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.

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.

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.

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.

Immunomodulatory Effects of Clozapine: More Than Just a Side Effect in Schizophrenia.

Recent evidence suggests a possible relationship between the immune system and schizophrenia spectrum disorders (SSDs), as neuroinflammation appears to play a role in major psychiatric conditions. Neuroinflammation is as a broad concept representing a physiological protective response to infection or injury, but in some cases, especially if chronic, it may represent an expression of maladaptive processes, potentially driving to clinical dysfunction and neurodegeneration. Several studies are concurrently highlighting the importance of microglia, the resident immune cells of the central nervous system, in a huge number of neurodegenerative diseases, including multiple sclerosis, Alzheimer's and Parkinson's diseases, as well as SSDs. A more fundamental phenomenon of maladaptive coupling of microglia may contribute to the genesis of dysfunctional brain inflammation involved in SSDs, from the onset of their neurophenomenological evolution. Clozapine and other antipsychotic drugs seem to express a provable immunomodulant effect and a more specific action on microglia, while neuroactive steroids and nonsteroidal anti-inflammatory drugs may reduce some SSDs symptoms in add-on therapy. Given these theoretical premises, this article aims to summarize and interpret the available scientific evidence about psychotropic and anti-inflammatory drugs that could express an immunomodulant activity on microglia.

Reactive hypoglycemia in binge eating disorder, food addiction, and the comorbid phenotype: unravelling the metabolic drive to disordered eating behaviours.

BACKGROUND: Impaired metabolic response such as blood glucose fast fluctuations may be hypothesized in binge eating disorder (BED) and food addiction (FA) by virtue of the repetitive consumption of highly processed food. Conversely, rapid changes in plasma glucose (i.e., hypoglycemia) may trigger craving for the same food products. The investigation of early glycemic disturbances in BED and FA could enhance the understanding of the metabolic mechanisms involved in the maintenance of the disorders. Present study investigated hypoglycemia events during a 5-h-long oral glucose tolerance test (OGTT) in people with BED, FA, and the comorbid phenotype. Further, the association between the severity of eating psychopathology and the variability in hypoglycaemia events was explored. METHODS: Two-hundred participants with high weight and no diabetes completed the extended OGTT and were screened for BED, FA, BED-FA, or no-BED/FA. The four groups were compared in hypoglycemia events, OGTT-derived measures, and eating psychopathology. The association between predictors (eating psychopathology), confounders (demographics, metabolic features), and the outcomes (hypoglycemia, early/late hypoglycemia, severe hypoglycemia, reactive hypoglycemia) was examined through logistic regression. RESULTS: Hypoglycemia in general, and reactive hypoglycemia were highly frequent (79% and 28% of the sample, respectively). Hypoglycemia events (< 70 mg/dL) were equally experienced among groups, whilst severe hypoglycemia (< 54 mg/dL) was more frequent in BED at the late stage of OGTT (5 h; χ2 = 1.120, p = .011). The FA and BED groups exhibited significantly higher number of reactive hypoglycemia (χ2 = 13.898, p = .003), in different times by diagnosis (FA: 210'-240'; BED: at the 270'). FA severity was the only predictor of early and reactive hypoglycemia. CONCLUSIONS: People with BED or FA are prone to experiencing reactive hypoglycemia; FA severity may predict early and symptomatic hypoglycemia events. This can further reinforce disordered eating behaviours by promoting addictive responses, both biologically and behaviourally. These results inform professionals dealing with eating disorders about the need to refer patients for metabolic evaluation. On the other hand, clinicians dealing with obesity should screen for and address BED and FA in patients seeking care for weight loss.

Impairment in blood glucose control may be attended in binge eating disorder (BED) and food addiction (FA), two distinct eating disorders which are characterized by the recurrent consumption of highly palatable food rich in high-glucose index carbohydrates. Conversely, rapid changes in blood glucose, such as hypoglycemia, may intensify craving for high-calorie products, thus reinforcing pathological eating behaviours. This study investigated the presence of hypoglycemia events in people suffering from BED, FA, both, or no eating disorder, and explored whether the severity of eating behaviours correlated with a higher probability of having hypoglycemia. Results showed that people with BED and FA experienced more episodes of symptomatic hypoglycemia than those with obesity but no eating disorder. The severity of binge eating was associated with more severe hypoglycemia events, indicated by lower plasma glucose values. Lastly, people with severe FA were more prone to experiencing early post-meal hypoglycemia accompanied by symptoms. These results inform professionals dealing with eating disorders about the need to refer patients for metabolic evaluation. On the other hand, clinicians dealing with obesity should screen for and address BED and FA in patients seeking care for weight loss.

