Effects of electroconvulsive therapy on cortical thickness in depression: a systematic review.

OBJECTIVE: Electroconvulsive therapy (ECT) is one of the most studied and validated available treatments for severe or treatment-resistant depression. However, little is known about the neural mechanisms underlying ECT. This systematic review aims to critically review all structural magnetic resonance imaging studies investigating longitudinal cortical thickness (CT) changes after ECT in patients with unipolar or bipolar depression. METHODS: We performed a search on PubMed, Medline, and Embase to identify all available studies published before April 20, 2023. A total of 10 studies were included. RESULTS: The investigations showed widespread increases in CT after ECT in depressed patients, involving mainly the temporal, insular, and frontal regions. In five studies, CT increases in a non-overlapping set of brain areas correlated with the clinical efficacy of ECT. The small sample size, heterogeneity in terms of populations, comorbidities, and ECT protocols, and the lack of a control group in some investigations limit the generalisability of the results. CONCLUSIONS: Our findings support the idea that ECT can increase CT in patients with unipolar and bipolar depression. It remains unclear whether these changes are related to the clinical response. Future larger studies with longer follow-up are warranted to thoroughly address the potential role of CT as a biomarker of clinical response after ECT.

Dimensions and predictors of clinical and personal recovery in first-episode psychoses: Results from a cross-sectional study.

INTRODUCTION: First episode psychosis (FEP) services ensure higher recovery rates compared to usual care. The aim of this study was to investigate the different dimensions of recovery and its predictors. METHODS: This cross-sectional study recruited within those admitted to the Ferrara FEP service since 2012 that at the time of analysis were still receiving psychiatric care. At admission, demographic, social and clinical information were collected. In September 2022, patients were assessed with the Health of the Nation Outcome Scale to evaluate clinical/functional recovery, the Recovery Assessment Scale to evaluate personal recovery, and the G12 item of the Positive and Negative Syndrome Scale to evaluate insight. Patients in recovery were compared to those not in recovery by bivariate analyses. Adjusted logistic regressions were performed to investigate predictors of recovery. RESULTS: Within 141 admitted, and 105 still receiving care, 54 patients completed the assessment. Most (51.9%) were in clinical/functional, 61.1% in personal recovery, and 38.8% both. Psychiatric hospitalization positively predicted clinical/functional recovery, whereas being prescribed oral antipsychotics was a negative predictor. Personal recovery was predicted by male sex and showed a negative association with overall severity of symptomatology. Those in personal recovery were more likely to have been prescribed long-acting antipsychotics, but this was not significant in the multivariable analysis. Poor insight negatively predicted clinical/functional recovery but had no impact on personal recovery. CONCLUSION: Our findings confirm that clinical/functional and personal recovery are semi-independent dimensions and not always overlap. Further research is needed to promote interventions targeted at all recovery dimensions.

Action prediction in psychosis.

Aberrant motor-sensory predictive functions have been linked to symptoms of psychosis, particularly reduced attenuation of self-generated sensations and misattribution of self-generated actions. Building on the parallels between prediction of self- and other-generated actions, this study aims to investigate whether individuals with psychosis also demonstrate abnormal perceptions and predictions of others' actions. Patients with psychosis and matched controls completed a two-alternative object size discrimination task. In each trial, they observed reaching actions towards a small and a large object, with varying levels of temporal occlusion ranging from 10% to 80% of movement duration. Their task was to predict the size of the object that would be grasped. We employed a novel analytic approach to examine how object size information was encoded and read out across progressive levels of occlusion with single-trial resolution. Patients with psychosis exhibited an overall pattern of reduced and discontinuous evidence integration relative to controls, characterized by a period of null integration up to 20% of movement duration, during which they did not read any size information. Surprisingly, this drop in accuracy in the initial integration period was not accompanied by a reduction in confidence. Difficulties in action prediction were correlated with the severity of negative symptoms and impaired functioning in social relationships.

Core-curriculum in psycho-oncology: Towards the certification of the psycho-oncologist profession.

