A transdiagnostic and diagnostic-specific approach on inflammatory biomarkers in eating disorders: A meta-analysis and systematic review.

Eating disorders (EDs) are severe mental illnesses with a multifactorial etiology and a chronic course. Among the biological factors related to pathogenesis and maintenance of EDs, inflammation acquired growing scientific interest. This study aimed to assess the inflammatory profile of EDs, focusing on anorexia nervosa, bulimia nervosa, and including for the first time binge eating disorder. A comprehensive research of existing literature identified 51 eligible studies for meta-analysis, comparing levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), osteoprotegerin (OPG), soluble receptor activator of nuclear factor kappa-B ligand (sRANKL), interleukin-1ß (IL-1ß), and interleukin-10 (IL-10) between patients with EDs and healthy controls (HCs). The systematic review explored other inflammatory biomarkers of interest, which did not meet the meta-analysis criteria. Results revealed significantly elevated levels of TNF-α, OPG, sRANKL, and IL-1ß in patients with EDs compared to HCs. Additionally, the results highlighted the heterogeneity of inflammatory state among patients with EDs, emphasizing the need for further research into the association between inflammatory biomarkers and psychopathological correlates. This approach should transcend categorical diagnoses, enabling more precise subcategorizations of patients. Overall, this study contributed to the understanding of the inflammatory pathways involved in EDs, emphasizing potential implications for diagnosis, staging, and targeted interventions.

Online content on eating disorders: a natural language processing study.

BACKGROUND: Online content can inform the personal risk of developing an eating disorder, and it can influence the time and motivation to seek treatment. Patients routinely seek information online, and access to information is crucial for both prevention and treatment. The primary aim of the current study was to quantify the readability scores of online content on eating disorders using natural language processing algorithms, across two languages: English and Italian. METHODS: Unique terms related to single diagnoses were searched using Google®. The content available on Wikipedia was also assessed. Readability was defined according to the Flesch Readability Ease (FRE) and the Rate Readability Index (RIX). The scientific support of retrieved content and the authoritativeness of sources were measured through standardized variables. RESULTS: In Italian, online content was more likely published by private psychotherapy institutes or by websites that promote diet-advice or weight-loss. In both languages, the most readable content was on Anorexia Nervosa (RIX 4.18, FRE-en 59.6, FRE-it 41.69), Bulimia Nervosa (RIX 3.99, FRE-en 66.27, FRE-it 39.66) or Binge Eating (RIX 4.01, FRE-en 68.10, FRE-it 38.62). English sources consistently had more references than Italian pages (range 35-182, vs 1-163, respectively). and had a higher percentage of citations available in the target language. The content of these references was mainly reflective of peer-reviewed or clinical manuals. CONCLUSION: Attention should be given to developing online content for Muscle Dysmorphia and Orthorexia Nervosa, as well as improving the overall readability of online content on eating disorders, especially for languages other than English.

Transdiagnostic markers across the psychosis continuum: a systematic review and meta-analysis of resting state fMRI studies.

Psychotic symptoms are among the most debilitating and challenging presentations of severe psychiatric diseases, such as schizophrenia, schizoaffective, and bipolar disorder. A pathophysiological understanding of intrinsic brain activity underlying psychosis is crucial to improve diagnosis and treatment. While a potential continuum along the psychotic spectrum has been recently described in neuroimaging studies, especially for what concerns absolute and relative amplitude of low-frequency fluctuations (ALFF and fALFF), these efforts have given heterogeneous results. A transdiagnostic meta-analysis of ALFF/fALFF in patients with psychosis compared to healthy controls is currently lacking. Therefore, in this pre-registered systematic review and meta-analysis PubMed, Scopus, and Embase were searched for articles comparing ALFF/fALFF between psychotic patients and healthy controls. A quantitative synthesis of differences in (f)ALFF between patients along the psychotic spectrum and healthy controls was performed with Seed-based d Mapping, adjusting for age, sex, duration of illness, clinical severity. All results were corrected for multiple comparisons by Family-Wise Error rates. While lower ALFF and fALFF were detected in patients with psychosis in comparison to controls, no specific finding survived correction for multiple comparisons. Lack of this correction might explain the discordant findings highlighted in previous literature. Other potential explanations include methodological issues, such as the lack of standardization in pre-processing or analytical procedures among studies. Future research on ALFF/fALFF differences for patients with psychosis should prioritize the replicability of individual studies. Systematic review registration: https://osf.io/, identifier (ycqpz).