Predicting outcome with Intranasal Esketamine treatment: A machine-learning, three-month study in Treatment-Resistant Depression (ESK-LEARNING).

Treatment-resistant depression (TRD) represents a severe clinical condition with high social and economic costs. Esketamine Nasal Spray (ESK-NS) has recently been approved for TRD by EMA and FDA, but data about predictors of response are still lacking. Thus, a tool that can predict the individual patients' probability of response to ESK-NS is needed. This study investigates sociodemographic and clinical features predicting responses to ESK-NS in TRD patients using machine learning techniques. In a retrospective, multicentric, real-world study involving 149 TRD subjects, psychometric data (Montgomery-Asberg-Depression-Rating-Scale/MADRS, Brief-Psychiatric-Rating-Scale/BPRS, Hamilton-Anxiety-Rating-Scale/HAM-A, Hamilton-Depression-Rating-Scale/HAMD-17) were collected at baseline and at one month/T1 and three months/T2 post-treatment initiation. We trained three different random forest classifiers, able to predict responses to ESK-NS with accuracies of 68.53% at T1 and 66.26% at T2 and remission at T2 with 68.60% of accuracy. Features like severe anhedonia, anxious distress, mixed symptoms as well as bipolarity were found to positively predict response and remission. At the same time, benzodiazepine usage and depression severity were linked to delayed responses. Despite some limitations (i.e., retrospective study, lack of biomarkers, lack of a correct interrater-reliability across the different centers), these findings suggest the potential of machine learning in personalized intervention for TRD.

Testing psychometric properties of Shared Decision Making Questionnaire - Physician Version (SDM-Q-Doc) in an Italian real-world psychiatric clinical sample.

OBJECTIVES: The Shared Decision Making Questionnaire-Physician Version (SDM-Q-Doc) is the main tool assessing SDM relationship between patient and physician using the clinician viewpoint. It is reliable in all medical fields, and the validation of its Italian version was still missing. Our aim was to validate the Italian version of the SDM-Q-Doc in a clinical sample of patients suffering from severe mental illness. METHODS: We approached 369 patients affected by major psychiatric disorders (including schizophrenia spectrum disorders, affective disorders and eating disorders) in a real-world outpatient clinical setting. We run the Confirmatory Factor Analysis (CFA) to test the SDM-Q-Doc structure. We calculated the correlations between the SDM-Q-Doc and the Observing Patient Involvement (OPTION) scale, used as comparing test, and McDonald ω coefficient to measure convergent validity and internal consistency respectively. RESULTS: We reached a response rate of 93.2% (344 final participants). The CFA showed a very good fit compared of the Italian version of SDM-Q-Doc (χ2/df=3.2, CFI=.99, TLI=.99, RMSEA=.08, SRMR=.04). We found several correlations between the SDM-Q-Doc and OPTION scale supporting a robust SDM-Q-Doc construct validity, while internal consistency of the scale was McDonald ω coefficient .92. Further, inter-item correlations ranged from .390 to .703, with a mean of .556. CONCLUSIONS: This study confirms the suitability of the Italian version of SDM-Q-Doc, with good reliability and soundness even when compared to other languages validated versions and to OPTION scale. SDM-Q-Doc represents an easy-to-use physician-centered measure to assess patients' involvement in medical decision-making, well performing in the Italian-speaking population.

Effect of affective temperament on illness characteristics of subjects with bipolar disorder and major depressive disorder.

