Metacognition as a transdiagnostic factor across eating disorders: a latent profile analysis study.

Background: Metacognition is a crucial aspect of understanding and attributing mental states, playing a key role in the psychopathology of eating disorders (EDs). This study aims to explore the diverse clinical profiles of metacognition among patients with EDs using latent profile analysis (LPA). Method: A total of 395 patients with a DSM-5 diagnosis of ED (116 AN-R, 30 AN/BP, 100 BN, 149 BED) participated in this study. They completed self-report measures assessing metacognition, eating psychopathology, depression, emotional dysregulation, personality traits, and childhood adversities. LPA and Welch ANOVAs were conducted to identify profiles based on metacognition scores and examine psychological differences between them. Logistic regression models were employed to explore associations between personal characteristics and different profiles. Results: A 3-class solution had a good fit to the data, revealing profiles of high functioning (HF), intermediate functioning (IF), and low functioning (LF) based on levels of metacognitive impairments. Participants in the IF group were older and had a higher BMI than those in the HF and LF groups. Individuals with BN were largely categorized into HF and LF profiles, whereas participants with BED were mainly included in the IF profile. Participants in the LF group reported an impaired psychological profile, with high levels of depression, emotional dysregulation, childhood adversity, and personality dysfunction. Multinomial logistic regression analyses showed significant associations between metacognitive profiles and emotional and neglect abuse, emotion dysregulation, and detachment. Conclusion: This exploratory study unveils distinct metacognitive profiles in EDs, providing a foundation for future research and targeted interventions. In this light, metacognitive interpersonal therapy could be a valid and effective treatment for EDs, as suggested by the initial promising results for these patients.

Parity of esteem: A global COVID-19 vaccination approach for people with mental illnesses, based on facts from 34 countries; recommendations and solutions.

Background: The coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has detrimental effects on physical and mental health. Patients with severe mental illness are at higher risk of contracting the virus due to social determinants of health. Vulnerable populations include the elderly, people with pre-existing conditions, and those exposed to SARS-CoV-2. Unfortunately, only a few countries have updated vaccination strategies to prioritize patients with mental illnesses. Therefore, we aimed to explore whether individuals with mental disorders are prioritized in vaccine allocation strategies in different world regions. They are often neglected in policymaking but are highly vulnerable to the threatening complications of COVID-19. Methods: A questionnaire was developed to record details regarding COVID-19 vaccination and prioritizations for groups of persons with non-communicable diseases (NCDs), mental disorders, and substance use disorders (SUDs). NCDs were defined according to the WHO as chronic diseases that are the result of a combination of genetic, physiological, environmental, and behavioral factors such as cardiovascular diseases, cancer, respiratory diseases, and diabetes. Results: Most countries surveyed (80%) reported healthcare delivery via a nationalized health service. It was found that 82% of the countries had set up advisory groups, but only 26% included a mental health professional. Most frequently, malignancy (68%) was prioritized followed by diabetes type 2 (62%) and type 1 (59%). Only nine countries (26%) prioritized mental health conditions. Conclusion: The spread of the coronavirus has exposed both the strengths and flaws of our healthcare systems. The most vulnerable groups suffered the most and were hit first and faced most challenges. These findings raise awareness that patients with mental illnesses have been overlooked in immunization campaigns. The range of their mortality, morbidity, and quality of life could have widened due to this delay.

The European psychiatric association (EPA) - early career psychiatrists committee survey on trainees' and early-career psychiatrists' attitudes towards therapeutic drug monitoring (TDM) use and utility during antipsychotic treatment.

OBJECTIVES: This survey assessed psychiatry residents'/early-career psychiatrists' attitudes towards the utility of therapeutic drug monitoring (TDM) of antipsychotics. METHODS: A previously developed questionnaire on attitudes on TDM utility during antipsychotic treatment was cross-sectionally disseminated by national coordinators between 01/01/2022-31/12/2023. The frequency of using TDM for antipsychotics other than clozapine was the main outcome in a linear regression analysis, including sex, clinical setting, caseload, and factors generated by an exploratory factor analysis. Comparisons between residents and early-career psychiatrists, respondents working in in- and outpatient settings, and low-/middle- and high-income countries were performed. RESULTS: Altogether, 1,237 respondents completed the survey, with 37.9% having never used TDM for antipsychotics. Seven factors explained 41% of response variance; six of them were associated with frequency of TDM use (p < 0.05). Items with highest loadings for factors included clinical benefits of TDM (factors A and E: 0.7), negative expectations for beliefs of patients towards TDM (factor B: 0.6-0.7), weak TDM scientific evidence (factor C: 0.8), and TDM availability (factor D: -0.8). Respondents from low-/middle-income countries were less likely to frequently/almost always use TDM compared to high-income countries (9.4% vs. 21.5%, p < 0.001). DISCUSSION: TDM use for antipsychotics was poor and associated with limited knowledge and insufficient availability.