Early traumatic experiences are linked to hypersexual behavior and erectile dysfunction in men through the mediation of body uneasiness and general psychopathology.

BACKGROUND: Childhood traumatic experiences have been associated with hypersexuality and sexual dysfunctions. However, the mediators of the interactions between these variables should be clarified in men. AIM: This study aimed to investigate the interaction of early traumatic experiences, psychopathology, and sexuality with respect to erectile dysfunction (ED) and hypersexual behavior. The hypothesized model expected that traumatic experiences would be associated with hypersexual behavior and reduced sexual functioning through the mediation of body uneasiness and psychological distress. METHODS: The study was cross-sectional and observational. A total of 317 men were enrolled. Male patients with a primary complaint of ED and an indication for psychiatry referral represented the clinical sample (n = 116; mean ± SD age, 42.82 ± 16.89 years). Clinical classification was assessed with the Structured Interview on Erectile Dysfunction. The second sample (n = 201, 30.82 ± 11.94 years) was recruited from the general population. All participants were administered the following questionnaires: Brief Symptom Inventory, Childhood Trauma Questionnaire-Short Form, Hypersexual Behavior Inventory, Body Uneasiness Test-A, and 5-item International Index of Erectile Function. OUTCOMES: Psychopathology and sexual functioning were assessed by a dimensional approach, and a multivariate model was computed by structural equation model analysis. RESULTS: When compared with the sample from the general population, the clinical sample exhibited a higher prevalence of early traumatic experiences, as measured by scores on the Childhood Trauma Questionnaire-Short Form (45.08 ± 14.25 vs 39.03 ± 10.22, F = 17.63, P < .001), and a higher tendency to engage in hypersexual behaviors (34.63 ± 13.55 vs 30.79 ± 12.44, F = 6.97, P < .01). Structural equation model analysis showed excellent fit indices indicating that early traumatic experiences predicted hypersexual behaviors and ED through the exacerbating mediating effect of body uneasiness and psychopathology. CLINICAL IMPLICATIONS: Clinicians should not limit their attention to the behavioral level when assessing sexual dysfunction in men; rather, they should also consider the complex psychopathologic consequences of childhood trauma. Integrated treatments that address the potential presence of childhood trauma with its wider psychological correlates (eg, emotion dysregulation, body uneasiness) might improve treatment response. STRENGTHS AND LIMITATIONS: The study reports novel data on the relationship among childhood maltreatment, male sexuality, and psychopathologic mediators with a dimensional assessment. However, the assessment was cross-sectional, and causality was mainly derived from previous studies. CONCLUSION: The present study enriches the current literature, strengthening the hypothesis that childhood traumatic experiences significantly shape development and sexuality. Body uneasiness and psychopathology can both tax sexual functioning, as assessed by erectile functioning or hypersexuality.

From Restriction to Intuition: Evaluating Intuitive Eating in a Sample of the General Population.

Intuitive eating (IE) is a non-dieting approach that promotes listening to internal cues of hunger and satiety, rather than adhering to external dietary restrictions aimed at weight loss. However, the role of IE in dieting behaviors related to weight-loss approaches is still unclear. To address this issue, the aim of this study was to compare IE levels between dieting and non-dieting individuals, exploring the relationship between IE and dieting-related psychological and physical factors. A sample of 2059 females was recruited via social media and self-reported questionnaires were administered to measure IE, eating psychopathology, self-efficacy, and quality of life. Individuals with a history of dieting exhibited lower IE levels, a higher BMI, and a greater eating psychopathology, as well as a reduced self-efficacy and quality of life, compared to non-dieters. IE showed a protective effect against dieting behaviors, with higher IE levels being associated with a lower likelihood of dieting. Additionally, higher BMI and eating psychopathology were predictors of dieting. Promoting IE could represent a relevant clinical target strategy to address disordered eating and enhance overall well-being, underscoring the need for interventions that foster a healthier relationship with food and bodily internal sensations.

