramount importance. Both functional impairment and frequency reduction of Tregs seem likely in GD pathogenesis. Genome-wide association studies in GD have identified polymorphisms of genes involved in Tregs' functions, such as CD25 (interleukin 2 receptor), and Forkhead box protein P3 (FOXP3). Clinical studies have reported both functional impairment and a reduction in Treg frequency or suppressive actions in GD, although their precise involvement remains a subject of debate. This review begins with an overview of Treg phenotype and functions, subsequently delves into the pathophysiology of GD and into the existing literature concerning the role of Tregs and the balance between Tregs and T helper 17 cells in GD, and finally explores the ongoing studies on target therapies for GD

Heme Oxygenase-1 and Brain Oxysterols Metabolism Are Linked to Egr-1 Expression in Aged Mice Cortex, but Not in Hippocampus

Throughout life, stress stimuli act upon the brain leading to morphological and functional changes in advanced age, when it is likely to develop neurodegenerative disorders. There is an increasing need to unveil the molecular mechanisms underlying aging, in a world where populations are getting older. Egr-1 (early growth response 1), a transcriptional factor involved in cell survival, proliferation and differentiation – with a role also in memory, cognition and synaptic plasticity, can be implicated in the molecular mechanism of the aging process. Moreover, Heme Oxygenase-1a (HO), a 32 kDa heat-shock protein that converts heme to iron, carbon monoxide and biliverdin, is a key enzyme with neuroprotective properties. Several in vitro and in vivo studies reported that HO-1 could regulate the metabolism of oxysterols, oxidation products of cholesterol that include markers of oxidative stress. Recently, a link between Egr-1 and HO-1 has been demonstrated in mouse lung cells exposed to cigarette smoke. In view of these data, we wanted to investigate whether Egr-1 can be implicated also in the oxysterol metabolism during brain aging. Our results show that Egr-1 expression is differently expressed in the cortex and hippocampus of old mice, as well as the oxysterol profile between these two brain areas. In particular, we show that the cortex experiences in an age-dependent fashion increasing levels of the Egr-1 protein, and that these correlate with the level of HO-1 expression and oxysterol abundance. Such a situation was not observed in the hippocampus. These results are further strenghtened by our observations made with Egr-1 KO mice, confirming our hypothesis concerning the influence of Egr-1 on oxysterol production and accumulation via regulation of the expression of HO-1 in the cortex, but not the hippocampus, of old mice. It is important to notice that most of the oxysterols involved in this process are those usually stimulated by oxidative stress, which would then represent the triggering factor for this mechanism

Association between Type-D Personality and Affective (Anxiety, Depression, Post-traumatic Stress) Symptoms and Maladaptive Coping in Breast Cancer Patients: A Longitudinal Study

Background: Type-D (distressed) personality has not been prospectively explored for its association with psychosocial distress symptoms in breast cancer patients. Objective: The objective of the study was to test the hypothesis that Type-D personality can be associated with psychosocial distress variables in cancer over a 2-point period (6 month-follow-up). Aims: The aim of the study was to analyze the role of Type-D personality in relation to anxiety, depression, post-traumatic stress symptoms, general distress, and maladaptive coping among cancer patients. Methods: 145 breast cancer patients were assessed within 6 months from diagnosis (T0) and again 6 months later (T1). The Type-D personality Scale, the Hospital Anxiety and Depression Scale, Depression subscale (HAD-D), the Brief Symptom Inventory (BSI-18) Anxiety subscale, the Distress Thermometer (DT), the Post-traumatic Symptoms (PTS) Impact of Event Scale (IES), and the Mini Mental Adjustment to Cancer (Mini-MAC) Anxious Preoccupation and Hopelessness scales were individually administered at T0 and T1. Results: One-quarter of cancer patients met the criteria for Type-D personality, which was stable over the follow-up time. The two main constructs of TypeD personality, namely social inhibition (SI) and negative affectivity (NA), were related to anxiety, depression, PTS, BSI-general distress and maladaptive coping (Mini-MAC anxious preoccupation and hopelessness). In regression analysis, Type-D SI was the most significant factor associated with the above-mentioned psychosocial variables, both at T0 and T1. Conclusion: Likewise other medical disorders (especially cardiology), Type-D personality has been confirmed to be a construct significantly related to psychosocial distress conditions and maladaptive coping that are usually part of assessment and intervention in cancer care. More attention to personality issues is important in oncology

Psychosocial determinants of healthcare use costs in kidney transplant recipients