BACKGROUND: Affective temperaments represent the stable, biologically determined substrates of mood disorders. The relationship between affective temperaments and bipolar disorder (BD) or major depressive disorder (MDD) has been described. However, the strength of such relationship should be tested while considering other factors influencing the diagnosis of BD/MDD. Literature also lacks a comprehensive description of the interplay between affective temperament and characteristics of mood disorders. The aim of the present study is to address these issues. METHODS: This is a multicentric observational study including 7 Italian university sites. Five-hundred-fifty-five euthymic subjects with BD/MDD were enrolled and further divided in those with hyperthymic (Hyper, N = 143), cyclothymic (Cyclo, N = 133), irritable (Irr, N = 49), dysthymic (Dysth, N = 155), and anxious (Anx N = 76) temperaments. Linear, binary, ordinal and logistic regressions were performed to assess the association between affective temperaments and i) diagnosis of BD/MDD; ii) characteristics of illness severity and course. RESULTS: Hyper, Cyclo and Irr were more likely to be associated with BD, together with earlier age of onset and presence of a first-degree relative with BD. Anx and Dysth were more associated with MDD. Differences in association between affective temperaments and characteristics of BD/MDD were observed for hospital admissions, phase-related psychotic symptoms, length and type of depression, comorbidity and pharmacological intake. LIMITATIONS: Small sample size, cross-sectional design, recall biases. CONCLUSION: Specific affective temperaments were associated to certain characteristics of illness severity and course of BD or MDD. Evaluation of affective temperaments might help a deeper understanding of mood disorders.

Effectiveness of SGA-LAIs on Clinical, Cognitive, and Social Domains in Schizophrenia: Results from a Prospective Naturalistic Study.

We hypothesized that shifting from oral second-generation antipsychotics (SGA) to their long-acting injectable (LAI) counterpart would be beneficial for the psychopathological, cognitive, social, and general health domains in outpatients suffering from schizophrenia. We aimed to evaluate the prospective usefulness of SGA-LAI treatment by carrying out a head-to-head comparison of two different medications (i.e., aripiprazole monohydrate (Ari-LAI) and paliperidone palmitate 1 and 3 month (PP1M, PP3M)) in a real-world setting, assessing the effectiveness and tolerability of Ari-LAI and PP1M/PP3M over a 15 month follow-up. A total of 69 consecutive individuals affected by schizophrenia were screened for eligibility. Finally, 46 outpatients (29 treated with Ari-LAI, 13 with PP1M, and four with PP3M) were evaluated through clinical, functional, and neuropsychological assessment administrated at baseline and after 3-, 12-, and 15-month follow-up periods. Moreover, periodic general medical evaluations were carried out. We estimated an overall improvement over time on the explored outcomes, without differences with respect to the type of LAI investigated, and with a global 16.4% dropout rate. Our findings suggest that switching from oral SGA to SGA-LAIs represents a valid and effective treatment strategy, with significant improvements on psychopathological, cognitive, social, and clinical variables for patients suffering from schizophrenia, regardless of the type of molecule chosen.

Tolerability profile of paliperidone palmitate formulations: A pharmacovigilance analysis of the EUDRAVigilance database.

Introduction: Long-acting injectable antipsychotics (LAIs) have proven to be effective in the maintenance treatment of patients suffering from schizophrenia, and their safety and tolerability profiles represent a key factor in their long-term use and choice in clinical practice. Paliperidone palmitate (PP) is the only second-generation LAI (SGA-LAI), available in both one- (PP1M) and 3-month (PP3M) formulations. However, real-world prospective studies on PP1M and PP3M are still few and mostly conducted on small samples. In this context, we aimed to better define the safety and tolerability profile of PP using real world pharmacovigilance data. Methods: We retrospectively analyzed the publicly available data regarding Individual Case Safety Reports (ICSRs), presenting PP1M and/or PP3M as suspected drugs, reported on EUDRAVigilance between 2011 and June 30th, 2022. ICSRs relative to at least one SGA-LAI other than PP, reported between 2003 and June 30th, 2022, were also examined as reference group. Data were evaluated with a descriptive analysis, and then, as disproportionality measures, crude reporting odds ratio (ROR) and 95% confidence interval (CI) were calculated. Results: A total of 8,152 ICSRs met the inclusion criteria, of those 77.7% (n = 6,332) presented as suspected drug PP1M, 21.2% (n = 1,731) PP3M, while 89 cases indicated both PP1M and PP3M. Significantly higher probabilities of reporting in PP-related reports were observed for the primary Standardized MedDRA Queries "Sexual Dysfunctions" (ROR = 1.45; 95% CI 1.23-1.70), "Haemodynamic oedema, effusions and fluid overload" (ROR = 1.42; 1.18-1.70), as well as "Fertility disorders" (ROR = 2.69; 1.51-4.80). Discussion: Our analysis indicates that the tolerability and safety profiles of PP are in line with what is known for the other SGA-LAIs. However, differences regarding endocrine system ADRs have been noticed. The results presented in this work do not discourage the prescription of SGA-LAI formulations but aim to enhance their safety.