Psychotic-like anomalous self-experiences in feeding and eating disorders: Their role in eating psychopathology through the mediation of body uneasiness and embodiment and identity disorders.

BACKGROUND: Psychotic-like anomalous self-experiences (ASEs) are core and early features of schizophrenia spectrum disorders, which have been recently also postulated to underlie embodiment disturbance in feeding and eating disorders (FEDs). The present study was aimed at investigating the interplay between ASEs and specific psychopathology in FED. METHODS: Ninety persons with Anorexia Nervosa and 41 with Bulimia Nervosa were evaluated with the inventory of psychotic-like anomalous self-experiences (IPASE), identity and eating disorders (IDEA), body uneasiness test (BUT), and eating disorder examination questionnaire (EDE-Q). The same assessment was performed for 92 subjects recruited from the general population. Structural equation modelling was employed to test the role of embodiment/identity disorders in mediating the relationship between ASEs and ED psychopathology. RESULTS: Patients with FED displayed high scores on IPASE, comparable with people with schizophrenia spectrum disorders. A significant correlation was also demonstrated between IPASE, BUT and EDE-Q. All IPASE domains were strongly related to feeling extraneous from one's own body by IDEA. All IPASE domains demonstrated a high relationship with BUT Depersonalization scale. A strong correlation was also reported between total scores of IPASE and IDEA. The mediation model confirmed that ASEs impact on FED symptomatology through the mediation of both embodiment/identity disorders and body image. DISCUSSION: Anomalous interoceptive processes may represent the first step of a maladaptive process-impairing embodiment, selfhood, and identity in FED. Assessment of ASEs might be a valid tool to identify an early-shared vulnerability of severe disorders characterized by embodiment alterations.

From early relational experiences to non-suicidal self-injury in anorexia and bulimia nervosa: a structural equation model unraveling the role of impairments in interoception.

PURPOSE: Individuals with anorexia nervosa (AN) and bulimia nervosa (BN) frequently exhibit Non-Suicidal Self-Injury (NSSI), yet their co-occurrence is still unclear. To address this issue, the aim of this study was to elucidate the role of impairments in interoception in explaining the NSSI phenomenon in AN and BN, providing an explanatory model that considers distal (insecure attachment/IA and traumatic childhood experiences/TCEs) and proximal (dissociation and emotional dysregulation) risk factors for NSSI. METHOD: 130 patients with AN and BN were enrolled and administered self-report questionnaires to assess the intensity of NSSI behaviors, interoceptive deficits, IA, TCEs, emotional dysregulation and dissociative symptoms. RESULTS: Results from structural equation modeling revealed that impairments in interoception acted as crucial mediators between early negative relational experiences and factors that contribute to NSSI in AN and BN, particularly emotional dysregulation and dissociation. Precisely, both aspects of IA (anxiety and avoidance) and various forms of TCEs significantly exacerbated interoceptive deficits, which in turn are associated to the emergence of NSSI behaviors through the increase in levels of dissociation and emotional dysregulation. CONCLUSIONS: The proposed model provided a novel explanation of the occurrence of NSSIs in patients with AN and BN by accounting for the significance of interoception. LEVEL OF EVIDENCE: Level V-Cross-sectional observational study.

On the interplay between state-dependent reconfigurations of global signal correlation and BOLD fluctuations: An fMRI study.

