Inflammatory profiles in women with eating disorder: Linking inflammatory biomarkers to clinical phenotypes.

INTRODUCTION: Eating disorders (ED) represent a group of very complex and serious diagnoses characterized by emotional dysregulation and impulsivity. New approaches are necessary to achieve effective diagnosis and treatments. Shifting biomarker research away from the constraints of diagnostic categories may effectively contribute to a dimensional differentiation across disorders according to neurobiology (e.g., inflammatory biomarkers). Thus, the aim of our study was to identify inflammatory profiles in patients with ED. METHODS: A sample of 100 women with an ED (23.4 ± 8.55 years) and 59 healthy controls (HC) (20.22 ± 4.18 years) was used. K-means cluster analysis was followed to identify inflammatory clusters considering seven blood biomarkers (iNOS, TNFα, COX2, p38, ERK, TBARS and PPARγ). Moreover, a wide assessment of clinical features was conducted. RESULTS: Two distinct clusters were identified. Cluster 1 patients were characterized by higher inflammatory levels of TNF-α, COX2, p38, and ERK, and had more restrictive anorexia diagnosis than cluster 2. Cluster 2 participants showed higher inflammatory levels of iNOS and were older than cluster 1 and controls and had lower BMI than HC. In addition, they had higher levels of bulimic symptoms than those from the cluster 1 and HC, and higher impulsivity than HC. All ED patients (regardless of cluster) showed higher ED symptoms and more trauma than HC. CONCLUSIONS: Our study revealed that inflammatory dysfunction may be linked with clinical endophenotypes in ED, one more restrictive (cluster 1) with an inflammation/oxidative endophenotype more cytokine and MAPK/ERK mediated, and the other more impulsive, with more bulimic symptoms (cluster 2) with NO free radical high output source iNOS. Trauma seems to be a vulnerability factor for both endophenotypes.

Oxidative stress and inflammatory pathways in female eating disorders and borderline personality disorders with emotional dysregulation as linking factors with impulsivity and trauma.

BACKGROUND: Borderline personality disorder (BPD) and eating disorders (ED) are both disorders with emotional dysregulation that may share some similar biological underpinnings, leading to oxidative/inflammatory alterations. Unfortunately, to date, no studies have assessed the relationship between clinical features, inflammatory alterations and childhood trauma across these disorders. Our aim was to identify the potential common and disorder-specific inflammatory pathways and examine possible associations between these dysregulated pathways and the clinical features. METHODS: We studied a sample of 108 women (m = 27.17 years; sd = 7.64), divided into four groups: 23 patients with a restrictive ED (ED-R), 23 patients with a bingeeating/ purging ED (ED-P) and 26 patients with BPD; whereas the control group included 23 healthy subjects. Several inflammatory/oxidative parameters: tumor necrosis factor alpha (TNFα), Thiobarbituric Acid Reactive Substances (TBARS), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), p38 mitogenactivated protein kinases, ERK mitogen-activated protein kinases and c-Jun NH2- terminal kinase (JNK), and some antiinflammatory antioxidant elements: glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), Kelch-like ECHassociated protein (Keap1) were determined in plasma or peripheral blood mononuclear cells. Furthermore, clinical, impulsivity, trauma and eating behavior questionnaires were administered. RESULTS: Three main inflammatory/oxidative components were extracted using principal component analysis (59.19 % of biomarker variance explained). Disorder-specific dysfunction in the inflammatory and oxidative pathways in patients with BPD and ED were revealed by means of relationships with specific principal components (p < .01). BPD patients showed higher levels of a component featured by elevated levels of JNK and lower of GPx and SOD. ED-R and impulsivity were associated with a component featured by the activation of ERK and negative influence of Keap1. The component featured by the suppression of catalase and COX2 was associated with both ED subtypes and trauma exposure. CONCLUSION: Several risk factors such as trauma, impulsivity and eating disorder symptoms were transdiagnostically associated with some inflammatory alterations regardless of diagnosis. These findings suggest that the clinical profile comprising trauma exposure and an emotional dysregulation disorder might constitute a specific endophenotype highly linked with inflammatory alterations.