BACKGROUND: Issues relating to certification of the Psycho-oncology profession require clarification in order to provide high quality comprehensive psychosocial care within oncology. We conducted a survey identifying existing training, professional registration requirements and accreditation programs, at national levels, for the specialty of psycho-oncology as well as the mandatory presence of this specialist in cancer teams. METHODS: This survey was conducted within the International Psycho-Oncology Society Federation of psycho-oncology societies and included representatives of each national federated society and some countries not belonging to the Federation. Survey questions were emailed requesting specific details, from the registered contact person, for each country, about psycho-oncology training, professional registration and accreditation. RESULTS: Of 43 countries contacted (34 Federated and 9 non-federated members), 39 replied and answered the questionnaire (90, 7%). Disparities were reported between countries, with details indicating differences from having no national program, to quite detailed and legally accredited requirements. The majority of countries had no formally recognized profession of "Psycho-oncologist," while some countries reported that it is mandatory (or recommended to have) a specialist in psycho-oncology in cancer centers and, thus, that an accredited, nationally recognized and certified training in this specialty exists. CONCLUSIONS: The study underlines the need to create a curriculum for the specialty (certification and accreditation) for the profession of psycho-oncology. Given the lack of internationally recognized core standards, ideas and proposals for minimum standards of good care and the training required to deliver this, are explored to clarify who may use the designation "Clinical Psycho-oncologist."

Sex differences in schizophrenia-spectrum diagnoses: results from a 30-year health record registry.

This study investigated sociodemographic and clinical differences between the sexes in individuals affected by schizophrenia-spectrum disorders (SSD) who accessed outpatient mental health services. Within a retrospective cohort of 45,361 outpatients receiving care in Ferrara (Italy) from 1991 to 2021, those with a SSD diagnosis were compared between the sexes for sociodemographic and clinical characteristics before and after the index date (when the ICD-9: 295.*diagnosis was first recorded) to assess early trajectory, age and type of diagnosis, and severity of illness indicated by medication use, hospitalization, and duration of psychiatric care. Predictors of discharge were also investigated. Among 2439 patients, 1191 were women (48.8%). Compared to men, women were significantly older at first visit (43.7 vs. 36.8 years) and at index date (47.8 vs. 40.6) with peak frequency at age 48 (vs. 30). The most frequent last diagnosis recorded before the index date was delusional disorder (27.7%) or personality disorder (24.3%) in men and depression (24%) and delusional disorder (30.1%) in women. After the index date, long-acting antipsychotics and clozapine were more frequently prescribed to men (46.5% vs. 36.3%; 13.2% vs. 9.4%, p < 0.05) and mood stabilizers and antidepressants to women (24.3% vs. 21.1%; 50.1% vs. 35.5%; p < 0.05). Women had fewer involuntary admissions (10.1% vs. 13.6%) and were more likely to be discharged as the time under care increased (p = 0.009). After adjusting for covariates, sex was not a significant predictor of discharge. Our study confirmed that sex differences exist in clinical and sociodemographic characteristics of outpatients with SSD and that gender considerations might influence the rapidity of diagnosis and medications prescribed. These findings highlight the need to implement a women-tailored approach in specialist care programs for psychoses.

Tamoxifen for the treatment of myeloproliferative neoplasms: A Phase II clinical trial and exploratory analysis.

Current therapies for myeloproliferative neoplasms (MPNs) improve symptoms but have limited effect on tumor size. In preclinical studies, tamoxifen restored normal apoptosis in mutated hematopoietic stem/progenitor cells (HSPCs). TAMARIN Phase-II, multicenter, single-arm clinical trial assessed tamoxifen's safety and activity in patients with stable MPNs, no prior thrombotic events and mutated JAK2V617F, CALRins5 or CALRdel52 peripheral blood allele burden ≥20% (EudraCT 2015-005497-38). 38 patients were recruited over 112w and 32 completed 24w-treatment. The study's A'herns success criteria were met as the primary outcome ( ≥ 50% reduction in mutant allele burden at 24w) was observed in 3/38 patients. Secondary outcomes included ≥25% reduction at 24w (5/38), ≥50% reduction at 12w (0/38), thrombotic events (2/38), toxicities, hematological response, proportion of patients in each IWG-MRT response category and ELN response criteria. As exploratory outcomes, baseline analysis of HSPC transcriptome segregates responders and non-responders, suggesting a predictive signature. In responder HSPCs, longitudinal analysis shows high baseline expression of JAK-STAT signaling and oxidative phosphorylation genes, which are downregulated by tamoxifen. We further demonstrate in preclinical studies that in JAK2V617F+ cells, 4-hydroxytamoxifen inhibits mitochondrial complex-I, activates integrated stress response and decreases pathogenic JAK2-signaling. These results warrant further investigation of tamoxifen in MPN, with careful consideration of thrombotic risk.