BACKGROUND: The dynamics of global, state-dependent reconfigurations in brain connectivity are yet unclear. We aimed at assessing reconfigurations of the global signal correlation coefficient (GSCORR), a measure of the connectivity between each voxel timeseries and the global signal, from resting-state to a stop-signal task. The secondary aim was to assess the relationship between GSCORR and blood-oxygen-level-dependent (BOLD) activations or deactivation across three different trial-conditions (GO, STOP-correct, and STOP-incorrect). METHODS: As primary analysis we computed whole-brain, voxel-wise GSCORR during resting-state (GSCORR-rest) and stop-signal task (GSCORR-task) in 107 healthy subjects aged 21-50, deriving GSCORR-shift as GSCORR-task minus GSCORR-rest. GSCORR-tr and trGSCORR-shift were also computed on the task residual time series to quantify the impact of the task-related activity during the trials. To test the secondary aim, brain regions were firstly divided in one cluster showing significant task-related activation and one showing significant deactivation across the three trial conditions. Then, correlations between GSCORR-rest/task/shift and activation/deactivation in the two clusters were computed. As sensitivity analysis, GSCORR-shift was computed on the same sample after performing a global signal regression and GSCORR-rest/task/shift were correlated with the task performance. RESULTS: Sensory and temporo-parietal regions exhibited a negative GSCORR-shift. Conversely, associative regions (ie. left lingual gyrus, bilateral dorsal posterior cingulate gyrus, cerebellum areas, thalamus, posterolateral parietal cortex) displayed a positive GSCORR-shift (FDR-corrected p < 0.05). GSCORR-shift showed similar patterns to trGSCORR-shift (magnitude increased) and after global signal regression (magnitude decreased). Concerning BOLD changes, Brodmann area 6 and inferior parietal lobule showed activation, while posterior parietal lobule, cuneus, precuneus, middle frontal gyrus showed deactivation (FDR-corrected p < 0.05). No correlations were found between GSCORR-rest/task/shift and beta-coefficients in the activation cluster, although negative correlations were observed between GSCORR-task and GO/STOP-correct deactivation (Pearson rho=-0.299/-0.273; Bonferroni-p < 0.05). Weak associations between GSCORR and task performance were observed (uncorrected p < 0.05). CONCLUSION: GSCORR state-dependent reconfiguration indicates a reallocation of functional resources to associative areas during stop-signal task. GSCORR, activation and deactivation may represent distinct proxies of brain states with specific neurofunctional relevance.

Development and validation of a prediction score to assess the risk of depression in primary care.

BACKGROUND: Major depression is the most frequent psychiatric disorder and primary care is a crucial setting for its early recognition. This study aimed to develop and validate the DEP-HScore as a tool to predict depression risk in primary care and increase awareness and investigation of this condition among General Practitioners (GPs). METHODS: The DEP-HScore was developed using data from the Italian Health Search Database (HSD). A cohort of 903,748 patients aged 18 years or older was selected and followed until the occurrence of depression, death or end of data availability (December 2019). Demographics, somatic signs/symptoms and psychiatric/medical comorbidities were entered in a multivariate Cox regression to predict the occurrence of depression. The coefficients formed the DEP-HScore for individual patients. Explained variance (pseudo-R2), discrimination (AUC) and calibration (slope estimating predicted-observed risk relationship) assessed the prediction accuracy. RESULTS: The DEP-HScore explained 18.1 % of the variation in occurrence of depression and the discrimination value was equal to 67 %. With an event horizon of three months, the slope and intercept were not significantly different from the ideal calibration. LIMITATIONS: The DEP-HScore has not been tested in other settings. Furthermore, the model was characterized by limited calibration performance when the risk of depression was estimated at the 1-year follow-up. CONCLUSIONS: The DEP-HScore is reliable tool that could be implemented in primary care settings to evaluate the risk of depression, thus enabling prompt and suitable investigations to verify the presence of this condition.

The maltreated eco-phenotype of eating disorders: A new diagnostic specifier? A systematic review of the evidence and comprehensive description.

This systematic review aimed to summarize the evidence on the existence of a distinct phenotypic expression of Eating Disorders (EDs) associated with childhood maltreatment (CM), the so-called maltreated eco-phenotype of EDs. PRISMA standards were followed. Articles providing data about the characteristics of individuals with an ED reporting CM were included. Relevant results were extracted and summarized. A quality assessment was performed. A total of 1207 records were identified and screened, and 97 articles published between 1994 and 2023 were included. Findings revealed distinct biological and clinical features in patients with EDs reporting CM, including neuroanatomical changes, altered stress responses, ghrelin levels, inflammation markers, and gut microbiota composition. Clinically, CM correlated with severer eating behaviors, higher psychiatric comorbidity, impulsivity, emotional dysregulation, and risky behaviors. Additionally, CM was associated with poorer treatment outcomes, especially in general psychopathology and psychiatric comorbidities. This review highlighted the need to move towards an etiologically informed nosography, recognizing CM not merely as a risk factor, but also as an etiologic agent shaping different eco-phenotypic variants of EDs.

