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Background: Several studies have shown the possible link between trauma and sleep disturbances, particularly in anxiety disorders. This issue could be because sympathetic hyperarousal is central to both disorders, probably caused by a dysregulation of the noradrenergic system. This study aimed to establish if the comorbidity with complex post-traumatic stress disorder (cPTSD) is associated with sleep disturbances in panic disorder (PD) and if the presence of poor sleep quality is associated with a higher psychopathological burden., Methods: Participants (N = 211) with PD completed the International Trauma Questionnaire concerning their most troubling experience, the Hamilton Anxiety Rating Scale (HAM-A), and the Pittsburgh Sleep Quality Index (PSQI) to assess anxiety symptoms and sleep disturbances, respectively., Results: The sample was divided into two subgroups based on the presence of cPTSD. No significant differences emerged in the bivariate analyses for what concerns sociodemographic features. As for the scores of the psychopathological scales, the analysis highlighted statistically significant differences between the subgroups. Subjects with cPTSD reported significantly higher HAM-A total scores. As for the disturbances in self-organization (DSO) and PSQI scores, these were all significantly higher in the cPTSD subsample. At the logistic regression, the presence of cPTSD was inserted as the dependent variable, while the PSQI scores of the subscales evaluating subjective sleep quality, sleep duration, sleep efficacy, and the use of hypnotics were used as independent variables. The presence of cPTSD was significantly associated with the PSQI subscores for subjective sleep quality and use of hypnotics., Conclusions: Patients with PD exhibit more severe sleep disturbances and a higher anxiety burden when experiencing prolonged trauma. Therapeutic advances are needed in this field to target these symptomatologic domains.

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.

Background: Pramipexole is a dopamine full agonist approved for the treatment of Parkinson's disease and restless legs syndrome. Its high affinity for the D3 receptor and neuroprotective, antioxidant, and anti-inflammatory activity provides a rationale for the treatment of depression. In this paper, we review studies on the effectiveness and safety of antidepressant pramipexole augmentation in treatment-resistant depression., Methods: This comprehensive systematic review and meta-analysis of observational studies on pramipexole-antidepressant augmentation included patients with resistant unipolar and bipolar depression. The primary outcome measure was the treatment response, measured at the study endpoint., Results: We identified 8 studies including 281 patients overall, 57% women and 39.5% with bipolar disorder and 60.5% with major depressive disorder. The mean follow-up duration was 27.3 weeks (range 8-69). The pooled estimate of treatment response was 62.5%, without significant differences between unipolar and bipolar depression. Safety was good, with nausea and somnolence the most frequent side effects., Conclusions: The findings of this systematic review, needing further confirmation, show that off-label use of pramipexole as augmentation of antidepressant treatment could be a useful and safe strategy for unipolar and bipolar treatment-resistant depression.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cicala, de Filippis, Barbieri, Cutroneo, De Fazio, Schoretsanitis and Spina.)

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.

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.

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.

Background: To identify demographic and clinical characteristics of bipolar depressed patients who require antidepressant (AD) augmentation, and to evaluate the short- and long-term effectiveness and safety of this therapeutic strategy., Methods: One hundred twenty-two bipolar depressed patients were consecutively recruited, 71.7% of them received mood stabilizers (MS)/second-generation antipsychotics (SGA) with AD-augmentation and 28.3% did not. Patients were evaluated at baseline, and after 12 weeks and 15 months of treatment., Results: The AD-augmentation was significantly higher in patients with bipolar II compared with bipolar I diagnosis. Patients with MS/SGA + AD had often a seasonal pattern, depressive polarity onset, depressive index episode with anxious features, a low number of previous psychotic and (hypo)manic episodes and of switch. They had a low irritable premorbid temperament, a low risk of suicide attempts, and a low number of manic symptoms at baseline. After 12 weeks of treatment, 82% of patients receiving ADs improved, 58% responded and 51% remitted, 3.8% had suicidal thoughts or projects, 6.1% had (hypo)manic switch, and 4.1% needed hospitalization. During the following 12 months, 92% of them remitted from index episode, 25.5% did not relapse, and 11% needed hospitalization. Although at the start advantaged, patients with AD-augmentation, compared with those without AD-augmentation, did not significantly differ on any outcome as well on adverse events in the short- and long-term treatment., Conclusion: Our findings indicate that ADs, combined with MS and/or SGA, are short and long term effective and safe in a specific subgroup for bipolar depressed patients.

