Applying a clinical staging model in patients affected by schizophrenia spectrum disorder.

Background: Clinical staging, already widespread in medicine, represents a new frontier in psychiatry. Our goal was to convert the existing theoretical staging model for schizophrenia into a feasible tool to have a timely assessment of patients' health status applicable in any psychiatric facility. Methods: We assessed the empirical soundness of a staging model for schizophrenia spectrum disorders (SSDs), primarily centered on their current status. This model delineated six sequential stages (1, 2A, 2B, 3A, 3B, and 4) based on factors like symptom recurrence, persistence, and progression, including functional decline. Our analysis involved data from 137 individuals affected by SSDs. We examined 22 baseline variables, 23 construct-related variables, and 31 potentially modifiable clinical variables. Results: The latter stages demonstrated significantly poorer outcomes compared to the early stages across various measures, indicating medium to large effect sizes and a dose-response pattern. This pattern confirmed the validity of the model. Notably, stages 2 and 3A exhibited pronounced differences in comparison to other stages, although variables from each validation category also distinguished between consecutive stages, particularly 3A and beyond. Conclusion: Baseline predictors, such as familial predisposition to schizophrenia, neurodevelopmental impairment, childhood adversities, treatment delay, negative symptoms, neurological impairment, and inadequate early response to treatment, independently largely explained the staging variance. The clinical staging model, grounded in the extended course of psychosis, exhibited sound validity and feasibility, even without the use of biological or neuroimaging markers, which could greatly improve the sensitivity of the model. These findings provide insights into stage indicators and predictors of clinical stages from the onset of psychosis.

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.

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.

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.

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.

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".

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.

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.

Cognitive biases are associated with aberrant salience experience in schizophrenia spectrum disorders.

INTRODUCTION: Cognitive models suggest the co-occurrence of cognitive biases and aberrant salience is unique to psychosis, but their interaction is not yet fully understood. Therefore, we aimed to elucidate the relationship between subjective cognitive biases and aberrant salience in individuals with schizophrenia spectrum disorders (SSDs) in this study. METHODS: A sample of 92 subjects with SSDs underwent an assessment using Davos Assessment Cognitive Biases (DACOBS) and the Aberrant Salience Inventory (ASI) in a cross-sectional design. We evaluated psychopathological differences based on ASI scores and conducted a linear regression analysis to examine the variables associated with aberrant salience. RESULTS: Subjects with an ASI score ≥14 demonstrated significantly higher scores across all subscales and total score of ASI and DACOBS (p<0.001). ASI subscales were significantly positive correlated with all DACOBS subscales, ranging from 0.250 for Increased Significance and Safety Behavior to 0.679 for Heightened Emotionality and Social cognition problems. The linear regression analysis revealed a positive association between aberrant salience and the DACOBS subscales jumping to conclusions (JTC) (ß=0.220), social cognition problems (ß=0.442), subjective cognitive problems (ß=0.405), and a negative association with the subscale belief inflexibility (ß=-0.350). CONCLUSIONS: Our findings suggest that JTC, social cognition problems and subjective cognitive problems may play a central role in the experience of aberrant salience in individuals with SSDs. This work informs about the need of developing prevention and intervention strategies that specifically target cognitive biases and aberrant salience in the treatment of psychosis.