Dysfunction of Inflammatory Pathways and Their Relationship with Anti-Hypothalamic Autoantibodies in Patients with Anorexia Nervosa.

BACKGROUND: Despite several attempts, the etiopathogenesis of anorexia nervosa (AN) is still unknown. However, the activation of the immune response in neuropsychiatric diseases, including AN, is increasingly evident. We aimed to explore immune response parameters in patients with AN and identify the link between the presence of specific autoantibodies for hypothalamic antigens and the inflammatory response. The relationship between inflammatory markers and the duration of the disease has been also investigated. METHODS: Twenty-two patients with AN were included, and none were under psychopharmacological treatment or suffering from autoimmune conditions. Serum concentrations of interleukin (IL)-6, IL-1ß, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-ß, and IL-21 were determined by ELISA kits. In addition, autoantibodies against hypothalamic antigens are quantitatively evaluated. RESULTS: IL-6, IL-1 ß, TNF-α, and TGF-ß are significantly increased in patients with AN. A positive correlation with body mass index and with the amount of autoantibody specific for hypothalamic antigens exists. Notably, a progressive reduction of cytokines correlates with the progression of AN. In addition, IL-21 is increased in the blood of patients with AN and negatively correlates with autoantibody concentrations. CONCLUSIONS: This study shows that the increased pro-inflammatory phenotype in patients affected by AN correlates with the concentration of autoantibody specific for hypothalamic antigens. Of interest, the pro-inflammatory state seems to be reduced with duration of AN. In addition, IL-21 could work as a stimulant of the immune response, thus possibly increasing the autoreactivity.

Linguistic profile automated characterisation in pluripotential clinical high-risk mental state (CHARMS) conditions: methodology of a multicentre observational study.

INTRODUCTION: Language is usually considered the social vehicle of thought in intersubjective communications. However, the relationship between language and high-order cognition seems to evade this canonical and unidirectional description (ie, the notion of language as a simple means of thought communication). In recent years, clinical high at-risk mental state (CHARMS) criteria (evolved from the Ultra-High-Risk paradigm) and the introduction of the Clinical Staging system have been proposed to address the dynamicity of early psychopathology. At the same time, natural language processing (NLP) techniques have greatly evolved and have been successfully applied to investigate different neuropsychiatric conditions. The combination of at-risk mental state paradigm, clinical staging system and automated NLP methods, the latter applied on spoken language transcripts, could represent a useful and convenient approach to the problem of early psychopathological distress within a transdiagnostic risk paradigm. METHODS AND ANALYSIS: Help-seeking young people presenting psychological distress (CHARMS+/- and Clinical Stage 1a or 1b; target sample size for both groups n=90) will be assessed through several psychometric tools and multiple speech analyses during an observational period of 1-year, in the context of an Italian multicentric study. Subjects will be enrolled in different contexts: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa-IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Mental Health Department-territorial mental services (ASL 3-Genoa), Genoa, Italy; and Mental Health Department-territorial mental services (AUSL-Piacenza), Piacenza, Italy. The conversion rate to full-blown psychopathology (CS 2) will be evaluated over 2 years of clinical observation, to further confirm the predictive and discriminative value of CHARMS criteria and to verify the possibility of enriching them with several linguistic features, derived from a fine-grained automated linguistic analysis of speech. ETHICS AND DISSEMINATION: The methodology described in this study adheres to ethical principles as formulated in the Declaration of Helsinki and is compatible with International Conference on Harmonization (ICH)-good clinical practice. The research protocol was reviewed and approved by two different ethics committees (CER Liguria approval code: 591/2020-id.10993; Comitato Etico dell'Area Vasta Emilia Nord approval code: 2022/0071963). Participants will provide their written informed consent prior to study enrolment and parental consent will be needed in the case of participants aged less than 18 years old. Experimental results will be carefully shared through publication in peer-reviewed journals, to ensure proper data reproducibility. TRIAL REGISTRATION NUMBER: DOI:10.17605/OSF.IO/BQZTN.

Meteorological Variables and Suicidal Behavior: Air Pollution and Apparent Temperature Are Associated With High-Lethality Suicide Attempts and Male Gender.

This study analyzed the impact of meteorological variables and high-lethality suicide attempts (HLSA) to assess a potential time shift of HLSA affected by climate evolution to predict the suicide attempt cases over different periods of the year. After attempting suicide, 225 subjects were admitted to the emergency ward of the IRCCS Ospedale Policlinico San Martino and later to the psychiatric unit from March 2016 to July 2018. Socio-demographic and clinical characteristics as well as the meteorological variables were collected. The Mann-Kendall test as well as redundancy and cross-correlation analyses were performed to analyze the trends, statistically correlations, and correspondence of the trends, respectively between suicidal behaviors and climatic factors. Sixty-seven (29.8%) committed a HLSA. Our findings indicate a significant association between HLSA and male gender and apparent temperature with a strong correlation of 75% with a phase shift of -1 month. Solar radiation and air pollution (PM2.5) have a positive correlation of 65 and 32%, respectively, with a zero-time lag. Limitations include that the data are limited to a single hospital; psychological factors, or other clinical variables that could be ruled out as a trigger have not been considered. Meteorological variables may not mirror the temperature that the patient is exposed to due to the air conditioning systems. Exploring those environmental factors associated with HLSA in a more detailed manner could lead to early intervention and prevention strategies for such distressing admissions.