Antipsychotic-Related DRESS Syndrome: Analysis of Individual Case Safety Reports of the WHO Pharmacovigilance Database.

INTRODUCTION: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is gaining attention in pharmacovigilance, but its association with antipsychotics, other than clozapine, is still unclear. METHODS: We conducted a case/non-case study with disproportionality analysis based on the World Health Organization (WHO) global spontaneous reporting database, VigiBase®. We analyzed individual case safety reports of DRESS syndrome related to antipsychotics compared to (1) all other medications in VigiBase®, (2) carbamazepine (a known positive control), and (3) within classes (typical/atypical) of antipsychotics. We calculated reporting odds ratio (ROR) and Bayesian information component (IC), with 95% confidence intervals (CIs). Disproportionate reporting was prioritized based on clinical importance, according to predefined criteria. Additionally, we compared characteristics of patients reporting with serious/non-serious reactions. RESULTS: A total of 1534 reports describing DRESS syndrome for 19 antipsychotics were identified. The ROR for antipsychotics as a class as compared to all other medications was 1.0 (95% CI 0.9-1.1). We found disproportionate reporting for clozapine (ROR 2.3, 95% CI 2.1-2.5; IC 1.2, 95% CI 1.1-1.3), cyamemazine (ROR 2.3, 95% CI 1.5-3.5; IC 1.2, 95% CI 0.5-1.7), and chlorpromazine (ROR 1.5, 95% CI 1.1-2.1; IC 0.6, 95% CI 0.1-1.0). We found 35.7% of cases with co-reported anticonvulsants, and 25% with multiple concurrent antipsychotics in serious compared to 8.6% in non-serious cases (p = 0.03). Fatal cases were 164 (10.7%). CONCLUSIONS: Apart from the expected association with clozapine, chlorpromazine and cyamemazine (sharing an aromatic heteropolycyclic molecular structure) emerged with a higher-than-expected reporting of DRESS. Better knowledge of the antipsychotic-related DRESS syndrome should increase clinicians' awareness leading to safer prescribing of antipsychotics.

Aberrant salience mediates the interplay between emotional abuse and positive symptoms in schizophrenia.

INTRODUCTION: Childhood trauma and adversities (CTA) and aberrant salience (AS) have a pivotal role in schizophrenia development, but their interplay with psychotic symptoms remains vague. We explored the mediation performed by AS between CTA and psychotic symptomatology in schizophrenia. METHODS: We approached 241 adults suffering from schizophrenia spectrum disorders (SSDs), who have been in the unit for at least 12 consecutive months, excluding the diagnosis of dementia, and recent substance abuse disorder, and cross-sectional evaluated through the Aberrant Salience Inventory (ASI), Childhood Trauma Questionnaire Short-Form (CTQ-SF), and Positive and Negative Symptom Scale (PANSS). We tested a path-diagram where AS mediated the relationship between CTA and psychosis, after verifying each measure one-dimensionality through confirmatory factor analysis. RESULTS: The final sample comprised 222 patients (36.9% female), with a mean age of 42.4 (± 13.3) years and an average antipsychotic dose of 453.6 (± 184.2) mg/day (chlorpromazine equivalents). The mean duration of untreated psychosis was 1.8 (± 2.0) years while the mean onset age was 23.9 (± 8.2) years. Significant paths were found from emotional abuse to ASI total score (ß = 0.39; p < .001) and from ASI total score to PANSS positive (ß = 0.17; p = .019). Finally, a statistically significant indirect association was found from emotional abuse to PANSS positive mediated by ASI total score (ß = 0.06; p = .041; CI 95% [0.01, 0.13]). CONCLUSION: Emotional abuse has an AS-mediated effect on positive psychotic symptomatology. AS evaluation could allow a better characterization of psychosis as well as explain the presence of positive symptoms in adults with SSDs who experienced CTA.