Establishment of a Public Mental Health Database for Research Purposes in the Ferrara Province: Development and Preliminary Evaluation Study.

Background: The immediate use of data exported from electronic health records (EHRs) for research is often limited by the necessity to transform data elements into an actual data set. Objective: This paper describes the methodology for establishing a data set that originated from an EHR registry that included clinical, health service, and sociodemographic information. Methods: The Extract, Transform, Load process was applied to raw data collected at the Integrated Department of Mental Health and Pathological Addictions in Ferrara, Italy, from 1925 to February 18, 2021, to build the new, anonymized Ferrara-Psychiatry (FEPSY) database. Information collected before the first EHR was implemented (ie, in 1991) was excluded. An unsupervised cluster analysis was performed to identify patient subgroups to support the proof of concept. Results: The FEPSY database included 3,861,432 records on 46,222 patients. Since 1991, each year, a median of 1404 (IQR 1117.5-1757.7) patients had newly accessed care, and a median of 7300 (IQR 6109.5-9397.5) patients were actively receiving care. Among 38,022 patients with a mental disorder, 2 clusters were identified; the first predominantly included male patients who were aged 25 to 34 years at first presentation and were living with their parents, and the second predominantly included female patients who were aged 35 to 44 years and were living with their own families. Conclusions: The process for building the FEPSY database proved to be robust and replicable with similar health care data, even when they were not originally conceived for research purposes. The FEPSY database will enable future in-depth analyses regarding the epidemiology and social determinants of mental disorders, access to mental health care, and resource utilization.

A genome-wide association study of blood cell morphology identifies cellular proteins implicated in disease aetiology.

Blood cells contain functionally important intracellular structures, such as granules, critical to immunity and thrombosis. Quantitative variation in these structures has not been subjected previously to large-scale genetic analysis. We perform genome-wide association studies of 63 flow-cytometry derived cellular phenotypes-including cell-type specific measures of granularity, nucleic acid content and reactivity-in 41,515 participants in the INTERVAL study. We identify 2172 distinct variant-trait associations, including associations near genes coding for proteins in organelles implicated in inflammatory and thrombotic diseases. By integrating with epigenetic data we show that many intracellular structures are likely to be determined in immature precursor cells. By integrating with proteomic data we identify the transcription factor FOG2 as an early regulator of platelet formation and α-granularity. Finally, we show that colocalisation of our associations with disease risk signals can suggest aetiological cell-types-variants in IL2RA and ITGA4 respectively mirror the known effects of daclizumab in multiple sclerosis and vedolizumab in inflammatory bowel disease.

Psychosocial determinants of healthcare use costs in kidney transplant recipients.

Introduction: Psychosocial factors frequently occur in kidney transplant recipients (KTRs), leading to behavioral alterations and reduced therapeutic adherence. However, the burden of psychosocial disorders on costs for KTRs is unknown. The aim of the study is to identify predictors of healthcare costs due to hospital admissions and emergency department access in KTRs. Methods: This is a longitudinal observational study conducted on KTRs aged >18 years, excluding patients with an insufficient level of autonomy and cognitive disorder. KTRs underwent psychosocial assessment via two interviews, namely the Mini-International Neuropsychiatric Interview 6.0 (MINI 6.0) and the Diagnostic Criteria for Psychosomatic Research Interview (DCPR) and via the Edmonton Symptom Assessment System Revised (ESAS-R) scale, a self-administrated questionnaire. Sociodemographic data and healthcare costs for hospital admissions and emergency department access were collected in the 2016-2021 period. Psychosocial determinants were as follows: (1) ESAS-R psychological and physical score; (2) symptomatic clusters determined by DCPR (illness behavior cluster, somatization cluster, and personological cluster); and (3) ICD diagnosis of adjustment disorder, anxiety disorder, and mood disorder. A multivariate regression model was used to test the association between psychosocial determinants and total healthcare costs. Results: A total of 134 KTRs were enrolled, of whom 90 (67%) were men with a mean age of 56 years. A preliminary analysis of healthcare costs highlighted that higher healthcare costs are correlated with worse outcomes and death (p < 0.001). Somatization clusters (p = 0.020) and mood disorder (p < 0.001) were positively associated with costs due to total healthcare costs. Conclusions: This study showed somatization and mood disorders could predict costs for hospital admissions and emergency department access and be possible risk factors for poor outcomes, including death, in KTRs.