Long-term mental health impact of COVID-19 on primary care health workers in northern Spain: Results from a two-phase longitudinal study.

Background: COVID-19 pandemic has affected the mental health of the general population, and in particular of health professionals. Primary care personnel are at greater risk due to being highly exposed to the disease and working regularly in direct contact with patients suffering COVID-19. However, there is not sufficient evidence on the long-term psychological impact these professionals may suffer. We aimed to explore the long-term psychological impact of COVID-19 on primary care professionals. Methods: We applied a two-phase design; a self-reported psychopathology screening (PHQ-9, GAD-7, ISI and IES-R) in phase-1, and a specialised psychiatric evaluation (MINI, HDRS and STAI) in phase-2 to confirm phase-1 results. Evaluations were carried at the beginning of the pandemic (May-June 2020) (n = 410) and one year later (n = 339). Chi-square, ANOVA and logistic regression tests were used for statistical analyses. Results: Primary care professionals presented high rates of depression, anxiety and psychological distress, measured by PHQ-9, GAD-7 and IES-R respectively, during the pandemic. Depressive symptoms' severity (PHQ-9: 7.5 vs 8.4, p = 0.013) increased after one year of COVID-19 pandemic. After one year nearly 40% of subjects presented depression. Being women, having suffered COVID-19 or a relative with COVID-19, and being a front-line professional were risk factors for presenting depression and anxiety. Conclusion: Primary Care professionals in Cantabria present a poor mental health during COVID-19 pandemic, which has even worsened at long-term, presenting a greater psychopathology severity one year after. Thus, it is critical implementing prevention and early-treatment programmes to help these essential professionals to cope with the pandemic.

Antecedentes: La pandemia de COVID-19 ha afectado la salud mental de la población general, y en particular de los sanitarios. El personal de atención primaria tiene mayor riesgo por estar más expuesto a la enfermedad y trabajar regularmente en contacto directo con pacientes que padecen COVID-19. Sin embargo, no existe suficiente evidencia sobre el impacto psicológico a largo plazo que pueden sufrir estos profesionales. Nuestro objetivo fue explorar el impacto psicológico a largo plazo de COVID-19 en los profesionales de atención primaria. Métodos: Se aplicó un diseño en dos fases; un cribado de psicopatología a través de cuestionarios autoaplicados (PHQ-9, GAD-7, ISI e IES-R) en la fase 1, y una evaluación psiquiátrica especializada (MINI, HDRS y STAI) en la fase 2 para confirmar los resultados de la fase 1. Las evaluaciones se realizaron al inicio de la pandemia (mayo-junio de 2020) (n = 410) y un año después (n = 339). Se utilizaron pruebas de X 2, ANOVA y regresión logística para los análisis estadísticos. Resultados: Los profesionales de atención primaria presentaron índices elevados de depresión, ansiedad y malestar psicológico, medidos por PHQ-9, GAD-7 e IES-R, respectivamente, durante la pandemia. La severidad de los síntomas depresivos (PHQ-9: 7,5 vs 8,4; p = 0,013) aumentó tras un año de pandemia COVID-19. Después de un año, casi 40% de los sujetos presentaron depresión. El sexo femenino, haber padecido COVID-19 o tener un familiar con COVID-19 y ser profesional de primera línea fueron factores de riesgo para presentar depresión y ansiedad. Conclusiones: Los profesionales de Atención Primaria en Cantabria presentaron una mala salud mental durante la pandemia de COVID-19, la cual además empeoró a largo plazo, presentando una mayor gravedad los síntomas un año después. Por lo tanto, es fundamental implementar programas de prevención y tratamiento temprano para ayudar a estos profesionales esenciales a hacer frente a la pandemia.

Dysfunction of Inflammatory Pathways and Their Relationship With Psychological Factors in Adult Female Patients With Eating Disorders.