Obsessive-Compulsive Disorder as an Epiphenomenon of Comorbid Bipolar Disorder? An Updated Systematic Review.

BACKGROUND: Bipolar disorder (BD) and obsessive-compulsive disorder (OCD) comorbidity is an emerging condition in psychiatry, with relevant nosological, clinical, and therapeutic implications. METHODS: We updated our previous systematic review on epidemiology and standard diagnostic validators (including phenomenology, course of illness, heredity, biological markers, and treatment response) of BD-OCD. Relevant papers published until (and including) 15 October 2023 were identified by searching the electronic databases MEDLINE, Embase, PsychINFO, and Cochrane Library, according to the PRISMA statement (PROSPERO registration number, CRD42021267685). RESULTS: We identified 38 new articles, which added to the previous 64 and raised the total to 102. The lifetime comorbidity prevalence ranged from 0.26 to 27.8% for BD and from 0.3 to 53.3% for OCD. The onset of the two disorders appears to be often overlapping, although the appearance of the primary disorder may influence the outcome. Compared to a single diagnosis, BD-OCD exhibited a distinct pattern of OC symptoms typically following an episodic course, occurring in up to 75% of cases (vs. 3%). Notably, these OC symptoms tended to worsen during depressive episodes (78%) and improve during manic or hypomanic episodes (64%). Similarly, a BD course appears to be chronic in individuals with BD-OCD in comparison to patients without. Additionally, individuals with BD-OCD comorbidity experienced more depressive episodes (mean of 8.9 ± 4.2) compared to those without comorbidity (mean of 4.1 ± 2.7). CONCLUSIONS: We found a greater likelihood of antidepressant-induced manic/hypomanic episodes (60% vs. 4.1%), and mood stabilizers with antipsychotic add-ons emerging as a preferred treatment. In line with our previous work, BD-OCD comorbidity encompasses a condition of greater nosological and clinical complexity than individual disorders.

Tolerability of vortioxetine compared to selective serotonin reuptake inhibitors in older adults with major depressive disorder (VESPA): a randomised, assessor-blinded and statistician-blinded, multicentre, superiority trial.

Background: Major depressive disorder (MDD) is prevalent and disabling among older adults. Standing on its tolerability profile, vortioxetine might be a promising alternative to selective serotonin reuptake inhibitors (SSRIs) in such a vulnerable population. Methods: We conducted a randomised, assessor- and statistician-blinded, superiority trial including older adults with MDD. The study was conducted between 02/02/2019 and 02/22/2023 in 11 Italian Psychiatric Services. Participants were randomised to vortioxetine or one of the SSRIs, selected according to common practice. Treatment discontinuation due to adverse events after six months was the primary outcome, for which we aimed to detect a 12% difference in favour of vortioxetine. The study was registered in the online repository clinicaltrials.gov (NCT03779789). Findings: The intention-to-treat population included 179 individuals randomised to vortioxetine and 178 to SSRIs. Mean age was 73.7 years (standard deviation 6.1), and 264 participants (69%) were female. Of those on vortioxetine, 78 (44%) discontinued the treatment due to adverse events at six months, compared to 59 (33%) of those on SSRIs (odds ratio 1.56; 95% confidence interval 1.01-2.39). Adjusted and per-protocol analyses confirmed point estimates in favour of SSRIs, but without a significant difference. With the exception of the unadjusted survival analysis showing SSRIs to outperform vortioxetine, secondary outcomes provided results consistent with a lack of substantial safety and tolerability differences between the two arms. Overall, no significant differences emerged in terms of response rates, depressive symptoms and quality of life, while SSRIs outperformed vortioxetine in terms of cognitive performance. Interpretation: As opposed to what was previously hypothesised, vortioxetine did not show a better tolerability profile compared to SSRIs in older adults with MDD in this study. Additionally, hypothetical advantages of vortioxetine on depression-related cognitive symptoms might be questioned. The study's statistical power and highly pragmatic design allow for generalisability to real-world practice. Funding: The study was funded by the Italian Medicines Agency within the "2016 Call for Independent Drug Research".