The facets of psychopathology in patients with cancer: Cross-sectional and longitudinal network analyses.

OBJECTIVE: Cancer patients display heterogeneous psychopathology, comprising depressive, anxiety, hostility, and somatic symptoms. Often, clinical pictures evolve over time deteriorating the individual functioning and prognosis. Network models can reveal the relationships between symptoms, thus providing clinical insights. METHOD: This study examined data of the Brief Symptom Inventory and the Distress Thermometer, from 1108 cancer outpatients. Gaussian Graphical Models were estimated using regularized and non-regularized Bayesian methods. In addition, we used community detection methods to identify the most relevant symptom groupings, and longitudinal network analyses on 515 participants to examine the connections between symptoms over three months. RESULTS: The network models derived from baseline data suggested symptoms clustered into three main complexes (depression/anxiety, hostility, and somatic symptoms). Symptoms related to depression and hostility were highly connected with suicidal and death thoughts. Faintness, weakness, chest pain, and dyspnoea, among somatic symptoms, were more strongly connected with psychopathological features. Longitudinal analyses revealed that sadness, irritability, nervousness, and tension predicted each other. Panic and death thoughts predicted fearfulness and faintness. CONCLUSIONS: Somatic symptoms, sadness, irritability, chronic and acute anxiety interact between each other, shaping the heterogeneous clinical picture of distress in cancer. This study, strengthened by robust methods, is the first to employ longitudinal network analyses in cancer patients. Further studies should evaluate whether targeting specific symptoms might prevent the onset of chronic distress and improve clinical outcomes in cancer patients.

Poor sleep quality may contribute to dysfunctional illness perception, physical and emotional distress in hospitalised patients: results of a national survey of the Italian Society of Consultation-Liaison Psychiatry.

Distress associated with physical illness is a well-known risk factor for adverse illness course in general hospitals. Understanding the factors contributing to it should be a priority and among them dysfunctional illness perception and poor sleep quality may contribute to it. As poor sleep quality is recognised as a major risk factor for health problems, we aimed to study its association with illness perception and levels of distress during hospitalisation. This cross-sectional study included a consecutive series of 409 individuals who were hospitalised in medical and surgical units of different hospitals located throughout the Italian national territory and required an assessment for psychopathological conditions. Sleep quality was assessed with the Pittsburgh (Sleep Quality Index), emotional and physical distress with the Edmonton Symptom Assessment System (ESAS), and illness perception with the Brief Illness Perception Questionnaire (BIPQ). Differences between groups, correlations and mediations analyses were computed. Patients with poor sleep quality were more frequently females, with psychiatric comorbidity, with higher scores in the ESAS and BIPQ. Poor sleep quality was related to dysfunctional illness perception, and to both emotional and physical distress. In particular, by affecting cognitive components of illness perception, poor sleep quality may, directly and indirectly, predict high levels of distress during hospitalisation. Poor sleep quality may affect >70% of hospitalised patients and may favour dysfunctional illness perception and emotional/physical distress.Assessing and treating sleep problems in hospitalised patients should be included in the routine of hospitalised patients.

Cancer mortality in Common Mental Disorders: A 10-year retrospective cohort study.