Purpose: The purpose of this double-blind randomized controlled trial (RCT) was to compare clinical improvement and radiographic findings up to 2 years of follow-up of a single intra-articular injection of bone marrow aspirate concentrate (BMAC) versus hyaluronic acid (HA) for the treatment of knee osteoarthritis (OA). The hypothesis was that BMAC injection could lead to better clinical and radiographic results compared to viscosupplementation., Methods: Patients with bilateral knee OA were randomized to one intra-articular injection of tibial-derived BMAC in one knee and one HA injection in the contralateral knee. Sixty patients were enrolled, and 56 were studied up to the final follow-up (35 men, 21 women, mean age 57.8 ± 8.9 years), for a total of 112 knees. Patients were evaluated before the injection and at 1, 3, 6, 12, and 24 months with the IKDC subjective score, VAS for pain, and the KOOS score. Minimal clinically important difference (MCID), patient treatment judgement, and adverse events were documented, as well as bilateral X-Rays (Rosenberg view) before and after treatment., Results: No severe adverse events nor differences were reported in terms of mild adverse events (7.1% vs 5.4%, p = ns) and treatment failures (10.7% vs 12.5%, p = ns) in BMAC and HA groups, respectively. The IKDC subjective score improved from baseline to all follow-ups for BMAC (p < 0.0005), while it improved up to 12 months (p < 0.0005) and then decreased at 24 months (p = 0.030) for HA. Compared to HA, BMAC showed a higher improvement for VAS pain at 12 (2.2 ± 2.6 vs 1.7 ± 2.5, p = 0.041) and 24 months (2.2 ± 2.6 vs 1.4 ± 2.8, p = 0.002). The analysis based on OA severity confirmed this difference only in Kellgren-Lawrence 1-2 knees, while comparable results were observed in moderate/severe OA. Radiographic evaluation did not show knee OA deterioration for both treatment groups, without intergroup differences., Conclusion: BMAC did not demonstrate a clinically significant superiority at short-term compared to viscosupplementation, reporting overall comparable results in terms of clinical scores, failures, adverse events, radiographic evaluation, MCID achievement, and patient treatment judgment. However, while HA results decreased over time, BMAC presented more durable results in mild OA knees., Level of Evidence: Level I., (© 2021. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Although immune checkpoint inhibitors (ICIs) have significantly improved the oncological outcomes, about one-third of patients affected by clear cell renal cell carcinoma (ccRCC) still experience recurrence. Current prognostic algorithms, such as the Leibovich score (LS), rely on morphological features manually assessed by pathologists and are therefore subject to bias. Moreover, these tools do not consider the heterogeneous molecular milieu present in the Tumour Microenvironment (TME), which may have prognostic value. We systematically developed a semi-automated method to investigate 62 markers and their combinations in 150 primary ccRCCs using Multiplex Immunofluorescence (mIF), NanoString GeoMx ® Digital Spatial Profiling (DSP) and Artificial Intelligence (AI)-assisted image analysis in order to find novel prognostic signatures and investigate their spatial relationship. We found that coexpression of cancer stem cell (CSC) and epithelial-to-mesenchymal transition (EMT) markers such as OCT4 and ZEB1 are indicative of poor outcome. OCT4 and the immune markers CD8, CD34, and CD163 significantly stratified patients at intermediate LS. Furthermore, augmenting the LS with OCT4 and CD34 improved patient stratification by outcome. Our results support the hypothesis that combining molecular markers has prognostic value and can be integrated with morphological features to improve risk stratification and personalised therapy. To conclude, GeoMx ® DSP and AI image analysis are complementary tools providing high multiplexing capability required to investigate the TME of ccRCC, while reducing observer bias.

Introduction: Depression and antidepressants are among risk factors for osteoporosis. However, there are still inconsistencies in literature regarding bone consequences of antidepressant drugs and the role of age and the natural decline of bone health in patients with depression., Objective: To investigate the relationship between antidepressant and bone mineral density (BMD)., Methods: We conducted a systematic review and metanalysis according to PRISMA guidelines searching on PubMed/Medline, Cochrane Database, and Scopus libraries and registered with PROSPERO (registration number CRD42021254006) using generic terms for antidepressants and BMD. Search was restricted to English language only and without time restriction from inception up to June 2021. Methodological quality was assessed with the Newcastle-Ottawa scale., Results: Eighteen papers were included in the qualitative analysis and five in the quantitative analysis. A total of 42,656 participants affected by different subtypes of depression were identified. Among the included studies, 10 used serotonin reuptake inhibitors (SSRIs) only, 6 involved the use of SSRIs and tricyclic antidepressants, and 2 the combined use of more than two antidepressants. No significant studies meeting the inclusion criteria for other most recent categories of antidepressants, such as vortioxetine and esketamine. Overall, we observed a significant effect of SSRI on decrease of BMD with a mean effect of 0.28 (95% CI = 0.08, 0.39)., Conclusion: Our data suggest that SSRIs are associated with a decrease of BMD. We aim to raise clinicians' awareness of the potential association between the use of antidepressants and bone fragility to increase monitoring of bone health., Competing Interests: The authors declare that they have no conflict of interests.

Objective: Self-reports or patient-reported outcome measures are seldom used in psychosis due to concerns about the ability of patients to accurately report their symptomatology, particularly in cases of low awareness of illness. The aim of this study was to assess the effect of insight on the accuracy of self-reported psychotic symptoms using a computerized adaptive testing tool (CAT-Psychosis)., Methods: A secondary analysis of data drawn from the CAT-Psychosis development and validation study was performed. The Brief Psychiatric Rating Scale and the Scale of Unawareness of Mental Disorders were administered by clinicians. Patients completed the self-reported version of the CAT-Psychosis. Patients were median-split regarding their insight level to compare the correlation between the two psychosis severity measures. A subgroup sensitivity analysis was performed only on patients with schizophrenia spectrum disorders., Results: A total of 159 patients with a psychotic disorder who completed both CAT-Psychosis and Scale of Unawareness of Mental Disorders were included. For the whole sample, CAT-Psychosis scores showed convergent validity with Brief Psychiatric Rating Scale ratings ( r  = 0.517, 95% confidence interval = [0.392, 0.622], p  < 0.001). Insight was found to moderate this correlation (β = -0.511, p  = 0.005), yet agreement between both measures remained statistically significant for both high ( r  = 0.621, 95% confidence interval = [0.476, 0.733], p  < 0.001) and low insight patients ( r  = 0.408, 95% confidence interval = [0.187, 0.589], p  < 0.001), while psychosis severity was comparable between these groups (for Brief Psychiatric Rating Scale: U  = 3057, z  = -0.129, p  = 0.897; disorganization: U  = 2986.5, z  = -0.274, p  = 0.784 and for CAT-Psychosis: U  = 2800.5, z  = -1.022, p  = 0.307). Subgroup of patients with schizophrenia spectrum disorders showed very similar results., Conclusions: Insight moderates the correlation between self-reported and clinician-rated severity of psychosis, yet CAT-Psychosis remains valid in patients with both high and low awareness of illness.