Influence of NUCB/Nesfatin-1 Polymorphism on Treatment Response to Naltrexone/Bupropion SR in Binge Eating Disorder and Obesity.

Background and Objectives: The NUCB2 gene and its polymorphisms were identified as novel players in the regulation of food intake, potentially leading to obesity (OBE) and altered eating behaviors. Naltrexone/bupropion SR (NB) showed good efficacy and tolerability for treating OBE and altered eating behaviors associated with binge eating disorder (BED). This prospective study investigates the influence of NUCB2 gene polymorphism on NB treatment response in OBE and BED. Materials and Methods: Body mass index (BMI), eating (EDE-Q, BES, NEQ, GQ, Y-FAS 2.0) and general psychopathology (BDI, STAI-S) were evaluated at baseline (t0) and after 16 weeks (t1) of NB treatment in patients with OBE and BED (Group 1; N = 22) vs. patients with OBE without BED (Group 2; N = 20). Differences were evaluated according to the rs757081 NUCB2 gene polymorphism. Results: NUCB2 polymorphism was equally distributed between groups. Although weight at t0 was higher in Group 1, weight loss was similar at t1 in both groups. BMI was not influenced by NUCB2 polymorphism. In Group 1, the CG-genotype reported significant improvement in eating psychopathology while the GG-genotype reported improvement only for FA. No differences were observed in Group 2. Conclusions: Patients diagnosed with BED and treated with NB exhibited a more favorable treatment response within the CG-genotype of the NUCB2 polymorphism.

Using latent class analysis to identify different clinical profiles according to food addiction symptoms in obesity with and without binge eating disorder.

Background and aims: Existing research suggests that food addiction (FA) is associated with binge eating disorder (BED) and obesity, but the clinical significance of this relationship remains unclear. This study aims to investigate the different clinical profiles of FA symptoms among patients who have obesity with/without BED using latent class analysis (LCA). Methods: 307 patients (n = 152 obesity and BED, n = 155 obesity without BED) completed a battery of self-report measures investigating eating psychopathology, depression, emotional dysregulation, alexithymia, schema domains, and FA. LCA and ANOVAs were conducted to identify profiles according to FA symptoms and examine differences between classes. Results: LCA identified five meaningful classes labeled as the "non-addicted" (40.4%), the "attempters" (20.2%), the "interpersonal problems" (7.2%), the "high-functioning addicted" (19.5%) and the "fully addicted" (12.7%) classes. Patients with BED and obesity appeared overrepresented in the "high-functioning addicted" and "fully addicted" classes; conversely, patients with obesity without BED were most frequently included in the "non-addicted" class. The most significant differences between the "high-functioning addicted" and "fully addicted" classes versus the "non-addicted" class regarded heightened severity of eating and general psychopathology. Discussion and conclusions: The results bring to light distinct clinical profiles based on FA symptoms. Notably, the "high-functioning addicted" class is particularly intriguing as its members demonstrate physical symptoms of FA (i.e., tolerance and withdrawal) and psychological ones (i.e., craving and consequences) but are not as functionally impaired as the "fully addicted" class. Identifying different profiles according to FA symptoms holds potential value in providing tailored and timely interventions.

Defining the minimum clinically important difference (MCID) in the hospital anxiety and depression scale (HADS) in patients undergoing total hip and knee arthroplasty.

INTRODUCTION: Total hip (THA) and knee (TKA) arthroplasty are effective procedures, but whose success depends on various factors, including patients' genetics, sociocultural environments, and psychological factors. Patient-reported outcome measures (PROMs) provide objective health status outcomes measurements, whose lowest significant variation is detected by the minimum clinically important difference (MCID). HYPOTHESIS: We aimed to find the MCID scores for the Hospital Anxiety and Depression Scale (HADS), HADS-A, and HADS-D in a cohort of individuals undergoing THA or TKA. PATIENTS AND METHODS: We enrolled 88 patients suffering from osteoarthritis (43 undergoing THA, and 45 TKA) by administering HADS, SF-12 and WOMAC at baseline and then with a 12-month prospective follow-up. The MCID for HADS, HADS-A, and HADS-D was calculated using the distribution-based approach, according to various techniques (0.5 standard deviation [0.5 SD]), the standard error of measurement (SEM), the effect size (ES), and the minimum detectable change (MDC). RESULTS: The analysis of HADS, HADS-A, and HADS-D scores revealed clinically significant improvements in symptoms in patients who underwent THA and TKA. The MCID range values were determined to be between 2.7-8.5 for the HADS, 1.4-4.4 for the HADS-A, and 1.5-4.8 for the HADS-D in the group of patients undergoing THA, and 2.1-6.7 for the HADS, 1.2-3.8 for the HADS-A, and 1.1-3.6 for the HADS-D in the TKA group. DISCUSSION: The study determined significant improvement in all scores applying MCID analysis, which can aid physicians in interpreting anxiety and depression scores and developing both preoperative and postoperative procedures to enhance outcomes for patients undergoing THA and TKA. LEVEL OF EVIDENCE: I; well-designed cohort study.