Are midwives trained to recognise perinatal depression symptoms? Results of MAMA (MAternal Mood Assessment) cross-sectional survey in Italy.

PURPOSE: To assess the knowledge, clinical experience, and attitudes of Italian midwives toward perinatal depression (PND) and to explore how these factors impact the quality of care. METHODS: We conducted a cross-sectional online survey among 152 midwives employed in public hospitals across Italy. The questionnaire covered a range of topics, including demographic data, professional experience, knowledge of PND symptoms, risk factors, and clinical management, as well as communication skills and personal experiences with PND cases. RESULTS: A concerning 76.3% of midwives displayed inadequate knowledge of PND based on current scientific literature. Those with a more comprehensive understanding were notably more confident in their practice, expressing significantly fewer apprehensions about communicating with mothers (25.8% vs 74.2%) and lesser concerns about the mothers' future well-being (38.9% vs 62.95%). The survey results also emphasised the midwives' call for specialised guidelines and formal training in PND management and underscored the value of communication skills, continuity of care, and family engagement in supporting affected mothers. CONCLUSION: This inaugural study sheds light on the current state of knowledge and attitudes among Italian midwives regarding PND. It pinpoints crucial areas for educational enhancement and practice improvement, suggesting that elevated levels of midwife expertise in PND could significantly elevate the standard of care and expedite early diagnosis and treatment.

The interplay between mentalization, personality traits and burnout in psychiatry training: Results from a large multicenter controlled study.

BACKGROUND: A better characterization of educational processes during psychiatry training is needed, both to foster personal resilience and occupational proficiency. METHODS: An adequate coverage of medical residents at the national level was reached (41.86% of the total reference population, 29 out of 36 training centers-80.55%). Controls were recruited among residents in other medical specialties. All participants were assessed by questionnaires to evaluate early life experiences, attachment style, personality traits, coping strategies, emotional competencies. A Structural Equation Model (SEM) framework was employed to investigate the interplay between individual factors. RESULTS: A total sample of 936 people was recruited (87.9% response-rate; 645 residents in psychiatry, 291 other medical residents). Psychiatry trainees reported a higher prevalence of adverse childhood experiences (emotional abuse, emotional neglect, physical neglect), greater attachment insecurity (anxious or avoidant) in comparison to other medical trainees. Psychiatry residents also reported higher social support-seeking as a coping strategy, lower problem-orientation, and lower transcendence. Lower neuroticism, higher openness to experience, and higher emotional awareness were also observed in psychiatry trainees. Psychiatry training was associated with a redefinition of conflict management skills as a function of seniority. The SEM model provided support for an interplay between early traumatic experiences, mentalization skills (coping strategies, emotion regulation), interpersonal competencies and occupational distress. CONCLUSIONS: The findings of the present study supported a theoretical model based on mentalization theory for the interactions between personal and relational competencies in psychiatry training, thus providing potential target of remodulation and redefinition of this specific process of education.

The primacy of ocular perception: a narrative review on the role of gender identity in eating disorders.

BACKGROUND: Phenomenological research has enriched the scientific and clinical understanding of Eating Disorders (ED), describing the significant role played by disorders of embodiment in shaping the lived experience of patients with ED. According to the phenomenological perspective, disorders of embodiment in ED are associated with feelings of alienation from one's own body, determining an excessive concern for external appearance as a form of dysfunctional coping. The purpose of the present narrative review is to address the role of gender identity as a risk factor for EDs in the light of phenomenological approaches. METHODS: Narrative review. RESULTS: The current study discusses the interplay between perception, gender identity, and embodiment, all posited to influence eating psychopathology. Internalized concerns for body appearance are described as potentially associated with self-objectification. Furthermore, concerns on body appearance are discussed in relation to gendered social expectations. The current review also explores how societal norms and gender stereotypes can contribute to dysfunctional self-identification with external appearances, particularly through an excessive focus on the optical dimension. The socio-cultural perspective on gender identity was considered as a further explanation of the lived experience of individuals with ED. CONCLUSIONS: By acknowledging the interplay between these factors, clinicians and researchers can gain a deeper understanding of these disorders and develop more effective interventions for affected individuals. LEVEL OF EVIDENCE: Level V narrative review.