The attempts to clarify the origin of eating disorders (ED) have not been completely successful and their etiopathogenesis remains unknown. Current research shows an activation of the immune response in neuropsychiatric diseases, including ED. We aimed to investigate immune response parameters in patients with ED and to identify psychological factors influencing the inflammatory response. The relationship between inflammation markers and impulsivity and affective symptomatology was explored as well. Thirty-four adult female patients with current diagnosis of ED, none of them under psychopharmacological treatment (excluding benzodiazepines), were included in this study. Patients were compared with a healthy control group of fifteen adult females. The levels of inflammatory markers and indicators of oxidative/nitrosative stress were evaluated in plasma and/or in peripheral blood mononuclear cells (PBMCs). Subjects were assessed by means of different ED evaluation tools. Additionally, the Barratt Impulsiveness Scale, the Montgomery-Asberg Depression Rating Scale and the Hamilton Anxiety Rating Scale were also employed. Patients with ED shown increased plasma levels of the pro-inflammatory nuclear factor kappa B (NFκB) and the cytokine tumor necrosis factor-alpha (TNF-α), among other factors and an increment in the oxidative/nitrosative stress as well as increased glucocorticoid receptor (GR) expression levels in their PBMCs. Moreover, the inflammatory prostaglandin E2 (PGE2) correlated with impulsiveness and the anti-inflammatory prostaglandin J2 (15d-PGJ2) correlated with depressive symptomatology. Our results point towards a relationship between the immune response and impulsiveness and between the immune response and depressive symptomatology in female adult patients with ED.

Low levels of proinflammatory cytokines in a transdiagnostic sample of young male and female early onset eating disorders without any previous treatment: A case control study.

Growing interest exists in the association of the immune system and its role in the development and maintenance of eating disorders (ED). Current evidence suggests that serum cytokine levels seem to be elevated in females with anorexia nervosa (AN). However, less is known in bulimia nervosa (BN) and other specified feeding and eating disorders (OSFED), specially in males. We aimed to perform a case-control study in a sample of forty eight young patients (38 females and 10 males) with early diagnosis of AN, BN or OSFED and without any previous treatment, compared with twenty nine healthy controls (19 females and 10 males) matched by age, sex and socioeconomic status. We evaluated eating-related psychopathology and depressive symptoms and measured serum concentration of proinflammatory cytokines IL-1ß, IL-6, and TNF-α and anti-inflammatory cytokine IL-10. Contrary to expectations, levels of IL-1ß and IL-6 were significantly lower in ED patients, compared with healthy controls. Comparing the different groups of females, we found elevated levels of IL-10 among ED patients therefore supporting the idea of an immunosuppressive status in the early stages. This could indicate that early onset patients without any previous treatment could remain in a reward-dependent state with a lower immune response.

A retrospective investigation of the prodromal stages of eating disorders and use of health services in young patients the year prior to the diagnosis.

AIM: The aim of this study was to analyse the characteristics and the frequency of medical consultations in the year prior to the diagnosis and the intervention onset of the Eating Disorder, as well as the different prodromal symptoms. The final aim was to understand the origin of all referrals and their possible influence on the duration of untreated illness. METHODS: We selected 99 young patients (15-25 years) and 61 healthy controls. Their primary and specialized care medical records were both studied retrospectively. RESULTS: 87.6% of patients attended different consultations (primary care, specialized care and emergency department) the year prior compared to 67.2% of the controls (p = .002). The average number of consultations was 3.59 in the case group and 1.57 in the control group (p < .001). These consultations were related to prodromal symptoms in 57.4% compared to 16.4% for the controls (p < .001). They ranged from 29.8% of unspecific digestive symptoms, 22.8% of psychological symptoms, 19.3% of gynaecologic symptoms, 11.9% of weight variation, 8.8% of analytical changes, to 5.3% of malnutrition symptoms. Patients were mainly referred by Primary Care (42.7%). Overall, the mean of the Duration of Untreated Illness was of 7.45 months. CONCLUSIONS: The majority of reasons for consultation were related to symptoms that could be prodromal symptoms, but the patients were not diagnosed with an eating disorder. These findings highlight the importance of professionals understanding how to identify the warning signs of an eating disorder, so they can refer patients to a specialized unit to establish an early treatment.