Pain experience in eating disorders: The mediating role of depression, alexithymia and interoceptive awareness.

OBJECTIVE: Evidence suggests reduced sensitivity to pain due to high pain threshold in anorexia and bulimia nervosa and a possible role of depression, alexithymia and interoceptive awareness on pain experience. This study examined whether self-report and real-time evoked pain experience were mediated by depression, alexithymia and interoceptive awareness in a comprehensive sample of patients with eating disorders (ED). METHOD: 145 participants (90 ED, 55 healthy controls (HC)) underwent a real-time evoked examination of pain and completed self-report questionnaires for pain (Pain Detect Questionnaire (PD-Q), PD-Q VAS, Leeds Assessment of Neuropathic Symptoms and Signs), depression (BDI-II), interoceptive awareness Multidimensional Assessment of Interoceptive Awareness (MAIA), and alexithymia (TAS-20). Three mediation models, with ED diagnosis as independent variable, and BDI, MAIA and TAS-20 as mediators, were tested. RESULTS: Participants with ED and HC exhibited similar pain type and intensity (self-report and real-time). Eating disorders diagnosis was associated with lower self-report pain intensity and non-neuropathic like pain experience (model 1-2). Depressive symptoms partially (model 1-2) or fully (model 3) mediated the association between ED diagnosis and pain experience, alone (model 1) or via alexithymia (model 3). Interoceptive awareness did not influence pain symptomatology. DISCUSSION: ED diagnosis is associated with non-neuropathic and lower pain experience. However, concurrent depression and alexithymia are associated with higher pain symptoms and neuropathic features. These results could inform clinicians about the influence of psychopathology on pain experience in ED.

Revealing the reporting disparity: VigiBase highlights underreporting of clozapine in other Western European countries compared to the UK.

BACKGROUND: Pharmacovigilance studies indicate clozapine history is marked by adverse drug reactions (ADRs). OBJECTIVE: In a 2021 article, the United Kingdom (UK) had >90 % of European clozapine-related fatal outcomes in VigiBase, the World Health Organization's pharmacovigilance database. Two possibly opposing hypotheses could explain this disparity: 1) fewer reported fatal outcomes in other Western European countries mainly reflect underreporting to VigiBase, and 2) the higher number of UK reports reflects higher real relative mortality. METHODS: VigiBase reports from clozapine's introduction to December 31, 2022, were studied for ADRs and the top 10 causes of fatal outcomes. The UK was compared with 11 other top reporting Western countries (Germany, Denmark, France, Finland, Ireland, Italy, Netherlands, Norway, Spain, Sweden and Switzerland). Nine countries (except Ireland and Switzerland) were compared after controlling for population and clozapine prescriptions. RESULTS: The UK accounted for 29 % of worldwide clozapine-related fatal outcomes, Germany 2 % and <1 % in each of the other countries. The nonspecific label "death" was the top cause in the world (46 %) and in the UK (33 %). "Pneumonia" was second in the world (8 %), the UK (12 %), Ireland (8 %) and Finland (14 %). Assuming that our corrections for population and clozapine use are correct, other countries underreported only 1-10 % of the UK clozapine fatal outcome number. CONCLUSIONS: Different Western European countries consistently underreport to VigiBase compared to the UK, but have different reporting/publishing styles for clozapine-related ADRs/fatal outcomes. Three Scandinavian registries suggest lives are saved as clozapine use increases, but this cannot be studied in pharmacovigilance databases.