Back to the Future: Is GnRHa Treatment in Transgender and Gender Diverse Adolescents Only an Extended Evaluation Phase?

CONTEXT: The role of body modifications induced by gonadal suppression in transgender and gender diverse adolescents on psychological functioning has not yet been evaluated. OBJECTIVE: The main aim of the present study was to explore several hormone, physical and psychological functioning changes during gonadotropin-releasing hormone analog (GnRHa) treatment in transgender and gender diverse adolescents (TGDAs). The potential relationship between the physical and hormone effects of GnRHa and psychological well-being, along with its magnitude, was assessed for the first time. METHODS: This prospective multidisciplinary study included 36 TGDA (22 assigned female at birth, and 14 assigned male at birth) who received psychological assessment followed by triptorelin prescription after referring to the Florence Gender Clinic. This study consisted of 3 time points: first referral (T0), psychological assessment (T1); and treatment with intramuscular injections of triptorelin for 3 up to 12 months (T2). Psychometric questionnaires were administered at each time point, and clinical and biochemical evaluations were performed at T1 and T2. RESULTS: The following results were found: (1) GnRHa showed efficacy in inhibiting puberty progression in TGDAs; (2) an increase in psychopathology was observed before starting GnRHa (T1) compared with baseline levels; (3) during GnRHa treatment (T2), a significant improvement in psychological functioning, as well as decrease in suicidality, body uneasiness, depression, and anxiety levels were observed; (4) hormone and physical changes (in terms of gonadotropin and sex steroid levels, height and body mass index percentiles, waist-hip ratio, and acne severity) observed during triptorelin treatment significantly correlated with a reduction in suicidal ideation, anxiety, and body image concerns. CONCLUSION: Psychological improvement in TGDA on GnRHa seems to be related to the objective body changes induced by a GnRHa. Therefore, the rationale for treatment with a GnRHa may not only be considered an extension of the evaluation phase, but also the start of a medical (even if reversible) gender-affirming path, especially in TGDAs whose puberty has already progressed.

Risk factors for eating disorders: an umbrella review of published meta-analyses

Objective: To grade the evidence about risk factors for eating disorders (anorexia nervosa, bulimia nervosa, and binge eating disorder) with an umbrella review approach. Methods: This was a systematic review of observational studies on risk factors for eating disorders published in PubMed/PsycInfo/Embase until December 11th, 2019. We recalculated random-effect meta-analyses, heterogeneity, small-study effect, excess significance bias and 95% prediction intervals, grading significant evidence (p < 0.05) from convincing to weak according to established criteria. Quality was assessed with the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool. Results: Of 2,197 meta-analyses, nine were included, providing evidence on 50 risk factors, 29,272 subjects with eating disorders, and 1,679,385 controls. Although no association was supported by convincing evidence, highly suggestive evidence supported the association between childhood sexual abuse and bulimia nervosa (k = 29, 1,103 cases with eating disorders, 8,496 controls, OR, 2.73, 95%CI 1.96-3.79, p = 2.1 x 10-9, AMSTAR-2 moderate quality) and between appearance-related teasing victimization and any eating disorder (k = 10, 1,341 cases with eating disorders, 3,295 controls, OR 2.91, 95%CI 2.05-4.12, p = 1.8x10-9, AMSTAR-2 moderate quality). Suggestive, weak, or no evidence supported 11, 29, and 8 associations, respectively. Conclusions: The most credible evidence indicates that early traumatic and stressful events are risk factors for eating disorders. Larger collaborative prospective cohort studies are needed to identify risk factors for eating disorders, particularly anorexia nervosa.