The mediation role of impulsivity between childhood trauma and dissociative symptomatology in bipolar disorder.

In bipolar disorder (BD) patients, trauma has been associated with emotional dysregulation, potentially leading to an increase in impulsivity and dissociative symptomatology. We aimed to investigate the relationship between childhood trauma, impulsivity, and dissociative symptomatology in BD with a special focus on the role of impulsivity as a mediator between childhood trauma and dissociative symptomatology. METHODS: We administered the Childhood Trauma Questionnaire (CTQ), Barratt Impulsivity Scale (BIS-11), Dissociative Experience Scale (DES-II), and Alda scale. Spearman correlation analysis assessed the independent variables associated with CTQ and DES-II. We performed a mediation analysis using the bootstrapping technique to verify the hypothesis that impulsivity represented an intervening variable between childhood trauma and dissociation. RESULTS: CTQ and DES-II scores in 100 BD patients were both significantly associated with the number of lifetime affective episodes, a clinical course of mania-depression-euthymia, suicidal ideation, a history of antidepressant-induced manic switch, poor response to mood stabilizers, mixed features, psychotic symptoms, aggressive behavior, and BIS-11 (p<0.01). At the regression analysis, CTQ was associated with DES-II (p<0.001), while DES-II was associated with the CTQ (p<0.001) and BIS-11 (p< 0.001), as well as with aggression (p=0.002). The mediation analysis showed that impulsivity significantly mediated the effect of childhood trauma on dissociative symptomatology (z=25.71; 0.930-1.084). CONCLUSIONS: Impulsivity might play a key role in onset and prognosis of BD patients. Our findings may help in increasing the knowledge about the possible association between impulsivity, childhood traumatic experiences and dissociative symptomatology. BD patients with dissociative symptoms might benefit from a tailored treatment which could include a training based on emotional and behavioral regulation.

Postoperative psychological factors and quality of life but not shoulder brace adherence affect clinical outcomes after arthroscopic rotator cuff repair.

BACKGROUND: Despite the high prevalence, there is no consensus for postsurgical management after rotator cuff repair. We aimed to assess the impact of psychological well-being on patients who underwent rotator cuff repair. We also investigated correlations and possible predictors between patient demographics and adherence to the use of the shoulder brace and outcomes in terms of shoulder functionality and quality of life. METHODS: We conducted a retrospective study with prospective data collection enrolling 120 consecutive patients who underwent shoulder arthroscopy for rotator cuff tear repair. Each patient was clinically evaluated after a mean follow-up of 24.2 (±9.8) months using (1) the Disability of the Arm, Shoulder and Hand (DASH) scale, (2) the Hospital Anxiety and Depression Scale (HADS), (3) the Rotator Cuff Quality of Life (RC-QoL), (4) the visual analog scale, and (5) the Medical Adherence Measure. RESULTS: The final sample consisted of 100 patients (45 females, 45%) averaging 60.9 (±8.5) years. The average brace wearing time was 3.4 (±0.6) weeks, with an adherence superior to 80% in 84% of cases, and 96% of patients were living with family members. The mean postoperative DASH scores were 20.1 (±16.7), 23.4 (±25), and 18.9 (±21.5) for the general, work, and sport sections, respectively. The mean Medical Adherence Measure score reached 72.5 (±14.2) points, and the RC-QoL mean score was 30.4% (±20.5). The Hospital Anxiety and Depression Scale-Anxiety and Hospital Anxiety and Depression Scale-Depression scores' continuous mean values were 5.1 (±3.4) and 3.9 (±3.6), respectively. The DASH, Hospital Anxiety and Depression Scale-Anxiety, Hospital Anxiety and Depression Scale-Depression, and RC-QoL scores directly correlated with each other, and all these questionnaires directly correlated with the visual analog scale scores. Moreover, we found a direct correlation (r = 0.204, P = .033) between the female sex and adherence to the brace and a direct correlation (r = 0.242, P = .015) between adherence to the brace and the number of weeks it was worn according to the medical recommendation. A correlation between lower educational qualifications and poorer outcomes was found. No correlation emerged between adherence to the brace and functional results. According to the regression analysis, diabetes was found to be a predictor of worse postoperative DASH scores (ß = 0.245, P = 0.28). CONCLUSION: A lower perceived quality of life was associated with worse functional results, anxiety and depression symptoms, and pain after rotator cuff repair surgery. The adherence to the use of the shoulder brace was associated with the female sex and a longer prognosis, but no correlation emerged between adherence to the brace and functional outcomes.