IntroductionPsychosocial factors frequently occur in kidney transplant recipients (KTRs), leading to behavioral alterations and reduced therapeutic adherence. However, the burden of psychosocial disorders on costs for KTRs is unknown. The aim of the study is to identify predictors of healthcare costs due to hospital admissions and emergency department access in KTRs.MethodsThis is a longitudinal observational study conducted on KTRs aged >18 years, excluding patients with an insufficient level of autonomy and cognitive disorder. KTRs underwent psychosocial assessment via two interviews, namely the Mini-International Neuropsychiatric Interview 6.0 (MINI 6.0) and the Diagnostic Criteria for Psychosomatic Research Interview (DCPR) and via the Edmonton Symptom Assessment System Revised (ESAS-R) scale, a self-administrated questionnaire. Sociodemographic data and healthcare costs for hospital admissions and emergency department access were collected in the 2016–2021 period. Psychosocial determinants were as follows: (1) ESAS-R psychological and physical score; (2) symptomatic clusters determined by DCPR (illness behavior cluster, somatization cluster, and personological cluster); and (3) ICD diagnosis of adjustment disorder, anxiety disorder, and mood disorder. A multivariate regression model was used to test the association between psychosocial determinants and total healthcare costs.ResultsA total of 134 KTRs were enrolled, of whom 90 (67%) were men with a mean age of 56 years. A preliminary analysis of healthcare costs highlighted that higher healthcare costs are correlated with worse outcomes and death (p < 0.001). Somatization clusters (p = 0.020) and mood disorder (p < 0.001) were positively associated with costs due to total healthcare costs.ConclusionsThis study showed somatization and mood disorders could predict costs for hospital admissions and emergency department access and be possible risk factors for poor outcomes, including death, in KTRs

Relationship between serum bilirubin and uric acid to oxidative stress markers in Italian and Czech populations

Summary Recently, a South-to-North oxidative stress marker gradient has been reported; consistent with known differences in the incidence of coronary heart disease between southern and northern European countries. The aim of the present study was to compare the plasma concentrations of 7-oxocholesterol (7OxCH) and 7β-hydroxycholesterol (7BCH) with systemic antioxidants in healthy Italian and Czech subjects. The study was performed in healthy subjects of Italian (n=131) and Czech (n=84) origins. In all subjects routine biochemistry work-ups were performed; additionally, plasma oxysterols and the peroxyl radicals scavenging activity (PERSA) of the sera were determined. Close relationship of serum bilirubin and uric acid to markers of oxidative stress was observed in both examined populations. Compared to the Czechs, the Italian population showed higher plasma concentrations of both oxysterols (7OxCH: 3.6 vs. 6.0 ng/ml, p −6 ; 7BCH: 5.3 vs. 8.6 ng/ml, p −6 ), lower PERSA (p −6 ), and lower serum concentrations of bilirubin and uric acid (p −6 in both cases). The dietary patterns of the Italian population did not match the Mediterranean style, but was more similar to the Continental type of diet, presumably due to non-adherence to a Mediterranean diet

The relationship between demoralization and depressive symptoms among patients from the general hospital: Network and exploratory graph analysis

Introduction: Depression and demoralization are highly prevalent among individuals with physical illnesses but their relationship is still unclear. Objective: To examine the relationship between clinical features of depression and demoralization with the network approach to psychopathology. Methods: Participants were recruited from the medical wards of a University Hospital in Italy. The Demoralization Scale (DS) was used to assess demoralization, while the Patient Health Questionnaire-9 (PHQ-9) to assess depressive symptoms. The structure of the depression-demoralization symptom network was examined and complemented by the analysis of topological overlap and Exploratory Graph Analysis (EGA) to identify the most relevant groupings (communities) of symptoms and their connections. The stability of network models was estimated with bootstrap procedures and results were compared with factor analysis. Results: Life feeling pointless, low mood/discouragement, hopelessness and feeling trapped were among the most central features of the network. EGA identified four communities: (1) Neurovegetative Depression, (2) Loss of purpose, (3) Frustrated Isolation and (4) Low mood and morale. Loss of purpose and low mood/morale were largely connected with other communities through anhedonia, hopelessness and items related to isolation and lack of emotional control. Results from EGA displayed good stability and were comparable to those from factor analysis. Limitations: Cross-sectional design; sample heterogeneity Conclusions: Among general hospital inpatients, features of depression and demoralization are independent, with the exception of low mood and self-reproach. The identification of symptom groupings around entrapment and helplessness may provide a basis for a dimensional characterization of depressed/demoralized patients, with possible implications for treatment