PURPOSE: Individuals with Common Mental Disorders (CMDs) may have a higher cancer mortality. The purpose of this study was to examine cancer-related mortality among patients with CMDs and verify which cancer types are predominantly involved. METHODS: We used the Regional Mental Health Registry of the Emilia-Romagna region, in Northern Italy to identify patients aged ≥ 18 years who received an ICD 9-CM diagnosis of CMDs (i.e., depressive and neurotic disorders) over a 10 year period (2008-2017). Information on cause of death was retrieved from the Regional Cause of Death Registry. Comparisons were made with data from the regional population without CMDs. RESULTS: Among 101,487 patients suffering from CMDs (55.7% depression; 44.3% neurotic disorders), 3,087 (37.8%) died from neoplasms. The total standardized mortality ratio (SMR) was 1.82 (95% CI 1.78-1.86) while the SMR for all neoplasms was 2.08 (95% CI 2.01-2.16). Individuals of both genders, with both depressive and neurotic disorders had a higher risk of death from almost all cancers compared with the regional population. CONCLUSION: Patients with CMDs have considerably higher cancer mortality risk than the general population. Higher mortality was observed for a broad range of cancers associated with different aetiologies. It is imperative to promote cancer awareness, prevention and treatment for people with CMDs.

The Italian validation of the Death and Dying Distress Scale.

OBJECTIVES: Death anxiety (DA), a condition characterized by fear, angst, or panic related to the awareness of one's own death, is commonly observed in advanced cancer patients. The aim of this study was to examine the psychometric properties of the Italian version of the Death and Dying Distress Scale (DADDS-IT) in a sample of patients with advanced cancer. METHODS: The sample included 200 Italian advanced cancer patients meeting eligibility criteria to access palliative care. Patients' levels of DA were assessed by using the DADDS-IT, while the levels of depression, anxiety, demoralization, spiritual well-being, and symptom burden were assessed using the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7, the Demoralization Scale, the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale, and the Edmonton Symptom Assessment System, respectively; Karnofsky Performance Status was used to measure functional impairment. Confirmatory factor analyses (CFA) of previous structures and exploratory factor analyses (EFA) were conducted. RESULTS: CFA revealed that none of the previous structures adequately fitted data from our sample. EFA revealed a 4-factor model comprising Finitude (α = 0.91), Regret (α = 0.86), Dying (α = 0.88), and Relational Burden (α = 0.73), accounting for the 77.1% of the variance. Dying subscore was higher in hospice patients than in those recruited in medical wards. SIGNIFICANCE OF RESULTS: The present study provides further evidence that DA is a condition that deserves attention and that DADDS-IT shows good psychometric properties to support its use in research and clinical settings.

Violence Against Physicians in the Workplace: Trends, Causes, Consequences, and Strategies for Intervention.

PURPOSE: Violence against healthcare professionals has become an emergency in many countries. Literature in this area has mainly focused on nurses while there are less studies on physicians, whose alterations in mental health and burnout have been linked to higher rates of medical errors and poorer quality of care. We summarized peer-reviewed literature and examined the epidemiology, main causes, consequences, and areas of intervention associated with workplace violence perpetrated against physicians. RECENT FINDINGS: We performed a review utilizing several databases, by including the most relevant studies in full journal articles investigating the problem. Workplace violence against doctors is a widespread phenomenon, present all over the world and related to a number of variables, including individual, socio-cultural, and contextual variables. During the COVID-19 pandemic, incidence of violence has increased. Data also show the possible consequences in physicians' deterioration of quality of life, burnout, and traumatic stress which are linked to physical and mental health problems, which, in a domino effect, fall on patients' quality of care. Violence against doctors is an urgent global problem with consequences on an individual and societal level. This review highlights the need to undertake initiatives aimed at enhancing understanding, prevention, and management of workplace violence in healthcare settings.

Machine Learning and Non-Affective Psychosis: Identification, Differential Diagnosis, and Treatment.

PURPOSE OF REVIEW: This review will cover the most relevant findings on the use of machine learning (ML) techniques in the field of non-affective psychosis, by summarizing the studies published in the last three years focusing on illness detection and treatment. RECENT FINDINGS: Multiple ML tools that include mostly supervised approaches such as support vector machine, gradient boosting, and random forest showed promising results by applying these algorithms to various sources of data: socio-demographic information, EEG, language, digital content, blood biomarkers, neuroimaging, and electronic health records. However, the overall performance, in the binary classification case, varied from 0.49, which is to be considered very low (i.e., noise), to over 0.90. These results are fully justified by different factors, some of which may be attributable to the preprocessing of the data, the wide variety of the data, and the a-priori setting of hyperparameters. One of the main limitations of the field is the lack of stratification of results based on biological sex, given that psychosis presents differently in men and women; hence, the necessity to tailor identification tools and data analytic strategies. Timely identification and appropriate treatment are key factors in reducing the consequences of psychotic disorders. In recent years, the emergence of new analytical tools based on artificial intelligence such as supervised ML approaches showed promises as a potential breakthrough in this field. However, ML applications in everyday practice are still in its infancy.