Calcium (Ca++) metabolism may be impaired in several psychiatric diseases. We hypothesize that calcium imbalance might also correlate with a specific chronotype and could be recognized as a marker of illness severity in bipolar disorder (BD). We aimed to (1) identify the association between calcium imbalance and a specific chronotype in a cohort of BD patients, and (2) test the mediation role of high parathyroid hormone (PTH) levels towards a specific chronotype and illness severity in BD patients. Patients’ socio-demographic and clinical characteristics were collected with an ad-hoc schedule. We administered the Hamilton Depression Rating Scale (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), the Young Mania Rating Scale (YMRS), and the Morningness Eveningness Questionnaire (MEQ). 100 patients affected by BD were recruited. The Kruskal-Wallis test showed a significant difference between the three MEQ groups in PTH levels (p < 0.001) and vitamin D levels (p = 0.048) but not in Ca++ levels (p = 0.426). Dwass-Steel-Critchlow-Fligner Pairwise analyses performed concerning three MEQ groups revealed significantly higher scores on PTH levels in MEQ-E subjects compared to MEQ-M and MEQ-I (in both cases, p < 0.001). No differences emerged between calcium levels among the three chronotypes. The mediation analysis has shown that elevated PTH levels are directly influenced by more severe HAM-A, HAM-D, and YMRS scores. MEQ-E could be a marker related to BD and predispose to various factors influencing mood symptoms. The combination of vitamin D therapy in MEQ-E may help to improve prognosis in this subtype of patients affected by BD.

Background: The degree of efficacy, safety, quality, and certainty of meta-analytic evidence of biological non-pharmacological treatments in mental disorders is unclear., Methods: We conducted an umbrella review (PubMed/Cochrane Library/PsycINFO-04-Jul-2021, PROSPERO/CRD42020158827) for meta-analyses of randomized controlled trials (RCTs) on deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), electro-convulsive therapy (ECT), and others. Co-primary outcomes were standardized mean differences (SMD) of disease-specific symptoms, and acceptability (for all-cause discontinuation). Evidence was assessed with AMSTAR/AMSTAR-Content/GRADE., Results: We selected 102 meta-analyses. Effective interventions compared to sham were in depressive disorders: ECT (SMD=0.91/GRADE=moderate), TMS (SMD=0.51/GRADE=moderate), tDCS (SMD=0.46/GRADE=low), DBS (SMD=0.42/GRADE=very low), light therapy (SMD=0.41/GRADE=low); schizophrenia: ECT (SMD=0.88/GRADE=moderate), tDCS (SMD=0.45/GRADE=very low), TMS (prefrontal theta-burst, SMD=0.58/GRADE=low; left-temporoparietal, SMD=0.42/GRADE=low); substance use disorder: TMS (high frequency-dorsolateral-prefrontal-deep (SMD=1.16/GRADE=moderate), high frequency-left dorsolateral-prefrontal (SMD=0.77/GRADE=very low); OCD: DBS (SMD=0.89/GRADE=moderate), TMS (SMD=0.64/GRADE=very low); PTSD: TMS (SMD=0.46/GRADE=moderate); generalized anxiety disorder: TMS (SMD=0.68/GRADE=low); ADHD: tDCS (SMD=0.23/GRADE=moderate); autism: tDCS (SMD=0.97/GRADE=very low). No significant differences for acceptability emerged. Median AMSTAR/AMSTAR-Content was 8/2 (suggesting high-quality meta-analyses/low-quality RCTs), GRADE low., Discussion: Despite limited certainty, biological non-pharmacological interventions are effective and safe for numerous mental conditions. Results inform future research, and guidelines., Funding: None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: The nine-item Shared Decision-Making Questionnaire (SDM-Q-9) is one of the most frequently used tools for assessing patients' involvement in medical decision-making, but so far, it not been validated in Italian. We aimed to validate the Italian version of the SDM-Q-9 in a clinical sample of patients suffering from major psychiatric disorders., Method: We involved 307 consecutive patients affected by major psychiatric disorders (including schizophrenia spectrum disorders, affective disorders and eating disorders) in a real-world outpatient clinical setting. Confirmatory Factor Analysis (CFA) was conducted to examine the latent structure of the SDM-Q-9. Cronbach's alpha and correlations between the SDM-Q-9 and the Observing Patient Involvement (OPTION) scale were calculated to measure internal consistency and convergent validity respectively., Results: The final sample was made up of 289 participants (response rate 94.1%) who completed the assessment. CFA confirmed the unidimensional structure as in the original version (χ2/df= 1.69; CFI= 0.98; TLI= 0.97; RMSEA= 0.05; SRMR= 0.08). Internal consistency of the total scale was Cronbach's α = .86. Regarding construct validity, we found several correlations between the SDM-Q-9 and OPTION scale., Conclusions: Our findings suggest that the Italian version of SDM-Q-9 performs well if compared to other languages validated versions, so it is a useful patient-centred measure to assess the involvement in medical decision-making (SDM) of patients from clinical samples from the Italian-speaking population., Competing Interests: Competing interests: None., (© 2022 Giovanni Fioriti Editore s.r.l.)