Sleep Disturbances in Generalized Anxiety Disorder: The Role of Calcium Homeostasis Imbalance.

Patients with a generalized anxiety disorder (GAD) often report preeminent sleep disturbances. Recently, calcium homeostasis gained interest because of its role in the regulation of sleep-wake rhythms and anxiety symptoms. This cross-sectional study aimed at investigating the association between calcium homeostasis imbalance, anxiety, and quality of sleep in patients with GAD. A total of 211 patients were assessed using the Hamilton Rating Scale for Anxiety (HAM-A), Pittsburgh Sleep Quality Index questionnaire (PSQI) and Insomnia Severity Index (ISI) scales. Calcium, vitamin D, and parathyroid hormone (PTH) levels were evaluated in blood samples. A correlation and linear regression analysis were run to evaluate the association of HAM-A, PSQI, and ISI scores with peripheral markers of calcium homeostasis imbalance. Significant correlations emerged between HAM-A, PSQI, ISI, PTH, and vitamin D. The regression models showed that patients with GAD displaying low levels of vitamin D and higher levels of PTH exhibit a poor subjective quality of sleep and higher levels of anxiety, underpinning higher psychopathological burden. A strong relationship between peripheral biomarkers of calcium homeostasis imbalance, insomnia, poor sleep quality, and anxiety symptomatology was underlined. Future studies could shed light on the causal and temporal relationship between calcium metabolism imbalance, anxiety, and sleep.

The Impact of Affective Temperaments on Suicidal Ideation and Behaviors: Results from an Observational Multicentric Study on Patients with Mood Disorders.

Suicide ideation and behaviors are major health issues in the field of mental health. Several psychological and psychosocial factors have been taken into account as possible predictors of suicidality. Only recently affective temperaments have been considered as possible factors linked to suicide. This study aims to investigate the relationship between affective temperaments and suicidality, including the lifetime onset of suicide ideation, lifetime presence of suicide attempts and the total number of lifetime suicide attempts. This is a naturalistic multicentric observational study, involving outpatient units of seven University sites in Italy. Patients were administered with the short version of TEMPS-M and the Columbia Suicide Severity Rating Scale. A total of 653 participants were recruited, with a diagnosis of bipolar (55.7%), unipolar (35.8%) and cyclothymic disorder (8.4%). Regression models showed that the presence of lifetime suicide behaviors was increased in patients presenting trait related impulsivity (p < 0.0001), poor free-interval functioning (p < 0.05), higher number of affective episodes (p < 0.01), higher number of hospitalizations (p < 0.0001), cyclothymic and irritable affective temperaments (p < 0.05 and p < 0.05, respectively). Conversely, the presence of hyperthymic affective disposition reduced the likelihood of having suicidal behaviors (p < 0.01). Lifetime suicidal ideation was associated with trait-related impulsivity (p < 0.001), poor free-interval functioning (p < 0.05), higher number of affective episodes (p < 0.001) and of hospitalizations (p < 0.001). Depressive temperaments increased the likelihood of presenting suicidal ideation (p < 0.05), along with irritable temperaments (p < 0.01), contrary to hyperthymic affective (p < 0.05). Results of the present study confirm that affective disposition has a significant impact on the onset of suicidal ideation and behaviors, and that affective dispositions should be assessed in clinical settings to identify people at risk of suicide. Moreover, a wider clinical evaluation, including different clinical psychopathological dimensions, should be taken into consideration to develop effective preventive interventions.