Changes of consultation-liaison psychiatry practice in Italian general hospitals: A comparative 20-year multicenter study.

Introduction: Conducted under the auspices of the Italian Society of Consultation Liaison Psychiatry (SIPC) the aim of this study was to describe the characteristics of Consultation Liaison Psychiatry (CLP) activity in Italy (SIPC-2-2018) over the past 20 years by comparing with data from the first Italian nation-wide study (SIPC-1-1998). Methods: We collected data on CLP visits of 3,943 patients from 10 Italian hospitals over a period of 1 year. Data were compared with those from the SIPC-1 1998 study (4,183 participants). Patients were assessed with the same ad hoc 60-item Patient Registration Form recording information from five different areas: Sociodemographic, hospitalization-related, consultation-related, interventions and outcome. Results: Compared with participants from the previous study, SIPC-2-2018 participants were significantly older (d = 0.54) and hospitalized for a longer duration (d = 0.20). The current study detected an increase in the proportion of referrals from surgical wards and for individuals affected by onco-hematologic diseases. Depressive disorders still represented the most frequent psychiatric diagnosis, followed by adjustment and stress disorders and delirium/dementia. Also, CLP psychiatrists prescribed more often antidepressants (Φ = 0.13), antipsychotics (Φ = 0.09), mood stabilizers (Φ = 0.24), and less often benzodiazepines (Φ = 0.07). Conclusion: CLP workload has increased considerably in the past 20 years in Italy, with changes in patient demographic and clinical characteristics. A trend toward increase in medication-based patient management was observed. These findings suggest that the psychiatric needs of patients admitted to the general hospital are more frequently addressed by referring physicians, although Italian CLP services still deserve better organization and autonomy.

Cognitive functioning as predictor and marker of response to repetitive transcranial magnetic stimulation in depressive disorders: A systematic review.

OBJECTIVE: Cognitive performance in Major Depressive Disorder (MDD) is frequently impaired and related to functional outcomes. Repetitive Transcranial Magnetic Stimulation (rTMS) may exert its effects on MDD acting both on depressive symptoms and neurocognition. Furthermore, cognitive status could predict the therapeutic response of depressive symptoms to rTMS. However, cognitive performances as a predictor of rTMS response in MDD has not been thoroughly investigated. This review aims to evaluate the role of pre-treatment cognitive performance as a predictor of clinical response to rTMS, and the effects of rTMS on neurocognition in MDD. METHOD: A systematic review of studies evaluating neurocognition in MDD as an outcome and/or predictor of response to rTMS was conducted using PubMed/Medline and Embase. RESULTS: Fifty-eight articles were identified: 25 studies included neurocognition as a predictor of response to rTMS; 56 used cognitive evaluation as an outcome of rTMS. Baseline cognitive performance and cognitive improvements after rTMS predicted clinical response to rTMS. Moreover, rTMS improved cognition in MDD. CONCLUSIONS: Cognitive assessment could predict improvement of depression in MDD patients undergoing rTMS and help selecting patients that could have beneficial effects from rTMS. A routine cognitive assessment might stratify MDD patients and track rTMS related cognitive improvement.

Suicide risk in medically ill inpatients referred to consultation-liaison psychiatric services: A multicenter study.