Introduction: Obesity is a major health problem with an increasing risk of mortality, associated with comorbidities and high rates of dropout. Research demonstrated that pathological eating behaviors could help to phenotype obese patients thus tailoring clinical interventions. Therefore, our aim was to develop (study 1), validate (study 2), and test in a clinical setting (study 3) the Eating Behaviors Assessment for Obesity (EBA-O)., Method: Study 1 included the exploratory factor analysis (EFA) and McDonald's ω in a general population sample (N = 471). Study 2 foresaw the confirmatory factor analysis (CFA) and convergent validity in 169 participants with obesity. Study 3 tested the capability of the EBA-O to characterize eating behaviors in a clinical sample of 74 patients with obesity., Results: Study 1. EFA identified five factors (i.e., food addiction, night eating, binge eating, sweet eating, and prandial hyperphagia), explaining 68.3% of the variance. The final EBA-O consisted of 18 items. McDonald's ω ranged between 0.80 (hyperphagia) and 0.92 (binge eating), indicating very good reliability., Study 2: A second-order five-factor model, through CFA, showed adequate fit: relative chi-square (χ 2 /df) = 1.95, CFI = 0.93, TLI = 0.92, RMSEA = 0.075, and SRMR = 0.06, thus suggesting the appropriateness of the EBA-O model. Significant correlations with psychopathological questionnaires demonstrated the convergent validity. Study 3. Significant associations between EBA-O factors and emotional-related eating behaviors emerged., Conclusion: The EBA-O demonstrated to be a reliable and easy-to-use clinical tool to identify pathological eating behaviors in obesity, particularly useful for non-experts in eating disorders., Level of Evidence: Level V, descriptive research., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Despite significant advances in early-intervention services for psychosis, delays in identifying patients continue to impede the delivery of prompt and effective treatments. We sought to develop and preliminarily validate a self-administered psychosis implicit association task (P-IAT) as a screening and diagnostic support tool for identifying individuals with psychotic illness in community settings. The P-IAT is a response latency task, designed to measure the extent to which individuals implicitly associate psychosis-related terms with the "self." The P-IAT was administered to 57 participants across 3 groups: healthy controls (N=19), inpatients hospitalized with active psychosis (N=19), and outpatients with psychotic disorders (N=19). Mean D-scores (the output of the task) differed significantly between the illness groups and healthy controls (Mann-Whitney U=138, p<.001). A receiver operating curve was plotted to assess the performance of D-scores in predicting a psychosis diagnosis, yielding an area under the curve of 0.81. When participant D-scores exceeded -0.24, the test achieved a specificity of 100% (sensitivity: 47%), with all 18 participants scoring above this threshold belonging to the illness groups. The discriminant performance of the P-IAT suggests its potential to augment existing screening instruments and inform referral decision making, particularly in settings with limited access to specialist providers., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Dissociative symptoms have been recently related to bipolar disorder (BD) symptomatology. Moreover, the disease burden carries on a share of perceived self-stigma that amplifies the BD impairment. Internalized stigma and dissociative symptoms often seem overlapping, leading toward common outcomes, with reduced treatment seeking and poor adherence. We hypothesize a potential relationship between dissociation and self-stigma in patients suffering from BD., Materials and Methods: In this cross-sectional study we enrolled a total of 120 adult clinically stable BD outpatients. All participants completed the Internalized Stigma of Mental Illness (ISMI), Dissociative Experiences Scale-II (DES-II), and Manchester Short Assessment of Quality of Life (MANSA)., Results: Average age and age at BD (BD-I n = 66, 55%; BD-II n = 54, 45%) onset were 46.14 (±4.23), and 27.45 (±10.35) years, with mean disease duration of 18.56 (±13.08) years. Most participants were female ( n = 71; 59.2%) and 40 (33%) of them experienced lifetime abuse, with an average of 1.05 (±0.78) suicide attempts. DES scores (mean 31.8, ±21.6) correlated with ISMI total-score, with significant association with spikes in Alienation (13.1, SD±3.1) ( p < 0.001) and Stereotype (13.8, SD±3.9) ( p < 0.001). Linear regression analysis has shown a significant association between DES total score and alienation ( p < 0.001), stereotype ( p < 0.001) and MANSA total-score ( p < 0.001)., Discussion: For the first time, our data suggests that self-stigma is associated to dissociative symptoms, reducing overall quality of life in BD. The early identification of at-risk patients with previous lifetime abuse and high perceived stigma could lead the way for an ever more precise tailoring of treatment management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 de Filippis, Menculini, D'Angelo, Carbone, Tortorella, De Fazio and Steardo.)

Background: The COVID-19 pandemic has captured the mental health discussion worldwide. Examining countries' representation in this discussion could prove instrumental in identifying potential gaps in terms of ensuring a truly global conversation in times of global crisis., Methods: We collected mental health and COVID-19-related journal articles published in PubMed in 2020. We focused on the corresponding authors' countries of affiliation to explore countries' representation. We also examined these articles' academic impact and correlations with their corresponding authors' countries of affiliation. Additional journals and countries' indicators were collected from the Web of Science and World Bank websites, respectively. Data were analyzed using the IBM SPSS Statistics and the VOSviewer software., Results: In total, 3492 publications were analyzed. Based on the corresponding author, high-income countries produced 61.9% of these publications. Corresponding authors from Africa, Latin America and the Caribbean, and the Middle East combined accounted for 11.8% of the publications. Europe hosted corresponding authors with the most publications and citations, and corresponding authors from North America had the largest mean journal impact factor., Conclusions: The global scientific discussion during the COVID-19 pandemic saw an increased contribution of academics from developing countries. However, authors from high-income countries have continued to shape this discussion. It is imperative to ensure the active participation of low- and middle-income countries in setting up the global mental health research agenda, particularly in situations of global crisis, such as the ongoing pandemic., (© The Author(s) 2022.)

Introduction: Varying public views on cannabis use across countries may explain the variation in the prevalence of use, policies, and research in individual countries, and global regulation of cannabis. This paper aims to describe the current state of cannabis use, policies, and research across sixteen countries., Methods: PubMed and Google Scholar were searched for studies published from 2010 to 2020. Searches were conducted using the relevant country of interest as a search term (e.g., "Iran"), as well as relevant predefined keywords such as "cannabis," "marijuana," "hashish," "bhang "dual diagnosis," "use," "addiction," "prevalence," "co-morbidity," "substance use disorder," "legalization" or "policy" (in English and non-English languages). These keywords were used in multiple combinations to create the search string for studies' titles and abstracts. Official websites of respective governments and international organizations were also searched in English and non-English languages (using countries national languages) to identify the current state of cannabis use, policies, and research in each of those countries., Results: The main findings were inconsistent and heterogeneous reporting of cannabis use, variation in policies (e.g., legalization), and variation in intervention strategies across the countries reviewed. European countries dominate the cannabis research output indexed on PubMed, in contrast to Asian countries (Thailand, Malaysia, India, Iran, and Nepal)., Conclusions: Although global cannabis regulation is ongoing, the existing heterogeneities across countries in terms of policies and epidemiology can increase the burden of cannabis use disorders disproportionately and unpredictably. There is an urgent need to develop global strategies to address these cross-country barriers to improve early detection, prevention, and interventions for cannabis use and related disorders., Competing Interests: No conflicts of interest declared concerning the publication of this article.

