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Background: Antipsychotic drugs appear to be related to reduced bone mineral density (BMD). We conducted a narrative review to collect the available literature investigating the relationship between antipsychotic use and bone fragility. Methods: A review of the published literature was conducted and reported through PubMed/Scopus/Cochrane libraries. We included studies using any antipsychotic treatment where the bone metabolism, osteoporosis, and/or risk of fractures has been assessed. Results: After screening 1707 items, we finally included 15 papers. A total of 3245 initial patients were identified, of whom 1357 patients with a mean age of 43.8 years underwent antipsychotic treatment and were analyzed. The mean antipsychotic treatment duration of the treated group was 15.8 ± 13.9 years. Among the included studies, two reported a statistically significant difference in lumbar BMD reduction between the antipsychotic exposed group and the control group. Femoral neck BMD levels had been reported in four of the case–control studies; two reported a statistically significant difference in femoral neck BMD reduction between the antipsychotic exposed group and the control group. Conclusions: Prolonged use of antipsychotic treatment seems to be associated with an increased risk of reduced BMD, and, consequentially, with an augmented risk of bone fragility and fractures. This effect is not limited to vulnerable groups, such as those with significant medical comorbidities, the elderly, and postmenopausal women, but may also apply to anyone using antipsychotics in the long-term. Clinicians' awareness of antipsychotic prescriptions should optimize their potential while reducing this risk. [ABSTRACT FROM AUTHOR]

Objective: Treatment-resistant depression (TRD) affects around 20-30% of people with major depressive disorder. In 2019, esketamine nasal spray was approved for TRD by both the US Food and Drug Administration and the European Medicines Agency. While its clinical efficacy and safety are proven, the mechanisms underlying its antidepressant effect remain unclear. The use of metabolomics may allow understanding the metabolic effects of esketamine and predicting biological features associated with clinical response in TRD. Nonetheless, there is a lack of studies exploring the predictive value of metabolomics. The Resistant Depression Response to Esketamine Assessing Metabolomics (ReDREAM) project aims at identifying metabolic biosignatures that may represent novel correlates of response to esketamine treatment. Study Design: This is the protocol of an observational, prospective study. Methods: We plan to select 60 people with TRD from 3 clinical sites in Italy. The participants will be administered with esketamine nasal spray, following standard clinical practice, twice a week for 4 weeks (“induction phase”), then once a week for 4 additional weeks (“maintenance phase”). We will test the correlations between baseline metabolic profile and depressive symptom improvement at study endpoints (weeks 4 and 8) and we will explore the likelihood of different metabolic phenotypes between responders and non-responders. Expected results: An involvement of energy metabolism, amino acid metabolism, urea cycle, and nitric oxide synthesis in response to treatment with esketamine nasal spray is hypothesized. Conclusion: Unbiased data from untargeted metabolomics associated with clinical changes after esketamine treatment may contribute to define new paradigms for precision psychiatry-oriented, personalized care of TRD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This survey assessed psychiatry residents'/early-career psychiatrists' attitudes towards the utility of therapeutic drug monitoring (TDM) of antipsychotics. 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. 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). TDM use for antipsychotics was poor and associated with limited knowledge and insufficient availability. [ABSTRACT FROM AUTHOR]

The editorial discusses the challenges of pharmacological treatments for mental disorders, particularly treatment-resistant cases, and the limitations of psychosocial interventions. It highlights the emergence of non-pharmacological biological treatments like deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS) for conditions such as obsessive-compulsive disorder (OCD). The collection of articles in the Research Topic focuses on updates in OCD management, including studies on motor cortical excitability, DBS effectiveness, psilocybin treatment, biomarkers in OCD patients, N-acetylcysteine augmentation therapy, and the cultural dimensions of OCD symptomatology. The authors stress the importance of further research into specific treatment protocols that respect cultural values and beliefs while providing evidence-based care. [Extracted from the article]