BACKGROUND: The aim of this multicenter study was to investigate the suicide risk in medically ill patients admitted to six Italian hospitals for whom a consultation-liaison intervention was requested. METHODS: Participants completed socio-demographic and clinical report forms and the Brief Illness Perception Questionnaire. Suicidality was assessed using the P4 screener that investigates the presence of Past suicide attempts, Plans to commit a suicide, Probability of completing suicide, and Preventive factors. Participants were categorized as being at no, low or high suicide risk. Univariate and multivariable associations of categorical and continuous variables with suicide risk were investigated using multinomial logistic regression. RESULTS: Of the 641 inpatients, with mean age 60 years (SD = 16.9) and 49.2 % male, 13.2 % were at high suicidal risk (HR), 7.6 % low risk (LR) and 79.2 % no risk. Contacts with psychiatrists in the previous six months were associated with LR and HR (OR = 2.159 and 2.634, respectively), ongoing benzodiazepine use was associated with a threefold likelihood of LR (OR = 3.005), and the experienced intensity of illness symptoms was associated with LR and HR (OR = 1.257 and OR = 1.248, respectively). CL psychiatrists prescribed appropriate psychotropic drugs and activated liaison interventions and psychological support for the level of suicidal risk. LIMITATIONS: The use of self-report measures bears the risk of recall bias. CONCLUSIONS: Our findings based on psychiatric consultations in the general hospital underscore the need to include suicide risk in the routine assessment of inpatients referred to CL psychiatric services and to plan an appropriate management of suicidal risk after discharge.

Monoclonal Antibody Sequence Variants Disguised as Fragments: Identification, Characterization, and Their Removal by Purification Process Optimization.

During early stage development of a therapeutic IgG1 monoclonal antibody, high levels of low molecular weight (LMW) peaks were observed by high performance size-exclusion chromatography and capillary electrophoresis. Further characterization of the LMW peak enriched HPSEC fractions using reversed phase liquid chromatography coupled to mass spectrometry showed these LMW species were 47 kDa and 50 kDa in size. However, the measured masses could not be matched to any fragments resulting from peptide bond hydrolysis. To identify these unknown LMW species, molecular characterization methods were employed, including high-throughput sequencing of RNA. Transcriptomic analysis revealed the LMW species were generated by mis-splicing events in the heavy chain transcript, which produced truncated heavy chain products that assembled with the light chain to mimic the appearance of fragments identified by routine purity assays. In an effort to improve product quality, an optimized purification process was developed. Characterization of the process intermediates confirmed removal of both LMW species by the optimized process. Our study demonstrates that deep-dive analytical characterization of biotherapeutics is critical to ensure product quality and inform process development. Transcriptomic analysis tools can help identify the cause of unknown species, and plays a key role in product and process characterization.

Circadian Rhythm Alterations May be Related to Impaired Resilience, Emotional Dysregulation and to the Severity of Mood Features in Bipolar I and II Disorders.

Objective: The study aimed to investigate the possible impact of resilience and emotion dysregulation on the clinical manifestations of bipolar disorders (BDs) focusing on the possible role of circadian rhythm alterations. Method: A sample of 197 inpatients suffering from BD of type I (BDI) or II (BDII) were assessed during a major depressive episode using the Structural Clinical Interview for DSM-5 (SCID-5), the Beck Depression Inventory-II (BDI-II), the Young Mania Rating Scale (YMRS), Resilience Scale for Adults (RSA), Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), Difficulties in Emotion Regulation Scale (DERS) and the Scale for Suicide Ideation (SSI). Participants with or without circadian rhythm disturbances as measured with Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), were compared; regression and mediation analyses were computed. Results: Participants with circadian rhythms disturbances showed a greater severity of depressive symptoms, of suicidal risk, lower resilience and more disturbances in emotion regulation including impulsivity and regulatory strategies. The logistic regression revealed that circadian rhythm disturbances was related to depressive symptoms (O.R. 4.0), suicidal risk (OR 2.51), emotion dysregulation (OR 2.28) and low resilience (OR 2.72). At the mediation analyses, circadian rhythm alterations showed an indirect effect on depressive symptoms by impairing resilience (Z= 3.17, p=0.0014)/ emotional regulation (Z= 4.36, p<0.001) and on suicidal risk by affecting resilience (Z= 2.00, p=0.045) and favoring impulsivity (Z= 2.14, p=0.032). Conclusions: The present findings may show that circadian rhythm alterations might play a key role in BD manifestations, as being correlated with more severe clinical presentations of depressive symptoms, suicidal risk, impaired resilience and emotional regulation. Addressing circadian rhythm alterations might potentially promote resilience and emotion regulation hence improving mood symptoms and suicidal risk in BDs.