Background: Aberrant salience is a well-known construct associated with the development and maintenance of psychotic symptoms in schizophrenia. However, only a few studies have investigated aberrance salience as a trait, with no study investigating the association between the five aberrant salience domains and psychotic symptoms. We aimed to explore the role of aberrant salience and its domains on psychotic dimensions in both clinically remitted and non-remitted patients., Methods: A sample of 102 patients diagnosed with schizophrenia spectrum disorders was divided according to the Positive and Negative Syndrome Scale (PANSS) remission criteria into two groups: remitted and non-remitted. Differences regarding psychotic symptomatology assessed by the PANSS and aberrant salience measured by the Aberrant Salience Inventory (ASI) were explored. Finally, a correlation analysis between the PANSS and the ASI was run., Results: Significantly higher ASI scores were evident among non-remitted patients. Positive symptoms (i.e. delusions, conceptual disorganization, and hallucinatory behaviour) and general psychopathology (i.e. postural mannerisms, unusual thought content) were correlated to the aberrant salience subscales 'sharpening of senses', 'heightened emotionality' and 'heightened cognition' and with the ASI total score. Significant correlations emerged between negative symptoms (blunted affect and social withdrawal) and 'heightened cognition'. Finally, lack of spontaneity of conversation was related to the subscales 'heightened emotionality' and 'heightened cognition', as well as to the ASI total score., Conclusions: These preliminary results support the hypothesis of an association between aberrant salience and psychotic symptoms in schizophrenia. Further research is needed, especially into the mechanisms underlying salience processing, in addition to social and environmental factors and cognitive variables., (© 2022. The Author(s).)

Clozapine-related drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare adverse reaction. We aimed to screen a large pharmacovigilance database to identify clozapine-related DRESS cases, even if otherwise reported and provide a clinical overview. We screened spontaneous reports of clozapine-related DRESS syndrome in EudraVigilance database applying the European Registry on Severe Cutaneous Adverse Drug Reactions (RegiSCAR) criteria and scores to identify probable/definite DRESS syndrome cases. Clinical and demographic characteristics of included cases were provided and associations between RegiSCAR scores, and time to develop/recover DRESS were assessed. In a total of 262,146 adverse drug reactions reports for 75,190 clozapine-treated patients, 596 cases fulfilled RegiSCAR criteria; ultimately, 51 cases were rated as probable/definite DRESS according to RegiSCAR scores, of which 4 were previously published as case reports. The mean age of patients was 41.06 years (43.1% females), with 13 patients (25.5%) receiving reported co-medication with other DRESS culprit drugs. Median time between clozapine initiation and DRESS symptoms was 25 days. Clozapine dose was associated with days to develop symptoms (Spearman's ρ 0.40, p = 0.03). Organ involvement was reported in all cases followed by fever (n = 49; 96.1%) and eosinophilia (n = 47; 92.2%). Treatment involved clozapine discontinuation for 37 patients (72.5%), while 3.9% (n = 2) of cases ended fatally. Clozapine rechallenge was undertaken in 25 patients (49.0%). The screening of the EudraVigilance database revealed 47 novel clozapine-related DRESS cases, and only one was originally reported as DRESS. Clozapine-related DRESS may occur with clozapine monotherapy not only during dose titration, but also during maintenance treatment., Competing Interests: Conflict of interest Dr. Kane has been a consultant and/or advisor for or has received honoraria from Alkermes, Allergan, LB Pharmaceuticals, H. Lundbeck, Intracellular Therapies, Janssen Pharmaceuticals, Johnson and Johnson, Merck, Minerva, Neurocrine, Newron, Otsuka, Pierre Fabre, Reviva, Roche, Sumitomo Dainippon, Sunovion, Takeda, Teva and UpToDate and is a shareholder in LB Pharmaceuticals and Vanguard Research Group. Dr. Schoretsanitis has served as consultant for HLS Therapeutics and Thermo Fisher. All other authors report no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

Objectives: The sudden COVID-19 crisis required a determined effort on the part of the healthcare workers (HCWs) and excessive workload increased the risk of depressive and anxious symptoms in frontliners. The aim of the study was to assess anxiety and depression levels among HCWs during times of pandemic and its potential aggravating factors., Materials and Methods: A web-based survey was conducted to assess the mental health outcomes of healthcare workers and related factors during the COVID-19 pandemic. For assessing depression and anxiety, the Hospital Anxiety and Depression Scale (HADS) comprised of 14 items with seven items for depression and seven for anxiety were used., Results: Of all 436 participants, 158 (36.2%) showed noticeable symptoms of depression and 220 (50.4%) showed substantial anxiety symptoms. The majority of them were females. It has been observed in the study that female gender, young, and unmarried marital status are associated with higher scores. HCWs working in urban regions show more depressive symptoms. Mild depression and anxiety ratio are very common among participants (21.3%). Factors found to be associated with higher anxiety and depression are the increased number of deceased patients with lower family support., Conclusions: Altogether, the present study findings present concerns about the psychological well-being of all HCWs during the acute COVID-19 outbreak. Therefore, steps should be taken to protect them from mental exhaustion, so they may fight with more zeal against the infectious pandemic that has caused significant impacts worldwide., Competing Interests: None., (© 2022 The Author(s).)

COVID-19 was accompanied with the increasing broadcast of fake news, misinformation and excessive information via social media platforms. This phenomenon has been termed "infodemic", to describe an overwhelming amount of mostly fake, false or inaccurate information which spreads rapidly and impacts negatively on achieving a solution. It would therefore be desirable to use a cautious approach which utilizes culturally sensitive and country specific measures to deal with this occurrence. We aim to raise awareness, likewise draw the attention of global scientific community on this topic of public and mental health concern and it calls for further comments on this issue.

Climate change has become a global emergency, which mental health effects are increasingly being described and understood. Children and adolescents, especially those in low income countries and minority communities, are particularly vulnerable to experience the worst impacts of climate change now and in the coming decades. Our group of early career mental health clinicians and researchers in nine culturally and socioeconomic different countries across three continents initiated a global, online discussion about the effects of climate change on the mental health of children and adolescents, based on literature and our professional experience. We identified a paucity of research and psychiatric education on the topic, and a need to advance global and local efforts in this direction. We also identified three main domains of mental health impact of climate change: direct, indirect, and through physical conditions. Our work offers a preliminary, up-to-date overview of the consequences of climate change on the mental health of children and adolescents, and provides recommendations to advance policies, public health efforts, research, education, and clinical care in the emerging area of 'Climate Psychiatry'.

Objectives: We examined the associations of lockdown stringency and duration with Google searches for four mental health concepts (i.e., "Anxiety," "Depression," "Suicide," "Mental Health") in nine countries (i.e., Hungary, India, Iran, Italy, Paraguay, Serbia, South Africa, Spain, Turkey) during the COVID-19 pandemic., Methods: We retrieved national-level data for each country from Google Trends and the Global Panel Database of Pandemic Policies. In our primary analysis, we used data from all countries to estimate a set of multilevel regression models examining associations of overall lockdown stringency and lockdown duration with relative search volumes for each mental health term. We repeated the models after replacing overall lockdown stringency with each of the lockdown stringency components., Results: A negative association was found between overall lockdown stringency and "Depression." Lockdown duration and the most stringent stay-at-home requirements were negatively associated with "Anxiety." Policies that recommended or required the cancelation of public events evidenced negative associations with "Depression," whereas associations between policies that required some or all levels of schooling to close and "Depression" were positive. Policies that recommended or required workplaces to close and those that enforced quarantines on non-citizens arriving from high-risk regions or closed borders entirely were negatively associated with "Suicide.", Conclusions: Lockdown duration and some lockdown policies during the COVID-19 pandemic were generally associated with significantly lower, rather than higher, Google searches for selected mental health terms. These findings could be used alongside other evidence to develop future lockdown strategies that are sensitive to mental health issues during public health crises., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Recently two instruments were developed to address the study of the cognitive biases in schizophrenia spectrum disorders (SSD): the Cognitive Biases Questionnaire for Psychosis (CBQ-P) and the Davos Assessment of Cognitive Biases Scale (DACOBS). Aim of this study was to validate the Italian version of the DACOBS., Methods: We investigated factor structure, reliability, discriminative and convergent validity of the instrument by comparing to the CBQ-P in an Italian sample of 102 patients diagnosed with SSD and 330 healthy controls (HC), matched by age, education and gender., Results: The second-order seven-factor solution provided the best results among the four models tested. Reliability proved to be very satisfactory, with ω coefficient ranged from 0.75 for Jumping to conclusions to 0.89 for Safety Behavior. The Italian version of DACOBS could discriminate psychosis from HC (Wilks' Lambda=0.64, F=34.284, p<0.001; h2=0.364). All seven DACOBS subscales were significantly correlated with the CBQ-P subscales (total sample: r=0.331-0.707; SSD group: r=0.424-0.735; HC group: r=0.177-0.460)., Conclusions: The Italian version of DACOBS is a valid instrument for measuring cognitive biases for patients with psychosis, confirming previous results regarding the psychometric properties of the tool.

Objectives: Although lithium renal effects have been extensively investigated, prevalence rates of chronic kidney disease (CKD) in lithium-treated patients vary. Our aim was to provide prevalence estimates and related moderators., Methods: We performed a systematic review in PubMed/Embase until November 01, 2021, conducting a random effects meta-analysis of studies evaluating CKD prevalence rates in lithium-treated patients calculating overall prevalence ±95% confidence intervals (CIs). Meta-regression analyses included sex, age, body mass index, smoking, hypertension, diabetes, cardiovascular disease, lithium-treatment dose, duration, and blood levels. Subgroup analyses included sample size, diagnoses, and study design. Pooled odds ratios (OR) were estimated for studies including patients receiving nonlithium treatment. Study quality was assessed using the Newcastle-Ottawa scale., Results: Five, nine, and six trials were rated as high, fair, and low quality, respectively. In 20 studies (n = 25,907 patients), we estimated an overall prevalence of 25.5% (95% CI = 19.8-32.2) of impaired kidney function; despite lack of differences (p = 0.18), prevalence rates were higher in elderly samples than mixed samples of elderly and nonelderly (35.6%, 95% CI = 21.4-52.9, k = 2, n = 3,161 vs. 25.1%, 95% CI = 19.1-31.3, k = 18, n = 22,746). Prevalence rates were associated with longer lithium treatment duration (p = 0.04). Cross-sectional studies provided lower rates than retrospective studies (14.5%, 95% CI = 13.5-15.5, k = 6, n = 4,758 vs. 29.5%, 95% CI = 22.1-38.0, k = 12, n = 17,988, p < 0.001). Compared with 722,529 patients receiving nonlithium treatment, the OR of impaired kidney function in 14,187 lithium-treated patients was 2.09 (95% CI = 1.24-3.51, k = 8, p = 0.005)., Conclusions: One-fourth of patients receiving long-term lithium may develop impaired kidney function, although research suffers from substantial heterogeneity between studies. This risk may be twofold higher compared with nonlithium treatment and may increase for a longer lithium treatment duration., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Although antidepressant drugs appear to play an active role in increasing fracture risk, their weight is still unclear. We conducted a PRISMA compliant systematic review and meta-analysis through PubMed/Scopus/Cochrane libraries and registered with PROSPERO (registration number CRD42021254006) to investigate the relationship between antidepressant drugs categories, including SSRIs, SNRIs, and TCAs, and the risk of hip and vertebral fractures. After screening 3122 items, we finally found 26 papers for qualitative analysis and 11 for quantitative synthesis. A total of 15,209,542 adult and elderly patients were identified, with a mean follow-up of 51 months and a major prevalence of women. We identified results largely for SSRIs, with only a small amount of data for SNRIs, TCAs, and NaSSA. No data were found among the most recent categories of antidepressants, such as vortioxetine and esketamine. All included studies reported hip fractures, while three of them also included vertebral fractures. Overall, we observed a significant effect of SSRIs on fracture risk with a mean effect of 0.98 (95% CI = 0.75-1.20). This meta-analysis reveals that the use of SSRIs increases the risk of fractures. Clinicians' awareness in antidepressant prescription should optimize their potential while reducing this risk.

Objective: Neurological correlates of impaired insight in non-affective psychosis remain unclear. This study aimed to review and meta-analyze the studies assessing the grey matter volumetric correlates of impaired insight in non-affective psychosis., Methods: This study consisted of a systematic review of 23 studies, and a meta-analysis with SDM-PSI of the 11 studies that were whole-brain and reported maps or peaks of correlation of studies investigating the grey matter volumetric correlates of insight assessments of non-affective psychosis, PubMed and OVID datasets were independently reviewed for articles reporting neuroimaging correlates of insight in non-affective psychosis. Quality assessment was realized following previous methodological approaches for the ABC quality assessment test of imaging studies, based on two main criteria: the statistical power and the multidimensional assessment of insight. Study peaks of correlation between grey matter volume and insight were used to recreate brain correlation maps., Results: A total of 418 records were identified through database searching. Of these records, twenty-three magnetic resonance imaging (MRI) studies that used different insight scales were included. The quality of the evidence was high in 11 studies, moderate in nine, and low in three. Patients with reduced insight showed decreases in the frontal, temporal (specifically in superior temporal gyrus), precuneus, cingulate, insula, and occipital lobes cortical grey matter volume. The meta-analysis indicated a positive correlation between grey matter volume and insight in the right insula (i.e., the smaller the grey matter, the lower the insight)., Conclusion: Several brain areas might be involved in impaired insight in patients with non-affective psychoses. The methodologies employed, such as the applied insight scales, may have contributed to the considerable discrepancies in the findings., (Copyright © 2021 SEP y SEPB. Published by Elsevier España, S.L.U. All rights reserved.)

Every health care system requires an adequate health care workforce, service delivery, financial support, and information technology. During the COVID-19 pandemic, global health systems were ill prepared to address the rising prevalence of mental health problems, especially in low- and middle-income countries (LMICs), thereby increasing treatment gaps. To close these gaps globally, task shifting and telepsychiatry should be made available and maximized, particularly in LMICs. Task shifting to nonspecialist health workers to improve essential mental health coverage and encourage efficient use of the available resources and technology has become the most viable strategy.

Pramipexole is a dopamine agonist with potential antidepressant, neuroprotective, antioxidant and anti-inflammatory activity. In the present study we investigated the 24 weeks effect and safety of traditional AD augmentation with pramipexole for treatment-resistant depression. The study includes 116 patients, 37 (32%) with bipolar disorders and 79 (68%) with major depressive disorder, who failed to respond to at least 2 ADs trials of different classes and that were treated with AD augmented with pramipexole. Mood stabilizers and/or second-generation antipsychotics were added in patients with bipolar or mixed depression. Exclusion criteria were psychotic depression, rapid cycling bipolar course and previous unsuccessful treatment with pramipexole. After 24 weeks of pramipexole augmentation (median max dose 1.05 mg/day, IQR 0.72-1.08) 74.1% of patients responded (≥50% reduction of baseline Hamilton Depression Rating Scale 21 total score) and 66.4% remitted (Hamilton Depression Rating Scale 21 total score < 7). Global Assessment of Functioning score significantly increase from 53 (50-60) at baseline to 80 (71-81) at 24 weeks (Wilcoxon signed rank test = 8.174, p < 0.001]. Ten patients (8.6%) dropped out (8 due to side effects and 2 for lack of efficacy) and 1 experienced an induced hypomanic switch. No patient committed a suicide attempt, had suicidal ideation, needed hospitalization, reported lethargy, gambling, hypersexuality and compulsive shopping. The limitations of the study are the observational design, the lack of a control group, the inclusion of outpatients only, the unblinded outcomes assessment, and the flexibility of the add-on schedule. The findings of the present study showed that off-label use of pramipexole as augmentation of traditional AD is an effective and safe 24 weeks treatment of resistant unipolar and bipolar depression. These results need confirmation from randomized clinical trials on larger samples., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Competing Interests: Conflict of interestThe authors declare that they do not have conflict of interest.

Purpose: Since the World Health Organization declared the coronavirus outbreak a global pandemic several million cases and more than three million deaths have been already confirmed worldwide due to COVID-19., Design and Methods: Early Career Psychiatrists from all over the world present an overview of what happened in their own countries and what they have learned so far by this experience in everyday clinical practice., Practice Implication: We tried to take a real time picture of this unexpected situation, drawing useful hints for now and the future., (© 2021 Wiley Periodicals LLC.)

Background: Coronavirus Disease 2019 (COVID-19) is a worldwide public health concern. It continues to spread rapidly throughout the world causing multiple physical and psychological consequences in the population. Especially, people affected by severe psychiatric or neurological diseases are highly susceptible to serious health complications not only due to the direct effect of the infection but also to the indirect effect of COVID-19 following social distancing during lockdowns and its general social consequences. Indeed, lockdown and difficulties in using the care services produced psychological consequences in caregivers such as depression, anxiety, and worsening of the quality of life which in turn affected the ability to manage patients. Our aim was to systematically review the psychological consequences of the COVID-19 lockdown in caregivers of patients with cognitive impairment and dementia and the impact on the health of their patients. Methods: A systematic literature search was conducted by searching in MEDLINE/PubMed, Scopus, and Web of Science by two independent researchers following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines. Data extraction and quality assessment were also performed. Papers were screened for eligibility by abstract and then those which met inclusion criteria were included in this review. Results: The initial search returned 410 records. After the abstract screening and the inclusion/exclusion criteria were applied, 315 were excluded because they were irrelevant, 30 because they were reviews, meta-analyses, letters to editors, editorials, guidelines, or case reports, and 10 because they were duplicates. Then, 38 out of 55 abstracts/full-text articles were excluded because they did not simultaneously assess mental health of patients and caregivers. In the end, 17 papers were deemed eligible and included in the present review. Conclusion: Based on current literature, the COVID-19 pandemic and the ensuing lockdown caused severe psychological consequences for caregivers of patients with dementia, worsening their mental health, and increasing the psychological and physical burden, independently from the severity of the disease of their relatives, which resulted also independently globally worsened., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Carbone, de Filippis, Roberti, Rania, Destefano, Russo, De Sarro, Segura-Garcia and De Fazio.)

Schizophrenia is a major psychotic disorder affecting nearly 23.6 million people globally and greatly impacting the cognitive and social functioning of individuals. Multiple risk factors, including genetic, environmental, and epigenetic factors have been identified. However, the exact mechanism by which some factors aid in the development of schizophrenia is still uncertain. Acute and/or long-standing inflammation has been implicated as both a cause and effect of schizophrenia. Heightened immune responses have been documented in large cohorts of individuals with schizophrenia. While not completely known, multiple hypotheses, such as disruption of the blood-brain barrier, alterations in the kynurenine/tryptophan pathway, and increased microglial activation, have been presented to correlate inflammation with schizophrenic symptoms. Measurement of C-reactive protein (CRP) is a commonly performed and inexpensive test on patients' serum to determine levels of systemic inflammation in the body. Multiple studies have reported an elevated CRP level in different stages of schizophrenia, indicating its potential to be used as a viable biomarker in the diagnosis and monitoring of schizophrenia along with assessing treatment response to conventional and non-conventional treatment regimens. This review aims to evaluate the role of inflammation, in general, and CRP, in particular, in the pathogenesis of schizophrenia and its potential significance in diagnostic, therapeutic, and preventative approaches towards schizophrenia and psychosis.

There is an increasing movement toward international collaboration and global discussion in mental health. If provided with the right opportunities, early career psychiatrists (ECPs) and researchers in mental health can contribute meaningfully to this discussion. However, they often experience multiple barriers when attempting to add their voices via academic publications. We represent a diverse group of ECPs and researchers from all six World Health Organization regions. In this piece, we discuss these barriers, grounded in our first-hand experiences, and put forth a series of recommendations. The most potentially beneficial and immediate way forward is ensuring a much-needed mentorship and support, particularly for low- and middle-income countries. In this regard, international organizations, especially those with a particular focus on education, such as the Section on Education in Psychiatry of the World Psychiatric Association, can play a pivotal role., (© 2021 John Wiley & Sons Australia, Ltd.)

Background: Somnambulism, or sleepwalking (SW), is one of the most common forms of arousal parasomnias. It is characterized by different complex motor behaviors leading to unwanted movements in bed or walking during sleep. It can be the consequence of psychological stress, abnormal breathing during sleep, high fever, or drug adverse effects. There is evidence of an association between antipsychotic treatment, including olanzapine, and SW., Methods: We present the case of a patient experiencing treatment-resistant anorexia nervosa whose somnambulism re-exacerbated after the addition of a low dose of olanzapine, following the CARE (CAse REport) Statement and Checklist. We also conducted a systematic review of the literature on olanzapine-induced somnambulism following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, PsychINFO, and the Cochrane Library databases were independently reviewed up to January 2021 for articles reporting olanzapine-related somnambulism cases, without language or time restriction., Results: We describe a case of somnambulism in a patient initially admitted to our hospital for anorexia nervosa and treated with a low dose of olanzapine. This is the first case of SW induced by olanzapine in eating disorders to be reported. Up-to-date olanzapine-related somnambulism was described in 8 patients experiencing psychiatric disorders (ie, schizophrenia and bipolar disorder)., Conclusions: To provide a reliable estimate of incidence and prevalence for olanzapine-related somnambulism, large-scale, pharmacovigilance studies are required, to allow for comparisons of overall clinical characteristics, outcomes, including time to recovery, between different treatment options. Clinician awareness should be enhanced, and attention should be given to such infrequent adverse effects associated with antipsychotics., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Dissociative symptoms are under recognized and scarcely studied by clinicians and researchers in patients with bipolar disorder (BD). We examined the relationship between dissociative symptoms and the psychotic features in patients with BD and assessed clinical and socio-demographic characteristics more frequently associated with dissociative symptoms and treatment response. Methods: Participants were 100 adult outpatients with BD. They were screened with semi-structured interview to collect socio-demographic and clinical characteristics; the Dissociative Experiences Scale-II (DES-II) and the ALDA scale were used to assess dissociative psychopathologies and response to treatment with mood stabilizers, respectively. Results: DES score (mean 31.7 ± 21.7) correlated with clinical variables, BD features, and course of illness. Psychotic symptoms, mixed features, and previous suicide attempts significantly predicted DES score [ F (3, 47) = 39.880, p < 0.001, R 2 corrected = 0.713]. Dissociative symptoms were inversely correlated with poor response to treatment ( r = -0.593; p < 0.001). Limitations: Cross-sectional design with a small sample and backward clinical assessment of psychotic symptoms. Conclusions: Dissociative phenomena are closely related to the presence of psychotic symptoms, mixed features, and previous suicide attempts in BD, especially in BD-I. Given the close association between dissociative and psychotic symptoms, this association could represent a diagnostic indicator of BD-I that may guide the clinician to plan the most appropriate treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Steardo, Carbone, Ventura, de Filippis, Luciano, Segura-Garcia and De Fazio.)